[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"_public_publisher_byId_24dbdf9f-3452-464f-802d-47316319180b":3,"_public_publication_all{\"sortAscending\":false,\"sortField\":\"updateTime\",\"page\":0,\"size\":10,\"facet\":true,\"searchKey\":\"publisherId:24dbdf9f-3452-464f-802d-47316319180b,\"}":157},{"code":4,"data":5,"meta":18},"SUCCESS",{"id":6,"createTime":7,"updateTime":8,"relativeEntities":9,"slug":10,"properties":11,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":20,"manageAffiliations":27,"indexDatabases":43,"url":18,"thumbnailPath":18,"statistic":78,"gsStatistic":18,"type":18,"analyzePriority":18},"24dbdf9f-3452-464f-802d-47316319180b","2024-04-18T04:10:10.232+00:00","2025-11-21T10:05:18.861+00:00",[],"Springer-Science-and-Business-Media-LLC",{"title":12,"eissn":14},{"EN":13},"Springer Science and Business Media LLC",{"VOID":15},"1550-7416","PUBLISHER","PENDING",null,0,[21],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":23,"label":24,"description":26,"parentId":18,"standard":18,"scholarHubFieldId":18},"988aad6e-c496-4836-b969-f61991a0eed2",[],{"EN":25},"Pharmaceutical Science",{},[28,36],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":30,"slug":18,"properties":31,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":34,"statistic":18},"1553eaa4-de45-4fd0-9ca3-a7b44788e9e7",[],{"title":32},{"EN":33},"Springer New York",[35],"9a7c7208-b28a-42c2-a634-5a7f90eee3ab",{"id":37,"createTime":18,"updateTime":18,"relativeEntities":38,"slug":18,"properties":39,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":42,"statistic":18},"26a19206-5cad-4456-bb2f-49abd254fbc6",[],{"title":40},{"EN":41},"SPRINGER",[],[44,61],{"id":45,"indexDatabase":46,"url":58,"indexYears":18,"academicFieldIds":59,"indexDatabaseRanking":18},"bde9b7d4-f219-4841-9e64-c0b7b30a77d6",{"id":47,"createTime":18,"updateTime":18,"relativeEntities":48,"label":49,"description":51,"key":54,"publicationTags":55,"standard":18},"a4921856-b128-4d9f-8f1f-e80813d3bbd4",[],{"EN":50,"VI":50},"ISI\u002FSCIE - Science Citation Index Expanded",{"EN":52,"VI":53},"SCIE database","Cơ sở dữ liệu SCIE","scie",[56,57],"SCIE","ISI","https:\u002F\u002Fmjl.clarivate.com\u002Fsearch-results?issn=1550-7416",[60],"2b943d65-24a8-4546-9232-a1e32c12cb6c",{"id":62,"indexDatabase":63,"url":73,"indexYears":74,"academicFieldIds":75,"indexDatabaseRanking":77},"8a66ae77-5f98-48a6-bda5-43dd0b0cda87",{"id":64,"createTime":18,"updateTime":18,"relativeEntities":65,"label":66,"description":68,"key":70,"publicationTags":71,"standard":18},"3c7051d4-eb7d-4c57-a56b-36fc74c5d1e9",[],{"EN":67,"VI":67},"Scopus - Elsevier",{"EN":67,"VI":69},"Cơ sở dữ liệu Scopus thuộc Elsevier","scopus",[72],"SCOPUS","https:\u002F\u002Fwww.scopus.com\u002Fsourceid\u002F4000148019","1999-2025",[76],"6e740848-171b-4f21-8d03-9fed10ed0384","SCOPUS__Q1",{"impactFactor":19,"impactFactorByYear":79,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":97,"totalCitation":117,"totalCitationByYear":118,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":137,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},0.02,0.1,0.87,0.59,0.68,0.77,0.74,0.51,0.63,1.06,1.11,0.95,0.45,0.43,180,24,1446,{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},12,61,26,55,63,49,53,94,71,105,103,104,113,74,66,85,67,47,17,12911,{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},141,1174,1435,363,1014,1792,1478,395,692,500,778,527,313,475,401,68,57,8.93,{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},11.75,19.25,23.52,13.96,18.44,28.44,30.16,7.45,7.36,7.04,7.41,5.12,3.01,6.88,6.42,6.08,1.66,1.01,59,{"meta":158,"data":160},{"total":159},"1454",[161,270,490,680,785,940,1425,2099,2373,2620],{"id":162,"createTime":163,"updateTime":164,"relativeEntities":165,"slug":166,"properties":167,"entityType":177,"verifyStatus":178,"verifyTime":179,"verifyNote":180,"languages":18,"translateLanguages":181,"viewCount":19,"primaryUrl":183,"fullTextUrl":184,"authors":185,"publicationType":216,"publisherRelationship":217,"citationCount":18,"citationInfo":18,"publishDate":266,"publishYear":267,"citationAnalyzeStatus":17,"lastCitationAnalyze":18,"indexDatabases":268,"openAccess":18,"references":18,"isForceReanalyzing":269},"402767d9-48d6-4d4d-8268-c46c76bc7511","2024-02-22T00:22:20.392+00:00","2026-09-09T10:13:30.898+00:00",[],"Predicting-the-Effects-of-Anti-angiogenic-Agents-Targeting-Specific-VEGF-Isoforms",{"abstract":168,"title":170,"references":173,"doi":175},{"EN":169},"Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis, whose effect on cancer growth and development is well characterized. Alternative splicing of VEGF leads to several different isoforms, which are differentially expressed in various tumor types and have distinct functions in tumor blood vessel formation. Many cancer therapies aim to inhibit angiogenesis by targeting VEGF and preventing intracellular signaling leading to tumor vascularization; however, the effects of targeting specific VEGF isoforms have received little attention in the clinical setting. In this work, we investigate the effects of selectively targeting a single VEGF isoform, as compared with inhibiting all isoforms. We utilize a molecular-detailed whole-body compartment model of VEGF transport and kinetics in the presence of breast tumor. The model includes two major VEGF isoforms, VEGF121 and VEGF165, receptors VEGFR1 and VEGFR2, and co-receptors Neuropilin-1 and Neuropilin-2. We utilize the model to predict the concentrations of free VEGF, the number of VEGF\u002FVEGFR2 complexes (considered to be pro-angiogenic), and the receptor occupancy profiles following inhibition of VEGF using isoform-specific anti-VEGF agents. We predict that targeting VEGF121 leads to a 54% and 84% reduction in free VEGF in tumors that secrete both VEGF isoforms or tumors that overexpress VEGF121, respectively. Additionally, 21% of the VEGFR2 molecules in the blood are ligated following inhibition of VEGF121, compared with 88% when both isoforms are targeted. Targeting VEGF121 reduces tumor free VEGF and is an effective treatment strategy. Our results provide a basis for clinical investigation of isoform-specific anti-VEGF agents.",{"EN":171,"VI":172},"Predicting the Effects of Anti-angiogenic Agents Targeting Specific VEGF Isoforms","Dự đoán tác dụng của các chất ức chế sinh mạch nhắm vào các isoform VEGF cụ thể",{"VOID":174},"citation_journal_title=Futur Oncol; citation_title=Therapeutic potential of manipulating VEGF splice isoforms in oncology; citation_author=ES Rennel, SJ Harper, DO Bates; citation_volume=5; citation_issue=5; citation_publication_date=2009; citation_pages=703-712; citation_doi=10.2217\u002Ffon.09.33; citation_id=CR1\ncitation_journal_title=Cancer Res; citation_title=VEGF165b, and inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma; citation_author=DO Bates, T-G Cui, JM Doughty, M Winkler, M Sugiono, JD Shields; citation_volume=62; citation_publication_date=2002; citation_pages=4123-4131; citation_id=CR2\ncitation_journal_title=J Cell Sci.; citation_title=Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors; citation_author=DG Nowak, J Woolard, EM Amin, O Konopatskaya, MA Saleem, AJ Churchill; citation_volume=121; citation_publication_date=2008; citation_pages=3487-3495; citation_doi=10.1242\u002Fjcs.016410; citation_id=CR3\ncitation_journal_title=Circul Res.; citation_title=The VEGF165b \"ICE-o-form\" puts a chill on the VEGF story; citation_author=AO Dokun, BH Annex; citation_volume=109; citation_publication_date=2011; citation_pages=246-247; citation_doi=10.1161\u002FCIRCRESAHA.111.249953; citation_id=CR4\ncitation_journal_title=Circul Res.; citation_title=Overexpression of VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, leads to insufficient angiogenesis in patients with systemic sclerosis; citation_author=M Manetti, S Guiducci, E Romano, C Ceccarelli, S Bellando-Randone, ML Conforti; citation_volume=109; citation_publication_date=2011; citation_pages=e14-e26; citation_doi=10.1161\u002FCIRCRESAHA.111.242057; citation_id=CR5\ncitation_journal_title=Molecular Cancer.; citation_title=VEGF121b and VEGF165b are weakly angiogenic isoforms of VEGF-A; citation_author=R Catena, L Larzabal, M Larrayoz, E Molina, J Hermida, J Agorreta; citation_volume=9; citation_publication_date=2010; citation_pages=320; citation_doi=10.1186\u002F1476-4598-9-320; citation_id=CR6\ncitation_journal_title=J Cell Biochem; citation_title=VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding; citation_author=S Soker, H-Q Miao, M Nomi, S Takashima, M Klagsbrun; citation_volume=85; citation_issue=2; citation_publication_date=2002; citation_pages=357-368; citation_doi=10.1002\u002Fjcb.10140; citation_id=CR7\ncitation_journal_title=J Biol Chem; citation_title=The interaction of neuropilin-1 with vascular endothelial growth factor and its receptor flt-1; citation_author=G Fuh, KC Garcia, AM Vos; citation_volume=275; citation_publication_date=2000; citation_pages=26690-26695; citation_id=CR8\ncitation_journal_title=Mol Biol Cell.; citation_title=The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF; citation_author=JE Park, G-A Keller, N Ferrara; citation_volume=4; citation_publication_date=1993; citation_pages=1317-1326; citation_id=CR9\ncitation_journal_title=J Biol Chem; citation_title=Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms; citation_author=K Houck, DW Leung, AM Rowland, J Winer, N Ferrara; citation_volume=268; citation_issue=36; citation_publication_date=1992; citation_pages=26031-26037; citation_id=CR10\ncitation_journal_title=Mol Cell Biol; citation_title=Isoforms of vascular endothelial growth factor act in a coordinate fashion to recruit and expand tumor vasculature; citation_author=J Grunstein, JJ Masbad, R Hickey, F Giordano, RS Johnson; citation_volume=20; citation_issue=19; citation_publication_date=2000; citation_pages=7292-1; citation_doi=10.1128\u002FMCB.20.19.7282-7291.2000; citation_id=CR11\ncitation_journal_title=Cancer Res; citation_title=Blood vessel maturation and response to vascular-disrupting therapy in single vascular endothelial growth factor-A isoform-producing tumors; citation_author=GM Tozer, S Akerman, NA Cross, PR Barber, MA Bjorndahl, O Greco; citation_volume=68; citation_publication_date=2008; citation_pages=2301-2311; citation_doi=10.1158\u002F0008-5472.CAN-07-2011; citation_id=CR12\ncitation_journal_title=Cancer Res; citation_title=Vascular endothelial growth factor isoform expression as a determinant of blood vessel patterning in human melanoma xenografts; citation_author=JL Yu, JW Rak, G Klement, RS Kerbel; citation_volume=62; citation_publication_date=2002; citation_pages=1838-1846; citation_id=CR13\ncitation_journal_title=J Clin Oncol; citation_title=Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer; citation_author=A Yuan, C-J Yu, S-H Kuo, W-J Chen, F-Y Lin, K-T Luh; citation_volume=19; citation_issue=2; citation_publication_date=2001; citation_pages=432-441; citation_id=CR14\ncitation_journal_title=Proc Natl Acad Sci U S A; citation_title=Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189; citation_author=S-Y Cheng, M Nagane, H-JS Huang, WK Cavenee; citation_volume=94; citation_issue=22; citation_publication_date=1997; citation_pages=12081-12087; citation_doi=10.1073\u002Fpnas.94.22.12081; citation_id=CR15\ncitation_journal_title=PLoS One; citation_title=Functional and structural characteristics of tumor angiogenesis in lung cancers overexpressing different VEGF isoforms assessed by DCE- and SSCE-MRI; citation_author=A Yuan, C-Y Lin, C-H Chou, C-M Shih, C-Y Chen, H-W Cheng; citation_volume=6; citation_issue=1; citation_publication_date=2011; citation_pages=e16062; citation_doi=10.1371\u002Fjournal.pone.0016062; citation_id=CR16\ncitation_journal_title=Br J Cancer; citation_title=Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer; citation_author=T Tokunaga, Y Oshika, Y Abe, Y Ozeki, S Sadahiro, H Kijima; citation_volume=77; citation_issue=6; citation_publication_date=1998; citation_pages=998-1002; citation_doi=10.1038\u002Fbjc.1998.164; citation_id=CR17\ncitation_journal_title=Br J Cancer; citation_title=Overexpression of VEGF121, but not VEGF165 or FGF-1, improves oxygenation in MCF-7 breast tumors; citation_author=BM Fenton, SF Paoni, W Liu, S-Y Cheng, B Hu, I Ding; citation_volume=90; citation_issue=2; citation_publication_date=2004; citation_pages=430-435; citation_doi=10.1038\u002Fsj.bjc.6601539; citation_id=CR18\ncitation_journal_title=Eur J Cancer; citation_title=Tumour control by whole brain irradiation of anti-VEGF-treated mice bearing intracerebral glioma; citation_author=JJC Verhoeff, LJA Stalpers, A Claes, KE Hovinga, GD Musters, WP Vandertop; citation_volume=45; citation_issue=17; citation_publication_date=2009; citation_pages=3074-3080; citation_doi=10.1016\u002Fj.ejca.2009.08.004; citation_id=CR19\ncitation_journal_title=J Biol Chem; citation_title=2′-Fluoropyrimidine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor (VEGF165). Inhibition of receptor binding and VEGF-induced vascular permeability through interactions requiring the exon 7-encoded domain; citation_author=J Ruckman, LS Green, J Beeson, S Waugh, WL Gillette, DD Henninger; citation_volume=273; citation_publication_date=1998; citation_pages=20556-20567; citation_doi=10.1074\u002Fjbc.273.32.20556; citation_id=CR20\ncitation_journal_title=Nat Rev Drug Discov.; citation_title=Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease; citation_author=EWM Ng, DT Shima, P Calias, ET Cunningham, DR Guyer, AP Adamis; citation_volume=5; citation_publication_date=2006; citation_pages=123-132; citation_doi=10.1038\u002Fnrd1955; citation_id=CR21\ncitation_journal_title=J Exp Med.; citation_title=VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization; citation_author=S Ishida, T Usui, K Yamashiro, Y Kaji, S Amano, Y Ogura; citation_volume=198; citation_issue=3; citation_publication_date=2003; citation_pages=483-489; citation_doi=10.1084\u002Fjem.20022027; citation_id=CR22\ncitation_journal_title=Clin Pharmacol Ther; citation_title=Network systems biology for drug discovery; citation_author=DK Arrell, A Terzic; citation_volume=8; citation_issue=1; citation_publication_date=2010; citation_pages=120-125; citation_doi=10.1038\u002Fclpt.2010.91; citation_id=CR23\ncitation_journal_title=Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.; citation_title=A systems biology view of cancer; citation_author=R Laubenbacher, V Hower, A Jarrah, SV Torti, V Shulaev, P Mendes; citation_volume=1796; citation_issue=2; citation_publication_date=2009; citation_pages=129-139; citation_doi=10.1016\u002Fj.bbcan.2009.06.001; citation_id=CR24\ncitation_journal_title=BMC Syst Biol; citation_title=Pharmacokinetics and pharmacodynamics of VEGF-neutralizing antibodies; citation_author=SD Finley, MO Engel-Stefanini, PI Imoukhuede, AS Popel; citation_volume=5; citation_publication_date=2011; citation_pages=193; citation_doi=10.1186\u002F1752-0509-5-193; citation_id=CR25\ncitation_journal_title=Cancer Res; citation_title=Increase of plasma VEGF after intravenous administration of bevacizumab is predicted by a pharmacokinetic model; citation_author=MO Stefanini, FTH Wu, F Mac Gabhann, AS Popel; citation_volume=70; citation_issue=23; citation_publication_date=2010; citation_pages=9886-9894; citation_doi=10.1158\u002F0008-5472.CAN-10-1419; citation_id=CR26\ncitation_journal_title=Science; citation_title=Lymphatic metastasis in the absence of functional intratumor lymphatics; citation_author=TP Padera, A Kadambi, E Tomaso, CM Carreira, EB Brown, Y Boucher; citation_volume=296; citation_issue=5574; citation_publication_date=2002; citation_pages=1883-1886; citation_doi=10.1126\u002Fscience.1071420; citation_id=CR27\ncitation_journal_title=Cancer Res; citation_title=Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation; citation_author=AJ Leu, DA Berk, A Lymboussaki, K Alitalo, RK Jain; citation_volume=60; citation_publication_date=2000; citation_pages=4324-4327; citation_id=CR28\ncitation_journal_title=Exp Cell Res.; citation_title=Quantification and cell-to-cell variation of vascular endothelial growth factor receptors; citation_author=PI Imoukhuede, AS Popel; citation_volume=317; citation_issue=7; citation_publication_date=2011; citation_pages=955-965; citation_doi=10.1016\u002Fj.yexcr.2010.12.014; citation_id=CR29\nGenentech, Inc. Avastin prescribing information [cited September2011]; Available from: \n                    http:\u002F\u002Fwww.avastin.com\u002Favastin\u002Fhcp\u002Foverview\u002Fabout\u002Fdosing\u002Findex.html\n                    \n                  .\ncitation_journal_title=J Clin Oncol; citation_title=Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer; citation_author=MS Gordon, K Margolin, M Talpaz, GW Sledge, E Holmgren, R Benjamin; citation_volume=19; citation_issue=3; citation_publication_date=2001; citation_pages=843-850; citation_id=CR31\ncitation_journal_title=Pharm Res; citation_title=Complexation of VEGF with bevacizumab decreases VEGF clearance in rats; citation_author=V Hsei, GG DeGuzman, A Nixon, J Gaudreault; citation_volume=19; citation_issue=11; citation_publication_date=2002; citation_pages=1753-1756; citation_doi=10.1023\u002FA:1020778001267; citation_id=CR32\ncitation_journal_title=J Biol Chem; citation_title=Cross-species vascular endothelial growth factor (VEGF)-blocking antibodies completely inhibit the growth of human tumor xenografts and measure the contribution of stromal VEGF; citation_author=W-C Liang, X Wu, FV Peale, CV Lee, YG Meng, J Gutierrez; citation_volume=281; citation_publication_date=2006; citation_pages=951-961; citation_doi=10.1074\u002Fjbc.M508199200; citation_id=CR33\ncitation_journal_title=Cancer Res; citation_title=Vascular endothelial growth factor isoforms display distinct activities in promoting tumor angiogenesis at different anatomic sites; citation_author=P Guo, L Xu, S Pan, RA Brekken, S-T Yang, GB Whitaker; citation_volume=61; citation_publication_date=2001; citation_pages=8569-8577; citation_id=CR34\ncitation_journal_title=Int J Cancer; citation_title=Increased expression of VEGF121\u002FVEGF165-189 ratio results in a significant enhancement of human prostate tumor angiogenesis; citation_author=R Catena, V Muniz-Medina, B Moralejo, B Javierre, CJM Best, MR Emmert-Buck; citation_volume=120; citation_publication_date=2007; citation_pages=2096-2109; citation_doi=10.1002\u002Fijc.22461; citation_id=CR35\ncitation_journal_title=Br J Cancer; citation_title=The 121 amino acid isoform of vascular endothelial growth factor is more strongly tumorigenic than other splice variants in vivo\n                  ; citation_author=H-T Zhang, PAE Scot, L Morbidelli, S Peak, J Moore, H Turley; citation_volume=83; citation_issue=1; citation_publication_date=2000; citation_pages=63-68; citation_doi=10.1054\u002Fbjoc.2000.1279; citation_id=CR36\ncitation_journal_title=Clin Cancer Res; citation_title=Vascular endothelial growth factor splice variants and their prognostic value in breast and ovarian cancer; citation_author=M Stimpfl, D Tong, B Fasching, E Schuster, A Obermair, S Leodolter; citation_volume=8; citation_issue=7; citation_publication_date=2002; citation_pages=2253-2259; citation_id=CR37\ncitation_journal_title=Lab Invest.; citation_title=Quantification of VEGF mRNA expression in non-small cell lung cancer using a real-time quantitative reverse transcription-PCR assay and a comparison with quantitative competitive reverse transcription-PCR; citation_author=A Yuan, CJ Yu, KT Luh, FY Lin, SH Kuo, PC Yang; citation_volume=2000; citation_issue=80; citation_publication_date=2000; citation_pages=11; citation_id=CR38\ncitation_journal_title=Hum Pathol; citation_title=Tissue-specific expression pattern of vascular endothelial growth factor isoforms in the malignant transformation of lung and colon; citation_author=N Cheung, MP Wong, ST Yuen, SY Leung, LP Chung; citation_volume=29; citation_issue=9; citation_publication_date=1998; citation_pages=910-914; citation_doi=10.1016\u002FS0046-8177(98)90195-2; citation_id=CR39\ncitation_journal_title=Urol Res; citation_title=Tumor vascular endothelial growth factor (VEGF) mRNA in relation to serum VEGF protein levels and tumour progression in human renal cell carcinoma; citation_author=B Ljungberg, J Jacobsen, S Haggstrom-Rudolfssson, T Rasmuson, G Lindh, K Grankvist; citation_volume=31; citation_issue=5; citation_publication_date=2003; citation_pages=335-340; citation_doi=10.1007\u002Fs00240-003-0346-x; citation_id=CR40\ncitation_journal_title=Clin Chem; citation_title=Quantitative real-time reverse transcription-PCR study of the expression of vascular endothelial growth factor (VEGF) splice variants and VEGF receptors (VEGFR-1 and VEGFR-2) in non-small cell lung cancer; citation_author=E Zygalaki, EG Tsaroucha, L Kaklamanis, ES Lianidou; citation_volume=53; citation_issue=8; citation_publication_date=2007; citation_pages=1433-1439; citation_doi=10.1373\u002Fclinchem.2007.086819; citation_id=CR41\ncitation_journal_title=Anticancer Res; citation_title=Expression of the vascular endothelial growth factor (VEGF) gene in epithelial ovarian cancer: an approach to anti-VEGF therapy; citation_author=K Hata, Y Watanabe, H Nakai, T Hata, H Hoshiai; citation_volume=31; citation_issue=2; citation_publication_date=2011; citation_pages=731-737; citation_id=CR42\ncitation_journal_title=Fibrogenesis Tissue Repair.; citation_title=Interstitial fluid: the overlooked component of the tumor microenvironment?; citation_author=H Wiig, O Tenstad, PO Iversen, R Kalluri, R Bjerkvig; citation_volume=3; citation_publication_date=2010; citation_pages=12; citation_doi=10.1186\u002F1755-1536-3-12; citation_id=CR43\ncitation_journal_title=J Pediatr Surg; citation_title=Highly specific antiangiogenic therapy is effective in suppressing growth of experimental Wilms tumors; citation_author=J Huang, J Moore, S Soffer, E Kim, D Rowe, CA Manley; citation_volume=36; citation_publication_date=2001; citation_pages=357-361; citation_doi=10.1053\u002Fjpsu.2001.20716; citation_id=CR44\ncitation_journal_title=Inflamm Bowel Dis.; citation_title=VEGF164 isoform specific regulation of T-cell-dependent experimental colitis in mice; citation_author=JH Chidlow, JD Glawe, CB Pattillo, S Pardue, S Zhang, CG Kevil; citation_volume=17; citation_publication_date=2011; citation_pages=1501-1512; citation_doi=10.1002\u002Fibd.21525; citation_id=CR45\ncitation_journal_title=Arch Ophthalmol; citation_title=Vascular endothelial growth factor in aqueous humor before and after intravitreal injection of bevacizumab in eyes with diabetic retinopathy; citation_author=O Sawada, H Kawamura, M Kakinoki, T Sawada, M Ohji; citation_volume=125; citation_issue=10; citation_publication_date=2007; citation_pages=1363-1366; citation_doi=10.1001\u002Farchopht.125.10.1363; citation_id=CR46\ncitation_journal_title=World J Gastroenterol; citation_title=Expression of VEGF121 in gastric carcinoma MGC803 cell line; citation_author=XJ Tian, J Wu, L Meng, ZW Dong, CC Shou; citation_volume=6; citation_issue=2; citation_publication_date=2000; citation_pages=281-283; citation_id=CR47\ncitation_journal_title=Cancer Res; citation_title=Overexpression of vascular endothelial growth factor by MCF-7 breast cancer cells promotes estrogen-independent tumor growth in vivo\n                  ; citation_author=P Guo, Q Fang, H-Q Tao, CA Schafer, BM Fenton, I Ding; citation_volume=63; citation_publication_date=2003; citation_pages=4684-4691; citation_id=CR48",{"VOID":176},"10.1208\u002Fs12248-012-9363-4","PUBLICATION","VERIFIED","2024-10-15T06:14:11.464+00:00","Auto Verify",[182],"VI","https:\u002F\u002Flink.springer.com\u002Farticle\u002F10.1208\u002Fs12248-012-9363-4","https:\u002F\u002Flink.springer.com\u002Fcontent\u002Fpdf\u002F10.1208\u002Fs12248-012-9363-4.pdf",[186,202],{"id":187,"sortIndex":19,"researcher":18,"roles":188,"affiliations":190,"properties":199,"displayName":201,"givenName":18,"familyName":18},"2f65fc0c-4651-4c83-adcf-384634253741",[189],"AUTHOR",[191],{"id":192,"sortIndex":19,"affiliation":193,"properties":18},"b40d8275-d24f-48c7-9263-b8a463ca7d02",{"id":192,"createTime":18,"updateTime":18,"relativeEntities":194,"slug":18,"properties":195,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":198,"statistic":18},[],{"title":196},{"VI":197},"Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, USA",[],{"title":200},{"VI":201},"Finley, Stacey D.",{"id":203,"sortIndex":204,"researcher":18,"roles":205,"affiliations":206,"properties":213,"displayName":215,"givenName":18,"familyName":18},"a2866dc4-9175-4656-83f0-9d62abf16e6c",1,[189],[207],{"id":192,"sortIndex":19,"affiliation":208,"properties":18},{"id":192,"createTime":18,"updateTime":18,"relativeEntities":209,"slug":18,"properties":210,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":212,"statistic":18},[],{"title":211},{"VI":197},[],{"title":214},{"VI":215},"Popel, Aleksander S.","ARTICLE",{"url":183,"publisher":218,"properties":259},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":219,"slug":10,"properties":220,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":223,"manageAffiliations":228,"indexDatabases":239,"url":18,"thumbnailPath":18,"statistic":254,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":221,"eissn":222},{"EN":13},{"VOID":15},[224],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":225,"label":226,"description":227,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[229,234],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":230,"slug":18,"properties":231,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":233,"statistic":18},[],{"title":232},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":235,"slug":18,"properties":236,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":238,"statistic":18},[],{"title":237},{"EN":41},[],[240,247],{"id":45,"indexDatabase":241,"url":58,"indexYears":18,"academicFieldIds":246,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":242,"label":243,"description":244,"key":54,"publicationTags":245,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":248,"url":73,"indexYears":74,"academicFieldIds":253,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":249,"label":250,"description":251,"key":70,"publicationTags":252,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":255,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":256,"totalCitation":117,"totalCitationByYear":257,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":258,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"issue":260,"pages":262,"volume":264},{"VOID":261},"3",{"VOID":263},"500-509",{"VOID":265},"14","2012-09-01",2012,[56,77],false,{"id":271,"createTime":272,"updateTime":273,"relativeEntities":274,"slug":275,"properties":276,"entityType":177,"verifyStatus":178,"verifyTime":286,"verifyNote":180,"languages":18,"translateLanguages":287,"viewCount":19,"primaryUrl":288,"fullTextUrl":18,"authors":289,"publicationType":216,"publisherRelationship":440,"citationCount":18,"citationInfo":18,"publishDate":487,"publishYear":488,"citationAnalyzeStatus":17,"lastCitationAnalyze":18,"indexDatabases":489,"openAccess":18,"references":18,"isForceReanalyzing":269},"607de609-f24a-4e68-9ffd-1f6701f88d68","2024-02-08T22:49:45.390+00:00","2026-09-07T08:14:48.060+00:00",[],"Development-and-Validation-of-a-Western-Blot-Method-to-Quantify-Mini-Dystrophin-in-Human-Skeletal-Muscle-Biopsies",{"abstract":277,"title":279,"references":282,"doi":284},{"EN":278},"Duchenne muscular dystrophy (DMD) is a degenerative muscular disease affecting roughly one in 5000 males at birth. The disease is often caused by inherited X-linked recessive pathogenic variants in the dystrophin gene, but may also arise from de novo mutations. Disease-causing variants include nonsense, out of frame deletions or duplications that result in loss of dystrophin protein expression. There is currently no cure for DMD and the few treatment options available aim at slowing muscle degradation. New advances in gene therapy and understanding of dystrophin (DYS) expression in other muscular dystrophies have opened new opportunities for treatment. Therefore, reliable methods are needed to monitor dystrophin expression and assess the efficacy of new therapies for muscular dystrophies such as DMD and Becker muscular dystrophy (BMD). Here, we describe the validation of a novel Western blot (WB) method for the quantitation of mini-dystrophin protein in human skeletal muscle tissues that is easy to adopt in most laboratory settings. This WB method was assessed through precision, accuracy, selectivity, dilution linearity, stability, and repeatability. Based on mini-DYS standard performance, the assay has a dynamic range of 0.5–15 ng protein (per 5 µg total protein per lane), precision of 3.3 to 25.5%, and accuracy of − 7.5 to 3.3%. Our stability assessment showed that the protein is stable after 4 F\u002FT cycles, up to 2 h at RT and after 7 months at − 70°C. Furthermore, our WB method was compared to the results from our recently published LC–MS method. Workflow for our quantitative WB method to determine mini-dystrophin levels in muscle tissues (created in Biorender.com). Step 1 involves protein extraction from skeletal muscle tissue lysates from control, DMD, or BMD biospecimen. Step 2 measures total protein concentrations. Step 3 involves running gel electrophoresis with wild-type dystrophin (wt-DYS) from muscle tissue extracts alongside mini-dystrophin STD curve and mini-DYS and protein normalization with housekeeping GAPDH. \n                  \n                    \n                      \n                    \n                  \n                ",{"EN":280,"VI":281},"Development and Validation of a Western Blot Method to Quantify Mini-Dystrophin in Human Skeletal Muscle Biopsies","Phát triển và xác thực phương pháp Western blot để định lượng mini-dystrophin trong mẫu sinh thiết cơ xương người",{"VOID":283},"Emery AE. The muscular dystrophies. Lancet. 2002;359(9307):687–95.\nAssociation MD. Duchenne muscular dystrophy (DMD) 2021 [Available from: https:\u002F\u002Fwww.mda.org\u002Fdisease\u002Fduchenne-muscular-dystrophy.\nCarter JC, Sheehan DW, Prochoroff A, Birnkrant DJ. Muscular dystrophies. Clin Chest Med. 2018;39(2):377–89.\nShieh PB. Muscular dystrophies and other genetic myopathies. Neurol Clin. 2013;31(4):1009–29.\nHerbelet S, De Paepe B, De Bleecker JL. Description of a novel mechanism possibly explaining the antiproliferative properties of glucocorticoids in Duchenne muscular dystrophy fibroblasts based on glucocorticoid receptor GR and NFAT5. Int J Mol Sci. 2020;21(23).\nWaldrop MA, Moore SA, Mathews KD, Darbro BW, Medne L, Finkel R, et al. Intron mutations and early transcription termination in Duchenne and Becker muscular dystrophy. Hum Mutat. 2022.\nDuan D, Goemans N, Takeda S, Mercuri E, Aartsma-Rus A. Duchenne muscular dystrophy. Nat Rev Dis Primers. 2021;7(1):13.\nRomitti PA, Zhu Y, Puzhankara S, James KA, Nabukera SK, Zamba GK, et al. Prevalence of Duchenne and Becker muscular dystrophies in the United States. Pediatrics. 2015;135(3):513–21.\nAngelini C, Marozzo R, Pegoraro V. Current and emerging therapies in Becker muscular dystrophy (BMD). Acta Myol. 2019;38(3):172–9.\nFarea M, Rani AQM, Maeta K, Nishio H, Matsuo M. Dystrophin Dp71ab is monoclonally expressed in human satellite cells and enhances proliferation of myoblast cells. Sci Rep. 2020;10(1):17123.\nDatta N, Ghosh PS. Update on muscular dystrophies with focus on novel treatments and biomarkers. Curr Neurol Neurosci Rep. 2020;20(6):14.\nDrachman DB, Toyka KV, Myer E. Prednisone in Duchenne muscular dystrophy. Lancet. 1974;2(7894):1409–12.\nDeSilva S, Drachman DB, Mellits D, Kuncl RW. Prednisone treatment in Duchenne muscular dystrophy. Long-term benefit Arch Neurol. 1987;44(8):818–22.\nWang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci U S A. 2000;97(25):13714–9.\nKoo T, Okada T, Athanasopoulos T, Foster H, Takeda S, Dickson G. Long-term functional adeno-associated virus-microdystrophin expression in the dystrophic CXMDj dog. J Gene Med. 2011;13(9):497–506.\nHarper SQ, Hauser MA, DelloRusso C, Duan D, Crawford RW, Phelps SF, et al. Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat Med. 2002;8(3):253–61.\nLe Guiner C, Servais L, Montus M, Larcher T, Fraysse B, Moullec S, et al. Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy. Nat Commun. 2017;8:16105.\nSchinkel S, Bauer R, Bekeredjian R, Stucka R, Rutschow D, Lochmuller H, et al. Long-term preservation of cardiac structure and function after adeno-associated virus serotype 9-mediated microdystrophin gene transfer in mdx mice. Hum Gene Ther. 2012;23(6):566–75.\nPillai-Kastoori L, Schutz-Geschwender AR, Harford JA. A systematic approach to quantitative Western blot analysis. Anal Biochem. 2020;593:113608.\nPillai-Kastoori L, Heaton S, Shiflett SD, Roberts AC, Solache A, Schutz-Geschwender AR. Antibody validation for Western blot: by the user, for the user. J Biol Chem. 2020;295(4):926–39.\nWaldrop MA, Gumienny F, El Husayni S, Frank DE, Weiss RB, Flanigan KM. Low-level dystrophin expression attenuating the dystrophinopathy phenotype. Neuromuscul Disord. 2018;28(2):116–21.\nBeekman C, Janson AA, Baghat A, van Deutekom JC, Datson NA. Use of capillary Western immunoassay (Wes) for quantification of dystrophin levels in skeletal muscle of healthy controls and individuals with Becker and Duchenne muscular dystrophy. PLoS ONE. 2018;13(4):e0195850.\nLi R, Shen Y. An old method facing a new challenge: re-visiting housekeeping proteins as internal reference control for neuroscience research. Life Sci. 2013;92(13):747–51.\nGilda JE, Ghosh R, Cheah JX, West TM, Bodine SC, Gomes AV. Western blotting inaccuracies with unverified antibodies: need for a Western Blotting Minimal Reporting Standard (WBMRS). PLoS ONE. 2015;10(8):e0135392.\nMcDonough AA, Veiras LC, Minas JN, Ralph DL. Considerations when quantitating protein abundance by immunoblot. Am J Physiol Cell Physiol. 2015;308(6):C426–33.\nFaden F, Eschen-Lippold L, Dissmeyer N. Normalized quantitative Western blotting based on standardized fluorescent labeling. Methods Mol Biol. 2016;1450:247–58.\nBass JJ, Wilkinson DJ, Rankin D, Phillips BE, Szewczyk NJ, Smith K, et al. An overview of technical considerations for Western blotting applications to physiological research. Scand J Med Sci Sports. 2017;27(1):4–25.\nSignore M, Manganelli V, Hodge A. Antibody validation by Western blotting. Methods Mol Biol. 2017;1606:51–70.\nDuan D, Systemic AAV. Micro-dystrophin gene therapy for Duchenne muscular dystrophy. Mol Ther. 2018;26(10):2337–56.\nBuscara L, Gross DA, Daniele N. Of rAAV and men: from genetic neuromuscular disorder efficacy and toxicity preclinical studies to clinical trials and back. J Pers Med. 2020;10(4).\nLee JW, Devanarayan V, Barrett YC, Weiner R, Allinson J, Fountain S, et al. Fit-for-purpose method development and validation for successful biomarker measurement. Pharm Res. 2006;23(2):312–28.\nFarrokhi V, Walsh J, Palandra J, Brodfuehrer J, Caiazzo T, Owens J, et al. Dystrophin and mini-dystrophin quantification by mass spectrometry in skeletal muscle for gene therapy development in Duchenne muscular dystrophy. Gene Ther. 2021.\nKoo T, Lu-Nguyen NB, Malerba A, Kim E, Kim D, Cappellari O, et al. Functional rescue of dystrophin deficiency in mice caused by frameshift mutations using Campylobacter jejuni Cas9. Mol Ther. 2018;26(6):1529–38.\nAssereto S, Piccirillo R, Baratto S, Scudieri P, Fiorillo C, Massacesi M, et al. The ubiquitin ligase tripartite-motif-protein 32 is induced in Duchenne muscular dystrophy. Lab Invest. 2016;96(8):862–71.\nCristina Bordea RV, Georgiana Stoica, D. Miscalencu, Anca Dinischiotu, Marieta Costache, Elena Ionica. Diagnosis of muscular dystrophies by Western blot. Proceedings of the Balkan scientific conference of biology. 2005:303–14.\nBanik SM, Pedram K, Wisnovsky S, Ahn G, Riley NM, Bertozzi CR. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature. 2020;584(7820):291–7.\nKirshner ZZ, Gibbs RB. Use of the REVERT((R)) total protein stain as a loading control demonstrates significant benefits over the use of housekeeping proteins when analyzing brain homogenates by Western blot: an analysis of samples representing different gonadal hormone states. Mol Cell Endocrinol. 2018;473:156–65.\nA study to evaluate the safety and tolerability of PF-06939926 gene therapy in Duchenne muscular dystrophy [NCT03362502] [Internet]. 2017. Available from: https:\u002F\u002Fclinicaltrials.gov\u002Fct2\u002Fshow\u002FNCT03362502.\nXiao X, inventor; Asklepios Biopharmaceutical, Inc., Chapel Hill, NC (US) assignee. DNA sequences comprising dystrophin minigenes and methods of use thereof. USA patent US 7,001,761 B2. 2006\nEfron B. Bootstrap methods: another look at the jackknife. Annals of Statistics. 7: Springer Series in Statistics; 1979. p. 1–26.\nHayes KG, Perl ML, Efron B. Application of the bootstrap statistical method to the tau-decay-mode problem. Phys Rev D Part Fields. 1989;39(1):274–9.\nEfron B, Halloran E, Holmes S. Bootstrap confidence levels for phylogenetic trees. Proc Natl Acad Sci U S A. 1996;93(23):13429–34.\nHaidar SH, Shakleya D, Wang J, Cai X, Faustino P. Evaluation of stability using one versus three tubes for each quality control concentration in matrix-based bioanalysis. Bioanalysis. 2019;11(20):1823–34.\nElangkovan N, Dickson G. Gene therapy for Duchenne muscular dystrophy. J Neuromuscul Dis. 2021;8(s2):S303–16.\nAnthony K, Arechavala-Gomeza V, Taylor LE, Vulin A, Kaminoh Y, Torelli S, et al. Dystrophin quantification: biological and translational research implications. Neurology. 2014;83(22):2062–9.\nComi GP, Prelle A, Bresolin N, Moggio M, Bardoni A, Gallanti A, et al. Clinical variability in Becker muscular dystrophy. Genetic, biochemical and immunohistochemical correlates. Brain. 1994;117(Pt 1):1–14.\nEdfors F, Hober A, Linderback K, Maddalo G, Azimi A, Sivertsson A, et al. Enhanced validation of antibodies for research applications. Nat Commun. 2018;9(1):4130.\nKurien BT, Scofield RH. Validating antibody specificities for immunohistochemistry by protein blotting methods. Methods Mol Biol. 2017;1554:61–73.\nZeitler AF, Gerrer KH, Haas R, Jimenez-Soto LF. Optimized semi-quantitative blot analysis in infection assays using the Stain-Free technology. J Microbiol Methods. 2016;126:38–41.\nKoeks Z, Janson AA, Beekman C, Signorelli M, van Duyvenvoorde HA, van den Bergen JC, et al. Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay. Sci Rep. 2021;11(1):5952.\nKrishna Kumar Singh AG, Charu Bharti, Himanchal Sharma Emerging techniques of Western blotting for purification and analysis of protein. Future J Pharm Sci. 2021;7:1-14.\nMendell JR, Sahenk Z, Lehman K, Nease C, Lowes LP, Miller NF, et al. Assessment of systemic delivery of rAAVrh74.MHCK7.micro-dystrophin in children with Duchenne muscular dystrophy: a nonrandomized controlled trial. JAMA Neurol. 2020;77(9):1122–31.\nCharleston JS, Schnell FJ, Dworzak J, Donoghue C, Lewis S, Chen L, et al. Eteplirsen treatment for Duchenne muscular dystrophy: exon skipping and dystrophin production. Neurology. 2018;90(24):e2146–54.\nTibshirani BEaRJ. An introduction to the bootstrap: Chapman & Hall\u002FCRC; 1993.\nTeam RC. R: A language and environment for statistical computing. R Foundation for Statistical Computing Vienna, Austria2014 [Available from: http:\u002F\u002Fwww.R-project.org\u002F.",{"VOID":285},"10.1208\u002Fs12248-022-00776-0","2025-01-22T13:29:57.156+00:00",[182],"https:\u002F\u002Flink.springer.com\u002Farticle\u002F10.1208\u002Fs12248-022-00776-0",[290,305,318,332,348,364,380,394,410,426],{"id":291,"sortIndex":19,"researcher":18,"roles":292,"affiliations":293,"properties":302,"displayName":304,"givenName":18,"familyName":18},"a3e3b3f4-aa88-41a8-b3eb-000092e4b7fb",[189],[294],{"id":295,"sortIndex":19,"affiliation":296,"properties":18},"c86f799e-1a52-4cae-b4e6-6b8cfae729af",{"id":295,"createTime":18,"updateTime":18,"relativeEntities":297,"slug":18,"properties":298,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":301,"statistic":18},[],{"title":299},{"VI":300},"Early Clinical Development, Precision Medicine, Cambridge, USA",[],{"title":303},{"VI":304},"Catherine I. Soderstrom",{"id":306,"sortIndex":204,"researcher":18,"roles":307,"affiliations":308,"properties":315,"displayName":317,"givenName":18,"familyName":18},"197c12ff-b980-41af-98c0-bb31d5bcd736",[189],[309],{"id":295,"sortIndex":19,"affiliation":310,"properties":18},{"id":295,"createTime":18,"updateTime":18,"relativeEntities":311,"slug":18,"properties":312,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":314,"statistic":18},[],{"title":313},{"VI":300},[],{"title":316},{"VI":317},"Jennifer Larsen",{"id":319,"sortIndex":320,"researcher":18,"roles":321,"affiliations":322,"properties":329,"displayName":331,"givenName":18,"familyName":18},"e4635aab-0551-459d-9251-5c5345df2e65",2,[189],[323],{"id":295,"sortIndex":19,"affiliation":324,"properties":18},{"id":295,"createTime":18,"updateTime":18,"relativeEntities":325,"slug":18,"properties":326,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":328,"statistic":18},[],{"title":327},{"VI":300},[],{"title":330},{"VI":331},"Carolina Owen",{"id":333,"sortIndex":334,"researcher":18,"roles":335,"affiliations":336,"properties":345,"displayName":347,"givenName":18,"familyName":18},"e430cc71-f1ae-4088-9809-97b4b2f45223",3,[189],[337],{"id":338,"sortIndex":19,"affiliation":339,"properties":18},"ba056ba5-40f6-4a3b-86e7-e7cd1e164d54",{"id":338,"createTime":18,"updateTime":18,"relativeEntities":340,"slug":18,"properties":341,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":344,"statistic":18},[],{"title":342},{"VI":343},"Clinical Assay Group, Global Product Development (GPD), Pfizer Inc, Groton, USA",[],{"title":346},{"VI":347},"David Gifondorwa",{"id":349,"sortIndex":350,"researcher":18,"roles":351,"affiliations":352,"properties":361,"displayName":363,"givenName":18,"familyName":18},"579b6616-b594-4f23-92cd-7f87559397d5",4,[189],[353],{"id":354,"sortIndex":19,"affiliation":355,"properties":18},"34d23cb9-3cbd-4a5f-842d-0d5d3b65b61a",{"id":354,"createTime":18,"updateTime":18,"relativeEntities":356,"slug":18,"properties":357,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":360,"statistic":18},[],{"title":358},{"VI":359},"Early Clinical Development, Precision Medicine, Pfizer Inc, Cambridge, USA",[],{"title":362},{"VI":363},"David Beidler",{"id":365,"sortIndex":366,"researcher":18,"roles":367,"affiliations":368,"properties":377,"displayName":379,"givenName":18,"familyName":18},"c77b10c5-b1a6-43b9-80e4-d0cf67f6a8b1",5,[189],[369],{"id":370,"sortIndex":19,"affiliation":371,"properties":18},"f3a0fb86-a561-4005-aedd-275029c998f0",{"id":370,"createTime":18,"updateTime":18,"relativeEntities":372,"slug":18,"properties":373,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":376,"statistic":18},[],{"title":374},{"VI":375},"Biostatistics, Early Clinical Development, Worldwide Research & Development, Pfizer Inc., Cambridge, USA",[],{"title":378},{"VI":379},"Florence H. Yong",{"id":381,"sortIndex":382,"researcher":18,"roles":383,"affiliations":384,"properties":391,"displayName":393,"givenName":18,"familyName":18},"4cb78baa-68fd-4377-93d7-c18c92db71cb",6,[189],[385],{"id":295,"sortIndex":19,"affiliation":386,"properties":18},{"id":295,"createTime":18,"updateTime":18,"relativeEntities":387,"slug":18,"properties":388,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":390,"statistic":18},[],{"title":389},{"VI":300},[],{"title":392},{"VI":393},"Patricia Conrad",{"id":395,"sortIndex":396,"researcher":18,"roles":397,"affiliations":398,"properties":407,"displayName":409,"givenName":18,"familyName":18},"e35270ef-4c4b-4d61-abd3-6bbce1de0101",7,[189],[399],{"id":400,"sortIndex":19,"affiliation":401,"properties":18},"53975412-6f07-4469-bd84-54a0f417ab51",{"id":400,"createTime":18,"updateTime":18,"relativeEntities":402,"slug":18,"properties":403,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":406,"statistic":18},[],{"title":404},{"VI":405},"Biomedicine Design, Worldwide Research & Development, Pfizer Inc., Andover, USA",[],{"title":408},{"VI":409},"Hendrik Neubert",{"id":411,"sortIndex":412,"researcher":18,"roles":413,"affiliations":414,"properties":423,"displayName":425,"givenName":18,"familyName":18},"c30c905c-bc3b-4069-b94d-cacaeb752663",8,[189],[415],{"id":416,"sortIndex":19,"affiliation":417,"properties":18},"80603534-0f2f-4bfc-b870-80621865635a",{"id":416,"createTime":18,"updateTime":18,"relativeEntities":418,"slug":18,"properties":419,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":422,"statistic":18},[],{"title":420},{"VI":421},"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, USA",[],{"title":424},{"VI":425},"Steven A. Moore",{"id":427,"sortIndex":428,"researcher":18,"roles":429,"affiliations":430,"properties":437,"displayName":439,"givenName":18,"familyName":18},"58b55593-5e08-4265-9f62-807e2a17f93b",9,[189],[431],{"id":354,"sortIndex":19,"affiliation":432,"properties":18},{"id":354,"createTime":18,"updateTime":18,"relativeEntities":433,"slug":18,"properties":434,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":436,"statistic":18},[],{"title":435},{"VI":359},[],{"title":438},{"VI":439},"Mohamed Hassanein",{"url":288,"publisher":441,"properties":482},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":442,"slug":10,"properties":443,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":446,"manageAffiliations":451,"indexDatabases":462,"url":18,"thumbnailPath":18,"statistic":477,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":444,"eissn":445},{"EN":13},{"VOID":15},[447],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":448,"label":449,"description":450,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[452,457],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":453,"slug":18,"properties":454,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":456,"statistic":18},[],{"title":455},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":458,"slug":18,"properties":459,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":461,"statistic":18},[],{"title":460},{"EN":41},[],[463,470],{"id":45,"indexDatabase":464,"url":58,"indexYears":18,"academicFieldIds":469,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":465,"label":466,"description":467,"key":54,"publicationTags":468,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":471,"url":73,"indexYears":74,"academicFieldIds":476,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":472,"label":473,"description":474,"key":70,"publicationTags":475,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":478,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":479,"totalCitation":117,"totalCitationByYear":480,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":481,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"pages":483,"volume":485},{"VOID":484},"1-12",{"VOID":486},"25","2022-12-20",2022,[56,77],{"id":491,"createTime":492,"updateTime":493,"relativeEntities":494,"slug":495,"properties":496,"entityType":177,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":508,"translateLanguages":510,"viewCount":19,"primaryUrl":511,"fullTextUrl":18,"authors":512,"publicationType":216,"publisherRelationship":577,"citationCount":19,"citationInfo":623,"publishDate":18,"publishYear":18,"citationAnalyzeStatus":17,"lastCitationAnalyze":18,"indexDatabases":625,"openAccess":18,"references":626,"isForceReanalyzing":269},"7859e28c-5c7b-47e8-beef-9f980943ad2f","2024-04-21T02:24:24.336+00:00","2026-09-05T09:21:40.568+00:00",[],"Implementation-of-a-Three-Way-Comparability-Assessment-for-a-Bioanalytical-Anti-Drug-Antibody-Method",{"openalex":497,"abstract":499,"title":501,"pm":504,"doi":506},{"VOID":498},"W4394908935",{"EN":500},"\u003Cjats:title>Abstract\u003C\u002Fjats:title>\u003Cjats:p>Immunogenicity evaluation is a critical part of drug development. Regulatory guidelines from multiple health agencies provide recommendations for the development and validation of anti-drug antibody (ADA) assays to assess immunogenicity in clinical trials. These recommendations primarily describe an ADA method run in one bioanalytical laboratory supporting a biotherapeutic molecule; however, there are increasing instances that may necessitate the support of the ADA method being run in more than one laboratory. A program can rapidly expand into multiple clinical studies within one or multiple countries, where the most appropriate way to support the program is by having multiple laboratories perform ADA sample analysis. In addition, there may be certain country-specific challenges that may make it infeasible to transport samples outside of the country for analysis. China for example has a lengthy sample exportation process that has potential to negatively impact study timelines. If multiple laboratories analyze samples using the same ADA method, comparable method performance should be established. Here, we describe a three-way assessment of ADA assay comparability between two US-based bioanalytical laboratories and one based in China.\u003C\u002Fjats:p>\n                \u003Cjats:p>\u003Cjats:bold>Graphical Abstract\u003C\u002Fjats:bold>\u003C\u002Fjats:p>",{"EN":502,"VI":503},"Implementation of a Three-Way Comparability Assessment for a Bioanalytical Anti-Drug Antibody Method","Triển khai đánh giá khả năng so sánh ba chiều cho phương pháp phân tích sinh học kháng thể kháng thuốc",{"VOID":505},"38637446",{"VOID":507},"10.1208\u002Fs12248-024-00917-7",[509],"EN",[182],"https:\u002F\u002Flink.springer.com\u002F10.1208\u002Fs12248-024-00917-7",[513,532,547,562],{"id":514,"sortIndex":19,"researcher":18,"roles":515,"affiliations":516,"properties":525,"displayName":529,"givenName":18,"familyName":18},"31ee8a70-33ea-492d-89ba-7d335d16af3c",[],[517],{"id":518,"sortIndex":19,"affiliation":519,"properties":18},"143de2fe-02d9-4ca6-a03a-1f10e2b495b0",{"id":518,"createTime":18,"updateTime":18,"relativeEntities":520,"slug":18,"properties":521,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":524,"statistic":18},[],{"title":522},{"EN":523},"Department of BioAnalytical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, California, 94080-4990, USA",[],{"orcid":526,"title":528,"openalex":530},{"VOID":527},"https:\u002F\u002Forcid.org\u002F0000-0002-9395-2240",{"EN":529},"Rosanna S. Kwok",{"VOID":531},"A5032486731",{"id":533,"sortIndex":204,"researcher":18,"roles":534,"affiliations":535,"properties":542,"displayName":544,"givenName":18,"familyName":18},"9a07a7fd-2008-41f9-b7a8-4658bc1854dc",[],[536],{"id":518,"sortIndex":19,"affiliation":537,"properties":18},{"id":518,"createTime":18,"updateTime":18,"relativeEntities":538,"slug":18,"properties":539,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":541,"statistic":18},[],{"title":540},{"EN":523},[],{"title":543,"openalex":545},{"EN":544},"Ihsan Nijem",{"VOID":546},"A5039182774",{"id":548,"sortIndex":320,"researcher":18,"roles":549,"affiliations":550,"properties":557,"displayName":559,"givenName":18,"familyName":18},"7b486bc6-745e-43ed-beaa-8b299d125c2d",[],[551],{"id":518,"sortIndex":19,"affiliation":552,"properties":18},{"id":518,"createTime":18,"updateTime":18,"relativeEntities":553,"slug":18,"properties":554,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":556,"statistic":18},[],{"title":555},{"EN":523},[],{"title":558,"openalex":560},{"EN":559},"Ann Brady",{"VOID":561},"A5006256404",{"id":563,"sortIndex":334,"researcher":18,"roles":564,"affiliations":565,"properties":572,"displayName":574,"givenName":18,"familyName":18},"403e0345-ba4b-4b18-96b6-17e3e527a290",[],[566],{"id":518,"sortIndex":19,"affiliation":567,"properties":18},{"id":518,"createTime":18,"updateTime":18,"relativeEntities":568,"slug":18,"properties":569,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":571,"statistic":18},[],{"title":570},{"EN":523},[],{"title":573,"openalex":575},{"EN":574},"Robert L. Hendricks",{"VOID":576},"A5048676830",{"url":18,"publisher":578,"properties":619},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":579,"slug":10,"properties":580,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":583,"manageAffiliations":588,"indexDatabases":599,"url":18,"thumbnailPath":18,"statistic":614,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":581,"eissn":582},{"EN":13},{"VOID":15},[584],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":585,"label":586,"description":587,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[589,594],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":590,"slug":18,"properties":591,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":593,"statistic":18},[],{"title":592},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":595,"slug":18,"properties":596,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":598,"statistic":18},[],{"title":597},{"EN":41},[],[600,607],{"id":45,"indexDatabase":601,"url":58,"indexYears":18,"academicFieldIds":606,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":602,"label":603,"description":604,"key":54,"publicationTags":605,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":608,"url":73,"indexYears":74,"academicFieldIds":613,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":609,"label":610,"description":611,"key":70,"publicationTags":612,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":615,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":616,"totalCitation":117,"totalCitationByYear":617,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":618,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"issue":620,"volume":621},{"VOID":261},{"VOID":622},"26",{"total":19,"publishYear":18,"statisticByYear":624},{},[],[627,631,634,637,640,644,648,652,655,658,662,666,670,674,677],{"id":18,"text":628,"url":18,"identifiers":629},"Koren E, Zuckerman LA, Mire-Sluis AR. Immune responses to therapeutic proteins in humans—clinical significance, assessment and prediction. Curr Pharm Biotechnol. 2002;3(4):349–60. https:\u002F\u002Fdoi.org\u002F10.2174\u002F1389201023378175.",{"doi":630},"10.2174\u002F1389201023378175",{"id":18,"text":632,"url":18,"identifiers":633},"U.S. Food and Drug Administration. Guidance for industry: immunogenicity testing of therapeutic protein products — developing and validating assays for anti-drug antibody detection. February 2019. https:\u002F\u002Fwww.fda.gov\u002Fregulatory-information\u002Fsearch-fda-guidance-documents\u002Fimmunogenicity-testing-therapeutic-protein-products-developing-and-validating-assays-anti-drug. Accessed 13 May 2023.",{},{"id":18,"text":635,"url":18,"identifiers":636},"National Medical Products Administration. Technical guidance for immunogenicity studies of drugs. March 2021. https:\u002F\u002Fwww.cde.org.cn\u002Fmain\u002Fatt\u002Fdownload\u002F7d89a3b3b078e2682e935bd5d85ce7a8. Accessed 13 May 2023.",{},{"id":18,"text":638,"url":18,"identifiers":639},"European Medicines Agency. Immunogenicity assessment of biotechnology-derived therapeutic proteins—– scientific guideline EMEA\u002FCHMP\u002FBMWP\u002F14327\u002F2006. May 2017. https:\u002F\u002Fwww.ema.europa.eu\u002Fdocuments\u002Fscientific-guideline\u002Fguideline-immunogenicity-assessment-therapeutic-proteins-revision-1_en.pdf. Accessed 13 May 2023.",{},{"id":18,"text":641,"url":18,"identifiers":642},"Tatarewicz S, Moxness M, Weeraratne D, Zhou L, Hale M, Swanson SJ, et al. A step-wise approach for transfer of immunogenicity assays during clinical drug development. AAPS J. 2009;11(3):526–34. https:\u002F\u002Fdoi.org\u002F10.1208\u002Fs12248-009-9130-3.",{"doi":643},"10.1208\u002Fs12248-009-9130-3",{"id":18,"text":645,"url":18,"identifiers":646},"Mora JR, White JT, Chilewski SD, Qu Q, Stocker D, Luo L, et al. Strategies for method comparison when changes in the immunogenicity method are needed within a clinical program. Bioanalysis. 2020;12(7):431–43. https:\u002F\u002Fdoi.org\u002F10.4155\u002Fbio-2019-0300.",{"doi":647},"10.4155\u002Fbio-2019-0300",{"id":18,"text":649,"url":18,"identifiers":650},"Qiu ZJ, Ying Y, Lewin-Koh S-C, Coleman D, Brignoli S, Hendricks R, et al. Strategies to compare clinical antitherapeutic antibody data when changing assay platforms: a case study. Bioanalysis. 2015;7(14):1775–83. https:\u002F\u002Fdoi.org\u002F10.4155\u002Fbio.15.91.",{"doi":651},"10.4155\u002Fbio.15.91",{"id":18,"text":653,"url":18,"identifiers":654},"U.S. Food and Drug Administration. Guidance for industry. Assay development and validation for immunogenicity testing of therapeutic protein products. Draft Guidance. April 2016. https:\u002F\u002Fwww.fda.gov\u002Fmedia\u002F77796\u002Fdownload. Accessed 19 February 2024.",{},{"id":18,"text":656,"url":18,"identifiers":657},"European Medicines Agency. Guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins. April 2008. https:\u002F\u002Fwww.ema.europa.eu\u002Fen\u002Fdocuments\u002Fscientific-guideline\u002Fguideline-immunogenicity-assessment-biotechnology-derived-therapeutic-proteins-first-version_en.pdf. Accessed 19 February 2024.",{},{"id":18,"text":659,"url":18,"identifiers":660},"Mire-Sluis AR, Barrett YC, Devanarayan V, Koren E, Liu H, Maia M, et al. Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. J Immunol Methods. 2004;289(1–2):1–16. https:\u002F\u002Fpubmed.ncbi.nlm.nih.gov\u002F15251407\u002F.",{"doi":661},"10.1016\u002Fj.jim.2004.06.002",{"id":18,"text":663,"url":18,"identifiers":664},"Shankar G, Devanarayan V, Amaravadi L, Barrett YC, Bowsher R, Finco-Kent D, et al. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. J Pharm Biomed Anal. 2008;48(5):1267–1281. https:\u002F\u002Fpubmed.ncbi.nlm.nih.gov\u002F18993008\u002F.",{"doi":665},"10.1016\u002Fj.jpba.2008.09.020",{"id":18,"text":667,"url":18,"identifiers":668},"Kim TW, Bedard PL, LoRusso P, Gordon MS, Bendell J, Oh D-Y, et al. Anti-TIGIT antibody tiragolumab alone or with atezolizumab in patients with advanced solid tumors. JAMA Oncol. 2023;9(11):1574–82. https:\u002F\u002Fdoi.org\u002F10.1001\u002Fjamaoncol.2023.3867.",{"doi":669},"10.1001\u002Fjamaoncol.2023.3867",{"id":18,"text":671,"url":18,"identifiers":672},"Garralda E, Oh DY, Italiano A, Bedard PL, Delord JP, Calvo E, et al. Pharmacokinetics (PK) of tiragolumab in first-in-human study in patients with mixed solid tumors (GO30103). J Clin Pharmacol. 2023. [Online ahead of print]. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fjcph.2397",{"doi":673},"10.1002\u002Fjcph.2397",{"id":18,"text":675,"url":18,"identifiers":676},"U.S. Food and Drug Administration. Guidance for industry: bioanalytical method validation. May 2018. https:\u002F\u002Fwww.fda.gov\u002Fregulatory-information\u002Fsearch-fda-guidance-documents\u002Fbioanalytical-method-validation-guidance-industry. Accessed 13 May 2023.",{},{"id":18,"text":678,"url":18,"identifiers":679},"U.S. Food and Drug Administration. M10 bioanalytical method validation and study sample analysis. November 2022. https:\u002F\u002Fwww.fda.gov\u002Fregulatory-information\u002Fsearch-fda-guidance-documents\u002Fm10-bioanalytical-method-validation-and-study-sample-analysis. Accessed 13 May 2023.",{},{"id":681,"createTime":682,"updateTime":683,"relativeEntities":684,"slug":685,"properties":686,"entityType":177,"verifyStatus":178,"verifyTime":697,"verifyNote":180,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":698,"fullTextUrl":18,"authors":699,"publicationType":216,"publisherRelationship":732,"citationCount":19,"citationInfo":778,"publishDate":781,"publishYear":779,"citationAnalyzeStatus":782,"lastCitationAnalyze":783,"indexDatabases":784,"openAccess":18,"references":18,"isForceReanalyzing":269},"28994ddb-b722-42e3-810e-6a148d03ff89","2024-02-18T23:51:21.577+00:00","2026-08-18T23:30:41.977+00:00",[],"Taurine-a-Naturally-Occurring-Amino-Acid-as-a-Physical-Stability-Enhancer-of-Different-Monoclonal-Antibodies",{"abstract":687,"title":689,"gsPaper":691,"references":693,"doi":695},{"EN":688},"Degradation of therapeutic monoclonal antibodies (mAbs) is a major concern as it affects efficacy, shelf-life, and safety of the product. Taurine, a naturally occurring amino acid, is investigated in this study as a potential mAb stabilizer with an extensive analytical characterization to monitor product degradation. Forced degradation of trastuzumab biosimilar (mAb1)–containing samples by thermal stress for 30 min resulted in high-molecular-weight species by more than 65% in sample without taurine compared to the sample with taurine. Samples containing mAb1 without taurine also resulted in higher Z-average diameter, altered protein structure, higher hydrophobicity, and lower melting temperature compared to samples with taurine. The stabilizing effect of taurine was retained at different mAb and taurine concentrations, time, temperatures, and buffers, and at the presence of polysorbate 80 (PS80). Even the lowest taurine concentration (10 mM) considered in this study, which is in the range of taurine levels in amino acid injections, resulted in enhanced mAb stability. Taurine-containing samples resulted in 90% less hemolysis than samples containing PS80. Additionally, mAb in the presence of taurine showed enhanced stability upon subjecting to stress with light of 365 nm wavelength, combination of light and H2O2, and combination of Fe2+ and H2O2, as samples containing mAb without taurine resulted in increased degradation products by more than 50% compared to samples with taurine upon subjecting to these stresses for 60 min. In conclusion, the presence of taurine enhanced physical stability of mAb by preventing aggregate formation, and the industry can consider it as a new mAb stabilizer. \n\n                  \n                    \n                  \n                ",{"EN":690},"Taurine, a Naturally Occurring Amino Acid, as a Physical Stability Enhancer of Different Monoclonal Antibodies",{"VOID":692},"[\"1764142474728137385\"]",{"VOID":694},"Breedveld FC. Therapeutic monoclonal antibodies. The Lancet. 2000;355(9205):735–40.\nJoubert MK, Luo Q, Nashed-Samuel Y, Wypych J, Narhi LO. Classification and characterization of therapeutic antibody aggregates. J Biol Chem. 2011;286(28):25118–33.\nBansal R, Dash R, Rathore AS. Impact of mAb aggregation on its biological activity: rituximab as a case study. J Pharm Sci. 2020;109(9):2684–98.\nSreenivasan S, Jiskoot W, Rathore AS. Rapid aggregation of therapeutic monoclonal antibodies by bubbling induced air\u002Fliquid interfacial and agitation stress at different conditions. Eur J Pharm Biopharm. 2021;168:97–109.\nJoubert MK, Hokom M, Eakin C, Zhou L, Deshpande M, Baker MP, Goletz TJ, Kerwin BA, Chirmule N, Narhi LO, Jawa V. Highly aggregated antibody therapeutics can enhance the in vitro innate and late-stage T-cell immune responses. J Biol Chem. 2012;287(30):25266–79.\nJoshi S, Rathore AS. Assessment of structural and functional comparability of biosimilar products: trastuzumab as a case study. BioDrugs. 2020;34:209–23.\nKannan A, Shieh IC, Hristov P, Fuller GG. In-use interfacial stability of monoclonal antibody formulations diluted in saline iv bags. J Pharm Sci. 2021;110(4):1687–92.\nDen Engelsman J, Garidel P, Smulders R, Koll H, Smith B, Bassarab S, Seidl A, Hainzl O, Jiskoot W. Strategies for the assessment of protein aggregates in pharmaceutical biotech product development. Pharm Res. 2011;28(4):920–33.\nDas TK, Narhi LO, Sreedhara A, Menzen T, Grapentin C, Chou DK, Antochshuk V, Filipe V. Stress factors in mAb drug substance production processes: critical assessment of impact on product quality and control strategy. J Pharm Sci. 2020;109(1):116–33.\nZheng JY, Janis LJ. Influence of pH, buffer species, and storage temperature on physicochemical stability of a humanized monoclonal antibody LA298. Int J Pharm. 2006;308(1–2):46–51.\nBansal R, Dhawan S, Chattopadhyay S, Maurya GP, Haridas V, Rathore AS. Peptide dendrons as thermal-stability amplifiers for immunoglobulin G1 monoclonal antibody biotherapeutics. Bioconjug Chem. 2017;28(10):2549–59.\nThiagarajan G, Semple A, James JK, Cheung JK, Shameem M. A comparison of biophysical characterization techniques in predicting monoclonal antibody stability. MAbs. 2016;8(6):1088–97.\nTajoddin NN, Konermann L. Structural dynamics of a thermally stressed monoclonal antibody characterized by temperature-dependent H\u002FD exchange mass spectrometry. Anal Chem. 2022;94(44):15499–509.\nLe Basle Y, Chennell P, Tokhadze N, Astier A, Sautou V. Physicochemical stability of monoclonal antibodies: a review. J Pharm Sci. 2020;109(1):169–90.\nHawe A, Kasper JC, Friess W, Jiskoot W. Structural properties of monoclonal antibody aggregates induced by freeze–thawing and thermal stress. Eur J Pharm Sci. 2009;38(2):79–87.\nBrader ML, Estey T, Bai S, Alston RW, Lucas KK, Lantz S, Landsman P, Maloney KM. Examination of thermal unfolding and aggregation profiles of a series of developable therapeutic monoclonal antibodies. Mol Pharm. 2015;12(4):1005–17.\nMason BD, Schöneich C, Kerwin BA. Effect of pH and light on aggregation and conformation of an IgG1 mAb. Mol Pharm. 2012;9(4):774–90.\nZheng K, Ren D, Wang YJ, Lilyestrom W, Scherer T, Hong JK, Ji JA. Monoclonal antibody aggregation associated with free radical induced oxidation. Int J Mol Sci. 2021;22(8):3952.\nShah DD, Zhang J, Hsieh MC, Sundaram S, Maity H, Mallela KM. Effect of peroxide-versus alkoxyl-induced chemical oxidation on the structure, stability, aggregation, and function of a therapeutic monoclonal antibody. J Pharm Sci. 2018;107(11):2789–803.\nShah DD, Zhang J, Maity H, Mallela KM. Effect of photo-degradation on the structure, stability, aggregation, and function of an IgG1 monoclonal antibody. Int J Pharm. 2018;547(1–2):438–49.\nChumsae C, Gaza-Bulseco G, Sun J, Liu H. Comparison of methionine oxidation in thermal stability and chemically stressed samples of a fully human monoclonal antibody. J Chromatogr B. 2007;850(1–2):285–94.\nSreenivasan S, Rathore AS. Combined presence of ferrous ions and hydrogen peroxide in normal saline and in vitro models induces enhanced aggregation of therapeutic IgG due to hydroxyl radicals. Mol Pharm. 2023.\nBhojane PP, Joshi S, Sahoo SJ, Rathore AS. Unexplored excipients in biotherapeutic formulations: natural osmolytes as potential stabilizers against thermally induced aggregation of IgG1 biotherapeutics. AAPS PharmSciTech. 2022;23:1–12.\nNayak PK, Goode M, Chang DP, Rajagopal K. Ectoine and hydroxyectoine stabilize antibodies in spray-dried formulations at elevated temperature and during a freeze\u002Fthaw process. Mol Pharm. 2020;17(9):3291–7.\nKang J, Lin X, Penera J. Rapid formulation development for monoclonal antibodies. BioProcess Int. 2016;14(4):40.\nCheng W, Joshi SB, He F, Brems DN, He B, Kerwin BA, Volkin DB, Russell Middaugh C. Comparison of high-throughput biophysical methods to identify stabilizing excipients for a model IgG2 monoclonal antibody: conformational stability and kinetic aggregation measurements. J Pharm Sci. 2012;101(5):1701–20.\nRamos I, Lourenço EC, Ascenso OS, Maycock CD, Dasika M, Dickson ML, Ventura MR. The effect of new compounds in stabilizing downstream monoclonal antibody (mAb) process intermediates. Int J Pharm. 2019;565:162–73.\nChaturvedi SK, Alam P, Khan JM, Siddiqui MK, Kalaiarasan P, Subbarao N, Ahmad Z, Khan RH. Biophysical insight into the anti-amyloidogenic behavior of taurine. Int J Biol Macromol. 2015;80:375–84.\nJacobsen JG, Smith LH. Biochemistry and physiology of taurine and taurine derivatives. Physiol Rev. 1968;48(2):424–511.\nMastrella L, Moretti P, Pieraccini S, Magi S, Piccirillo S, Ortore MG. Taurine stabilizing effect on lysozyme. Life. 2022;12(1):133.\nBhat MA, Ahmad K, Khan MSA, Bhat MA, Almatroudi A, Rahman S, Jan AT. Expedition into taurine biology: structural insights and therapeutic perspective of taurine in neurodegenerative diseases. Biomolecules. 2020;10(6):863.\nBruździak P, Panuszko A, Kaczkowska E, Piotrowski B, Daghir A, Demkowicz S, Stangret J. Taurine as a water structure breaker and protein stabilizer. Amino Acids. 2018;50:125–40.\nDraganov GB, Pencheva IP, Todorova KA. UV-spectrophotometry determination of taurine in energy drink mixtures. Int J Nutr Food Sci. 2014;3(2):123–6.\nNguyen TD, Nguyen MH, Vu MT, Duong HA, Pham HV, Mai TD. Dual-channeled capillary electrophoresis coupled with contactless conductivity detection for rapid determination of choline and taurine in energy drinks and dietary supplements. Talanta. 2019;193:168–75.\nCaine JJ, Geracioti TD. Taurine, energy drinks, and neuroendocrine effects. Cleve Clin J Med. 2016;83(12):895–904. https:\u002F\u002Fdoi.org\u002F10.3949\u002Fccjm.83a.15050.\nChesney RW, Helms RA, Christensen M, Budreau AM, Han X, Sturman JA. The role of taurine in infant nutrition. Taurine 3: Cellular and Regulatory Mechanisms. 1998. p. 463–76.\nMojtabavi S, Samadi N, Faramarzi MA. Osmolyte-induced folding and stability of proteins: concepts and characterization. Iran J Pharm Res IJPR. 2019;18(Suppl1):13.\nMilitante JD, Lombardini JB. Treatment of hypertension with oral taurine: experimental and clinical studies. Amino Acids. 2002;23(4):381–93.\nHawe A, Wiggenhorn M, van de Weert M, Garbe JH, Mahler HC, Jiskoot W. Forced degradation of therapeutic proteins. J Pharm Sci. 2012;101(3):895–913. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fjps.22812.\nDavies JG, Gao D, Kim YJ, Harris R, Cash PW, Schofield TL, et al. ICH Q5C stability testing of biotechnological\u002Fbiological products. ICH Quality Guidelines: An Implementation Guide. 2017. p. 345–73.\nJaccoulet E, Daniel T, Prognon P, Caudron E. Forced degradation of monoclonal antibodies after compounding: impact on routine hospital quality control. J Pharm Sci. 2019;108(10):3252–61.\nPisupati K, Benet A, Tian Y, Okbazghi S, Kang J, Ford M, Saveliev S, Sen KI, Carlson E, Tolbert TJ, Ruotolo BT. Biosimilarity under stress: a forced degradation study of Remicade® and Remsima™. MAbs. 2017;9(7):1197–209. https:\u002F\u002Fdoi.org\u002F10.1080\u002F19420862.2017.1347741.\nSreenivasan S, Sonawat D, Mandal S, Khare K, Rathore AS. Novel semi-automated fluorescence microscope imaging algorithm for monitoring IgG aggregates in serum. Sci Rep. 2021;11(1):11375.\nPaul M, Vieillard V, Jaccoulet E, Astier A. Long-term stability of diluted solutions of the monoclonal antibody rituximab. Int J Pharm. 2012;436(1–2):282–90.\nMezhebovsky T, Routhier E, Sass P, Shahrokh Z. Enabling freeze-thaw stability of PBS-based formulations of a monoclonal antibody. BioPharm Int. 2016;29:33–9.\nWang W, Singh S, Zeng DL, King K, Nema S. Antibody structure, instability, and formulation. J Pharm Sci. 2007;96(1):1–26.\nXu X. In vivo characterization of therapeutic monoclonal antibodies. J Appl Bioanal. 2016;2(1):553.\nBoullata JI, Mirtallo JM, Sacks GS, Salman G, Gura K, Canada T, Maguire A, ASPEN Parenteral Nutrition Safety Committee. Parenteral nutrition compatibility and stability: a comprehensive review. J Parenter Enter Nutr. 2022;46(2):273–99.\nCober MP, Gura KM. Enteral and parenteral nutrition considerations in pediatric patients. Am J Health Syst Pharm. 2019;76(19):1492–510.\nGianturco SL, Pavlech LL, Storm KD, Yoon SJ, Yuen MV, Mattingly AN. Taurine: Summary Report. 2020. https:\u002F\u002Farchive.hshsl.umaryland.edu\u002Fhandle\u002F10713\u002F12358.\nNicoud L, Jagielski J, Pfister D, Lazzari S, Massant J, Lattuada M, Morbidelli M. Kinetics of monoclonal antibody aggregation from dilute toward concentrated conditions. J Phys Chem B. 2016;120(13):3267–80.\nVázquez-Rey M, Lang DA. Aggregates in monoclonal antibody manufacturing processes. Biotechnol Bioeng. 2011;108(7):1494–508.\nAgarkhed M, O’Dell C, Hsieh MC, Zhang J, Goldstein J, Srivastava A. Effect of polysorbate 80 concentration on thermal and photostability of a monoclonal antibody. AAPS PharmSciTech. 2013;14:1–9.\nSingla A, Bansal R, Joshi V, Rathore AS. Aggregation kinetics for IgG1-based monoclonal antibody therapeutics. AAPS J. 2016;18(3):689–702.\nAwotwe-Otoo D, Agarabi C, Read EK, Lute S, Brorson KA, Khan MA, Shah RB. Impact of controlled ice nucleation on process performance and quality attributes of a lyophilized monoclonal antibody. Int J Pharm. 2013;450(1–2):70–8.\nJong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids. 2012;42:2223–32.\nLorenz CM, Wolk BM, Quan CP, Alcala EW, Eng M, McDonald DJ, Matthews TC. The effect of low intensity ultraviolet-C light on monoclonal antibodies. Biotechnol Prog. 2009;25(2):476–82.\nMcAvan BS, Bowsher LA, Powell T, O’Hara JF, Spitali M, Goodacre R, Doig AJ. Raman spectroscopy to monitor post-translational modifications and degradation in monoclonal antibody therapeutics. Anal Chem. 2020;92(15):10381–9.\nGlover ZK, Wecksler A, Aryal B, Mehta S, Pegues M, Chan W, Lehtimaki M, Luo A, Sreedhara A, Rao VA. Physicochemical and biological impact of metal-catalyzed oxidation of IgG1 monoclonal antibodies and antibody-drug conjugates via reactive oxygen species. Mabs. 2022;14(1):2122957.\nWeiss CH, Merkel C, Zimmer A. Impact of iron raw materials and their impurities on CHO metabolism and recombinant protein product quality. Biotechnol Prog. 2021;37(4): e3148.\nBranch SK. Guidelines from the International Conference on Harmonisation (ICH). J Pharm Biomed Anal. 2005;38(5):798–805.\nKerwin BA. Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways. J Pharm Sci. 2008;97(8):2924–35.",{"VOID":696},"10.1208\u002Fs12248-024-00893-y","2024-06-24T16:27:42.068+00:00","https:\u002F\u002Flink.springer.com\u002Farticle\u002F10.1208\u002Fs12248-024-00893-y",[700,717],{"id":701,"sortIndex":19,"researcher":18,"roles":702,"affiliations":703,"properties":712,"displayName":714,"givenName":18,"familyName":18},"2a4b0179-d503-4af4-a451-17f2489bd24f",[189],[704],{"id":705,"sortIndex":19,"affiliation":706,"properties":18},"a3553846-df64-4a43-a020-9778b2bc5a45",{"id":705,"createTime":18,"updateTime":18,"relativeEntities":707,"slug":18,"properties":708,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":711,"statistic":18},[],{"title":709},{"VI":710},"Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi, India",[],{"title":713,"gsAuthor":715},{"VI":714},"Shravan Sreenivasan",{"VOID":716},"[\"cpOoxm8AAAAJ\"]",{"id":718,"sortIndex":204,"researcher":18,"roles":719,"affiliations":720,"properties":727,"displayName":729,"givenName":18,"familyName":18},"bffd5e17-41b6-407e-9cc1-10b802b233df",[189],[721],{"id":705,"sortIndex":19,"affiliation":722,"properties":18},{"id":705,"createTime":18,"updateTime":18,"relativeEntities":723,"slug":18,"properties":724,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":726,"statistic":18},[],{"title":725},{"VI":710},[],{"title":728,"gsAuthor":730},{"VI":729},"Anurag S. Rathore",{"VOID":731},"[\"REmxCyQAAAAJ\"]",{"url":698,"publisher":733,"properties":774},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":734,"slug":10,"properties":735,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":738,"manageAffiliations":743,"indexDatabases":754,"url":18,"thumbnailPath":18,"statistic":769,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":736,"eissn":737},{"EN":13},{"VOID":15},[739],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":740,"label":741,"description":742,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[744,749],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":745,"slug":18,"properties":746,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":748,"statistic":18},[],{"title":747},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":750,"slug":18,"properties":751,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":753,"statistic":18},[],{"title":752},{"EN":41},[],[755,762],{"id":45,"indexDatabase":756,"url":58,"indexYears":18,"academicFieldIds":761,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":757,"label":758,"description":759,"key":54,"publicationTags":760,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":763,"url":73,"indexYears":74,"academicFieldIds":768,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":764,"label":765,"description":766,"key":70,"publicationTags":767,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":770,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":771,"totalCitation":117,"totalCitationByYear":772,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":773,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"pages":775,"volume":777},{"VOID":776},"1-16",{"VOID":622},{"total":19,"publishYear":779,"statisticByYear":780},2024,{},"2024-02-14","ERROR_IN_ANALYZE_CITATION","2026-08-18T23:30:41.976+00:00",[56,77],{"id":786,"createTime":787,"updateTime":788,"relativeEntities":789,"slug":790,"properties":791,"entityType":177,"verifyStatus":178,"verifyTime":802,"verifyNote":180,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":803,"fullTextUrl":18,"authors":804,"publicationType":216,"publisherRelationship":889,"citationCount":18,"citationInfo":18,"publishDate":936,"publishYear":267,"citationAnalyzeStatus":937,"lastCitationAnalyze":938,"indexDatabases":939,"openAccess":18,"references":18,"isForceReanalyzing":269},"7990bebc-43c3-4c63-8171-4c5f9b23186a","2023-12-11T12:22:50.345+00:00","2026-08-17T19:53:07.798+00:00",[],"Validation-of-a-Ligand-Binding-Assay-Using-Dried-Blood-Spot-Sampling",{"abstract":792,"title":794,"gsPaper":796,"references":798,"doi":800},{"EN":793},"Dried blood spots (DBS) technology has been introduced as a microsampling alternative to traditional plasma or serum sampling for pharmacokinetics or toxicokinetics evaluation. The application of DBS has been established for many small molecule drugs at discovery, nonclinical, and clinical stages. However, the application of DBS for large molecule therapeutics development is not yet well-established. This article describes the method validation of a ligand binding assay (LBA) for DBS sampling of a therapeutic monoclonal antibody—AMG 162 (Denosumab). The original serum LBA was modified for the DBS method. A fit-for-purpose method validation was performed to evaluate accuracy and precision, selectivity, dilutional linearity, and stability. In addition, the parameters relevant to DBS, such as spot volume, extraction recovery, whole blood stability, and hematocrit effects, were evaluated. The validation results demonstrated assay robustness with inter-assay precision of ≤19%, inter-assay accuracy of ≤9%, and total error of ≤24%. Selectivity, extraction recovery, dilutional linearity, and stability were demonstrated. The validation results revealed some limitations of the possible effect of blood hematocrit on therapeutic concentration measurements and the caution required using whole blood for standards and quality controls preparation. This is the first article to describe a thorough method validation of an LBA using DBS for a therapeutic monoclonal antibody. The lessons learned can serve as a model process for future method validation of other LBAs for large molecule therapeutics or biomarkers using the DBS sampling method.",{"EN":795},"Validation of a Ligand Binding Assay Using Dried Blood Spot Sampling",{"VOID":797},"[]",{"VOID":799},"Edelbroek PM, Heijden J, Stolk LML. Dried blood spot methods in therapeutic drug monitoring: methods, assays, and pitfalls. Ther Drug Monit. 2009;31(3):327–36.\nTanna S, Lawson G. Analytical methods used in conjunction with dried blood spots. Anal Methods. 2011;3:1709–18.\nPrince PJ, Matsuda KC, Retter MW, Scott G. Assessment of DBS technology for the detection of therapeutic antibodies. Bioanalysis. 2010;2(8):1449–60.\nMcDade TW, Williams S, Snodgrass JJ. What a drop can do: dried blood spots as a minimally invasive method for integrating biomarkers into population based research. Demography. 2007;44(4):899–925.\nGuthrie R, Susi A. A simple phenylalanine method for detecting PKU in large populations of newborn infants. Pediatrics. 1963;32:338–43.\nBeaudette P, Bateman KP. Discovery stage pharmacokinetics using dried blood spots. J Chromatogr B. 2004;809:153–8.\nClark GT, Haynes JJ, Bayliss MAJ, Burrows L. Utilization of DBS within drug discovery: development of a serial micro sampling pharmacokinetic study in mice. Bioanalysis. 2010;2:1477–88.\nEvans CA. Dried blood spot analysis: a paradigm shift. AAPS Newsmagazine. April 2010.\nSpooner N, Lad R, Barfield M. Dried blood spot as sample collection technique for the determination of pharmacokinetics in clinical studies: considerations for the validation of qualitative bioanalytical method. Anal Chem. 2009;81:1557–63.\nArnaud C. Technology renews a basic approach: dried blood spots offer advantages, but also challenges for pharmaceutical analysis. Chem Eng News. 2011;89(3):13–7.\nPatel P, Mulla H, Tanna S, Pandya H. Facilitating pharmacokinetic studies in children: a new use of dried blood spots. Arch Dis Child. 2010;95:484–7.\nCorran P, Cook J, Lynch C, et al. Dried blood spots as a source of anti-malarial antibodies for epidemiological studies. Malar J. 2008;7:195.\nSolomon SS, Solomon S, Rodriguez I, et al. Dried blood spots: a valuable tool for HIV surveillance in developing\u002Ftropical countries. Int J STD AIDS. 2002;13:25–8.\nLi W, Tse FLS. Dried blood spot sampling in combination with LC-MS\u002FMS for quantitative analysis of small molecules. Biomed Chromatogr. 2010;24(1):49–65.\nEmmons G, Rowland M. Pharmacokinetic considerations as to when to use dried blood spot sampling. Bioanalysis. 2010;2(11):1791–6.\nHeinig K, Wirz T, Bucheli F, Gajate-Perez A. Determination of oseltamivir (Tamiflu®) and oseltamivir carboxylate in dried blood spots using offline or online extraction. Bioanalysis. 2011;3(4):421–37.\nRajendran S. Dried blood spot (DBS) assays for determination of biologics in whole blood. Oral presentation at the Mini Symposium Session—Dried Blood Spot Analysis for Biotherapeutics and Biomarkers (#190), 2011 AAPS—National Biotechnology Conference, San Francisco, CA, 17 May 2011.\nBurns D, Rajendran S, Wang J, DeSilva B, Ma M. Validation feasibility of large molecules of differing modalities using dried blood spot samples. Poster presented at the 2011 AAPS—National Biotechnology Conference, San Francisco, CA, 17 May 2011.\nBeharry M. DBS: a UK (MHRA) regulatory perspective. Bioanalysis. 2010;2(8):1363–4.\nDavis CP. Hematocrit blood test. http:\u002F\u002Fwww.emedicinehealth.com\u002Fhematocrit_blood_test\u002Farticle_em.htm. Accessed 13 July 2012.\nFDA. Guidance for industry—bioanalytical methods validation. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), May 2001.\nEMA Guideline on Validation of Bioanalytical Methods. Committee for Medicinal Products for Human Use, 1 Feb 2012.\nWang J, Lee JW, Burns D, Doherty D, Brunner L, Peterson M, DeSilva B. “Fit-for-purpose” method validation and application of a biomarker (C-terminal telopeptides of type 1 collagen) in denosumab clinical studies. AAPS J. 2009;11:385–94.\nBlood Bank. Wikipedia, the free encyclopedia. http:\u002F\u002Fen.wikipedia.org\u002Fwiki\u002FBlood_bank. Accessed 13 Jul 2012.\nWang SS. What’s the shelf life of blood? Wall Street Journal. 1 December 2009. http:\u002F\u002Fonline.wsj.com\u002Farticle\u002FSB10001424052748703939404574567771148801570.html. Accessed 13 Jul 2012.\nMascheroni M. Extending the shelf life of donated blood. Innovation. 2008; 6(3). http:\u002F\u002Fwww.innovation-america.org\u002Fextending-shelf-life-donated-blood. Accessed 13 Jul 2012.\nTimmerman P, White S, Globig S, Ludtke S, Brunet L, Smeraglia J. White paper\u002FEBF recommendation on the validation of bioanalytical methods for dried blood spots. Bioanalysis. 2011;3(14):1567–75.\nDenniff P, Spooner N. The effect of hematocrit on assay bias when using DBS samples for the quantitative bioanalysis of drugs. Bioanalysis. 2010;2(8):1385–95.",{"VOID":801},"10.1208\u002Fs12248-012-9430-x","2024-09-05T04:48:21.141+00:00","http:\u002F\u002Flink.springer.com\u002F10.1208\u002Fs12248-012-9430-x",[805,820,835,850,863,876],{"id":806,"sortIndex":19,"researcher":18,"roles":807,"affiliations":808,"properties":817,"displayName":819,"givenName":18,"familyName":18},"1a37793c-b6cb-4a5f-96d7-aad4113ac82e",[189],[809],{"id":810,"sortIndex":19,"affiliation":811,"properties":18},"17da8613-0a39-44f4-bfa8-b32227caf84e",{"id":810,"createTime":18,"updateTime":18,"relativeEntities":812,"slug":18,"properties":813,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":816,"statistic":18},[],{"title":814},{"VI":815},"Pharmacokinetics and Drug Metabolism Department, Amgen Inc., Thousand Oaks, USA",[],{"title":818},{"VI":819},"Daniel Burns",{"id":821,"sortIndex":204,"researcher":18,"roles":822,"affiliations":823,"properties":832,"displayName":834,"givenName":18,"familyName":18},"1391ed08-a586-4bb9-8533-1e848de82237",[189],[824],{"id":825,"sortIndex":19,"affiliation":826,"properties":18},"ac6dbc3a-e911-439a-bd15-70caab5579bc",{"id":825,"createTime":18,"updateTime":18,"relativeEntities":827,"slug":18,"properties":828,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":831,"statistic":18},[],{"title":829},{"VI":830},"Key Account Management, Sartorius Stedim Biotech North America, Bohemia, USA",[],{"title":833},{"VI":834},"Laura Brunner",{"id":836,"sortIndex":320,"researcher":18,"roles":837,"affiliations":838,"properties":847,"displayName":849,"givenName":18,"familyName":18},"4f9bb84c-d5e2-4f9f-a2b8-43701bd80ee0",[189],[839],{"id":840,"sortIndex":19,"affiliation":841,"properties":18},"d56ade7e-8ec5-435e-bd27-623a01e11f61",{"id":840,"createTime":18,"updateTime":18,"relativeEntities":842,"slug":18,"properties":843,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":846,"statistic":18},[],{"title":844},{"VI":845},"Bioanalytical Science, Bristol-Myers Squibb, Princeton, USA",[],{"title":848},{"VI":849},"Surendran Rajendran",{"id":851,"sortIndex":334,"researcher":18,"roles":852,"affiliations":853,"properties":860,"displayName":862,"givenName":18,"familyName":18},"427e91f1-bfc6-404d-9a10-5c698ba353aa",[189],[854],{"id":810,"sortIndex":19,"affiliation":855,"properties":18},{"id":810,"createTime":18,"updateTime":18,"relativeEntities":856,"slug":18,"properties":857,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":859,"statistic":18},[],{"title":858},{"VI":815},[],{"title":861},{"VI":862},"Beth Johnson",{"id":864,"sortIndex":350,"researcher":18,"roles":865,"affiliations":866,"properties":873,"displayName":875,"givenName":18,"familyName":18},"173d1926-0b9d-4bc4-94cc-daf21c9cf7c8",[189],[867],{"id":810,"sortIndex":19,"affiliation":868,"properties":18},{"id":810,"createTime":18,"updateTime":18,"relativeEntities":869,"slug":18,"properties":870,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":872,"statistic":18},[],{"title":871},{"VI":815},[],{"title":874},{"VI":875},"Mark Ma",{"id":877,"sortIndex":366,"researcher":18,"roles":878,"affiliations":879,"properties":886,"displayName":888,"givenName":18,"familyName":18},"f4ccf55d-ce41-46f0-9dd9-a61b8f56f568",[189],[880],{"id":810,"sortIndex":19,"affiliation":881,"properties":18},{"id":810,"createTime":18,"updateTime":18,"relativeEntities":882,"slug":18,"properties":883,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":885,"statistic":18},[],{"title":884},{"VI":815},[],{"title":887},{"VI":888},"Jin Wang",{"url":803,"publisher":890,"properties":931},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":891,"slug":10,"properties":892,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":895,"manageAffiliations":900,"indexDatabases":911,"url":18,"thumbnailPath":18,"statistic":926,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":893,"eissn":894},{"EN":13},{"VOID":15},[896],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":897,"label":898,"description":899,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[901,906],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":902,"slug":18,"properties":903,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":905,"statistic":18},[],{"title":904},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":907,"slug":18,"properties":908,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":910,"statistic":18},[],{"title":909},{"EN":41},[],[912,919],{"id":45,"indexDatabase":913,"url":58,"indexYears":18,"academicFieldIds":918,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":914,"label":915,"description":916,"key":54,"publicationTags":917,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":920,"url":73,"indexYears":74,"academicFieldIds":925,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":921,"label":922,"description":923,"key":70,"publicationTags":924,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":927,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":928,"totalCitation":117,"totalCitationByYear":929,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":930,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"pages":932,"volume":934},{"VOID":933},"123-131",{"VOID":935},"15","2012-11-08","ERROR_IN_GET_PLATFORM_ID","2026-08-17T19:53:07.797+00:00",[56,77],{"id":941,"createTime":942,"updateTime":943,"relativeEntities":944,"slug":945,"properties":946,"entityType":177,"verifyStatus":178,"verifyTime":959,"verifyNote":180,"languages":960,"translateLanguages":18,"viewCount":19,"primaryUrl":961,"fullTextUrl":18,"authors":962,"publicationType":216,"publisherRelationship":1228,"citationCount":19,"citationInfo":1274,"publishDate":18,"publishYear":18,"citationAnalyzeStatus":782,"lastCitationAnalyze":943,"indexDatabases":1276,"openAccess":18,"references":1277,"isForceReanalyzing":269},"366aed72-7214-4f27-806f-392fc35c0289","2024-04-18T07:50:53.434+00:00","2026-07-31T06:42:52.033+00:00",[],"A-Novel-Milli-fluidic-Liver-Tissue-Chip-with-Continuous-Recirculation-for-Predictive-Pharmacokinetics-Applications",{"openalex":947,"abstract":949,"title":951,"gsPaper":953,"pm":955,"doi":957},{"VOID":948},"W4387968320",{"EN":950},"\u003Cjats:title>Abstract\u003C\u002Fjats:title>\u003Cjats:p>A crucial step in lead selection during drug development is accurate estimation and optimization of hepatic clearance using \u003Cjats:italic>in vitro\u003C\u002Fjats:italic> methods. However, current methods are limited by factors such as lack of physiological relevance, short culture\u002Fincubation times that are not consistent with drug exposure patterns in patients, use of drug absorbing materials, and evaporation during long-term incubation. To address these technological needs, we developed a novel milli-fluidic human liver tissue chip (LTC) that was designed with continuous media recirculation and optimized for hepatic cultures using human primary hepatocytes. Here, we characterized the LTC using a series of physiologically relevant metrics and test compounds to demonstrate that we could accurately predict the PK of both low- and high-clearance compounds. The non-biological characterization indicated that the cyclic olefin copolymer (COC)–based LTC exhibited negligible evaporation and minimal non-specific binding of drugs of varying ionic states and lipophilicity. Biologically, the LTC exhibited functional and polarized hepatic culture with sustained metabolic CYP activity for at least 15 days. This long-term culture was then used for drug clearance studies for low- and high-clearance compounds for at least 12 days, and clearance was estimated for a range of compounds with high \u003Cjats:italic>in vitro\u003C\u002Fjats:italic>-\u003Cjats:italic>in vivo\u003C\u002Fjats:italic> correlation (IVIVC). We also demonstrated that LTC can be induced by rifampicin, and the culture age had insignificant effect on depletion kinetic and predicted clearance value. Thus, we used advances in bioengineering to develop a novel purpose-built platform with high reproducibility and minimal variability to address unmet needs for PK applications.\u003C\u002Fjats:p>\n                \u003Cjats:p>\u003Cjats:bold>Graphical Abstract\u003C\u002Fjats:bold>\u003C\u002Fjats:p>",{"EN":952},"A Novel Milli-fluidic Liver Tissue Chip with Continuous Recirculation for Predictive Pharmacokinetics Applications",{"VOID":954},"[\"6904519034969640182\"]",{"VOID":956},"37891356",{"VOID":958},"10.1208\u002Fs12248-023-00870-x","2024-05-04T03:27:40.565+00:00",[509],"https:\u002F\u002Flink.springer.com\u002F10.1208\u002Fs12248-023-00870-x",[963,982,999,1016,1033,1048,1063,1082,1097,1112,1127,1145,1163,1178,1194,1212],{"id":964,"sortIndex":19,"researcher":18,"roles":965,"affiliations":966,"properties":975,"displayName":977,"givenName":18,"familyName":18},"30649585-3902-4587-b4bb-ff9c4a26d1bb",[],[967],{"id":968,"sortIndex":19,"affiliation":969,"properties":18},"d298d613-e00a-4e79-b940-192b49d92d59",{"id":968,"createTime":18,"updateTime":18,"relativeEntities":970,"slug":18,"properties":971,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":974,"statistic":18},[],{"title":972},{"EN":973},"Javelin Biotech Inc, 299 Washington street, Woburn, Massachusetts, 01801, USA",[],{"title":976,"gsAuthor":978,"openalex":980},{"EN":977},"Shiny Amala Priya Rajan",{"VOID":979},"[\"c0DnZDAAAAAJ\"]",{"VOID":981},"A5037772945",{"id":983,"sortIndex":204,"researcher":18,"roles":984,"affiliations":985,"properties":992,"displayName":994,"givenName":18,"familyName":18},"6c8470d3-9964-49d6-8e54-39465dbfea0c",[],[986],{"id":968,"sortIndex":19,"affiliation":987,"properties":18},{"id":968,"createTime":18,"updateTime":18,"relativeEntities":988,"slug":18,"properties":989,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":991,"statistic":18},[],{"title":990},{"EN":973},[],{"title":993,"gsAuthor":995,"openalex":997},{"EN":994},"Jason Sherfey",{"VOID":996},"[\"r-qMIgYAAAAJ\"]",{"VOID":998},"A5091972493",{"id":1000,"sortIndex":320,"researcher":18,"roles":1001,"affiliations":1002,"properties":1009,"displayName":1011,"givenName":18,"familyName":18},"c3ca608d-8acb-49e2-a2e0-9292ebfc4f12",[],[1003],{"id":968,"sortIndex":19,"affiliation":1004,"properties":18},{"id":968,"createTime":18,"updateTime":18,"relativeEntities":1005,"slug":18,"properties":1006,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1008,"statistic":18},[],{"title":1007},{"EN":973},[],{"title":1010,"gsAuthor":1012,"openalex":1014},{"EN":1011},"Shivam Ohri",{"VOID":1013},"[\"7tzq2ecAAAAJ\"]",{"VOID":1015},"A5091972494",{"id":1017,"sortIndex":334,"researcher":18,"roles":1018,"affiliations":1019,"properties":1026,"displayName":1030,"givenName":18,"familyName":18},"2bf4275c-b121-4e41-8b1a-828173a7f01f",[],[1020],{"id":968,"sortIndex":19,"affiliation":1021,"properties":18},{"id":968,"createTime":18,"updateTime":18,"relativeEntities":1022,"slug":18,"properties":1023,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1025,"statistic":18},[],{"title":1024},{"EN":973},[],{"orcid":1027,"title":1029,"openalex":1031},{"VOID":1028},"https:\u002F\u002Forcid.org\u002F0000-0002-5599-8547",{"EN":1030},"Lauren M. Nichols",{"VOID":1032},"A5038014996",{"id":1034,"sortIndex":350,"researcher":18,"roles":1035,"affiliations":1036,"properties":1043,"displayName":1045,"givenName":18,"familyName":18},"3ea9991d-6155-451a-b162-d5a376a54b0c",[],[1037],{"id":968,"sortIndex":19,"affiliation":1038,"properties":18},{"id":968,"createTime":18,"updateTime":18,"relativeEntities":1039,"slug":18,"properties":1040,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1042,"statistic":18},[],{"title":1041},{"EN":973},[],{"title":1044,"openalex":1046},{"EN":1045},"Jeff Smith",{"VOID":1047},"A5039406215",{"id":1049,"sortIndex":366,"researcher":18,"roles":1050,"affiliations":1051,"properties":1058,"displayName":1060,"givenName":18,"familyName":18},"24f5ec44-b81e-4e8a-9c0e-ad4acbcd68eb",[],[1052],{"id":968,"sortIndex":19,"affiliation":1053,"properties":18},{"id":968,"createTime":18,"updateTime":18,"relativeEntities":1054,"slug":18,"properties":1055,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1057,"statistic":18},[],{"title":1056},{"EN":973},[],{"title":1059,"openalex":1061},{"EN":1060},"P.C. Parekh",{"VOID":1062},"A5078038529",{"id":1064,"sortIndex":382,"researcher":18,"roles":1065,"affiliations":1066,"properties":1075,"displayName":1079,"givenName":18,"familyName":18},"b822b9b2-b3f6-45cb-b259-91d9aad24a1e",[],[1067],{"id":1068,"sortIndex":19,"affiliation":1069,"properties":18},"543d717e-6ba4-40f4-94e7-57435955d104",{"id":1068,"createTime":18,"updateTime":18,"relativeEntities":1070,"slug":18,"properties":1071,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1074,"statistic":18},[],{"title":1072},{"EN":1073},"Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut, 06340, USA",[],{"orcid":1076,"title":1078,"openalex":1080},{"VOID":1077},"https:\u002F\u002Forcid.org\u002F0000-0003-3724-6517",{"EN":1079},"Eugene P. Kadar",{"VOID":1081},"A5006667010",{"id":1083,"sortIndex":396,"researcher":18,"roles":1084,"affiliations":1085,"properties":1092,"displayName":1094,"givenName":18,"familyName":18},"fd03f11c-a951-4cc2-858d-c5496c6b6f20",[],[1086],{"id":1068,"sortIndex":19,"affiliation":1087,"properties":18},{"id":1068,"createTime":18,"updateTime":18,"relativeEntities":1088,"slug":18,"properties":1089,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1091,"statistic":18},[],{"title":1090},{"EN":1073},[],{"title":1093,"openalex":1095},{"EN":1094},"Frances Clark",{"VOID":1096},"A5086816874",{"id":1098,"sortIndex":412,"researcher":18,"roles":1099,"affiliations":1100,"properties":1107,"displayName":1109,"givenName":18,"familyName":18},"d9eadb55-0953-4538-a543-0490d51edd58",[],[1101],{"id":1068,"sortIndex":19,"affiliation":1102,"properties":18},{"id":1068,"createTime":18,"updateTime":18,"relativeEntities":1103,"slug":18,"properties":1104,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1106,"statistic":18},[],{"title":1105},{"EN":1073},[],{"title":1108,"openalex":1110},{"EN":1109},"Bernard George",{"VOID":1111},"A5026499029",{"id":1113,"sortIndex":428,"researcher":18,"roles":1114,"affiliations":1115,"properties":1122,"displayName":1124,"givenName":18,"familyName":18},"d2a3b033-f6e7-48f7-bc70-3deb537287be",[],[1116],{"id":1068,"sortIndex":19,"affiliation":1117,"properties":18},{"id":1068,"createTime":18,"updateTime":18,"relativeEntities":1118,"slug":18,"properties":1119,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1121,"statistic":18},[],{"title":1120},{"EN":1073},[],{"title":1123,"openalex":1125},{"EN":1124},"Lauren Gregory",{"VOID":1126},"A5072208241",{"id":1128,"sortIndex":1129,"researcher":18,"roles":1130,"affiliations":1131,"properties":1138,"displayName":1142,"givenName":18,"familyName":18},"45c46361-d055-42ff-bf65-2788630e930d",10,[],[1132],{"id":1068,"sortIndex":19,"affiliation":1133,"properties":18},{"id":1068,"createTime":18,"updateTime":18,"relativeEntities":1134,"slug":18,"properties":1135,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1137,"statistic":18},[],{"title":1136},{"EN":1073},[],{"orcid":1139,"title":1141,"openalex":1143},{"VOID":1140},"https:\u002F\u002Forcid.org\u002F0000-0001-5843-7959",{"EN":1142},"David A. Tess",{"VOID":1144},"A5002080538",{"id":1146,"sortIndex":1147,"researcher":18,"roles":1148,"affiliations":1149,"properties":1158,"displayName":1160,"givenName":18,"familyName":18},"3a452e65-37e5-4506-b152-4619c74c7ebf",11,[],[1150],{"id":1151,"sortIndex":19,"affiliation":1152,"properties":18},"abbfa5f1-8fba-4d28-af44-7956c080251c",{"id":1151,"createTime":18,"updateTime":18,"relativeEntities":1153,"slug":18,"properties":1154,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1157,"statistic":18},[],{"title":1155},{"EN":1156},"Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, Massachusetts, 02139, USA",[],{"title":1159,"openalex":1161},{"EN":1160},"J Gosset",{"VOID":1162},"A5081117201",{"id":1164,"sortIndex":98,"researcher":18,"roles":1165,"affiliations":1166,"properties":1173,"displayName":1175,"givenName":18,"familyName":18},"a8844156-58e3-4c2b-bfb2-7abb6f57776f",[],[1167],{"id":1151,"sortIndex":19,"affiliation":1168,"properties":18},{"id":1151,"createTime":18,"updateTime":18,"relativeEntities":1169,"slug":18,"properties":1170,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1172,"statistic":18},[],{"title":1171},{"EN":1156},[],{"title":1174,"openalex":1176},{"EN":1175},"Jennifer Liras",{"VOID":1177},"A5060566337",{"id":1179,"sortIndex":1180,"researcher":18,"roles":1181,"affiliations":1182,"properties":1189,"displayName":1191,"givenName":18,"familyName":18},"8cddb3e0-c4a0-4a54-b07f-4c30f9896dec",13,[],[1183],{"id":968,"sortIndex":19,"affiliation":1184,"properties":18},{"id":968,"createTime":18,"updateTime":18,"relativeEntities":1185,"slug":18,"properties":1186,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1188,"statistic":18},[],{"title":1187},{"EN":973},[],{"title":1190,"openalex":1192},{"EN":1191},"Emily Geishecker",{"VOID":1193},"A5006786729",{"id":1195,"sortIndex":1196,"researcher":18,"roles":1197,"affiliations":1198,"properties":1205,"displayName":1209,"givenName":18,"familyName":18},"b027c4f5-a413-44e6-8b06-0e2a8ec45d18",14,[],[1199],{"id":1068,"sortIndex":19,"affiliation":1200,"properties":18},{"id":1068,"createTime":18,"updateTime":18,"relativeEntities":1201,"slug":18,"properties":1202,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1204,"statistic":18},[],{"title":1203},{"EN":1073},[],{"orcid":1206,"title":1208,"openalex":1210},{"VOID":1207},"https:\u002F\u002Forcid.org\u002F0000-0002-6604-401X",{"EN":1209},"R. Scott Obach",{"VOID":1211},"A5068385082",{"id":1213,"sortIndex":1214,"researcher":18,"roles":1215,"affiliations":1216,"properties":1223,"displayName":1225,"givenName":18,"familyName":18},"2dd7bbe1-2b15-468f-a209-f0e9e31a19e3",15,[],[1217],{"id":968,"sortIndex":19,"affiliation":1218,"properties":18},{"id":968,"createTime":18,"updateTime":18,"relativeEntities":1219,"slug":18,"properties":1220,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1222,"statistic":18},[],{"title":1221},{"EN":973},[],{"title":1224,"openalex":1226},{"EN":1225},"Murat Cirit",{"VOID":1227},"A5037960640",{"url":18,"publisher":1229,"properties":1270},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1230,"slug":10,"properties":1231,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":1234,"manageAffiliations":1239,"indexDatabases":1250,"url":18,"thumbnailPath":18,"statistic":1265,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":1232,"eissn":1233},{"EN":13},{"VOID":15},[1235],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":1236,"label":1237,"description":1238,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[1240,1245],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":1241,"slug":18,"properties":1242,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1244,"statistic":18},[],{"title":1243},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":1246,"slug":18,"properties":1247,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1249,"statistic":18},[],{"title":1248},{"EN":41},[],[1251,1258],{"id":45,"indexDatabase":1252,"url":58,"indexYears":18,"academicFieldIds":1257,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":1253,"label":1254,"description":1255,"key":54,"publicationTags":1256,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":1259,"url":73,"indexYears":74,"academicFieldIds":1264,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":1260,"label":1261,"description":1262,"key":70,"publicationTags":1263,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":1266,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":1267,"totalCitation":117,"totalCitationByYear":1268,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":1269,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"issue":1271,"volume":1273},{"VOID":1272},"6",{"VOID":486},{"total":19,"publishYear":18,"statisticByYear":1275},{},[],[1278,1282,1286,1290,1294,1298,1302,1306,1310,1314,1318,1322,1326,1330,1334,1338,1342,1346,1350,1354,1358,1362,1366,1370,1374,1378,1382,1386,1390,1394,1398,1402,1406,1410,1414,1418,1421],{"id":18,"text":1279,"url":18,"identifiers":1280},"Lai Y, Chu X, Di L, Gao W, Guo Y, Liu X, et al. Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development. Acta Pharm Sin B. 2022;12(6):2751–77. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.apsb.2022.03.009.",{"doi":1281},"10.1016\u002Fj.apsb.2022.03.009",{"id":18,"text":1283,"url":18,"identifiers":1284},"Fowler S, Chen WLK, Duignan DB, Gupta A, Hariparsad N, Kenny JR, et al. Microphysiological systems for ADME-related applications: current status and recommendations for system development and characterization. Lab Chip. 2020;20(3):446–67. https:\u002F\u002Fdoi.org\u002F10.1039\u002Fc9lc00857h.",{"doi":1285},"10.1039\u002Fc9lc00857h",{"id":18,"text":1287,"url":18,"identifiers":1288},"Kenna JG, Taskar KS, Battista C, Bourdet DL, Brouwer KLR, Brouwer KR, et al. Can bile salt export pump inhibition testing in drug discovery and development reduce liver injury risk? An international transporter consortium perspective. Clin Pharmacol Ther. 2018;104(5):916–32. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fcpt.1222.",{"doi":1289},"10.1002\u002Fcpt.1222",{"id":18,"text":1291,"url":18,"identifiers":1292},"Knobeloch D, Ehnert S, Schyschka L, Büchler P, Schoenberg M, Kleeff J, et al. Human hepatocytes: isolation, culture, and quality procedures. Methods Mol Biol. 2012;806:99–120. https:\u002F\u002Fdoi.org\u002F10.1007\u002F978-1-61779-367-7_8.",{"doi":1293},"10.1007\u002F978-1-61779-367-7_8",{"id":18,"text":1295,"url":18,"identifiers":1296},"Godoy P, Hewitt NJ, Albrecht U, Andersen ME, Ansari N, Bhattacharya S, et al. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol. 2013;87(8):1315–530. https:\u002F\u002Fdoi.org\u002F10.1007\u002Fs00204-013-1078-5.",{"doi":1297},"10.1007\u002Fs00204-013-1078-5",{"id":18,"text":1299,"url":18,"identifiers":1300},"Tetsuka K, Ohbuchi M, Tabata K. Recent progress in hepatocyte culture models and their application to the assessment of drug metabolism, transport, and toxicity in drug discovery: the value of tissue engineering for the successful development of a microphysiological system. J Pharm Sci. 2017;106(9):2302–11. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.xphs.2017.05.010.",{"doi":1301},"10.1016\u002Fj.xphs.2017.05.010",{"id":18,"text":1303,"url":18,"identifiers":1304},"Baudy AR, Otieno MA, Hewitt P, Gan J, Roth A, Keller D, et al. Liver microphysiological systems development guidelines for safety risk assessment in the pharmaceutical industry. Lab on a Chip. 2020;20(2):215–25. https:\u002F\u002Fdoi.org\u002F10.1039\u002FC9LC00768G.",{"doi":1305},"10.1039\u002FC9LC00768G",{"id":18,"text":1307,"url":18,"identifiers":1308},"Cirit M, Stokes CL. Maximizing the impact of microphysiological systems with in vitro–in vivo translation. Lab on a Chip. 2018;18(13):1831–7. https:\u002F\u002Fdoi.org\u002F10.1039\u002FC8LC00039E.",{"doi":1309},"10.1039\u002FC8LC00039E",{"id":18,"text":1311,"url":18,"identifiers":1312},"Lim KB, Özbal CC, Kassel DB. Development of a high-throughput online solid-phase extraction\u002Ftandem mass spectrometry method for cytochrome P450 inhibition screening. J Biomol Screen. 2010;15(4):447–52. https:\u002F\u002Fdoi.org\u002F10.1177\u002F1087057110362581.",{"doi":1313},"10.1177\u002F1087057110362581",{"id":18,"text":1315,"url":18,"identifiers":1316},"Zientek M, Miller H, Smith D, Dunklee MB, Heinle L, Thurston A, et al. Development of an in vitro drug-drug interaction assay to simultaneously monitor five cytochrome P450 isoforms and performance assessment using drug library compounds. J Pharmacol Toxicol Methods. 2008;58(3):206–14. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.vascn.2008.05.131.",{"doi":1317},"10.1016\u002Fj.vascn.2008.05.131",{"id":18,"text":1319,"url":18,"identifiers":1320},"Pillai VC, Strom SC, Caritis SN, Venkataramanan R. A sensitive and specific CYP cocktail assay for the simultaneous assessment of human cytochrome P450 activities in primary cultures of human hepatocytes using LC–MS\u002FMS. J Pharm Biomed Anal. 2013;74:126–32. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.jpba.2012.10.016.",{"doi":1321},"10.1016\u002Fj.jpba.2012.10.016",{"id":18,"text":1323,"url":18,"identifiers":1324},"Kim L, Toh Y-C, Voldman J, Yu H. A practical guide to microfluidic perfusion culture of adherent mammalian cells. Lab Chip. 2007;7(6):681–94. https:\u002F\u002Fdoi.org\u002F10.1039\u002FB704602B.",{"doi":1325},"10.1039\u002FB704602B",{"id":18,"text":1327,"url":18,"identifiers":1328},"Meier SJ, Hatton TA, Wang DIC. Cell death from bursting bubbles: role of cell attachment to rising bubbles in sparged reactors. Biotechnol Bioeng. 1999;62(4):468–78. https:\u002F\u002Fdoi.org\u002F10.1002\u002F(SICI)1097-0290(19990220)62:4%3c468::AID-BIT10%3e3.0.CO;2-N.",{"doi":1329},"10.1002\u002F(SICI)1097-0290(19990220)62:4\u003C468::AID-BIT10>3.0.CO;2-N",{"id":18,"text":1331,"url":18,"identifiers":1332},"Michaels JD, Mallik AK, Papoutsakis ET. Sparging and agitation-induced injury of cultured animals cells: do cell-to-bubble interactions in the bulk liquid injure cells? Biotechnol Bioeng. 1996;51(4):399–409. https:\u002F\u002Fdoi.org\u002F10.1002\u002F(sici)1097-0290(19960820)51:4%3c399::Aid-bit3%3e3.0.Co;2-d.",{"doi":1333},"10.1002\u002F(sici)1097-0290(19960820)51:4\u003C399::Aid-bit3>3.0.Co;2-d",{"id":18,"text":1335,"url":18,"identifiers":1336},"Allen JW, Bhatia SN. Formation of steady-state oxygen gradients in vitro: application to liver zonation. Biotechnol Bioeng. 2003;82(3):253–62. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fbit.10569.",{"doi":1337},"10.1002\u002Fbit.10569",{"id":18,"text":1339,"url":18,"identifiers":1340},"Allen JW, Khetani SR, Bhatia SN. In vitro zonation and toxicity in a hepatocyte bioreactor. Toxicol Sci. 2005;84(1):110–9. https:\u002F\u002Fdoi.org\u002F10.1093\u002Ftoxsci\u002Fkfi052.",{"doi":1341},"10.1093\u002Ftoxsci\u002Fkfi052",{"id":18,"text":1343,"url":18,"identifiers":1344},"Balis UJ, Behnia K, Dwarakanath B, Bhatia SN, Sullivan SJ, Yarmush ML, et al. Oxygen consumption characteristics of porcine hepatocytes. Meta Eng. 1999;1(1):49–62. https:\u002F\u002Fdoi.org\u002F10.1006\u002Fmben.1998.0105.",{"doi":1345},"10.1006\u002Fmben.1998.0105",{"id":18,"text":1347,"url":18,"identifiers":1348},"Rashidi H, Alhaque S, Szkolnicka D, Flint O, Hay DC. Fluid shear stress modulation of hepatocyte-like cell function. Arch Toxicol. 2016;90(7):1757–61. https:\u002F\u002Fdoi.org\u002F10.1007\u002Fs00204-016-1689-8.",{"doi":1349},"10.1007\u002Fs00204-016-1689-8",{"id":18,"text":1351,"url":18,"identifiers":1352},"Kietzmann T. Metabolic zonation of the liver: the oxygen gradient revisited. Redox Biol. 2017;11:622–30. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.redox.2017.01.012.",{"doi":1353},"10.1016\u002Fj.redox.2017.01.012",{"id":18,"text":1355,"url":18,"identifiers":1356},"Jungermann K, Kietzmann T. Oxygen: modulator of metabolic zonation and disease of the liver. Hepatology (Baltimore, Md). 2000;31(2):255–60. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fhep.510310201.",{"doi":1357},"10.1002\u002Fhep.510310201",{"id":18,"text":1359,"url":18,"identifiers":1360},"Li N, Schwartz M, Ionescu-Zanetti C. PDMS compound adsorption in context. J Biomol Screen. 2009;14(2):194–202. https:\u002F\u002Fdoi.org\u002F10.1177\u002F1087057108327326.",{"doi":1361},"10.1177\u002F1087057108327326",{"id":18,"text":1363,"url":18,"identifiers":1364},"van Meer BJ, de Vries H, Firth KSA, van Weerd J, Tertoolen LGJ, Karperien HBJ, et al. Small molecule absorption by PDMS in the context of drug response bioassays. Biochem Biophys Res Comm. 2017;482(2):323–8. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.bbrc.2016.11.062.",{"doi":1365},"10.1016\u002Fj.bbrc.2016.11.062",{"id":18,"text":1367,"url":18,"identifiers":1368},"Tsamandouras N, Kostrzewski T, Stokes CL, Griffith LG, Hughes DJ, Cirit M. Quantitative assessment of population variability in hepatic drug metabolism using a perfused three-dimensional human liver microphysiological system. J Pharmacol Exp Ther. 2017;360(1):95–105. https:\u002F\u002Fdoi.org\u002F10.1124\u002Fjpet.116.237495.",{"doi":1369},"10.1124\u002Fjpet.116.237495",{"id":18,"text":1371,"url":18,"identifiers":1372},"Edington CD, Chen WLK, Geishecker E, Kassis T, Soenksen LR, Bhushan BM, et al. Interconnected microphysiological systems for quantitative biology and pharmacology studies. Sci Rep. 2018;8(1):4530. https:\u002F\u002Fdoi.org\u002F10.1038\u002Fs41598-018-22749-0.",{"doi":1373},"10.1038\u002Fs41598-018-22749-0",{"id":18,"text":1375,"url":18,"identifiers":1376},"Tsamandouras N, Chen WLK, Edington CD, Stokes CL, Griffith LG, Cirit M. Integrated gut and liver microphysiological systems for quantitative in vitro pharmacokinetic studies. Aaps J. 2017;19(5):1499–512. https:\u002F\u002Fdoi.org\u002F10.1208\u002Fs12248-017-0122-4.",{"doi":1377},"10.1208\u002Fs12248-017-0122-4",{"id":18,"text":1379,"url":18,"identifiers":1380},"Docci L, Milani N, Ramp T, Romeo AA, Godoy P, Franyuti DO, et al. Exploration and application of a liver-on-a-chip device in combination with modelling and simulation for quantitative drug metabolism studies. Lab Chip. 2022;22(6):1187–205. https:\u002F\u002Fdoi.org\u002F10.1039\u002FD1LC01161H.",{"doi":1381},"10.1039\u002FD1LC01161H",{"id":18,"text":1383,"url":18,"identifiers":1384},"Treyer A, Müsch A. Hepatocyte polarity. Compr Physiol. 2013;3(1):243–87. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fcphy.c120009.",{"doi":1385},"10.1002\u002Fcphy.c120009",{"id":18,"text":1387,"url":18,"identifiers":1388},"Hegde M, Jindal R, Bhushan A, Bale SS, McCarty WJ, Golberg I, et al. Dynamic interplay of flow and collagen stabilizes primary hepatocytes culture in a microfluidic platform. Lab Chip. 2014;14(12):2033–9. https:\u002F\u002Fdoi.org\u002F10.1039\u002FC4LC00071D.",{"doi":1389},"10.1039\u002FC4LC00071D",{"id":18,"text":1391,"url":18,"identifiers":1392},"Bi Y-A, Kazolias D, Duignan DB. Use of cryopreserved human hepatocytes in sandwich culture to measure hepatobiliary transport. Drug Metab Dispos. 2006;34(9):1658–65. https:\u002F\u002Fdoi.org\u002F10.1124\u002Fdmd.105.009118.",{"doi":1393},"10.1124\u002Fdmd.105.009118",{"id":18,"text":1395,"url":18,"identifiers":1396},"Church RJ, Watkins PB. The transformation in biomarker detection and management of drug-induced liver injury. Liver International. 2017;37(11):1582–90. https:\u002F\u002Fdoi.org\u002F10.1111\u002Fliv.13441.",{"doi":1397},"10.1111\u002Fliv.13441",{"id":18,"text":1399,"url":18,"identifiers":1400},"Church RJ, Kullak-Ublick GA, Aubrecht J, Bonkovsky HL, Chalasani N, Fontana RJ, et al. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: an international collaborative effort. Hepatology (Baltimore, Md). 2019;69(2):760–73. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fhep.29802.",{"doi":1401},"10.1002\u002Fhep.29802",{"id":18,"text":1403,"url":18,"identifiers":1404},"Shakeri A, Jarad NA, Khan S, Didar TF. Bio-functionalization of microfluidic platforms made of thermoplastic materials: a review. Analytica Chimica Acta. 2022;1209:339283. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.aca.2021.339283.",{"doi":1405},"10.1016\u002Fj.aca.2021.339283",{"id":18,"text":1407,"url":18,"identifiers":1408},"Di L, Trapa P, Obach RS, Atkinson K, Bi Y-A, Wolford AC, et al. A novel relay method for determining low-clearance values. Drug Metab Dispos. 2012;40(9):1860–5. https:\u002F\u002Fdoi.org\u002F10.1124\u002Fdmd.112.046425.",{"doi":1409},"10.1124\u002Fdmd.112.046425",{"id":18,"text":1411,"url":18,"identifiers":1412},"Chan TS, Yu H, Moore A, Khetani SR, Tweedie D. Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model. HepatoPac Drug Metab Dispos. 2013;41(12):2024–32. https:\u002F\u002Fdoi.org\u002F10.1124\u002Fdmd.113.053397.",{"doi":1413},"10.1124\u002Fdmd.113.053397",{"id":18,"text":1415,"url":18,"identifiers":1416},"Bonn B, Svanberg P, Janefeldt A, Hultman IA, Grime K. Determination of human hepatocyte intrinsic clearance for slowly metabolized compounds: comparison of a primary hepatocyte\u002Fstromal cell co-culture with plated primary hepatocytes and HepaRG. Drug Metab Dispos. 2016;44(4):527–33.",{"doi":1417},"10.1124\u002Fdmd.115.067769",{"id":18,"text":1419,"url":18,"identifiers":1420},"Edington CD, Chen WLK, Geishecker E, et al. Interconnected microphysiological systems for quantitative biology and pharmacology studies. Sci Rep. 2018;8:4530.",{"doi":1373},{"id":18,"text":1422,"url":18,"identifiers":1423},"Yu J, Cilfone NA, Large EM, Sarkar U, Wishnok JS, Tannenbaum SR, et al. Quantitative systems pharmacology approaches applied to microphysiological systems (MPS): data interpretation and multi-MPS integration. CPT Pharmacometrics Syst Pharmacol. 2015;4(10):585–94.",{"doi":1424},"10.1002\u002Fpsp4.12010",{"id":1426,"createTime":1427,"updateTime":1428,"relativeEntities":1429,"slug":1430,"properties":1431,"entityType":177,"verifyStatus":178,"verifyTime":1446,"verifyNote":180,"languages":1447,"translateLanguages":18,"viewCount":19,"primaryUrl":1448,"fullTextUrl":18,"authors":1449,"publicationType":216,"publisherRelationship":1484,"citationCount":19,"citationInfo":1526,"publishDate":1528,"publishYear":267,"citationAnalyzeStatus":1529,"lastCitationAnalyze":1530,"indexDatabases":1531,"openAccess":18,"references":1532,"isForceReanalyzing":269},"b437db5b-7366-4a18-8121-6c7cacdda95d","2024-04-15T16:37:52.504+00:00","2026-07-26T06:07:10.288+00:00",[],"Challenges-in-Development-of-Targeted-Liposomal-Therapeutics",{"mag":1432,"gsPaper":1434,"pmc":1436,"openalex":1438,"title":1440,"pm":1442,"doi":1444},{"VOID":1433},"2029772834",{"VOID":1435},"[\"1802414292429350352\"]",{"VOID":1437},"3326155",{"VOID":1439},"W2029772834",{"EN":1441},"Challenges in Development of Targeted Liposomal Therapeutics",{"VOID":1443},"22415612",{"VOID":1445},"10.1208\u002Fs12248-012-9330-0","2024-06-22T23:46:02.544+00:00",[509],"http:\u002F\u002Flink.springer.com\u002F10.1208\u002Fs12248-012-9330-0",[1450,1467],{"id":1451,"sortIndex":19,"researcher":18,"roles":1452,"affiliations":1453,"properties":1462,"displayName":1464,"givenName":18,"familyName":18},"2a170066-bde9-43cf-b786-74c5437785e4",[],[1454],{"id":1455,"sortIndex":19,"affiliation":1456,"properties":18},"e18afe39-cdc7-40ff-baa3-f02ab426a158",{"id":1455,"createTime":18,"updateTime":18,"relativeEntities":1457,"slug":18,"properties":1458,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1461,"statistic":18},[],{"title":1459},{"EN":1460},"Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA",[],{"title":1463,"openalex":1465},{"EN":1464},"Rupa R. Sawant",{"VOID":1466},"A5034153270",{"id":1468,"sortIndex":204,"researcher":18,"roles":1469,"affiliations":1470,"properties":1477,"displayName":1479,"givenName":18,"familyName":18},"1ea9ed0b-309e-4dbf-a8b9-5749a9c91cb8",[],[1471],{"id":1455,"sortIndex":19,"affiliation":1472,"properties":18},{"id":1455,"createTime":18,"updateTime":18,"relativeEntities":1473,"slug":18,"properties":1474,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1476,"statistic":18},[],{"title":1475},{"EN":1460},[],{"title":1478,"gsAuthor":1480,"openalex":1482},{"EN":1479},"Vladimir P. Torchilin",{"VOID":1481},"[\"OKSa6s8AAAAJ\"]",{"VOID":1483},"A5084391530",{"url":18,"publisher":1485,"properties":18},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1486,"slug":10,"properties":1487,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":1490,"manageAffiliations":1495,"indexDatabases":1506,"url":18,"thumbnailPath":18,"statistic":1521,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":1488,"eissn":1489},{"EN":13},{"VOID":15},[1491],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":1492,"label":1493,"description":1494,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[1496,1501],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":1497,"slug":18,"properties":1498,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1500,"statistic":18},[],{"title":1499},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":1502,"slug":18,"properties":1503,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1505,"statistic":18},[],{"title":1504},{"EN":41},[],[1507,1514],{"id":45,"indexDatabase":1508,"url":58,"indexYears":18,"academicFieldIds":1513,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":1509,"label":1510,"description":1511,"key":54,"publicationTags":1512,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":1515,"url":73,"indexYears":74,"academicFieldIds":1520,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":1516,"label":1517,"description":1518,"key":70,"publicationTags":1519,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":1522,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":1523,"totalCitation":117,"totalCitationByYear":1524,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":1525,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"total":19,"publishYear":267,"statisticByYear":1527},{},"2012-06-01","DONE_ANALYZE_CITATION","2026-07-26T06:07:10.287+00:00",[56,77],[1533,1537,1540,1544,1548,1551,1555,1559,1562,1566,1570,1574,1578,1582,1586,1590,1594,1598,1602,1606,1610,1613,1616,1620,1624,1627,1631,1634,1637,1641,1645,1648,1652,1656,1660,1664,1668,1672,1676,1680,1684,1687,1691,1695,1699,1703,1706,1709,1712,1715,1718,1722,1726,1730,1734,1738,1742,1746,1750,1754,1757,1761,1765,1769,1773,1777,1781,1785,1789,1793,1797,1801,1804,1808,1812,1816,1820,1824,1828,1832,1836,1840,1844,1847,1850,1853,1856,1860,1863,1867,1871,1875,1879,1883,1887,1891,1895,1899,1902,1905,1909,1913,1917,1921,1925,1929,1933,1937,1941,1945,1949,1953,1957,1961,1965,1969,1973,1977,1980,1983,1986,1990,1994,1998,2002,2006,2009,2013,2017,2021,2025,2029,2033,2036,2039,2043,2047,2051,2055,2059,2063,2067,2071,2075,2079,2083,2087,2091,2095],{"id":18,"text":1534,"url":18,"identifiers":1535},"Torchilin VP. Drug targeting. Eur J Pharm Sci. 2000;11 Suppl 2:S81–91.",{"doi":1536},"10.1016\u002FS0928-0987(00)00166-4",{"id":18,"text":1538,"url":18,"identifiers":1539},"Lasic DD. Liposomes: from physics to applications. Amsterdam: Elsevier; 1993.",{},{"id":18,"text":1541,"url":18,"identifiers":1542},"Klibanov AL, Maruyama K, Torchilin VP, Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990;268(1):235–7.",{"doi":1543},"10.1016\u002F0014-5793(90)81016-H",{"id":18,"text":1545,"url":18,"identifiers":1546},"Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000;65(1–2):271–84.",{"doi":1547},"10.1016\u002FS0168-3659(99)00248-5",{"id":18,"text":1549,"url":18,"identifiers":1550},"Maeda H. Enhanced permeability and retention (EPR) effect: basis for drug targeting to tumors. In: Muzykantov V, Torchilin VP, editors. Biomedical aspects of drug targeting. Boston, MA: Kluwer; 2003. p. 211–28.",{},{"id":18,"text":1552,"url":18,"identifiers":1553},"Torchilin V. Tumor delivery of macromolecular drugs based on the EPR effect. Adv Drug Deliv Rev. 2011;63(3):131–5.",{"doi":1554},"10.1016\u002Fj.addr.2010.03.011",{"id":18,"text":1556,"url":18,"identifiers":1557},"Blume G, Cevc G. Molecular mechanism of the lipid vesicle longevity in vivo. Biochim Biophys Acta. 1993;1146(2):157–68.",{"doi":1558},"10.1016\u002F0005-2736(93)90351-Y",{"id":18,"text":1560,"url":18,"identifiers":1561},"Connor J, Huang L. pH-sensitive immunoliposomes as an efficient and target-specific carrier for antitumor drugs. Cancer Res. 1986;46(7):3431–5.",{},{"id":18,"text":1563,"url":18,"identifiers":1564},"Torchilin VP, Klibanov AL, Huang L, O'Donnell S, Nossiff ND, Khaw BA. Targeted accumulation of polyethylene glycol-coated immunoliposomes in infarcted rabbit myocardium. FASEB J. 1992;6(9):2716–9.",{"doi":1565},"10.1096\u002Ffasebj.6.9.1612296",{"id":18,"text":1567,"url":18,"identifiers":1568},"Abra RM, Bankert RB, Chen F, Egilmez NK, Huang K, Saville R, et al. The next generation of liposome delivery systems: recent experience with tumor-targeted, sterically-stabilized immunoliposomes and active-loading gradients. J Liposome Res. 2002;12(1–2):1–3.",{"doi":1569},"10.1081\u002FLPR-120004770",{"id":18,"text":1571,"url":18,"identifiers":1572},"Ishida T, Kirchmeier MJ, Moase EH, Zalipsky S, Allen TM. Targeted delivery and triggered release of liposomal doxorubicin enhances cytotoxicity against human B lymphoma cells. Biochim Biophys Acta. 2001;1515(2):144–58.",{"doi":1573},"10.1016\u002FS0005-2736(01)00409-6",{"id":18,"text":1575,"url":18,"identifiers":1576},"Kale AA, Torchilin VP. Enhanced transfection of tumor cells in vivo using \"Smart\" pH-sensitive TAT-modified pegylated liposomes. J Drug Target. 2007;15(7–8):538–45.",{"doi":1577},"10.1080\u002F10611860701498203",{"id":18,"text":1579,"url":18,"identifiers":1580},"Drummond DC, Zignani M, Leroux J. Current status of pH-sensitive liposomes in drug delivery. Prog Lipid Res. 2000;39(5):409–60.",{"doi":1581},"10.1016\u002FS0163-7827(00)00011-4",{"id":18,"text":1583,"url":18,"identifiers":1584},"Ponce AM, Vujaskovic Z, Yuan F, Needham D, Dewhirst MW. Hyperthermia mediated liposomal drug delivery. Int J Hyperthermia. 2006;22(3):205–13.",{"doi":1585},"10.1080\u002F02656730600582956",{"id":18,"text":1587,"url":18,"identifiers":1588},"Yatvin MB, Weinstein JN, Dennis WH, Blumenthal R. Design of liposomes for enhanced local release of drugs by hyperthermia. Science. 1978;202(4374):1290–3.",{"doi":1589},"10.1126\u002Fscience.364652",{"id":18,"text":1591,"url":18,"identifiers":1592},"Sabate R, Barnadas-Rodriguez R, Callejas-Fernandez J, Hidalgo-Alvarez R, Estelrich J. Preparation and characterization of extruded magnetoliposomes. Int J Pharm. 2008;347(1–2):156–62.",{"doi":1593},"10.1016\u002Fj.ijpharm.2007.06.047",{"id":18,"text":1595,"url":18,"identifiers":1596},"Fortin-Ripoche JP, Martina MS, Gazeau F, Menager C, Wilhelm C, Bacri JC, et al. Magnetic targeting of magnetoliposomes to solid tumors with MR imaging monitoring in mice: feasibility. Radiology. 2006;239(2):415–24.",{"doi":1597},"10.1148\u002Fradiol.2392042110",{"id":18,"text":1599,"url":18,"identifiers":1600},"West KR, Otto S. Reversible covalent chemistry in drug delivery. Curr Drug Discov Technol. 2005;2(3):123–60.",{"doi":1601},"10.2174\u002F1570163054866882",{"id":18,"text":1603,"url":18,"identifiers":1604},"Hobbs SK, Monsky WL, Yuan F, Roberts WG, Griffith L, Torchilin VP, et al. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci USA. 1998;95(8):4607–12.",{"doi":1605},"10.1073\u002Fpnas.95.8.4607",{"id":18,"text":1607,"url":18,"identifiers":1608},"Jain RK. Transport of molecules, particles, and cells in solid tumors. Annu Rev Biomed Eng. 1999;1:241–63.",{"doi":1609},"10.1146\u002Fannurev.bioeng.1.1.241",{"id":18,"text":1611,"url":18,"identifiers":1612},"Huang SK, Mayhew E, Gilani S, Lasic DD, Martin FJ, Papahadjopoulos D. Pharmacokinetics and therapeutics of sterically stabilized liposomes in mice bearing C-26 colon carcinoma. Cancer Res. 1992;52(24):6774–81.",{},{"id":18,"text":1614,"url":18,"identifiers":1615},"Yuan F, Leunig M, Huang SK, Berk DA, Papahadjopoulos D, Jain RK. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res. 1994;54(13):3352–6.",{},{"id":18,"text":1617,"url":18,"identifiers":1618},"Jain RK. Delivery of novel therapeutic agents in tumors: physiological barriers and strategies. J Natl Cancer Inst. 1989;81(8):570–6.",{"doi":1619},"10.1093\u002Fjnci\u002F81.8.570",{"id":18,"text":1621,"url":18,"identifiers":1622},"Gabizon A, Chemla M, Tzemach D, Horowitz AT, Goren D. Liposome longevity and stability in circulation: effects on the in vivo delivery to tumors and therapeutic efficacy of encapsulated anthracyclines. J Drug Target. 1996;3(5):391–8.",{"doi":1623},"10.3109\u002F10611869608996830",{"id":18,"text":1625,"url":18,"identifiers":1626},"Yuan F, Dellian M, Fukumura D, Leunig M, Berk DA, Torchilin VP, et al. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res. 1995;55(17):3752–6.",{},{"id":18,"text":1628,"url":18,"identifiers":1629},"Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145–60.",{"doi":1630},"10.1038\u002Fnrd1632",{"id":18,"text":1632,"url":18,"identifiers":1633},"Gabizon A, Dagan A, Goren D, Barenholz Y, Fuks Z. Liposomes as in vivo carriers of adriamycin: reduced cardiac uptake and preserved antitumor activity in mice. Cancer Res. 1982;42(11):4734–9.",{},{"id":18,"text":1635,"url":18,"identifiers":1636},"Gabizon AA. Liposomal anthracyclines. Hematol Oncol Clin North Am. 1994;8(2):431–50.",{},{"id":18,"text":1638,"url":18,"identifiers":1639},"Gabizon A, Chisin R, Amselem S, Druckmann S, Cohen R, Goren D, et al. Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin. Br J Cancer. 1991;64(6):1125–32.",{"doi":1640},"10.1038\u002Fbjc.1991.476",{"id":18,"text":1642,"url":18,"identifiers":1643},"Liu D, Hu Q, Song YK. Liposome clearance from blood: different animal species have different mechanisms. Biochim Biophys Acta. 1995;1240(2):277–84.",{"doi":1644},"10.1016\u002F0005-2736(95)00184-0",{"id":18,"text":1646,"url":18,"identifiers":1647},"Proffitt RT, Williams LE, Presant CA, Tin GW, Uliana JA, Gamble RC, et al. Tumor-imaging potential of liposomes loaded with In-111-NTA: biodistribution in mice. J Nucl Med. 1983;24(1):45–51.",{},{"id":18,"text":1649,"url":18,"identifiers":1650},"Gill PS, Wernz J, Scadden DT, Cohen P, Mukwaya GM, von Roenn JH, et al. Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma. J Clin Oncol. 1996;14(8):2353–64.",{"doi":1651},"10.1200\u002FJCO.1996.14.8.2353",{"id":18,"text":1653,"url":18,"identifiers":1654},"Gabizon A, Papahadjopoulos D. Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. Proc Natl Acad Sci USA. 1988;85(18):6949–53.",{"doi":1655},"10.1073\u002Fpnas.85.18.6949",{"id":18,"text":1657,"url":18,"identifiers":1658},"Torchilin VP, Trubetskoy VS. Which polymers can make nanoparticulate drug carriers long-circulating? Adv Drug Deliv Rev. 1995;16:141–55.",{"doi":1659},"10.1016\u002F0169-409X(95)00022-Y",{"id":18,"text":1661,"url":18,"identifiers":1662},"Allen TM, Chonn A. Large unilamellar liposomes with low uptake into the reticuloendothelial system. FEBS Lett. 1987;223(1):42–6.",{"doi":1663},"10.1016\u002F0014-5793(87)80506-9",{"id":18,"text":1665,"url":18,"identifiers":1666},"Papahadjopoulos D, Allen TM, Gabizon A, Mayhew E, Matthay K, Huang SK, et al. Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA. 1991;88(24):11460–4.",{"doi":1667},"10.1073\u002Fpnas.88.24.11460",{"id":18,"text":1669,"url":18,"identifiers":1670},"Woodle MC, Lasic DD. Sterically stabilized liposomes. Biochim Biophys Acta. 1992;1113(2):171–99.",{"doi":1671},"10.1016\u002F0304-4157(92)90038-C",{"id":18,"text":1673,"url":18,"identifiers":1674},"Allen TM, Hansen C, Martin F, Redemann C, Yau-Young A. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim Biophys Acta. 1991;1066(1):29–36.",{"doi":1675},"10.1016\u002F0005-2736(91)90246-5",{"id":18,"text":1677,"url":18,"identifiers":1678},"Lasic DD, Martin FJ, Gabizon A, Huang SK, Papahadjopoulos D. Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. Biochim Biophys Acta. 1991;1070(1):187–92.",{"doi":1679},"10.1016\u002F0005-2736(91)90162-2",{"id":18,"text":1681,"url":18,"identifiers":1682},"Needham D, Hristova K, McIntosh TJ, Dewhirst MW, Lasic DD. Polymer grafted liposomes: physical basis for the \"stealth\" property. J Liposome Res. 1992;2:411–30.",{"doi":1683},"10.3109\u002F08982109209010218",{"id":18,"text":1685,"url":18,"identifiers":1686},"Lasic DD, Martin F. Stealth liposomes. Boca Raton, FL: CRC; 1995.",{},{"id":18,"text":1688,"url":18,"identifiers":1689},"Allen TM. The use of glycolipids and hydrophilic polymers in avoiding rapid uptake of liposomes by the mononuclear phagocyte system. Adv Drug Deliv Rev. 1994;13:285–309.",{"doi":1690},"10.1016\u002F0169-409X(94)90016-7",{"id":18,"text":1692,"url":18,"identifiers":1693},"Chonn A, Semple SC, Cullis PR. Separation of large unilamellar liposomes from blood components by a spin column procedure: towards identifying plasma proteins which mediate liposome clearance in vivo. Biochim Biophys Acta. 1991;1070(1):215–22.",{"doi":1694},"10.1016\u002F0005-2736(91)90167-7",{"id":18,"text":1696,"url":18,"identifiers":1697},"Senior J, Delgado C, Fisher D, Tilcock C, Gregoriadis G. Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: studies with poly(ethylene glycol)-coated vesicles. Biochim Biophys Acta. 1991;1062(1):77–82.",{"doi":1698},"10.1016\u002F0005-2736(91)90337-8",{"id":18,"text":1700,"url":18,"identifiers":1701},"Woodle MC. Surface-modified liposomes: assessment and characterization for increased stability and prolonged blood circulation. Chem Phys Lipids. 1993;64(1–3):249–62.",{"doi":1702},"10.1016\u002F0009-3084(93)90069-F",{"id":18,"text":1704,"url":18,"identifiers":1705},"Senior JH. Fate and behavior of liposomes in vivo: a review of controlling factors. Crit Rev Ther Drug Carrier Syst. 1987;3(2):123–93.",{},{"id":18,"text":1707,"url":18,"identifiers":1708},"Huang SK, Stauffer PR, Hong K, Guo JW, Phillips TL, Huang A, et al. Liposomes and hyperthermia in mice: increased tumor uptake and therapeutic efficacy of doxorubicin in sterically stabilized liposomes. Cancer Res. 1994;54(8):2186–91.",{},{"id":18,"text":1710,"url":18,"identifiers":1711},"Gabizon A, Catane R, Uziely B, Kaufman B, Safra T, Cohen R, et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res. 1994;54(4):987–92.",{},{"id":18,"text":1713,"url":18,"identifiers":1714},"Boman NL, Masin D, Mayer LD, Cullis PR, Bally MB. Liposomal vincristine which exhibits increased drug retention and increased circulation longevity cures mice bearing P388 tumors. Cancer Res. 1994;54(11):2830–3.",{},{"id":18,"text":1716,"url":18,"identifiers":1717},"Allen TM, Mehra T, Hansen C, Chin YC. Stealth liposomes: an improved sustained release system for 1-beta-d-arabinofuranosylcytosine. Cancer Res. 1992;52(9):2431–9.",{},{"id":18,"text":1719,"url":18,"identifiers":1720},"Kim ES, Lu C, Khuri FR, Tonda M, Glisson BS, Liu D, et al. A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands). 2001;34(3):427–32.",{"doi":1721},"10.1016\u002FS0169-5002(01)00278-1",{"id":18,"text":1723,"url":18,"identifiers":1724},"Gabizon AA. Liposome circulation time and tumor targeting: implications for cancer chemotherapy. Adv Drug Deliv Rev. 1995;16:285–94.",{"doi":1725},"10.1016\u002F0169-409X(95)00030-B",{"id":18,"text":1727,"url":18,"identifiers":1728},"Gabizon AA. Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Cancer Invest. 2001;19(4):424–36.",{"doi":1729},"10.1081\u002FCNV-100103136",{"id":18,"text":1731,"url":18,"identifiers":1732},"Whiteman KR, Subr V, Ulbrich K, Torchilin VP. Poly(Hpma)-coated liposomes demonstrate prolonged circulation in mice. J Liposome Res. 2001;11(2–3):153–64.",{"doi":1733},"10.1081\u002FLPR-100108459",{"id":18,"text":1735,"url":18,"identifiers":1736},"Torchilin VP, Levchenko TS, Whiteman KR, Yaroslavov AA, Tsatsakis AM, Rizos AK, et al. Amphiphilic poly-N-vinylpyrrolidones: synthesis, properties and liposome surface modification. Biomaterials. 2001;22(22):3035–44.",{"doi":1737},"10.1016\u002FS0142-9612(01)00050-3",{"id":18,"text":1739,"url":18,"identifiers":1740},"Metselaar JM, Bruin P, de Boer LW, de Vringer T, Snel C, Oussoren C, et al. A novel family of l-amino acid-based biodegradable polymer-lipid conjugates for the development of long-circulating liposomes with effective drug-targeting capacity. Bioconjug Chem. 2003;14(6):1156–64.",{"doi":1741},"10.1021\u002Fbc0340363",{"id":18,"text":1743,"url":18,"identifiers":1744},"Takeuchi H, Kojima H, Yamamoto H, Kawashima Y. Evaluation of circulation profiles of liposomes coated with hydrophilic polymers having different molecular weights in rats. J Control Release. 2001;75(1–2):83–91.",{"doi":1745},"10.1016\u002FS0168-3659(01)00368-6",{"id":18,"text":1747,"url":18,"identifiers":1748},"Moein Moghimi S, Hamad I, Bunger R, Andresen TL, Jorgensen K, Hunter AC, et al. Activation of the human complement system by cholesterol-rich and PEGylated liposomes-modulation of cholesterol-rich liposome-mediated complement activation by elevated serum LDL and HDL levels. J Liposome Res. 2006;16(3):167–74.",{"doi":1749},"10.1080\u002F08982100600848801",{"id":18,"text":1751,"url":18,"identifiers":1752},"Holland JW, Hui C, Cullis PR, Madden TD. Poly(ethylene glycol)–lipid conjugates regulate the calcium-induced fusion of liposomes composed of phosphatidylethanolamine and phosphatidylserine. Biochemistry. 1996;35(8):2618–24.",{"doi":1753},"10.1021\u002Fbi952000v",{"id":18,"text":1755,"url":18,"identifiers":1756},"Hong RL, Huang CJ, Tseng YL, Pang VF, Chen ST, Liu JJ, et al. Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: is surface coating with polyethylene glycol beneficial? Clin Cancer Res. 1999;5(11):3645–52.",{},{"id":18,"text":1758,"url":18,"identifiers":1759},"Erbacher P, Bettinger T, Belguise-Valladier P, Zou S, Coll JL, Behr JP, et al. Transfection and physical properties of various saccharide, poly(ethylene glycol), and antibody-derivatized polyethylenimines (PEI). J Gene Med. 1999;1(3):210–22.",{"doi":1760},"10.1002\u002F(SICI)1521-2254(199905\u002F06)1:3\u003C210::AID-JGM30>3.0.CO;2-U",{"id":18,"text":1762,"url":18,"identifiers":1763},"Boomer JA, Qualls MM, Inerowicz HD, Haynes RH, Patri VS, Kim JM, et al. Cytoplasmic delivery of liposomal contents mediated by an acid-labile cholesterol-vinyl ether-PEG conjugate. Bioconjug Chem. 2009;20(1):47–59.",{"doi":1764},"10.1021\u002Fbc800239b",{"id":18,"text":1766,"url":18,"identifiers":1767},"Guo X, Szoka Jr FC. Steric stabilization of fusogenic liposomes by a low-pH sensitive PEG–diortho ester–lipid conjugate. Bioconjug Chem. 2001;12(2):291–300.",{"doi":1768},"10.1021\u002Fbc000110v",{"id":18,"text":1770,"url":18,"identifiers":1771},"Li W, Huang Z, MacKay JA, Grube S, Szoka Jr FC. Low-pH-sensitive poly(ethylene glycol) (PEG)-stabilized plasmid nanolipoparticles: effects of PEG chain length, lipid composition and assembly conditions on gene delivery. J Gene Med. 2005;7(1):67–79.",{"doi":1772},"10.1002\u002Fjgm.634",{"id":18,"text":1774,"url":18,"identifiers":1775},"Sawant RM, Hurley JP, Salmaso S, Kale A, Tolcheva E, Levchenko TS, et al. \"SMART\" drug delivery systems: double-targeted pH-responsive pharmaceutical nanocarriers. Bioconjug Chem. 2006;17(4):943–9.",{"doi":1776},"10.1021\u002Fbc060080h",{"id":18,"text":1778,"url":18,"identifiers":1779},"Boomer JA, Inerowicz HD, Zhang Z-Y, Bergstrand N, Edwards K, Kim J-M, et al. Acid triggered release from sterically-stabilized fusogenic vesicles via a hydrolytic dePEGylation strategy. Langmuir. 2003;19:6408–15.",{"doi":1780},"10.1021\u002Fla030104y",{"id":18,"text":1782,"url":18,"identifiers":1783},"Zalipsky S, Qazen M, Walker 2nd JA, Mullah N, Quinn YP, Huang SK. New detachable poly(ethylene glycol) conjugates: cysteine-cleavable lipopolymers regenerating natural phospholipid, diacyl phosphatidylethanolamine. Bioconjug Chem. 1999;10(5):703–7.",{"doi":1784},"10.1021\u002Fbc990031n",{"id":18,"text":1786,"url":18,"identifiers":1787},"Barenholz Y. Design of liposome-based drug carriers: from basic research to application as approved drugs. In: Lasic DD, Papahadjopoulos D, editors. Medical applications of liposomes. New York: Elsevier; 1998. p. 545–65.",{"doi":1788},"10.1016\u002FB978-044482917-7\u002F50031-4",{"id":18,"text":1790,"url":18,"identifiers":1791},"Papahadjopoulos D, Jacobson K, Nir S, Isac T. Phase transitions in phospholipid vesicles. Fluorescence polarization and permeability measurements concerning the effect of temperature and cholesterol. Biochim Biophys Acta. 1973;311(3):330–48.",{"doi":1792},"10.1016\u002F0005-2736(73)90314-3",{"id":18,"text":1794,"url":18,"identifiers":1795},"Gregoriadis G, Davis C. Stability of liposomes in vivo and in vitro is promoted by their cholesterol content and the presence of blood cells. Biochem Biophys Res Commun. 1979;89(4):1287–93.",{"doi":1796},"10.1016\u002F0006-291X(79)92148-X",{"id":18,"text":1798,"url":18,"identifiers":1799},"Senior J, Gregoriadis G. Stability of small unilamellar liposomes in serum and clearance from the circulation: the effect of the phospholipid and cholesterol components. Life Sci. 1982;30(24):2123–36.",{"doi":1800},"10.1016\u002F0024-3205(82)90455-6",{"id":18,"text":1802,"url":18,"identifiers":1803},"Drummond DC, Meyer O, Hong K, Kirpotin DB, Papahadjopoulos D. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev. 1999;51(4):691–743.",{},{"id":18,"text":1805,"url":18,"identifiers":1806},"Abra RM, Hunt CA. Liposome disposition in vivo. III. Dose and vesicle-size effects. Biochim Biophys Acta. 1981;666(3):493–503.",{"doi":1807},"10.1016\u002F0005-2760(81)90311-8",{"id":18,"text":1809,"url":18,"identifiers":1810},"Senior J, Crawley JC, Gregoriadis G. Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection. Biochim Biophys Acta. 1985;839(1):1–8.",{"doi":1811},"10.1016\u002F0304-4165(85)90174-6",{"id":18,"text":1813,"url":18,"identifiers":1814},"Allen TM, Hansen C, Rutledge J. Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues. Biochim Biophys Acta. 1989;981(1):27–35.",{"doi":1815},"10.1016\u002F0005-2736(89)90078-3",{"id":18,"text":1817,"url":18,"identifiers":1818},"Gabizon A, Papahadjopoulos D. The role of surface charge and hydrophilic groups on liposome clearance in vivo. Biochim Biophys Acta. 1992;1103(1):94–100.",{"doi":1819},"10.1016\u002F0005-2736(92)90061-P",{"id":18,"text":1821,"url":18,"identifiers":1822},"Bae YH. Drug targeting and tumor heterogeneity. J Control Release. 2009;133(1):2–3.",{"doi":1823},"10.1016\u002Fj.jconrel.2008.09.074",{"id":18,"text":1825,"url":18,"identifiers":1826},"Heldin CH, Rubin K, Pietras K, Ostman A. High interstitial fluid pressure—an obstacle in cancer therapy. Nat Rev Cancer. 2004;4(10):806–13.",{"doi":1827},"10.1038\u002Fnrc1456",{"id":18,"text":1829,"url":18,"identifiers":1830},"Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303(5665):1818–22.",{"doi":1831},"10.1126\u002Fscience.1095833",{"id":18,"text":1833,"url":18,"identifiers":1834},"Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005;5(3):161–71.",{"doi":1835},"10.1038\u002Fnrc1566",{"id":18,"text":1837,"url":18,"identifiers":1838},"Kirpotin D, Park JW, Hong K, Zalipsky S, Li WL, Carter P, et al. Sterically stabilized anti-HER2 immunoliposomes: design and targeting to human breast cancer cells in vitro. Biochemistry. 1997;36(1):66–75.",{"doi":1839},"10.1021\u002Fbi962148u",{"id":18,"text":1841,"url":18,"identifiers":1842},"Park JW, Hong K, Carter P, Asgari H, Guo LY, Keller GA, et al. Development of anti-p185HER2 immunoliposomes for cancer therapy. Proc Natl Acad Sci USA. 1995;92(5):1327–31.",{"doi":1843},"10.1073\u002Fpnas.92.5.1327",{"id":18,"text":1845,"url":18,"identifiers":1846},"Sapra P, Allen TM. Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs. Cancer Res. 2002;62(24):7190–4.",{},{"id":18,"text":1848,"url":18,"identifiers":1849},"Liebert M, Wedemeyer GA, Stein JA, Washington Jr RW, Flint A, Ren LQ, et al. Identification by monoclonal antibodies of an antigen shed by human bladder cancer cells. Cancer Res. 1989;49(23):6720–6.",{},{"id":18,"text":1851,"url":18,"identifiers":1852},"Lopes de Menezes DE, Pilarski LM, Allen TM. In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. Cancer Res. 1998;58(15):3320–30.",{},{"id":18,"text":1854,"url":18,"identifiers":1855},"Park JW, Hong K, Kirpotin DB, Colbern G, Shalaby R, Baselga J, et al. Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery. Clin Cancer Res. 2002;8(4):1172–81.",{},{"id":18,"text":1857,"url":18,"identifiers":1858},"Goren D, Horowitz AT, Zalipsky S, Woodle MC, Yarden Y, Gabizon A. Targeting of stealth liposomes to erbB-2 (Her\u002F2) receptor: in vitro and in vivo studies. Br J Cancer. 1996;74(11):1749–56.",{"doi":1859},"10.1038\u002Fbjc.1996.625",{"id":18,"text":1861,"url":18,"identifiers":1862},"Torchilin VP. Liposomes as targetable drug carriers. Crit Rev Ther Drug Carrier Syst. 1985;2(1):65–115.",{},{"id":18,"text":1864,"url":18,"identifiers":1865},"Mamot C, Drummond DC, Noble CO, Kallab V, Guo Z, Hong K, et al. Epidermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugs in vivo. Cancer Res. 2005;65(24):11631–8.",{"doi":1866},"10.1158\u002F0008-5472.CAN-05-1093",{"id":18,"text":1868,"url":18,"identifiers":1869},"Maruyama K. PEG-immunoliposome. Biosci Rep. 2002;22(2):251–66.",{"doi":1870},"10.1023\u002FA:1020138622686",{"id":18,"text":1872,"url":18,"identifiers":1873},"Lee RJ, Low PS. Delivery of liposomes into cultured KB cells via folate receptor-mediated endocytosis. J Biol Chem. 1994;269(5):3198–204.",{"doi":1874},"10.1016\u002FS0021-9258(17)41848-5",{"id":18,"text":1876,"url":18,"identifiers":1877},"Blume G, Cevc G, Crommelin MD, Bakker-Woudenberg IA, Kluft C, Storm G. Specific targeting with poly(ethylene glycol)-modified liposomes: coupling of homing devices to the ends of the polymeric chains combines effective target binding with long circulation times. Biochim Biophys Acta. 1993;1149(1):180–4.",{"doi":1878},"10.1016\u002F0005-2736(93)90039-3",{"id":18,"text":1880,"url":18,"identifiers":1881},"Maruyama K, Takizawa T, Yuda T, Kennel SJ, Huang L, Iwatsuru M. Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol)s conjugated at their distal terminals to monoclonal antibodies. Biochim Biophys Acta. 1995;1234(1):74–80.",{"doi":1882},"10.1016\u002F0005-2736(94)00263-O",{"id":18,"text":1884,"url":18,"identifiers":1885},"Medina OP, Zhu Y, Kairemo K. Targeted liposomal drug delivery in cancer. Curr Pharm Des. 2004;10(24):2981–9.",{"doi":1886},"10.2174\u002F1381612043383467",{"id":18,"text":1888,"url":18,"identifiers":1889},"Lopes De Menezes DE, Kirchmeier MJ, Gagne J-F, Pilarski LM, Allen TM. Cellular trafficking and cytotoxicity of anti-Cd19-targeted liposomal doxorubicin in B lymphoma cells. J Liposome Res. 1999;9:199–228.",{"doi":1890},"10.3109\u002F08982109909024786",{"id":18,"text":1892,"url":18,"identifiers":1893},"Sapra P, Allen TM. Ligand-targeted liposomal anticancer drugs. Prog Lipid Res. 2003;42(5):439–62.",{"doi":1894},"10.1016\u002FS0163-7827(03)00032-8",{"id":18,"text":1896,"url":18,"identifiers":1897},"Torchilin VP, Levchenko TS, Lukyanov AN, Khaw BA, Klibanov AL, Rammohan R, et al. p-Nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups. Biochim Biophys Acta. 2001;1511(2):397–411.",{"doi":1898},"10.1016\u002FS0005-2728(01)00165-7",{"id":18,"text":1900,"url":18,"identifiers":1901},"Torchilin VP, Rammohan R, Weissig V, Khaw BA, Klibanov A, Samokhin GP, editors. PEG-Immunoliposomes: attachment of monoclonal antibody to distal ends of PEG chains via p-nitrophenylcarbonyl groups. 27th International Symposium on Controlled Release of Bioactive Materials; 2000; Paris: Controlled Release Society, Inc",{},{"id":18,"text":1903,"url":18,"identifiers":1904},"Torchilin VP, Weissig V, Martin FJ, Heath TD, New RRC. Surface modifications of liposomes. In: Torchilin VP, Weissig V, editors. Liposomes: a practical approach. 2nd ed. Oxford: Oxford University Press; 2003. p. 193–229.",{},{"id":18,"text":1906,"url":18,"identifiers":1907},"Hansen CB, Kao GY, Moase EH, Zalipsky S, Allen TM. Attachment of antibodies to sterically stabilized liposomes: evaluation, comparison and optimization of coupling procedures. Biochim Biophys Acta. 1995;1239(2):133–44.",{"doi":1908},"10.1016\u002F0005-2736(95)00138-S",{"id":18,"text":1910,"url":18,"identifiers":1911},"Ishida T, Iden DL, Allen TM. A combinatorial approach to producing sterically stabilized (stealth) immunoliposomal drugs. FEBS Lett. 1999;460(1):129–33.",{"doi":1912},"10.1016\u002FS0014-5793(99)01320-4",{"id":18,"text":1914,"url":18,"identifiers":1915},"Sofou S, Sgouros G. Antibody-targeted liposomes in cancer therapy and imaging. Expert Opin Drug Deliv. 2008;5(2):189–204.",{"doi":1916},"10.1517\u002F17425247.5.2.189",{"id":18,"text":1918,"url":18,"identifiers":1919},"Torchilin V. Antibody-modified liposomes for cancer chemotherapy. Expert Opin Drug Deliv. 2008;5(9):1003–25.",{"doi":1920},"10.1517\u002F17425247.5.9.1003",{"id":18,"text":1922,"url":18,"identifiers":1923},"Martin FJ, Papahadjopoulos D. Irreversible coupling of immunoglobulin fragments to preformed vesicles. An improved method for liposome targeting. J Biol Chem. 1982;257(1):286–8.",{"doi":1924},"10.1016\u002FS0021-9258(19)68359-6",{"id":18,"text":1926,"url":18,"identifiers":1927},"Moreira JN, Ishida T, Gaspar R, Allen TM. Use of the post-insertion technique to insert peptide ligands into pre-formed stealth liposomes with retention of binding activity and cytotoxicity. Pharm Res. 2002;19(3):265–9.",{"doi":1928},"10.1023\u002FA:1014434732752",{"id":18,"text":1930,"url":18,"identifiers":1931},"Elbayoumi TA, Torchilin VP. Tumor-specific anti-nucleosome antibody improves therapeutic efficacy of doxorubicin-loaded long-circulating liposomes against primary and metastatic tumor in mice. Mol Pharm. 2009;6(1):246–54.",{"doi":1932},"10.1021\u002Fmp8001528",{"id":18,"text":1934,"url":18,"identifiers":1935},"Kirpotin DB, Drummond DC, Shao Y, Shalaby MR, Hong K, Nielsen UB, et al. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 2006;66(13):6732–40.",{"doi":1936},"10.1158\u002F0008-5472.CAN-05-4199",{"id":18,"text":1938,"url":18,"identifiers":1939},"Xiong XB, Huang Y, Lu WL, Zhang H, Zhang X, Zhang Q. Enhanced intracellular uptake of sterically stabilized liposomal doxorubicin in vitro resulting in improved antitumor activity in vivo. Pharm Res. 2005;22(6):933–9.",{"doi":1940},"10.1007\u002Fs11095-005-4588-x",{"id":18,"text":1942,"url":18,"identifiers":1943},"Xiong XB, Huang Y, Lu WL, Zhang X, Zhang H, Nagai T, et al. Intracellular delivery of doxorubicin with RGD-modified sterically stabilized liposomes for an improved antitumor efficacy: in vitro and in vivo. J Pharm Sci. 2005;94(8):1782–93.",{"doi":1944},"10.1002\u002Fjps.20397",{"id":18,"text":1946,"url":18,"identifiers":1947},"Allen TM, Ahmad I, Lopes de Menezes DE, Moase EH. Immunoliposome-mediated targeting of anti-cancer drugs in vivo. Biochem Soc Trans. 1995;23(4):1073–9.",{"doi":1948},"10.1042\u002Fbst0231073",{"id":18,"text":1950,"url":18,"identifiers":1951},"Vingerhoeds MH, Steerenberg PA, Hendriks JJ, Dekker LC, Van Hoesel QG, Crommelin DJ, et al. Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo. Br J Cancer. 1996;74(7):1023–9.",{"doi":1952},"10.1038\u002Fbjc.1996.484",{"id":18,"text":1954,"url":18,"identifiers":1955},"Moase EH, Qi W, Ishida T, Gabos Z, Longenecker BM, Zimmermann GL, et al. Anti-MUC-1 immunoliposomal doxorubicin in the treatment of murine models of metastatic breast cancer. Biochim Biophys Acta. 2001;1510(1–2):43–55.",{"doi":1956},"10.1016\u002FS0005-2736(00)00334-5",{"id":18,"text":1958,"url":18,"identifiers":1959},"Lukyanov AN, Elbayoumi TA, Chakilam AR, Torchilin VP. Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody. J Control Release. 2004;100(1):135–44.",{"doi":1960},"10.1016\u002Fj.jconrel.2004.08.007",{"id":18,"text":1962,"url":18,"identifiers":1963},"Gupta B, Torchilin VP. Monoclonal antibody 2 C5-modified doxorubicin-loaded liposomes with significantly enhanced therapeutic activity against intracranial human brain U-87 MG tumor xenografts in nude mice. Cancer Immunol Immunother. 2007;56(8):1215–23.",{"doi":1964},"10.1007\u002Fs00262-006-0273-0",{"id":18,"text":1966,"url":18,"identifiers":1967},"Park JW, Kirpotin DB, Hong K, Shalaby R, Shao Y, Nielsen UB, et al. Tumor targeting using anti-her2 immunoliposomes. J Control Release. 2001;74(1–3):95–113.",{"doi":1968},"10.1016\u002FS0168-3659(01)00315-7",{"id":18,"text":1970,"url":18,"identifiers":1971},"Shmeeda H, Tzemach D, Mak L, Gabizon A. Her2-targeted pegylated liposomal doxorubicin: retention of target-specific binding and cytotoxicity after in vivo passage. J Control Release. 2009;136(2):155–60.",{"doi":1972},"10.1016\u002Fj.jconrel.2009.02.002",{"id":18,"text":1974,"url":18,"identifiers":1975},"Kamps JA, Koning GA, Velinova MJ, Morselt HW, Wilkens M, Gorter A, et al. Uptake of long-circulating immunoliposomes, directed against colon adenocarcinoma cells, by liver metastases of colon cancer. J Drug Target. 2000;8(4):235–45.",{"doi":1976},"10.3109\u002F10611860008997902",{"id":18,"text":1978,"url":18,"identifiers":1979},"Mamot C, Drummond DC, Greiser U, Hong K, Kirpotin DB, Marks JD, et al. Epidermal growth factor receptor (EGFR)-targeted immunoliposomes mediate specific and efficient drug delivery to EGFR- and EGFRvIII-overexpressing tumor cells. Cancer Res. 2003;63(12):3154–61.",{},{"id":18,"text":1981,"url":18,"identifiers":1982},"Gabizon A, Horowitz AT, Goren D, Tzemach D, Shmeeda H, Zalipsky S. In vivo fate of folate-targeted polyethylene-glycol liposomes in tumor-bearing mice. Clin Cancer Res. 2003;9(17):6551–9.",{},{"id":18,"text":1984,"url":18,"identifiers":1985},"Yokota T, Milenic DE, Whitlow M, Schlom J. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res. 1992;52(12):3402–8.",{},{"id":18,"text":1987,"url":18,"identifiers":1988},"Lee RJ, Low PS. Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro. Biochim Biophys Acta. 1995;1233(2):134–44.",{"doi":1989},"10.1016\u002F0005-2736(94)00235-H",{"id":18,"text":1991,"url":18,"identifiers":1992},"Park JW, Hong K, Kirpotin DB, Papahadjopoulos D, Benz CC. Immunoliposomes for cancer treatment. Adv Pharmacol. 1997;40:399–435.",{"doi":1993},"10.1016\u002FS1054-3589(08)60146-5",{"id":18,"text":1995,"url":18,"identifiers":1996},"Storm G, Steerenberg PA, Emmen F, van Borssum Waalkes M, Crommelin DJ. Release of doxorubicin from peritoneal macrophages exposed in vivo to doxorubicin-containing liposomes. Biochim Biophys Acta. 1988;965(2–3):136–45.",{"doi":1997},"10.1016\u002F0304-4165(88)90049-9",{"id":18,"text":1999,"url":18,"identifiers":2000},"Chu CJ, Dijkstra J, Lai MZ, Hong K, Szoka FC. Efficiency of cytoplasmic delivery by pH-sensitive liposomes to cells in culture. Pharm Res. 1990;7(8):824–34.",{"doi":2001},"10.1023\u002FA:1015908831507",{"id":18,"text":2003,"url":18,"identifiers":2004},"Trubetskaya OV, Trubetskoy VS, Domogatsky SP, Rudin AV, Popov NV, Danilov SM, et al. Monoclonal antibody to human endothelial cell surface internalization and liposome delivery in cell culture. FEBS Lett. 1988;228(1):131–4.",{"doi":2005},"10.1016\u002F0014-5793(88)80601-X",{"id":18,"text":2007,"url":18,"identifiers":2008},"Allen TM, Hansen C, Stuart DD. Targeted stericalliy stabilized liposomal drug delivery. In: Lasic DD, Papahadjopoulos D, editors. Medical applications of liposomes. New York: Elsevier; 1998. p. 545–65.",{},{"id":18,"text":2010,"url":18,"identifiers":2011},"Zhou Y, Drummond DC, Zou H, Hayes ME, Adams GP, Kirpotin DB, et al. Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. J Mol Biol. 2007;371(4):934–47.",{"doi":2012},"10.1016\u002Fj.jmb.2007.05.011",{"id":18,"text":2014,"url":18,"identifiers":2015},"Sapra P, Allen TM. Improved outcome when B-cell lymphoma is treated with combinations of immunoliposomal anticancer drugs targeted to both the CD19 and CD20 epitopes. Clin Cancer Res. 2004;10(7):2530–7.",{"doi":2016},"10.1158\u002F1078-0432.CCR-03-0376",{"id":18,"text":2018,"url":18,"identifiers":2019},"Allen TM, Mumbengegwi DR, Charrois GJ. Anti-CD19-targeted liposomal doxorubicin improves the therapeutic efficacy in murine B-cell lymphoma and ameliorates the toxicity of liposomes with varying drug release rates. Clin Cancer Res. 2005;11(9):3567–73.",{"doi":2020},"10.1158\u002F1078-0432.CCR-04-2517",{"id":18,"text":2022,"url":18,"identifiers":2023},"Hosokawa S, Tagawa T, Niki H, Hirakawa Y, Nohga K, Nagaike K. Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner. Br J Cancer. 2003;89(8):1545–51.",{"doi":2024},"10.1038\u002Fsj.bjc.6601341",{"id":18,"text":2026,"url":18,"identifiers":2027},"Emanuel N, Kedar E, Bolotin EM, Smorodinsky NI, Barenholz Y. Targeted delivery of doxorubicin via sterically stabilized immunoliposomes: pharmacokinetics and biodistribution in tumor-bearing mice. Pharm Res. 1996;13(6):861–8.",{"doi":2028},"10.1023\u002FA:1016096910822",{"id":18,"text":2030,"url":18,"identifiers":2031},"Allen TM, Brandeis E, Hansen CB, Kao GY, Zalipsky S. A new strategy for attachment of antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells. Biochim Biophys Acta. 1995;1237(2):99–108.",{"doi":2032},"10.1016\u002F0005-2736(95)00085-H",{"id":18,"text":2034,"url":18,"identifiers":2035},"Kamps JA, Scherphof GL. Receptor versus non-receptor mediated clearance of liposomes. Adv Drug Deliv Rev. 1998;32(1–2):81–97.",{},{"id":18,"text":2037,"url":18,"identifiers":2038},"Flavell DJ, Noss A, Pulford KA, Ling N, Flavell SU. Systemic therapy with 3BIT, a triple combination cocktail of anti-CD19, -CD22, and -CD38-saporin immunotoxins, is curative of human B-cell lymphoma in severe combined immunodeficient mice. Cancer Res. 1997;57(21):4824–9.",{},{"id":18,"text":2040,"url":18,"identifiers":2041},"Anabousi S, Bakowsky U, Schneider M, Huwer H, Lehr CM, Ehrhardt C. In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer. Eur J Pharm Sci. 2006;29(5):367–74.",{"doi":2042},"10.1016\u002Fj.ejps.2006.07.004",{"id":18,"text":2044,"url":18,"identifiers":2045},"Hatakeyama H, Akita H, Maruyama K, Suhara T, Harashima H. Factors governing the in vivo tissue uptake of transferrin-coupled polyethylene glycol liposomes in vivo. Int J Pharm. 2004;281(1–2):25–33.",{"doi":2046},"10.1016\u002Fj.ijpharm.2004.05.025",{"id":18,"text":2048,"url":18,"identifiers":2049},"Li X, Ding L, Xu Y, Wang Y, Ping Q. Targeted delivery of doxorubicin using stealth liposomes modified with transferrin. Int J Pharm. 2009;373(1–2):116–23.",{"doi":2050},"10.1016\u002Fj.ijpharm.2009.01.023",{"id":18,"text":2052,"url":18,"identifiers":2053},"Ishida O, Maruyama K, Tanahashi H, Iwatsuru M, Sasaki K, Eriguchi M, et al. Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo. Pharm Res. 2001;18(7):1042–8.",{"doi":2054},"10.1023\u002FA:1010960900254",{"id":18,"text":2056,"url":18,"identifiers":2057},"Leamon CP, Low PS. Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis. Proc Natl Acad Sci USA. 1991;88(13):5572–6.",{"doi":2058},"10.1073\u002Fpnas.88.13.5572",{"id":18,"text":2060,"url":18,"identifiers":2061},"Yamada A, Taniguchi Y, Kawano K, Honda T, Hattori Y, Maitani Y. Design of folate-linked liposomal doxorubicin to its antitumor effect in mice. Clin Cancer Res. 2008;14(24):8161–8.",{"doi":2062},"10.1158\u002F1078-0432.CCR-08-0159",{"id":18,"text":2064,"url":18,"identifiers":2065},"Lu Y, Wu J, Wu J, Gonit M, Yang X, Lee A, et al. Role of formulation composition in folate receptor-targeted liposomal doxorubicin delivery to acute myelogenous leukemia cells. Mol Pharm. 2007;4(5):707–12.",{"doi":2066},"10.1021\u002Fmp070058l",{"id":18,"text":2068,"url":18,"identifiers":2069},"Gupta B, Levchenko TS, Torchilin VP. Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv Drug Deliv Rev. 2005;57(4):637–51.",{"doi":2070},"10.1016\u002Fj.addr.2004.10.007",{"id":18,"text":2072,"url":18,"identifiers":2073},"Kale AA, Torchilin VP. Design, synthesis, and characterization of pH-sensitive PEG-PE conjugates for stimuli-sensitive pharmaceutical nanocarriers: the effect of substitutes at the hydrazone linkage on the ph stability of PEG-PE conjugates. Bioconjug Chem. 2007;18(2):363–70.",{"doi":2074},"10.1021\u002Fbc060228x",{"id":18,"text":2076,"url":18,"identifiers":2077},"Torchilin V. Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. Eur J Pharm Biopharm. 2009;71(3):431–44.",{"doi":2078},"10.1016\u002Fj.ejpb.2008.09.026",{"id":18,"text":2080,"url":18,"identifiers":2081},"ElBayoumi TA, Torchilin VP. Tumor-targeted nanomedicines: enhanced antitumor efficacy in vivo of doxorubicin-loaded, long-circulating liposomes modified with cancer-specific monoclonal antibody. Clin Cancer Res. 2009;15(6):1973–80.",{"doi":2082},"10.1158\u002F1078-0432.CCR-08-2392",{"id":18,"text":2084,"url":18,"identifiers":2085},"Elbayoumi TA, Torchilin VP. Enhanced cytotoxicity of monoclonal anticancer antibody 2 C5-modified doxorubicin-loaded PEGylated liposomes against various tumor cell lines. Eur J Pharm Sci. 2007;32(3):159–68.",{"doi":2086},"10.1016\u002Fj.ejps.2007.05.113",{"id":18,"text":2088,"url":18,"identifiers":2089},"Yang T, Choi MK, Cui FD, Lee SJ, Chung SJ, Shim CK, et al. Antitumor effect of paclitaxel-loaded PEGylated immunoliposomes against human breast cancer cells. Pharm Res. 2007;24(12):2402–11.",{"doi":2090},"10.1007\u002Fs11095-007-9425-y",{"id":18,"text":2092,"url":18,"identifiers":2093},"Zhao H, Wang JC, Sun QS, Luo CL, Zhang Q. RGD-based strategies for improving antitumor activity of paclitaxel-loaded liposomes in nude mice xenografted with human ovarian cancer. J Drug Target. 2009;17(1):10–8.",{"doi":2094},"10.1080\u002F10611860802368966",{"id":18,"text":2096,"url":18,"identifiers":2097},"Hatakeyama H, Akita H, Ishida E, Hashimoto K, Kobayashi H, Aoki T, et al. Tumor targeting of doxorubicin by anti-MT1-MMP antibody-modified PEG liposomes. Int J Pharm. 2007;342(1–2):194–200.",{"doi":2098},"10.1016\u002Fj.ijpharm.2007.04.037",{"id":2100,"createTime":2101,"updateTime":2102,"relativeEntities":2103,"slug":2104,"properties":2105,"entityType":177,"verifyStatus":178,"verifyTime":2120,"verifyNote":180,"languages":2121,"translateLanguages":18,"viewCount":19,"primaryUrl":2122,"fullTextUrl":18,"authors":2123,"publicationType":216,"publisherRelationship":2177,"citationCount":2226,"citationInfo":2227,"publishDate":2230,"publishYear":2228,"citationAnalyzeStatus":1529,"lastCitationAnalyze":2231,"indexDatabases":2232,"openAccess":18,"references":2233,"isForceReanalyzing":269},"a00e3c58-f828-487e-8112-c56ba63f90c1","2024-04-17T17:32:33.783+00:00","2026-07-25T11:54:21.183+00:00",[],"CYP3A4-Mediates-Oxidative-Metabolism-of-the-Synthetic-Cannabinoid-AKB-48",{"mag":2106,"gsPaper":2108,"pmc":2110,"openalex":2112,"title":2114,"pm":2116,"doi":2118},{"VOID":2107},"278068762",{"VOID":2109},"[\"8426002673964685219\"]",{"VOID":2111},"4540740",{"VOID":2113},"W278068762",{"EN":2115},"CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48",{"VOID":2117},"26002511",{"VOID":2119},"10.1208\u002Fs12248-015-9788-7","2024-06-24T06:44:57.508+00:00",[509],"http:\u002F\u002Flink.springer.com\u002F10.1208\u002Fs12248-015-9788-7",[2124,2143,2158],{"id":2125,"sortIndex":19,"researcher":18,"roles":2126,"affiliations":2127,"properties":2136,"displayName":2140,"givenName":18,"familyName":18},"25778a1f-8d46-4317-b22e-bcfedf45736e",[],[2128],{"id":2129,"sortIndex":19,"affiliation":2130,"properties":18},"d200043f-4239-4528-b5db-7da0875b9ae9",{"id":2129,"createTime":18,"updateTime":18,"relativeEntities":2131,"slug":18,"properties":2132,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2135,"statistic":18},[],{"title":2133},{"EN":2134},"Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V’s Vej 11, 3rd floor, 2100, Copenhagen, Denmark",[],{"orcid":2137,"title":2139,"openalex":2141},{"VOID":2138},"https:\u002F\u002Forcid.org\u002F0000-0002-6750-5527",{"EN":2140},"Niels Bjerre Holm",{"VOID":2142},"A5004937841",{"id":2144,"sortIndex":204,"researcher":18,"roles":2145,"affiliations":2146,"properties":2153,"displayName":2155,"givenName":18,"familyName":18},"5e0ad383-4768-42c9-9b49-fb2c961c7c0a",[],[2147],{"id":2129,"sortIndex":19,"affiliation":2148,"properties":18},{"id":2129,"createTime":18,"updateTime":18,"relativeEntities":2149,"slug":18,"properties":2150,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2152,"statistic":18},[],{"title":2151},{"EN":2134},[],{"title":2154,"openalex":2156},{"EN":2155},"Line Marie Nielsen",{"VOID":2157},"A5077445298",{"id":2159,"sortIndex":320,"researcher":18,"roles":2160,"affiliations":2161,"properties":2168,"displayName":2172,"givenName":18,"familyName":18},"3364385a-e6fe-4b05-8b2f-3ebd8dbdcd2a",[],[2162],{"id":2129,"sortIndex":19,"affiliation":2163,"properties":18},{"id":2129,"createTime":18,"updateTime":18,"relativeEntities":2164,"slug":18,"properties":2165,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2167,"statistic":18},[],{"title":2166},{"EN":2134},[],{"orcid":2169,"title":2171,"gsAuthor":2173,"openalex":2175},{"VOID":2170},"https:\u002F\u002Forcid.org\u002F0000-0001-6974-5535",{"EN":2172},"Kristían Línnet",{"VOID":2174},"[\"4dwplR4AAAAJ\"]",{"VOID":2176},"A5078174062",{"url":18,"publisher":2178,"properties":2219},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":2179,"slug":10,"properties":2180,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":2183,"manageAffiliations":2188,"indexDatabases":2199,"url":18,"thumbnailPath":18,"statistic":2214,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":2181,"eissn":2182},{"EN":13},{"VOID":15},[2184],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":2185,"label":2186,"description":2187,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[2189,2194],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":2190,"slug":18,"properties":2191,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2193,"statistic":18},[],{"title":2192},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":2195,"slug":18,"properties":2196,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2198,"statistic":18},[],{"title":2197},{"EN":41},[],[2200,2207],{"id":45,"indexDatabase":2201,"url":58,"indexYears":18,"academicFieldIds":2206,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":2202,"label":2203,"description":2204,"key":54,"publicationTags":2205,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":2208,"url":73,"indexYears":74,"academicFieldIds":2213,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":2209,"label":2210,"description":2211,"key":70,"publicationTags":2212,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":2215,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":2216,"totalCitation":117,"totalCitationByYear":2217,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":2218,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"issue":2220,"pages":2222,"volume":2224},{"VOID":2221},"5",{"VOID":2223},"1237-1245",{"VOID":2225},"17",58,{"total":2226,"publishYear":2228,"statisticByYear":2229},2015,{"2015":320,"2016":412,"2017":412,"2018":382,"2019":396,"2020":366,"2021":412,"2022":366,"2023":334,"2024":320,"2025":320,"2026":320},"2015-09-01","2026-07-25T11:54:21.182+00:00",[56,77],[2234,2238,2242,2246,2250,2253,2257,2261,2265,2268,2272,2276,2280,2284,2288,2292,2295,2299,2303,2307,2311,2315,2318,2321,2324,2327,2331,2335,2338,2342,2345,2349,2353,2357,2361,2365,2369],{"id":18,"text":2235,"url":18,"identifiers":2236},"Pertwee RG. Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. Addict Biol. 2008;13(2):147–59.",{"doi":2237},"10.1111\u002Fj.1369-1600.2008.00108.x",{"id":18,"text":2239,"url":18,"identifiers":2240},"Auwarter V, Dresen S, Weinmann W, Muller M, Putz M, Ferreiros N. ‘Spice’ and other herbal blends: harmless incense or cannabinoid designer drugs? J Mass Spectrom. 2009;44(5):832–7.",{"doi":2241},"10.1002\u002Fjms.1558",{"id":18,"text":2243,"url":18,"identifiers":2244},"Uchiyama N, Kikura-Hanajiri R, Kawahara N, Haishima Y, Goda Y. Identification of a cannabinoid analog as a new type of designer drug in a herbal product. Chem Pharm Bull (Tokyo). 2009;57(4):439–41.",{"doi":2245},"10.1248\u002Fcpb.57.439",{"id":18,"text":2247,"url":18,"identifiers":2248},"Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y. URB-754: a new class of designer drug and 12 synthetic cannabinoids detected in illegal products. Forensic Sci Int. 2013;227(1-3):21–32.",{"doi":2249},"10.1016\u002Fj.forsciint.2012.08.047",{"id":18,"text":2251,"url":18,"identifiers":2252},"New psychoactive substances in Europe: An update from the EU Early Warning System (March 2015). European Monitoring Centre for Drugs and Drug Addiction. 2015. http:\u002F\u002Fwww.emcdda.europa.eu\u002Fpublications\u002F2015\u002Fnew-psychoactive-substances . Accessed 6 May 2015.",{},{"id":18,"text":2254,"url":18,"identifiers":2255},"Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend. 2014;144:12–41.",{"doi":2256},"10.1016\u002Fj.drugalcdep.2014.08.005",{"id":18,"text":2258,"url":18,"identifiers":2259},"Meyer MR, Peters FT. Analytical toxicology of emerging drugs of abuse—an update. Ther Drug Monit. 2012;34(6):615–21.",{"doi":2260},"10.1097\u002FFTD.0b013e31826d0915",{"id":18,"text":2262,"url":18,"identifiers":2263},"Wohlfarth A, Weinmann W. Bioanalysis of new designer drugs. Bioanalysis. 2010;2(5):965–79.",{"doi":2264},"10.4155\u002Fbio.10.32",{"id":18,"text":2266,"url":18,"identifiers":2267},"Castaneto MS, Scheidweiler KB, Gandhi A, Wohlfarth A, Klette KL, Martin TM, et al. Quantitative urine confirmatory testing for synthetic cannabinoids in randomly collected urine specimens. Drug Test Anal. 2014. doi: 10.1002\u002Fdta.1709 .",{},{"id":18,"text":2269,"url":18,"identifiers":2270},"Hutter M, Broecker S, Kneisel S, Auwarter V. Identification of the major urinary metabolites in man of seven synthetic cannabinoids of the aminoalkylindole type present as adulterants in ‘herbal mixtures’ using LC-MS\u002FMS techniques. J Mass Spectrom. 2012;47(1):54–65.",{"doi":2271},"10.1002\u002Fjms.2026",{"id":18,"text":2273,"url":18,"identifiers":2274},"Chimalakonda KC, Bratton SM, Le VH, Yiew KH, Dineva A, Moran CL, et al. Conjugation of synthetic cannabinoids JWH-018 and JWH-073, metabolites by human UDP-glucuronosyltransferases. Drug Metab Dispos. 2011;39(10):1967–76.",{"doi":2275},"10.1124\u002Fdmd.111.040709",{"id":18,"text":2277,"url":18,"identifiers":2278},"Forrester MB, Kleinschmidt K, Schwarz E, Young A. Synthetic cannabinoid and marijuana exposures reported to poison centers. Hum Exp Toxicol. 2012;31(10):1006–11.",{"doi":2279},"10.1177\u002F0960327111421945",{"id":18,"text":2281,"url":18,"identifiers":2282},"Holm NB, Pineda RS, Andersen DW, Rasmussen BS, Dalsgaard PW, Hoegberg L, et al. Screening of Danish traffic cases for synthetic cannabinoids in whole blood by LC-MS\u002FMS. Scand J Forensic Sci. 2013;19(2):45–51.",{"doi":2283},"10.2478\u002Fsjfs-2013-0008",{"id":18,"text":2285,"url":18,"identifiers":2286},"Chimalakonda KC, Seely KA, Bratton SM, Brents LK, Moran CL, Endres GW, et al. Cytochrome P450-mediated oxidative metabolism of abused synthetic cannabinoids found in K2\u002Fspice: identification of novel cannabinoid receptor ligands. Drug Metab Dispos. 2012;40(11):2174–84.",{"doi":2287},"10.1124\u002Fdmd.112.047530",{"id":18,"text":2289,"url":18,"identifiers":2290},"Chimalakonda KC, James LP, Radominska-Pandya A, Moran JH. Sulfaphenazole and alpha-naphthoflavone attenuate the metabolism of the synthetic cannabinoids JWH-018 and AM2201 found in K2\u002Fspice. Drug Metab Lett. 2013;7(1):34–8.",{"doi":2291},"10.2174\u002F187231280701131211151523",{"id":18,"text":2293,"url":18,"identifiers":2294},"Thomsen R, Nielsen LM, Holm NB, Rasmussen HB, Linnet K. Synthetic cannabimimetic agents metabolized by carboxylesterases. Drug Test Anal. 2014. doi: 10.1002\u002Fdta.1731 .",{},{"id":18,"text":2296,"url":18,"identifiers":2297},"Gandhi AS, Zhu M, Pang S, Wohlfarth A, Scheidweiler KB, Liu HF, et al. First characterization of AKB-48 metabolism, a novel synthetic cannabinoid, using human hepatocytes and high-resolution mass spectrometry. AAPS J. 2013;15(4):1091–8.",{"doi":2298},"10.1208\u002Fs12248-013-9516-0",{"id":18,"text":2300,"url":18,"identifiers":2301},"Holm NB, Pedersen AJ, Dalsgaard PW, Linnet K. Metabolites of 5F-AKB-48, a synthetic cannabinoid receptor agonist, identified in human urine and liver microsomal preparations using liquid chromatography high-resolution mass spectrometry. Drug Test Anal. 2015;7(3):199–206.",{"doi":2302},"10.1002\u002Fdta.1663",{"id":18,"text":2304,"url":18,"identifiers":2305},"Sobolevsky T, Prasolov I, Rodchenkov G. Study on the phase I metabolism of novel synthetic cannabinoids, APICA and its fluorinated analogue. Drug Test Anal. 2015;7(2):131–42.",{"doi":2306},"10.1002\u002Fdta.1756",{"id":18,"text":2308,"url":18,"identifiers":2309},"Gandhi AS, Wohlfarth A, Zhu M, Pang S, Castaneto M, Scheidweiler KB, et al. High-resolution mass spectrometric metabolite profiling of a novel synthetic designer drug, N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (STS-135), using cryopreserved human hepatocytes and assessment of metabolic stability with human liver microsomes. Drug Test Anal. 2015;7(3):187–98.",{"doi":2310},"10.1002\u002Fdta.1662",{"id":18,"text":2312,"url":18,"identifiers":2313},"Grigoryev A, Kavanagh P, Melnik A. The detection of the urinary metabolites of 3-[(adamantan-1-yl)carbonyl]-1-pentylindole (AB-001), a novel cannabimimetic, by gas chromatography-mass spectrometry. Drug Test Anal. 2012;4(6):519–24.",{"doi":2314},"10.1002\u002Fdta.350",{"id":18,"text":2316,"url":18,"identifiers":2317},"Bekendtgørelse om euforiserende stoffer. BEK 557 af 31\u002F05\u002F2011. Ministeriet for Sundhed og Forebyggelse. https:\u002F\u002Fwww.retsinformation.dk\u002FForms\u002FR0710.aspx?id=138271#B1 . Accessed 8 Apr 2015.",{},{"id":18,"text":2319,"url":18,"identifiers":2320},"2.5 Synthetic cannabinoids. In: 2013 Annual Report. National Forensic Laboratory Information System. 2014. https:\u002F\u002Fwww.nflis.deadiversion.usdoj.gov\u002FDesktopModules\u002FReportDownloads\u002FReports\u002FNFLIS2013AR.pdf . Accessed 8 Apr 2015.",{},{"id":18,"text":2322,"url":18,"identifiers":2323},"Illegale stoffer i Danmark. In: Illegale stoffer i Danmark, Årsrapport 2013. Sundhedsstyrelsen. 2014. https:\u002F\u002Fsundhedsstyrelsen.dk\u002Fda\u002Fsundhed\u002Fnarkotika\u002Findhold-i-illegale-stoffer~\u002Fmedia\u002F0F7441B6213B4FA3A8E874B00984B964.ashx . Accessed 8 Apr 2015.",{},{"id":18,"text":2325,"url":18,"identifiers":2326},"Drug Development and Drug Interactions: Table of substrates, inhibitors and inducers. In: Development & approval process (drugs). U.S. Food and Drug Administration. 2014. http:\u002F\u002Fwww.fda.gov\u002Fdrugs\u002Fdevelopmentapprovalprocess\u002Fdevelopmentresources\u002Fdruginteractionslabeling\u002Fucm093664.htm . Accessed 8 Apr 2015.",{},{"id":18,"text":2328,"url":18,"identifiers":2329},"Ko JW, Desta Z, Soukhova NV, Tracy T, Flockhart DA. In vitro inhibition of the cytochrome P450 (CYP450) system by the antiplatelet drug ticlopidine: potent effect on CYP2C19 and CYP2D6. Br J Clin Pharmacol. 2000;49(4):343–51.",{"doi":2330},"10.1046\u002Fj.1365-2125.2000.00175.x",{"id":18,"text":2332,"url":18,"identifiers":2333},"Olesen OV, Linnet K. Identification of the human cytochrome P450 isoforms mediating in vitro N-dealkylation of perphenazine. Br J Clin Pharmacol. 2000;50(6):563–71.",{"doi":2334},"10.1046\u002Fj.1365-2125.2000.00298.x",{"id":18,"text":2336,"url":18,"identifiers":2337},"Yamazaki H, Inoue K, Shaw PM, Checovich WJ, Guengerich FP, Shimada T. Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: effects of contents of these two forms in individual human samples. J Pharmacol Exp Ther. 1997;283(2):434–42.",{},{"id":18,"text":2339,"url":18,"identifiers":2340},"Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138(1):103–41.",{"doi":2341},"10.1016\u002Fj.pharmthera.2012.12.007",{"id":18,"text":2343,"url":18,"identifiers":2344},"Scheen AJ. Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacol Ther. 2010;49(9):573–88.",{},{"id":18,"text":2346,"url":18,"identifiers":2347},"Su H, Boulton DW, Barros Jr A, Wang L, Cao K, Bonacorsi Jr SJ, et al. Characterization of the in vitro and in vivo metabolism and disposition and cytochrome P450 inhibition\u002Finduction profile of saxagliptin in human. Drug Metab Dispos. 2012;40(7):1345–56.",{"doi":2348},"10.1124\u002Fdmd.112.045450",{"id":18,"text":2350,"url":18,"identifiers":2351},"He H, Tran P, Yin H, Smith H, Batard Y, Wang L, et al. Absorption, metabolism, and excretion of [14C]vildagliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans. Drug Metab Dispos. 2009;37(3):536–44.",{"doi":2352},"10.1124\u002Fdmd.108.023010",{"id":18,"text":2354,"url":18,"identifiers":2355},"Anzenbacher P, Anzenbacherova E. Cytochromes P450 and metabolism of xenobiotics. Cell Mol Life Sci. 2001;58(5-6):737–47.",{"doi":2356},"10.1007\u002FPL00000897",{"id":18,"text":2358,"url":18,"identifiers":2359},"Forrester MB, Kleinschmidt K, Schwarz E, Young A. Synthetic cannabinoid exposures reported to Texas poison centers. J Addict Dis. 2011;30(4):351–8.",{"doi":2360},"10.1080\u002F10550887.2011.609807",{"id":18,"text":2362,"url":18,"identifiers":2363},"Zhou X, Gao ZW, Meng J, Chen XY, Zhong DF. Effects of ketoconazole and rifampicin on the pharmacokinetics of GLS4, a novel anti-hepatitis B virus compound, in dogs. Acta Pharmacol Sin. 2013;34(11):1420–6.",{"doi":2364},"10.1038\u002Faps.2013.76",{"id":18,"text":2366,"url":18,"identifiers":2367},"Dresen S, Ferreiros N, Putz M, Westphal F, Zimmermann R, Auwarter V. Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. J Mass Spectrom. 2010;45(10):1186–94.",{"doi":2368},"10.1002\u002Fjms.1811",{"id":18,"text":2370,"url":18,"identifiers":2371},"Hudson S, Ramsey J, King L, Timbers S, Maynard S, Dargan PI, et al. Use of high-resolution accurate mass spectrometry to detect reported and previously unreported cannabinomimetics in “herbal high” products. J Anal Toxicol. 2010;34(5):252–60.",{"doi":2372},"10.1093\u002Fjat\u002F34.5.252",{"id":2374,"createTime":2375,"updateTime":2376,"relativeEntities":2377,"slug":2378,"properties":2379,"entityType":177,"verifyStatus":178,"verifyTime":2389,"verifyNote":180,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":2390,"fullTextUrl":18,"authors":2391,"publicationType":216,"publisherRelationship":2569,"citationCount":18,"citationInfo":18,"publishDate":2616,"publishYear":2617,"citationAnalyzeStatus":937,"lastCitationAnalyze":2618,"indexDatabases":2619,"openAccess":18,"references":18,"isForceReanalyzing":269},"a85ea3fe-597f-47b7-815a-47ae8a36ae99","2023-12-06T13:36:26.491+00:00","2026-07-23T14:35:20.295+00:00",[],"Optimal-Sampling-Strategies-for-Irinotecan-CPT-11-and-its-Active-Metabolite-SN-38-in-Cancer-Patients",{"abstract":2380,"title":2382,"gsPaper":2384,"references":2385,"doi":2387},{"EN":2381},"Irinotecan (CPT-11) is an anticancer agent widely used in the treatment of a variety of adult solid tumors. The objective of this study was to develop an optimal sampling strategy model that accurately estimates pharmacokinetic parameters of CPT-11 and its active metabolite, SN-38. This study included 221 patients with advanced solid tumors or lymphoma receiving CPT-11 single or combination therapy with 5-fluorouracil (5-FU)\u002Fleucovorin (LV) (FOLFIRI) plus bevacizumab from 4 separate clinical trials. Population pharmacokinetic analysis of CPT-11 and SN-38 was performed by non-linear mixed effects modeling. The optimal sampling strategy model was developed using D-optimality with expected distribution approach. The pharmacokinetic profiles of CPT-11 and SN-38 were best described by a 3- and 2-compartment model, respectively, with first-order elimination. Body surface area and co-administration with 5-FU\u002FLV plus bevacizumab were significant covariates (p \u003C 0.01) for volumes of the central compartment of CPT-11 and SN-38, and clearance of CPT-11. Pre-treatment total bilirubin and co-administration with 5-FU\u002FLV and bevacizumab were significant covariates (p \u003C 0.01) for clearance of SN-38. Accurate and precise predictive performance (r2 > 0.99, -2 \u003C bias (%ME) \u003C 0, precision (% RMSE) \u003C 12) of both CPT-11 and SN-38 was achieved using: (i) 6 fixed sampling times collected at 1.5, 3.5, 4, 5.75, 22, 23.5 hours post-infusion; or (ii) 1 fixed time and 2 sampling windows collected at 1.5, [3-5.75], [22-23.5] hours post-infusion. The present study demonstrates that an optimal sampling design with three blood samples achieves accurate and precise pharmacokinetic parameter estimates for both CPT-11 and SN-38.",{"EN":2383},"Optimal Sampling Strategies for Irinotecan (CPT-11) and its Active Metabolite (SN-38) in Cancer Patients",{"VOID":797},{"VOID":2386},"Kingsbury WD, Boehm JC, Jakas DR, Holden KG, Hecht SM, Gallagher G, et al. Synthesis of water-soluble (aminoalkyl)camptothecin analogues: inhibition of topoisomerase I and antitumor activity. J Med Chem. 1991 Jan;34(1):98–107.\nCAMPTOSAR® (irinotecan HCl) Dosage and Administration | Pfizer Medical Information - US [Internet]. 2019. Available from: https:\u002F\u002Fwww.pfizermedicalinformation.com\u002Fen-us\u002Fcamptosar\u002Fdosage-admin\nSaltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan study group. N Engl J Med. 2000;343(13):905–14.\nRothenberg ML, Kuhn JG, Burris HA, Nelson J, Eckardt JR, Tristan-Morales M, et al. Phase I and pharmacokinetic trial of weekly CPT-11. J Clin Oncol. 1993;11(11):2194–204.\nFuchs CS, Moore MR, Harker G, Villa L, Rinaldi D, Hecht JR. Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol. 2003;21(5):807–14.\nRatain MJ. Irinotecan dosing: does the CPT in CPT-11 stand for “Can’t predict toxicity”? J Clin Oncol. 2002;20(1):7–8.\nXie R, Mathijssen RHJ, Sparreboom A, Verweij J, Karlsson MO. Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea. Clin Pharmacol Ther. 2002;72(3):265–75.\nXie R, Mathijssen RHJ, Sparreboom A, Verweij J, Karlsson MO. Clinical pharmacokinetics of irinotecan and its metabolites: a population analysis. J Clin Oncol. 2002;20(15):3293–301.\nKlein CE, Gupta E, Reid JM, Atherton PJ, Sloan JA, Pitot HC, et al. Population pharmacokinetic model for irinotecan and two of its metabolites, SN-38 and SN-38 glucuronide. Clin Pharmacol Ther. 2002;72(6):638–47.\nChabot GG, Abigerges D, Catimel G, Culine S, de Forni M, Extra JM, et al. Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during phase I trials. Ann Oncol. 1995;6(2):141–51.\nde Man FM, Goey AKL, van Schaik RHN, Mathijssen RHJ, Bins S. Individualization of Irinotecan treatment: a review of pharmacokinetics, pharmacodynamics, and Pharmacogenetics. Clin Pharmacokinet. 2018;57(10):1229–54. https:\u002F\u002Fdoi.org\u002F10.1007\u002Fs40262-018-0644-7.\nAndo Y, Saka H, Ando M, Sawa T, Muro K, Ueoka H, et al. Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res. 2000;60(24):6921–6.\nHan J-Y, Lim H-S, Shin ES, Yoo Y-K, Park YH, Lee J-E, et al. Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol. 2006;24(15):2237–44.\nInnocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, et al. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004;22(8):1382–8.\nMinami H, Sai K, Saeki M, Saito Y, Ozawa S, Suzuki K, et al. Irinotecan pharmacokinetics\u002Fpharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Pharmacogenet Genomics. 2007;17(7):497–504.\nToffoli G, Cecchin E, Corona G, Russo A, Buonadonna A, D’Andrea M, et al. The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer. J Clin Oncol. 2006;24(19):3061–8.\nInnocenti F, Schilsky RL, Ramírez J, Janisch L, Undevia S, House LK, et al. Dose-finding and pharmacokinetic study to optimize the dosing of irinotecan according to the UGT1A1 genotype of patients with cancer. J Clin Oncol. 2014;32(22):2328–34.\nMarcuello E, Páez D, Paré L, Salazar J, Sebio A, del Rio E, et al. A genotype-directed phase I-IV dose-finding study of irinotecan in combination with fluorouracil\u002Fleucovorin as first-line treatment in advanced colorectal cancer. Br J Cancer. 2011;105(1):53–7.\nToffoli G, Cecchin E, Gasparini G, D’Andrea M, Azzarello G, Basso U, et al. Genotype-driven phase I study of irinotecan administered in combination with fluorouracil\u002Fleucovorin in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28(5):866–71.\nPerera MA, Innocenti F, Ratain MJ. Pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 polymorphisms: are we there yet? Pharmacotherapy. 2008;28(6):755–68.\nPanetta JC, Iacono LC, Adamson PC, Stewart CF. The importance of pharmacokinetic limited sampling models for childhood cancer drug development. Clin Cancer Res. 2003;9(14):5068–77.\nNakashima H, Lieberman R, Karato A, Arioka H, Ohmatsu H, Nomura N, et al. Efficient sampling strategies for forecasting pharmacokinetic parameters of irinotecan (CPT-11): implication for area under the concentration-time curve monitoring. Ther Drug Monit. 1995;17(3):221–9.\nSasaki Y, Mizuno S, Fujii H, Ohtsu T, Wakita H, Igarashi T, et al. A limited sampling model for estimating pharmacokinetics of CPT-11 and its metabolite SN-38. Jpn J Cancer Res. 1995 Jan;86(1):117–23.\nMick R, Gupta E, Vokes EE, Ratain MJ. Limited-sampling models for irinotecan pharmacokinetics- pharmacodynamics: prediction of biliary index and intestinal toxicity. J Clin Oncol. 1996;14(7):2012–9.\nMathijssen RH, van Alphen RJ, de Jonge MJ, Verweij J, de Bruijn P, Loos WJ, et al. Sparse-data set analysis for irinotecan and SN-38 pharmacokinetics in cancer patients co-treated with cisplatin. Anti-Cancer Drugs. 1999;10(1):9–16.\nPoujol S, Pinguet F, Ychou M, Abderrahim A, Duffour J, Bressolle F. A limited sampling strategy to estimate the pharmacokinetic parameters of irinotecan and its active metabolite, SN-38, in patients with metastatic digestive cancer receiving the FOLFIRI regimen. Oncol Rep. 2007;15.\nD’Argenio DZ. Incorporating prior parameter uncertainty in the design of sampling schedules for pharmacokinetic parameter estimation experiments. Math Biosci. 1990;99(1):105–18.\nD’Argenio DZ. Optimal sampling times for pharmacokinetic experiments. J Pharmacokinet Biopharm. 1981;9(6):739–56.\nForacchia M, Hooker A, Vicini P, Ruggeri A. POPED, a software for optimal experiment design in population kinetics. Comput Methods Prog Biomed. 2004;74(1):29–46.\nNyberg J, Ueckert S, Strömberg EA, Hennig S, Karlsson MO, Hooker AC. PopED: an extended, parallelized, nonlinear mixed effects models optimal design tool. Comput Methods Prog Biomed. 2012;108(2):789–805.\nIyer L, Das S, Janisch L, Wen M, Ramírez J, Karrison T, et al. UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J. 2002;2(1):43–7.\nInnocenti F, Kroetz DL, Schuetz E, Dolan ME, Ramírez J, Relling M, et al. Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics. J Clin Oncol. 2009;27(16):2604–14.\nvan der Bol JM, Mathijssen RHJ, Creemers G-JM, Planting AST, Loos WJ, Wiemer EAC, et al. A CYP3A4 phenotype-based dosing algorithm for individualized treatment of Irinotecan. Clin Cancer Res. 2010;16(2):736–42.\nMathijssen RHJ, de Jong FA, van Schaik RHN, Lepper ER, Friberg LE, Rietveld T, et al. Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. J Natl Cancer Inst. 2004;96(21):1585–92.\nde Jong FA, Kehrer DFS, Mathijssen RHJ, Creemers G-J, de Bruijn P, van Schaik RHN, et al. Prophylaxis of irinotecan-induced diarrhea with neomycin and potential role for UGT1A1*28 genotype screening: a double-blind, randomized, placebo-controlled study. Oncologist. 2006;11(8):944–54.\nToffoli G, Sharma MR, Marangon E, Posocco B, Gray E, Mai Q, et al. Genotype-guided dosing study of FOLFIRI plus Bevacizumab in patients with metastatic colorectal Cancer. Clin Cancer Res. 2017;23(4):918–24.\nBeal SL. Ways to fit a PK model with some data below the quantification limit. J Pharmacokinet Pharmacodyn. 2001;28(5):481–504.\nMonolix 2018R1 User guide [Internet]. Monolix 2017. 2019. Available from: http:\u002F\u002Fmonolix.lixoft.com\u002Fsingle-page\u002F\nPopulation parameter using SAEM algorithm [Internet]. Monolix 2017. 2019. Available from: http:\u002F\u002Fmonolix.lixoft.com\u002Ftasks\u002Fpopulation-parameter-estimation-using-saem\u002F\nAkaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19(6):716–23.\nSchwarz G. Estimating the dimension of a model. Ann Stat. 1978 Jul 14;6(2):461–4.\nRsmlx package | R Documentation [Internet]. 2019. Available from: https:\u002F\u002Fwww.rdocumentation.org\u002Fpackages\u002FRsmlx\u002Fversions\u002F2.0.2\nPopED package | R Documentation [Internet]. 2019. Available from: https:\u002F\u002Fwww.rdocumentation.org\u002Fpackages\u002FPopED\u002Fversions\u002F0.4.0\nOgungbenro K, Aarons L. An effective approach for obtaining optimal sampling windows for population pharmacokinetic experiments. J Biopharm Stat. 2009;19(1):174–89.\nmlxR package | R Documentation [Internet]. 2019. Available from: https:\u002F\u002Fwww.rdocumentation.org\u002Fpackages\u002FmlxR\u002Fversions\u002F4.0.0\nlme4 package | R Documentation [Internet]. 2019. Available from: https:\u002F\u002Fwww.rdocumentation.org\u002Fpackages\u002Flme4\u002Fversions\u002F1.1-19\nRowinsky EK, Grochow LB, Ettinger DS, Sartorius SE, Lubejko BG, Chen TL, et al. Phase I and pharmacological study of the novel topoisomerase I inhibitor 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) administered as a ninety-minute infusion every 3 weeks. Cancer Res. 1994;54(2):427–36.\nde Forni M, Bugat R, Chabot GG, Culine S, Extra JM, Gouyette A, et al. Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients. Cancer Res. 1994;54(16):4347–54.\nAbigerges D, Chabot GG, Armand JP, Hérait P, Gouyette A, Gandia D. Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. J Clin Oncol. 1995;13(1):210–21.\nCanal P, Gay C, Dezeuze A, Douillard JY, Bugat R, Brunet R, et al. Pharmacokinetics and pharmacodynamics of irinotecan during a phase II clinical trial in colorectal cancer. Pharmacology and molecular mechanisms Group of the European Organization for research and treatment of Cancer. J Clin Oncol. 1996;14(10):2688–95.\nMathijssen RHJ, Verweij J, Loos WJ, de Bruijn P, Nooter K, Sparreboom A. Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38. Br J Cancer. 2002;87(2):144–50.\nSasaki Y, Hakusui H, Mizuno S, Morita M, Miya T, Eguchi K, et al. A pharmacokinetic and pharmacodynamic analysis of CPT-11 and its active metabolite SN-38. Jpn J Cancer Res. 1995;86(1):101–10.\nSlatter JG, Schaaf LJ, Sams JP, Feenstra KL, Johnson MG, Bombardt PA, et al. Pharmacokinetics, metabolism, and excretion of irinotecan (CPT-11) following I.V. infusion of [(14)C]CPT-11 in cancer patients. Drug Metab Dispos. 2000;28(4):423–33.\nSparreboom A, de Jonge MJ, de Bruijn P, Brouwer E, Nooter K, Loos WJ, et al. Irinotecan (CPT-11) metabolism and disposition in cancer patients. Clin Cancer Res. 1998;4(11):2747–54.\nSchaaf LJ, Hammond LA, Tipping SJ, Goldberg RM, Goel R, Kuhn JG, et al. Phase 1 and pharmacokinetic study of intravenous irinotecan in refractory solid tumor patients with hepatic dysfunction. Clin Cancer Res. 2006;12(12):3782–91.\nBosma PJ, Seppen J, Goldhoorn B, Bakker C, Oude Elferink RP, Chowdhury JR, et al. Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem. 1994;269(27):17960–4.\nRivory LP, Robert J. Identification and kinetics of a beta-glucuronide metabolite of SN-38 in human plasma after administration of the camptothecin derivative irinotecan. Cancer Chemother Pharmacol. 1995;36(2):176–9.\nSaltz LB, Kanowitz J, Kemeny NE, Schaaf L, Spriggs D, Staton BA, et al. Phase I clinical and pharmacokinetic study of irinotecan, fluorouracil, and leucovorin in patients with advanced solid tumors. J Clin Oncol. 1996;14(11):2959–67.",{"VOID":2388},"10.1208\u002Fs12248-020-0429-4","2024-06-25T07:20:13.692+00:00","http:\u002F\u002Flink.springer.com\u002F10.1208\u002Fs12248-020-0429-4",[2392,2407,2420,2433,2448,2463,2478,2491,2504,2519,2532,2556],{"id":2393,"sortIndex":19,"researcher":18,"roles":2394,"affiliations":2395,"properties":2404,"displayName":2406,"givenName":18,"familyName":18},"dba90d56-f354-43f1-b19a-df4974bab333",[189],[2396],{"id":2397,"sortIndex":19,"affiliation":2398,"properties":18},"1a9046f3-fe86-4ec2-8252-087cc7391a23",{"id":2397,"createTime":18,"updateTime":18,"relativeEntities":2399,"slug":18,"properties":2400,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2403,"statistic":18},[],{"title":2401},{"VI":2402},"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, USA",[],{"title":2405},{"VI":2406},"Spinel Karas",{"id":2408,"sortIndex":204,"researcher":18,"roles":2409,"affiliations":2410,"properties":2417,"displayName":2419,"givenName":18,"familyName":18},"05e11b5e-d58c-4505-b1ac-cc0c98ff9818",[189],[2411],{"id":2397,"sortIndex":19,"affiliation":2412,"properties":18},{"id":2397,"createTime":18,"updateTime":18,"relativeEntities":2413,"slug":18,"properties":2414,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2416,"statistic":18},[],{"title":2415},{"VI":2402},[],{"title":2418},{"VI":2419},"Amy S. Etheridge",{"id":2421,"sortIndex":320,"researcher":18,"roles":2422,"affiliations":2423,"properties":2430,"displayName":2432,"givenName":18,"familyName":18},"f1f432e2-fe22-4aae-b233-19d2ed35c4d7",[189],[2424],{"id":2397,"sortIndex":19,"affiliation":2425,"properties":18},{"id":2397,"createTime":18,"updateTime":18,"relativeEntities":2426,"slug":18,"properties":2427,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2429,"statistic":18},[],{"title":2428},{"VI":2402},[],{"title":2431},{"VI":2432},"Eleftheria Tsakalozou",{"id":2434,"sortIndex":334,"researcher":18,"roles":2435,"affiliations":2436,"properties":2445,"displayName":2447,"givenName":18,"familyName":18},"440fbdbd-12fa-4d11-819a-00c13576ee4b",[189],[2437],{"id":2438,"sortIndex":19,"affiliation":2439,"properties":18},"b1a4b6ac-34a5-44fa-a34e-2d6f76fa4b5e",{"id":2438,"createTime":18,"updateTime":18,"relativeEntities":2440,"slug":18,"properties":2441,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2444,"statistic":18},[],{"title":2442},{"VI":2443},"Department of Medicine, University of Chicago, Chicago, USA",[],{"title":2446},{"VI":2447},"Jacqueline Ramírez",{"id":2449,"sortIndex":350,"researcher":18,"roles":2450,"affiliations":2451,"properties":2460,"displayName":2462,"givenName":18,"familyName":18},"cd6ca705-ffec-48b3-bd47-1f998f66a51f",[189],[2452],{"id":2453,"sortIndex":19,"affiliation":2454,"properties":18},"6b26649c-8e2e-4f0b-8a15-1ac4c41b84cd",{"id":2453,"createTime":18,"updateTime":18,"relativeEntities":2455,"slug":18,"properties":2456,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2459,"statistic":18},[],{"title":2457},{"VI":2458},"Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy",[],{"title":2461},{"VI":2462},"Erika Cecchin",{"id":2464,"sortIndex":366,"researcher":18,"roles":2465,"affiliations":2466,"properties":2475,"displayName":2477,"givenName":18,"familyName":18},"f495324b-239b-4d86-81a3-c0c9a7b31f4c",[189],[2467],{"id":2468,"sortIndex":19,"affiliation":2469,"properties":18},"114042d8-5c45-4760-b1ef-1a177f3dbd8d",{"id":2468,"createTime":18,"updateTime":18,"relativeEntities":2470,"slug":18,"properties":2471,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2474,"statistic":18},[],{"title":2472},{"VI":2473},"Department of Clinical Chemistry, Erasmus MC, Rotterdam, Netherlands",[],{"title":2476},{"VI":2477},"Ron H.N. van Schaik",{"id":2479,"sortIndex":382,"researcher":18,"roles":2480,"affiliations":2481,"properties":2488,"displayName":2490,"givenName":18,"familyName":18},"3c815d7d-e77c-4cc3-84cf-ff8b7227bf6f",[189],[2482],{"id":2453,"sortIndex":19,"affiliation":2483,"properties":18},{"id":2453,"createTime":18,"updateTime":18,"relativeEntities":2484,"slug":18,"properties":2485,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2487,"statistic":18},[],{"title":2486},{"VI":2458},[],{"title":2489},{"VI":2490},"Giuseppe Toffoli",{"id":2492,"sortIndex":396,"researcher":18,"roles":2493,"affiliations":2494,"properties":2501,"displayName":2503,"givenName":18,"familyName":18},"84bd09cb-a064-4c48-b1be-c692e3ec7191",[189],[2495],{"id":2438,"sortIndex":19,"affiliation":2496,"properties":18},{"id":2438,"createTime":18,"updateTime":18,"relativeEntities":2497,"slug":18,"properties":2498,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2500,"statistic":18},[],{"title":2499},{"VI":2443},[],{"title":2502},{"VI":2503},"Mark J. Ratain",{"id":2505,"sortIndex":412,"researcher":18,"roles":2506,"affiliations":2507,"properties":2516,"displayName":2518,"givenName":18,"familyName":18},"e5efa530-eaa7-4d74-ab53-38ce22a5cc54",[189],[2508],{"id":2509,"sortIndex":19,"affiliation":2510,"properties":18},"af0c5aa5-47a9-472a-8c6e-782a12be7ad8",{"id":2509,"createTime":18,"updateTime":18,"relativeEntities":2511,"slug":18,"properties":2512,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2515,"statistic":18},[],{"title":2513},{"VI":2514},"Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands",[],{"title":2517},{"VI":2518},"Ron H.J. Mathijssen",{"id":2520,"sortIndex":428,"researcher":18,"roles":2521,"affiliations":2522,"properties":2529,"displayName":2531,"givenName":18,"familyName":18},"5704257b-a6d7-4963-91ca-dc93d3887f75",[189],[2523],{"id":2397,"sortIndex":19,"affiliation":2524,"properties":18},{"id":2397,"createTime":18,"updateTime":18,"relativeEntities":2525,"slug":18,"properties":2526,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2528,"statistic":18},[],{"title":2527},{"VI":2402},[],{"title":2530},{"VI":2531},"Alan Forrest",{"id":2533,"sortIndex":1129,"researcher":18,"roles":2534,"affiliations":2535,"properties":2553,"displayName":2555,"givenName":18,"familyName":18},"5947ed3c-8dc4-4a9e-ac69-d5869c9a18b0",[189],[2536,2544],{"id":2537,"sortIndex":19,"affiliation":2538,"properties":18},"6436083d-0d7b-47eb-8d24-a7ef01be9af3",{"id":2537,"createTime":18,"updateTime":18,"relativeEntities":2539,"slug":18,"properties":2540,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2543,"statistic":18},[],{"title":2541},{"VI":2542},"Department of Pharmaceutical Sciences, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, USA",[],{"id":2545,"sortIndex":204,"affiliation":2546,"properties":2552},"c31074b8-7c22-479c-b2c7-4fdd54c950c9",{"id":2545,"createTime":18,"updateTime":18,"relativeEntities":2547,"slug":18,"properties":2548,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2551,"statistic":18},[],{"title":2549},{"VI":2550},"Computational and Data Enabled Sciences and Engineering Program, University at Buffalo, State University of New York at Buffalo, NY, USA",[],{},{"title":2554},{"VI":2555},"Robert R. Bies",{"id":2557,"sortIndex":1147,"researcher":18,"roles":2558,"affiliations":2559,"properties":2566,"displayName":2568,"givenName":18,"familyName":18},"0a8dd4c0-fdbb-4e0f-95a8-bbe2d75ab8d3",[189],[2560],{"id":2397,"sortIndex":19,"affiliation":2561,"properties":18},{"id":2397,"createTime":18,"updateTime":18,"relativeEntities":2562,"slug":18,"properties":2563,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2565,"statistic":18},[],{"title":2564},{"VI":2402},[],{"title":2567},{"VI":2568},"Federico Innocenti",{"url":2390,"publisher":2570,"properties":2611},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":2571,"slug":10,"properties":2572,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":2575,"manageAffiliations":2580,"indexDatabases":2591,"url":18,"thumbnailPath":18,"statistic":2606,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":2573,"eissn":2574},{"EN":13},{"VOID":15},[2576],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":2577,"label":2578,"description":2579,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[2581,2586],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":2582,"slug":18,"properties":2583,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2585,"statistic":18},[],{"title":2584},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":2587,"slug":18,"properties":2588,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2590,"statistic":18},[],{"title":2589},{"EN":41},[],[2592,2599],{"id":45,"indexDatabase":2593,"url":58,"indexYears":18,"academicFieldIds":2598,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":2594,"label":2595,"description":2596,"key":54,"publicationTags":2597,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":2600,"url":73,"indexYears":74,"academicFieldIds":2605,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":2601,"label":2602,"description":2603,"key":70,"publicationTags":2604,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":2607,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":2608,"totalCitation":117,"totalCitationByYear":2609,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":2610,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"pages":2612,"volume":2614},{"VOID":2613},"1-14",{"VOID":2615},"22","2020-03-17",2020,"2026-07-23T14:35:20.294+00:00",[56,77],{"id":2621,"createTime":2622,"updateTime":2623,"relativeEntities":2624,"slug":2625,"properties":2626,"entityType":177,"verifyStatus":178,"verifyTime":2641,"verifyNote":180,"languages":2642,"translateLanguages":18,"viewCount":19,"primaryUrl":2643,"fullTextUrl":18,"authors":2644,"publicationType":216,"publisherRelationship":2698,"citationCount":19,"citationInfo":2747,"publishDate":2750,"publishYear":2748,"citationAnalyzeStatus":17,"lastCitationAnalyze":2751,"indexDatabases":2752,"openAccess":18,"references":2753,"isForceReanalyzing":269},"e3a8a608-2751-46eb-80c6-51b4f7807580","2024-04-17T17:11:13.815+00:00","2026-07-22T21:51:53.151+00:00",[],"R4-Regulator-of-G-Protein-Signaling-RGS-Proteins-in-Inflammation-and-Immunity",{"mag":2627,"gsPaper":2629,"pmc":2631,"openalex":2633,"title":2635,"pm":2637,"doi":2639},{"VOID":2628},"2179510469",{"VOID":2630},"[\"8814473730954087715\"]",{"VOID":2632},"4779105",{"VOID":2634},"W2179510469",{"EN":2636},"R4 Regulator of G Protein Signaling (RGS) Proteins in Inflammation and Immunity",{"VOID":2638},"26597290",{"VOID":2640},"10.1208\u002Fs12248-015-9847-0","2024-05-12T03:16:54.916+00:00",[509],"http:\u002F\u002Flink.springer.com\u002F10.1208\u002Fs12248-015-9847-0",[2645,2664,2679],{"id":2646,"sortIndex":19,"researcher":18,"roles":2647,"affiliations":2648,"properties":2657,"displayName":2661,"givenName":18,"familyName":18},"c374ee7d-571d-4f55-b2ad-f9f83cd0e5c3",[],[2649],{"id":2650,"sortIndex":19,"affiliation":2651,"properties":18},"bd9d7316-c0f2-4cca-821f-cb4e9aa3d703",{"id":2650,"createTime":18,"updateTime":18,"relativeEntities":2652,"slug":18,"properties":2653,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2656,"statistic":18},[],{"title":2654},{"EN":2655},"Molecular Signal Transduction Section, Laboratory of Allergic Diseases, NIAID\u002FNIH, 50 South Drive Room 4154, Bethesda, Maryland, 20892, USA",[],{"orcid":2658,"title":2660,"openalex":2662},{"VOID":2659},"https:\u002F\u002Forcid.org\u002F0000-0003-4699-5093",{"EN":2661},"Zhihui Xie",{"VOID":2663},"A5023092411",{"id":2665,"sortIndex":204,"researcher":18,"roles":2666,"affiliations":2667,"properties":2674,"displayName":2676,"givenName":18,"familyName":18},"36ac8a14-f8a6-4485-92e4-dbbadae2b13f",[],[2668],{"id":2650,"sortIndex":19,"affiliation":2669,"properties":18},{"id":2650,"createTime":18,"updateTime":18,"relativeEntities":2670,"slug":18,"properties":2671,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2673,"statistic":18},[],{"title":2672},{"EN":2655},[],{"title":2675,"openalex":2677},{"EN":2676},"Eunice C. Chan",{"VOID":2678},"A5010584488",{"id":2680,"sortIndex":320,"researcher":18,"roles":2681,"affiliations":2682,"properties":2689,"displayName":2693,"givenName":18,"familyName":18},"c97febd9-0fc6-497d-9b2c-16e655e18631",[],[2683],{"id":2650,"sortIndex":19,"affiliation":2684,"properties":18},{"id":2650,"createTime":18,"updateTime":18,"relativeEntities":2685,"slug":18,"properties":2686,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2688,"statistic":18},[],{"title":2687},{"EN":2655},[],{"orcid":2690,"title":2692,"gsAuthor":2694,"openalex":2696},{"VOID":2691},"https:\u002F\u002Forcid.org\u002F0000-0002-5834-6501",{"EN":2693},"Kirk M. Druey",{"VOID":2695},"[\"Wx0rs0cAAAAJ\"]",{"VOID":2697},"A5004382885",{"url":18,"publisher":2699,"properties":2740},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":2700,"slug":10,"properties":2701,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":2704,"manageAffiliations":2709,"indexDatabases":2720,"url":18,"thumbnailPath":18,"statistic":2735,"gsStatistic":18,"type":18,"analyzePriority":18},[],{"title":2702,"eissn":2703},{"EN":13},{"VOID":15},[2705],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":2706,"label":2707,"description":2708,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[2710,2715],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":2711,"slug":18,"properties":2712,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2714,"statistic":18},[],{"title":2713},{"EN":33},[35],{"id":37,"createTime":18,"updateTime":18,"relativeEntities":2716,"slug":18,"properties":2717,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2719,"statistic":18},[],{"title":2718},{"EN":41},[],[2721,2728],{"id":45,"indexDatabase":2722,"url":58,"indexYears":18,"academicFieldIds":2727,"indexDatabaseRanking":18},{"id":47,"createTime":18,"updateTime":18,"relativeEntities":2723,"label":2724,"description":2725,"key":54,"publicationTags":2726,"standard":18},[],{"EN":50,"VI":50},{"EN":52,"VI":53},[56,57],[60],{"id":62,"indexDatabase":2729,"url":73,"indexYears":74,"academicFieldIds":2734,"indexDatabaseRanking":77},{"id":64,"createTime":18,"updateTime":18,"relativeEntities":2730,"label":2731,"description":2732,"key":70,"publicationTags":2733,"standard":18},[],{"EN":67,"VI":67},{"EN":67,"VI":69},[72],[76],{"impactFactor":19,"impactFactorByYear":2736,"i10Index":94,"i10IndexLast5Year":95,"totalPublication":96,"totalPublicationByYear":2737,"totalCitation":117,"totalCitationByYear":2738,"totalCitationPerPublication":136,"totalCitationPerPublicationByYear":2739,"hindexLast5Year":156,"hindex":156},{"2007":80,"2008":81,"2012":82,"2013":83,"2014":84,"2015":85,"2016":86,"2017":87,"2018":88,"2019":89,"2020":90,"2021":91,"2022":92,"2023":93},{"2004":98,"2005":99,"2006":99,"2007":100,"2008":101,"2009":102,"2010":103,"2011":104,"2012":105,"2013":106,"2014":107,"2015":108,"2016":109,"2017":110,"2018":111,"2019":112,"2020":113,"2021":114,"2022":111,"2023":115,"2024":116},{"2004":119,"2005":120,"2006":121,"2007":122,"2008":123,"2009":124,"2010":125,"2011":126,"2012":127,"2013":128,"2014":129,"2015":130,"2016":131,"2017":129,"2018":132,"2019":133,"2020":119,"2021":134,"2022":135},{"2004":138,"2005":139,"2006":140,"2007":141,"2008":142,"2009":143,"2010":144,"2011":145,"2012":146,"2013":147,"2014":148,"2015":149,"2016":150,"2017":151,"2018":152,"2019":153,"2020":154,"2021":155,"2022":85},{"issue":2741,"pages":2743,"volume":2745},{"VOID":2742},"2",{"VOID":2744},"294-304",{"VOID":2746},"18",{"total":19,"publishYear":2748,"statisticByYear":2749},2016,{},"2016-03-01","2026-07-22T21:51:53.150+00:00",[56,77],[2754,2758,2762,2766,2770,2774,2777,2781,2785,2789,2793,2797,2801,2805,2809,2813,2817,2821,2825,2829,2833,2837,2841,2845,2849,2853,2857,2861,2865,2869,2873,2877,2881,2885,2889,2893,2897,2901,2905,2909,2913,2917,2921,2925,2929,2933,2937,2941,2945,2949,2953,2957,2961,2965,2969,2973,2977,2981,2985,2989,2993,2997,3001,3005,3009,3013,3017,3021,3025,3029,3033,3037,3040,3044,3048,3052,3056,3060,3064,3068,3072,3076,3080,3084,3088,3092,3096,3100,3104,3108,3112,3116,3120,3124,3128,3132,3136,3140,3144,3148,3152,3156,3159,3163,3167,3170,3174,3178,3182,3186,3190,3194,3198,3202,3206,3210,3214],{"id":18,"text":2755,"url":18,"identifiers":2756},"Sellge G, Kufer TA. PRR-signaling pathways: learning from microbial tactics. Semin Immunol. 2015;27:75–84.",{"doi":2757},"10.1016\u002Fj.smim.2015.03.009",{"id":18,"text":2759,"url":18,"identifiers":2760},"Zugasti O, Bose N, Squiban B, Belougne J, Kurz CL, Schroeder FC, et al. Activation of a G protein-coupled receptor by its endogenous ligand triggers the innate immune response of Caenorhabditis elegans. Nat Immunol. 2014;15:833–8.",{"doi":2761},"10.1038\u002Fni.2957",{"id":18,"text":2763,"url":18,"identifiers":2764},"Bloes DA, Kretschmer D, Peschel A. Enemy attraction: bacterial agonists for leukocyte chemotaxis receptors. Nat Rev Microbiol. 2015;13:95–104.",{"doi":2765},"10.1038\u002Fnrmicro3390",{"id":18,"text":2767,"url":18,"identifiers":2768},"Lian J, Luster AD. Chemokine-guided cell positioning in the lymph node orchestrates the generation of adaptive immune responses. Curr Opin Cell Biol. 2015;36:1–6.",{"doi":2769},"10.1016\u002Fj.ceb.2015.05.003",{"id":18,"text":2771,"url":18,"identifiers":2772},"Anders HJ, Romagnani P, Mantovani A. Pathomechanisms: homeostatic chemokines in health, tissue regeneration, and progressive diseases. Trends Mol Med. 2014;20:154–65.",{"doi":2773},"10.1016\u002Fj.molmed.2013.12.002",{"id":18,"text":2775,"url":18,"identifiers":2776},"Arnon TI, Cyster JG. Blood, sphingosine-1-phosphate and lymphocyte migration dynamics in the spleen. Curr Top Microbiol Immunol. 2014;378:107–28.",{},{"id":18,"text":2778,"url":18,"identifiers":2779},"Gilman AG. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–49.",{"doi":2780},"10.1146\u002Fannurev.bi.56.070187.003151",{"id":18,"text":2782,"url":18,"identifiers":2783},"Beck TC, Gomes AC, Cyster JG, Pereira JP. CXCR4 and a cell-extrinsic mechanism control immature B lymphocyte egress from bone marrow. J Exp Med. 2014;211:2567–81.",{"doi":2784},"10.1084\u002Fjem.20140457",{"id":18,"text":2786,"url":18,"identifiers":2787},"Mocsai A, Walzog B, Lowell CA. Intracellular signalling during neutrophil recruitment. Cardiovasc Res. 2015;107:373–85.",{"doi":2788},"10.1093\u002Fcvr\u002Fcvv159",{"id":18,"text":2790,"url":18,"identifiers":2791},"Packiriswamy N, Parameswaran N. G-protein-coupled receptor kinases in inflammation and disease. Genes Immun. 2015;16(6):367–77.",{"doi":2792},"10.1038\u002Fgene.2015.26",{"id":18,"text":2794,"url":18,"identifiers":2795},"Clister T, Mehta S, Zhang J. Single-cell analysis of G-protein signal transduction. J Biol Chem. 2015;290:6681–8.",{"doi":2796},"10.1074\u002Fjbc.R114.616391",{"id":18,"text":2798,"url":18,"identifiers":2799},"Kimple AJ, Bosch DE, Giguere PM, Siderovski DP. Regulators of G-protein signaling and their Galpha substrates: promises and challenges in their use as drug discovery targets. Pharmacol Rev. 2011;63:728–49.",{"doi":2800},"10.1124\u002Fpr.110.003038",{"id":18,"text":2802,"url":18,"identifiers":2803},"Sjogren B, Blazer LL, Neubig RR. Regulators of G protein signaling proteins as targets for drug discovery. Prog Mol Biol Transl Sci. 2010;91:81–119.",{"doi":2804},"10.1016\u002FS1877-1173(10)91004-1",{"id":18,"text":2806,"url":18,"identifiers":2807},"Bansal G, Druey KM, Xie Z. R4 RGS proteins: regulation of G-protein signaling and beyond. Pharmacol Ther. 2007;116:473–95.",{"doi":2808},"10.1016\u002Fj.pharmthera.2007.09.005",{"id":18,"text":2810,"url":18,"identifiers":2811},"Heximer SP, Srinivasa SP, Bernstein LS, Bernard JL, Linder ME, Hepler JR, et al. G protein selectivity is a determinant of RGS2 function. J Biol Chem. 1999;274:34253–9.",{"doi":2812},"10.1074\u002Fjbc.274.48.34253",{"id":18,"text":2814,"url":18,"identifiers":2815},"Kach J, Sethakorn N, Dulin NO. A finer tuning of G-protein signaling through regulated control of RGS proteins. Am J Physiol Heart Circ Physiol. 2012;303:H19–35.",{"doi":2816},"10.1152\u002Fajpheart.00764.2011",{"id":18,"text":2818,"url":18,"identifiers":2819},"Berman DM, Wilkie TM, Gilman AG. GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits. Cell. 1996;86:445–52.",{"doi":2820},"10.1016\u002FS0092-8674(00)80117-8",{"id":18,"text":2822,"url":18,"identifiers":2823},"Kimple AJ, Willard FS, Giguere PM, Johnston CA, Mocanu V, Siderovski DP. The RGS protein inhibitor CCG-4986 is a covalent modifier of the RGS4 Galpha-interaction face. Biochim Biophys Acta. 2007;1774(9):1213–20.",{"doi":2824},"10.1016\u002Fj.bbapap.2007.06.002",{"id":18,"text":2826,"url":18,"identifiers":2827},"DiBello PR, Garrison TR, Apanovitch DM, Hoffman G, Shuey DJ, Mason K, et al. Selective uncoupling of RGS action by a single point mutation in the G protein alpha-subunit. J Biol Chem. 1998;273:5780–4.",{"doi":2828},"10.1074\u002Fjbc.273.10.5780",{"id":18,"text":2830,"url":18,"identifiers":2831},"Huang X, Charbeneau RA, Fu Y, Kaur K, Gerin I, MacDougald OA, et al. Resistance to diet-induced obesity and improved insulin sensitivity in mice with a regulator of G protein signaling-insensitive G184S Gnai2 allele. Diabetes. 2008;57:77–85.",{"doi":2832},"10.2337\u002Fdb07-0599",{"id":18,"text":2834,"url":18,"identifiers":2835},"Kaur K, Kehrl JM, Charbeneau RA, Neubig RR. RGS-insensitive Galpha subunits: probes of Galpha subtype-selective signaling and physiological functions of RGS proteins. Methods Mol Biol. 2011;756:75–98.",{"doi":2836},"10.1007\u002F978-1-61779-160-4_4",{"id":18,"text":2838,"url":18,"identifiers":2839},"Neubig RR. RGS-insensitive G proteins as in vivo probes of RGS function. Prog Mol Biol Transl Sci. 2015;133:13–30.",{"doi":2840},"10.1016\u002Fbs.pmbts.2015.04.010",{"id":18,"text":2842,"url":18,"identifiers":2843},"Han SB, Moratz C, Huang NN, Kelsall B, Cho H, Shi CS, et al. Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles. Immunity. 2005;22:343–54.",{"doi":2844},"10.1016\u002Fj.immuni.2005.01.017",{"id":18,"text":2846,"url":18,"identifiers":2847},"Hwang IY, Park C, Kehrl JH. Impaired trafficking of Gnai2+\u002F− and Gnai2−\u002F− T lymphocytes: implications for T cell movement within lymph nodes. J Immunol. 2007;179:439–48.",{"doi":2848},"10.4049\u002Fjimmunol.179.1.439",{"id":18,"text":2850,"url":18,"identifiers":2851},"Hwang IY, Park C, Luong T, Harrison KA, Birnbaumer L, Kehrl JH. The loss of Gnai2 and Gnai3 in B cells eliminates B lymphocyte compartments and leads to a hyper-IgM like syndrome. PLoS One. 2013;8, e72596.",{"doi":2852},"10.1371\u002Fannotation\u002Fb02313dc-840f-4f03-91a2-77cb55a3a4c9",{"id":18,"text":2854,"url":18,"identifiers":2855},"Hwang IY, Park C, Harrison K, Boularan C, Gales C, Kehrl JH. An essential role for RGS protein\u002FGalphai2 interactions in B lymphocyte-directed cell migration and trafficking. J Immunol. 2015;194:2128–39.",{"doi":2856},"10.4049\u002Fjimmunol.1401952",{"id":18,"text":2858,"url":18,"identifiers":2859},"Cho H, Kamenyeva O, Yung S, Gao JL, Hwang IY, Park C, et al. The loss of RGS protein-Galpha(i2) interactions results in markedly impaired mouse neutrophil trafficking to inflammatory sites. Mol Cell Biol. 2012;32:4561–71.",{"doi":2860},"10.1128\u002FMCB.00651-12",{"id":18,"text":2862,"url":18,"identifiers":2863},"Hong JX, Wilson GL, Fox CH, Kehrl JH. Isolation and characterization of a novel B cell activation gene. J Immunol. 1993;150:3895–904.",{"doi":2864},"10.4049\u002Fjimmunol.150.9.3895",{"id":18,"text":2866,"url":18,"identifiers":2867},"Moratz C, Kang VH, Druey KM, Shi CS, Scheschonka A, Murphy PM, et al. Regulator of G protein signaling 1 (RGS1) markedly impairs Gi alpha signaling responses of B lymphocytes. J Immunol. 2000;164:1829–38.",{"doi":2868},"10.4049\u002Fjimmunol.164.4.1829",{"id":18,"text":2870,"url":18,"identifiers":2871},"Agenes F, Bosco N, Mascarell L, Fritah S, Ceredig R. Differential expression of regulator of G-protein signalling transcripts and in vivo migration of CD4+ naive and regulatory T cells. Immunology. 2005;115:179–88.",{"doi":2872},"10.1111\u002Fj.1365-2567.2005.02146.x",{"id":18,"text":2874,"url":18,"identifiers":2875},"Kveberg L, Ryan JC, Rolstad B, Inngjerdingen M. Expression of regulator of G protein signalling proteins in natural killer cells, and their modulation by Ly49A and Ly49D. Immunology. 2005;115:358–65.",{"doi":2876},"10.1111\u002Fj.1365-2567.2005.02174.x",{"id":18,"text":2878,"url":18,"identifiers":2879},"Shi GX, Harrison K, Han SB, Moratz C, Kehrl JH. Toll-like receptor signaling alters the expression of regulator of G protein signaling proteins in dendritic cells: implications for G protein-coupled receptor signaling. J Immunol. 2004;172:5175–84.",{"doi":2880},"10.4049\u002Fjimmunol.172.9.5175",{"id":18,"text":2882,"url":18,"identifiers":2883},"Denecke B, Meyerdierks A, Bottger EC. RGS1 is expressed in monocytes and acts as a GTPase-activating protein for G-protein-coupled chemoattractant receptors. J Biol Chem. 1999;274:26860–8.",{"doi":2884},"10.1074\u002Fjbc.274.38.26860",{"id":18,"text":2886,"url":18,"identifiers":2887},"Moratz C, Hayman JR, Gu H, Kehrl JH. Abnormal B-cell responses to chemokines, disturbed plasma cell localization, and distorted immune tissue architecture in Rgs1−\u002F− mice. Mol Cell Biol. 2004;24:5767–75.",{"doi":2888},"10.1128\u002FMCB.24.13.5767-5775.2004",{"id":18,"text":2890,"url":18,"identifiers":2891},"Hwang IY, Park C, Harrision KA, Huang NN, Kehrl JH. Variations in Gnai2 and Rgs1 expression affect chemokine receptor signaling and the organization of secondary lymphoid organs. Genes Immun. 2010;11:384–96.",{"doi":2892},"10.1038\u002Fgene.2010.27",{"id":18,"text":2894,"url":18,"identifiers":2895},"Rudolph U, Finegold MJ, Rich SS, Harriman GR, Srinivasan Y, Brabet P, et al. Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet. 1995;10:143–50.",{"doi":2896},"10.1038\u002Fng0695-143",{"id":18,"text":2898,"url":18,"identifiers":2899},"Gibbons DL, Abeler-Dorner L, Raine T, Hwang IY, Jandke A, Wencker M, et al. Cutting edge: regulator of G protein signaling-1 selectively regulates gut T cell trafficking and colitic potential. J Immunol. 2011;187:2067–71.",{"doi":2900},"10.4049\u002Fjimmunol.1100833",{"id":18,"text":2902,"url":18,"identifiers":2903},"Wan W, Murphy PM. Regulation of atherogenesis by chemokines and chemokine receptors. Arch Immunol Ther Exp (Warsz). 2013;61:1–14.",{"doi":2904},"10.1007\u002Fs00005-012-0202-1",{"id":18,"text":2906,"url":18,"identifiers":2907},"Riekenberg S, Farhat K, Debarry J, Heine H, Jung G, Wiesmuller KH, et al. Regulators of G-protein signalling are modulated by bacterial lipopeptides and lipopolysaccharide. FEBS J. 2009;276:649–59.",{"doi":2908},"10.1111\u002Fj.1742-4658.2008.06813.x",{"id":18,"text":2910,"url":18,"identifiers":2911},"Patel J, McNeill E, Douglas G, Hale AB, de Bono J, Lee R, et al. RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling. Nat Commun. 2015;6:6614.",{"doi":2912},"10.1038\u002Fncomms7614",{"id":18,"text":2914,"url":18,"identifiers":2915},"Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359:2767–77.",{"doi":2916},"10.1056\u002FNEJMoa0807917",{"id":18,"text":2918,"url":18,"identifiers":2919},"Hunt KA, Zhernakova A, Turner G, Heap GA, Franke L, Bruinenberg M, et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet. 2008;40:395–402.",{"doi":2920},"10.1038\u002Fng.102",{"id":18,"text":2922,"url":18,"identifiers":2923},"Johnson BA, Wang J, Taylor EM, Caillier SJ, Herbert J, Khan OA, et al. Multiple sclerosis susceptibility alleles in African Americans. Genes Immun. 2010;11:343–50.",{"doi":2924},"10.1038\u002Fgene.2009.81",{"id":18,"text":2926,"url":18,"identifiers":2927},"Comabella M, Khoury SJ. Immunopathogenesis of multiple sclerosis. Clin Immunol. 2012;142:2–8.",{"doi":2928},"10.1016\u002Fj.clim.2011.03.004",{"id":18,"text":2930,"url":18,"identifiers":2931},"International Multiple Sclerosis Genetics, C. IL12A, MPHOSPH9\u002FCDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci. Genes Immun. 2010;11:397–405.",{"doi":2932},"10.1038\u002Fgene.2010.28",{"id":18,"text":2934,"url":18,"identifiers":2935},"International Multiple Sclerosis Genetics, C, Wellcome Trust Case Control, C, Sawcer S, Hellenthal G, Pirinen M, Spencer CC, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476:214–9.",{"doi":2936},"10.1038\u002Fnature10251",{"id":18,"text":2938,"url":18,"identifiers":2939},"Habek M, Brinar VV, Borovecki F. Genes associated with multiple sclerosis: 15 and counting. Expert Rev Mol Diagn. 2010;10:857–61.",{"doi":2940},"10.1586\u002Ferm.10.77",{"id":18,"text":2942,"url":18,"identifiers":2943},"Perga S, Montarolo F, Martire S, Berchialla P, Malucchi S, Bertolotto A. Anti-inflammatory genes associated with multiple sclerosis: a gene expression study. J Neuroimmunol. 2015;279:75–8.",{"doi":2944},"10.1016\u002Fj.jneuroim.2015.01.004",{"id":18,"text":2946,"url":18,"identifiers":2947},"Wostradowski T, Gudi V, Pul R, Gingele S, Lindquist JA, Stangel M, et al. Effect of IFN beta-1b on CXCR4-dependent chemotaxis in T cells from multiple sclerosis patients. Clin Exp Immunol. 2015;182(2):162–72.",{"doi":2948},"10.1111\u002Fcei.12689",{"id":18,"text":2950,"url":18,"identifiers":2951},"Tran T, Paz P, Velichko S, Cifrese J, Belur P, Yamaguchi KD, et al. Interferonbeta-1b induces the expression of RGS1 a negative regulator of G-protein signaling. Int J Cell Biol. 2010;2010:529376.",{"doi":2952},"10.1155\u002F2010\u002F529376",{"id":18,"text":2954,"url":18,"identifiers":2955},"Hoppmann N, Graetz C, Paterka M, Poisa-Beiro L, Larochelle C, Hasan M, et al. New candidates for CD4 T cell pathogenicity in experimental neuroinflammation and multiple sclerosis. Brain. 2015;138:902–17.",{"doi":2956},"10.1093\u002Fbrain\u002Fawu408",{"id":18,"text":2958,"url":18,"identifiers":2959},"Heximer SP, Knutsen RH, Sun X, Kaltenbronn KM, Rhee MH, Peng N, et al. Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. J Clin Invest. 2003;111:445–52.",{"doi":2960},"10.1172\u002FJCI15598",{"id":18,"text":2962,"url":18,"identifiers":2963},"Wang X, Adams LD, Pabon LM, Mahoney Jr WM, Beaudry D, Gunaje J, et al. RGS5, RGS4, and RGS2 expression and aortic contractibility are dynamically co-regulated during aortic banding-induced hypertrophy. J Mol Cell Cardiol. 2008;44:539–50.",{"doi":2964},"10.1016\u002Fj.yjmcc.2007.11.019",{"id":18,"text":2966,"url":18,"identifiers":2967},"Kehrl JH, Sinnarajah S. RGS2: a multifunctional regulator of G-protein signaling. Int J Biochem Cell Biol. 2002;34:432–8.",{"doi":2968},"10.1016\u002FS1357-2725(01)00141-8",{"id":18,"text":2970,"url":18,"identifiers":2971},"Nance MR, Kreutz B, Tesmer VM, Sterne-Marr R, Kozasa T, Tesmer JJ. Structural and functional analysis of the regulator of G protein signaling 2-galphaq complex. Structure. 2013;21:438–48.",{"doi":2972},"10.1016\u002Fj.str.2012.12.016",{"id":18,"text":2974,"url":18,"identifiers":2975},"Roy AA, Nunn C, Ming H, Zou MX, Penninger J, Kirshenbaum LA, et al. Up-regulation of endogenous RGS2 mediates cross-desensitization between Gs and Gq signaling in osteoblasts. J Biol Chem. 2006;281:32684–93.",{"doi":2976},"10.1074\u002Fjbc.M604416200",{"id":18,"text":2978,"url":18,"identifiers":2979},"Noe L, Di Michele M, Giets E, Thys C, Wittevrongel C, De Vos R, et al. Platelet Gs hypofunction and abnormal morphology resulting from a heterozygous RGS2 mutation. J Thromb Haemost. 2010;8:1594–603.",{"doi":2980},"10.1111\u002Fj.1538-7836.2010.03885.x",{"id":18,"text":2982,"url":18,"identifiers":2983},"Banno F, Nojiri T, Matsumoto S, Kamide K, Miyata T. RGS2 deficiency in mice does not affect platelet thrombus formation at sites of vascular injury. J Thromb Haemost. 2012;10:309–11.",{"doi":2984},"10.1111\u002Fj.1538-7836.2011.04575.x",{"id":18,"text":2986,"url":18,"identifiers":2987},"Oliveira-Dos-Santos AJ, Matsumoto G, Snow BE, Bai D, Houston FP, Whishaw IQ, et al. Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc Natl Acad Sci U S A. 2000;97:12272–7.",{"doi":2988},"10.1073\u002Fpnas.220414397",{"id":18,"text":2990,"url":18,"identifiers":2991},"Johnson EN, Druey KM. Functional characterization of the G protein regulator RGS13. J Biol Chem. 2002;277:16768–74.",{"doi":2992},"10.1074\u002Fjbc.M200751200",{"id":18,"text":2994,"url":18,"identifiers":2995},"Shi GX, Harrison K, Wilson GL, Moratz C, Kehrl JH. RGS13 regulates germinal center B lymphocytes responsiveness to CXC chemokine ligand (CXCL)12 and CXCL13. J Immunol. 2002;169:2507–15.",{"doi":2996},"10.4049\u002Fjimmunol.169.5.2507",{"id":18,"text":2998,"url":18,"identifiers":2999},"Estes JD, Thacker TC, Hampton DL, Kell SA, Keele BF, Palenske EA, et al. Follicular dendritic cell regulation of CXCR4-mediated germinal center CD4 T cell migration. J Immunol. 2004;173:6169–78.",{"doi":3000},"10.4049\u002Fjimmunol.173.10.6169",{"id":18,"text":3002,"url":18,"identifiers":3003},"Bansal G, Xie Z, Rao S, Nocka KH, Druey KM. Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13. Nat Immunol. 2008;9:73–80.",{"doi":3004},"10.1038\u002Fni1533",{"id":18,"text":3006,"url":18,"identifiers":3007},"Bansal G, DiVietro JA, Kuehn HS, Rao S, Nocka KH, Gilfillan AM, et al. RGS13 controls g protein-coupled receptor-evoked responses of human mast cells. J Immunol. 2008;181:7882–90.",{"doi":3008},"10.4049\u002Fjimmunol.181.11.7882",{"id":18,"text":3010,"url":18,"identifiers":3011},"Islam TC, Asplund AC, Lindvall JM, Nygren L, Liden J, Kimby E, et al. High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of cyclin D1 in mantle cell lymphoma. Leukemia. 2003;17:1880–90.",{"doi":3012},"10.1038\u002Fsj.leu.2403057",{"id":18,"text":3014,"url":18,"identifiers":3015},"Pise-Masison CA, Radonovich M, Dohoney K, Morris JC, O’Mahony D, Lee MJ, et al. Gene expression profiling of ATL patients: compilation of disease-related genes and evidence for TCF4 involvement in BIRC5 gene expression and cell viability. Blood. 2009;113:4016–26.",{"doi":3016},"10.1182\u002Fblood-2008-08-175901",{"id":18,"text":3018,"url":18,"identifiers":3019},"Sethakorn N, Dulin NO. RGS expression in cancer: oncomining the cancer microarray data. J Recept Signal Transduct Res. 2013;33:166–71.",{"doi":3020},"10.3109\u002F10799893.2013.773450",{"id":18,"text":3022,"url":18,"identifiers":3023},"Raedler D, Ballenberger N, Klucker E, Bock A, Otto R, Prazeres da Costa O, et al. Identification of novel immune phenotypes for allergic and nonallergic childhood asthma. J Allergy Clin Immunol. 2015;135:81–91.",{"doi":3024},"10.1016\u002Fj.jaci.2014.07.046",{"id":18,"text":3026,"url":18,"identifiers":3027},"Hwang IY, Hwang KS, Park C, Harrison KA, Kehrl JH. Rgs13 constrains early B cell responses and limits germinal center sizes. PLoS One. 2013;8, e60139.",{"doi":3028},"10.1371\u002Fannotation\u002Fbb3baaad-6b58-41a0-96cc-7bdc819de411",{"id":18,"text":3030,"url":18,"identifiers":3031},"Hsu HC, Yang P, Wang J, Wu Q, Myers R, Chen J, et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol. 2008;9:166–75.",{"doi":3032},"10.1038\u002Fni1552",{"id":18,"text":3034,"url":18,"identifiers":3035},"Ding Y, Li J, Wu Q, Yang P, Luo B, Xie S, et al. IL-17RA is essential for optimal localization of follicular Th cells in the germinal center light zone to promote autoantibody-producing B cells. J Immunol. 2013;191:1614–24.",{"doi":3036},"10.4049\u002Fjimmunol.1300479",{"id":18,"text":3038,"url":18,"identifiers":3039},"Wang JH, New JS, Xie S, Yang P, Wu Q, Li J, et al. Extension of the germinal center stage of B cell development promotes autoantibodies in BXD2 mice. Arthritis Rheum. 2013;65:2703–12.",{},{"id":18,"text":3041,"url":18,"identifiers":3042},"Xie Z, Geiger TR, Johnson EN, Nyborg JK, Druey KM. RGS13 acts as a nuclear repressor of CREB. Mol Cell. 2008;31:660–70.",{"doi":3043},"10.1016\u002Fj.molcel.2008.06.024",{"id":18,"text":3045,"url":18,"identifiers":3046},"Chen C, Zheng B, Han J, Lin SC. Characterization of a novel mammalian RGS protein that binds to Galpha proteins and inhibits pheromone signaling in yeast. J Biol Chem. 1997;272:8679–85.",{"doi":3047},"10.1074\u002Fjbc.272.13.8679",{"id":18,"text":3049,"url":18,"identifiers":3050},"Kim SD, Sung HJ, Park SK, Kim TW, Park SC, Kim SK, et al. The expression patterns of RGS transcripts in platelets. Platelets. 2006;17:493–7.",{"doi":3051},"10.1080\u002F09537100600758123",{"id":18,"text":3053,"url":18,"identifiers":3054},"Beadling C, Druey KM, Richter G, Kehrl JH, Smith KA. Regulators of G protein signaling exhibit distinct patterns of gene expression and target G protein specificity in human lymphocytes. J Immunol. 1999;162:2677–82.",{"doi":3055},"10.4049\u002Fjimmunol.162.5.2677",{"id":18,"text":3057,"url":18,"identifiers":3058},"Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16:45–56.",{"doi":3059},"10.1038\u002Fni.3049",{"id":18,"text":3061,"url":18,"identifiers":3062},"Lippert E, Yowe DL, Gonzalo JA, Justice JP, Webster JM, Fedyk ER, et al. Role of regulator of G protein signaling 16 in inflammation-induced T lymphocyte migration and activation. J Immunol. 2003;171:1542–55.",{"doi":3063},"10.4049\u002Fjimmunol.171.3.1542",{"id":18,"text":3065,"url":18,"identifiers":3066},"Shankar SP, Wilson MS, DiVietro JA, Mentink-Kane MM, Xie Z, Wynn TA, et al. RGS16 attenuates pulmonary Th2\u002FTh17 inflammatory responses. J Immunol. 2012;188:6347–56.",{"doi":3067},"10.4049\u002Fjimmunol.1103781",{"id":18,"text":3069,"url":18,"identifiers":3070},"Suurvali J, Pahtma M, Saar R, Paalme V, Nutt A, Tiivel T, et al. RGS16 restricts the pro-inflammatory response of monocytes. Scand J Immunol. 2015;81:23–30.",{"doi":3071},"10.1111\u002Fsji.12250",{"id":18,"text":3073,"url":18,"identifiers":3074},"Perrier P, Martinez FO, Locati M, Bianchi G, Nebuloni M, Vago G, et al. Distinct transcriptional programs activated by interleukin-10 with or without lipopolysaccharide in dendritic cells: induction of the B cell-activating chemokine, CXC chemokine ligand 13. J Immunol. 2004;172:7031–42.",{"doi":3075},"10.4049\u002Fjimmunol.172.11.7031",{"id":18,"text":3077,"url":18,"identifiers":3078},"Timmusk S, Merlot E, Lovgren T, Jarvekulg L, Berg M, Fossum C. Regulator of G protein signalling 16 is a target for a porcine circovirus type 2 protein. J Gen Virol. 2009;90:2425–36.",{"doi":3079},"10.1099\u002Fvir.0.008896-0",{"id":18,"text":3081,"url":18,"identifiers":3082},"Choi CY, Rho SB, Kim HS, Han J, Bae J, Lee SJ, et al. The ORF3 protein of porcine circovirus type 2 promotes secretion of IL-6 and IL-8 in porcine epithelial cells by facilitating proteasomal degradation of regulator of G protein signalling 16 through physical interaction. J Gen Virol. 2015;96:1098–108.",{"doi":3083},"10.1099\u002Fvir.0.000046",{"id":18,"text":3085,"url":18,"identifiers":3086},"Nagata Y, Oda M, Nakata H, Shozaki Y, Kozasa T, Todokoro K. A novel regulator of G-protein signaling bearing GAP activity for Galphai and Galphaq in megakaryocytes. Blood. 2001;97:3051–60.",{"doi":3087},"10.1182\u002Fblood.V97.10.3051",{"id":18,"text":3089,"url":18,"identifiers":3090},"Park IK, Klug CA, Li K, Jerabek L, Li L, Nanamori M, et al. Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells. J Biol Chem. 2001;276:915–23.",{"doi":3091},"10.1074\u002Fjbc.M005947200",{"id":18,"text":3093,"url":18,"identifiers":3094},"Yowe D, Weich N, Prabhudas M, Poisson L, Errada P, Kapeller R, et al. RGS18 is a myeloerythroid lineage-specific regulator of G-protein-signalling molecule highly expressed in megakaryocytes. Biochem J. 2001;359:109–18.",{"doi":3095},"10.1042\u002Fbj3590109",{"id":18,"text":3097,"url":18,"identifiers":3098},"Gagnon AW, Murray DL, Leadley RJ. Cloning and characterization of a novel regulator of G protein signalling in human platelets. Cell Signal. 2002;14:595–606.",{"doi":3099},"10.1016\u002FS0898-6568(02)00012-8",{"id":18,"text":3101,"url":18,"identifiers":3102},"Johnson KD, Boyer ME, Kang JA, Wickrema A, Cantor AB, Bresnick EH. Friend of GATA-1-independent transcriptional repression: a novel mode of GATA-1 function. Blood. 2007;109:5230–3.",{"doi":3103},"10.1182\u002Fblood-2007-02-072983",{"id":18,"text":3105,"url":18,"identifiers":3106},"Berthebaud M, Riviere C, Jarrier P, Foudi A, Zhang Y, Compagno D, et al. RGS16 is a negative regulator of SDF-1-CXCR4 signaling in megakaryocytes. Blood. 2005;106:2962–8.",{"doi":3107},"10.1182\u002Fblood-2005-02-0526",{"id":18,"text":3109,"url":18,"identifiers":3110},"Iwai K, Koike M, Ohshima S, Miyatake K, Uchiyama Y, Saeki Y, et al. RGS18 acts as a negative regulator of osteoclastogenesis by modulating the acid-sensing OGR1\u002FNFAT signaling pathway. J Bone Min Res : Off J Am Soc Bone Min Res. 2007;22:1612–20.",{"doi":3111},"10.1359\u002Fjbmr.070612",{"id":18,"text":3113,"url":18,"identifiers":3114},"Gegenbauer K, Elia G, Blanco-Fernandez A, Smolenski A. Regulator of G-protein signaling 18 integrates activating and inhibitory signaling in platelets. Blood. 2012;119:3799–807.",{"doi":3115},"10.1182\u002Fblood-2011-11-390369",{"id":18,"text":3117,"url":18,"identifiers":3118},"Delesque-Touchard N, Pendaries C, Volle-Challier C, Millet L, Salel V, Herve C, et al. Regulator of G-protein signaling 18 controls both platelet generation and function. PLoS One. 2014;9, e113215.",{"doi":3119},"10.1371\u002Fjournal.pone.0113215",{"id":18,"text":3121,"url":18,"identifiers":3122},"Alshbool FZ, Karim ZA, Vemana HP, Conlon C, Lin OA, Khasawneh FT. The regulator of G-protein signaling 18 regulates platelet aggregation, hemostasis and thrombosis. Biochem Biophys Res Commun. 2015;462:378–82.",{"doi":3123},"10.1016\u002Fj.bbrc.2015.04.143",{"id":18,"text":3125,"url":18,"identifiers":3126},"Lu Q, Sun EE, Klein RS, Flanagan JG. Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction. Cell. 2001;105:69–79.",{"doi":3127},"10.1016\u002FS0092-8674(01)00297-5",{"id":18,"text":3129,"url":18,"identifiers":3130},"Qiu R, Wang J, Tsark W, Lu Q. Essential role of PDZ-RGS3 in the maintenance of neural progenitor cells. Stem Cells. 2010;28:1602–10.",{"doi":3131},"10.1002\u002Fstem.478",{"id":18,"text":3133,"url":18,"identifiers":3134},"Williams JW, Yau D, Sethakorn N, Kach J, Reed EB, Moore TV, et al. RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation. Am J Physiol Lung Cell Mol Physiol. 2013;305:L693–701.",{"doi":3135},"10.1152\u002Fajplung.00214.2013",{"id":18,"text":3137,"url":18,"identifiers":3138},"Mighiu AS, Heximer SP. Controlling parasympathetic regulation of heart rate: a gatekeeper role for RGS proteins in the sinoatrial node. Front Physiol. 2012;3:204.",{"doi":3139},"10.3389\u002Ffphys.2012.00204",{"id":18,"text":3141,"url":18,"identifiers":3142},"Han MH, Renthal W, Ring RH, Rahman Z, Psifogeorgou K, Howland D, et al. Brain region specific actions of regulator of G protein signaling 4 oppose morphine reward and dependence but promote analgesia. Biol Psychiatry. 2010;67:761–9.",{"doi":3143},"10.1016\u002Fj.biopsych.2009.08.041",{"id":18,"text":3145,"url":18,"identifiers":3146},"Stratinaki M, Varidaki A, Mitsi V, Ghose S, Magida J, Dias C, et al. Regulator of G protein signaling 4 [corrected] is a crucial modulator of antidepressant drug action in depression and neuropathic pain models. Proc Natl Acad Sci U S A. 2013;110:8254–9.",{"doi":3147},"10.1073\u002Fpnas.1214696110",{"id":18,"text":3149,"url":18,"identifiers":3150},"Cho H, Park C, Hwang IY, Han SB, Schimel D, Despres D, et al. Rgs5 targeting leads to chronic low blood pressure and a lean body habitus. Mol Cell Biol. 2008;28:2590–7.",{"doi":3151},"10.1128\u002FMCB.01889-07",{"id":18,"text":3153,"url":18,"identifiers":3154},"Qin M, Huang H, Wang T, Hu H, Liu Y, Cao H, et al. Absence of Rgs5 prolongs cardiac repolarization and predisposes to ventricular tachyarrhythmia in mice. J Mol Cell Cardiol. 2012;53:880–90.",{"doi":3155},"10.1016\u002Fj.yjmcc.2012.10.003",{"id":18,"text":3157,"url":18,"identifiers":3158},"Qin M, Huang H, Wang T, Hu H, Liu Y, Gu Y, et al. Atrial tachyarrhythmia in Rgs5-null mice. PLoS One. 2012;7, e46856.",{},{"id":18,"text":3160,"url":18,"identifiers":3161},"Cheng WL, Wang PX, Wang T, Zhang Y, Du C, Li H, Ji Y (2014) Regulator of G-protein signalling 5 protects against atherosclerosis in apolipoprotein E-deficient mice. Br J Pharmacol. doi: 10.1111\u002Fbph.12991 .",{"doi":3162},"10.1111\u002Fbph.12991",{"id":18,"text":3164,"url":18,"identifiers":3165},"Takata Y, Liu J, Yin F, Collins AR, Lyon CJ, Lee CH, et al. PPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis. Proc Natl Acad Sci U S A. 2008;105:4277–82.",{"doi":3166},"10.1073\u002Fpnas.0708647105",{"id":18,"text":3168,"url":18,"identifiers":3169},"Kuwata H, Nakao K, Harada T, Matsuda I, Aiba A. Generation of RGS8 null mutant mice by Cre\u002FloxP system. Kobe J Med Sci. 2007;53:275–81.",{},{"id":18,"text":3171,"url":18,"identifiers":3172},"Saitoh O, Kubo Y, Miyatani Y, Asano T, Nakata H. RGS8 accelerates G-protein-mediated modulation of K+ currents. Nature. 1997;390:525–9.",{"doi":3173},"10.1038\u002F37385",{"id":18,"text":3175,"url":18,"identifiers":3176},"Benians A, Nobles M, Tinker A. Participation of RGS8 in the ternary complex of agonist, receptor and G-protein. Biochem Soc Trans. 2004;32:1045–7.",{"doi":3177},"10.1042\u002FBST0321045",{"id":18,"text":3179,"url":18,"identifiers":3180},"Laroche G, Giguere PM, Roth BL, Trejo J, Siderovski DP. RNA interference screen for RGS protein specificity at muscarinic and protease-activated receptors reveals bidirectional modulation of signaling. Am J Physiol Cell Physiol. 2010;299:C654–64.",{"doi":3181},"10.1152\u002Fajpcell.00441.2009",{"id":18,"text":3183,"url":18,"identifiers":3184},"von Buchholtz L, Elischer A, Tareilus E, Gouka R, Kaiser C, Breer H, et al. RGS21 is a novel regulator of G protein signalling selectively expressed in subpopulations of taste bud cells. Eur J Neurosci. 2004;19:1535–44.",{"doi":3185},"10.1111\u002Fj.1460-9568.2004.03257.x",{"id":18,"text":3187,"url":18,"identifiers":3188},"Li X, Chen L, Ji C, Liu B, Gu J, Xu J, et al. Isolation and expression pattern of RGS21 gene, a novel RGS member. Acta Biochim Pol. 2005;52:943–6.",{"doi":3189},"10.18388\u002Fabp.2005_3412",{"id":18,"text":3191,"url":18,"identifiers":3192},"Kimple AJ, Garland AL, Cohen SP, Setola V, Willard FS, Zielinski T, et al. RGS21, a regulator of taste and mucociliary clearance? Laryngoscope. 2014;124:E56–63.",{"doi":3193},"10.1002\u002Flary.24326",{"id":18,"text":3195,"url":18,"identifiers":3196},"Blazer LL, Storaska AJ, Jutkiewicz EM, Turner EM, Calcagno M, Wade SM, et al. Selectivity and anti-Parkinson’s potential of thiadiazolidinone RGS4 inhibitors. ACS Chem Neurosci. 2015;6:911–9.",{"doi":3197},"10.1021\u002Facschemneuro.5b00063",{"id":18,"text":3199,"url":18,"identifiers":3200},"Monroy CA, Doorn JA, Roman DL. Modification and functional inhibition of regulator of G-protein signaling 4 (RGS4) by 4-hydroxy-2-nonenal. Chem Res Toxicol. 2013;26:1832–9.",{"doi":3201},"10.1021\u002Ftx400212q",{"id":18,"text":3203,"url":18,"identifiers":3204},"Yoon SY, Woo J, Park JO, Choi EJ, Shin HS, Roh DH, et al. Intrathecal RGS4 inhibitor, CCG50014, reduces nociceptive responses and enhances opioid-mediated analgesic effects in the mouse formalin test. Anesth Analg. 2015;120:671–7.",{"doi":3205},"10.1213\u002FANE.0000000000000607",{"id":18,"text":3207,"url":18,"identifiers":3208},"Lee PC, Sowa ME, Gygi SP, Harper JW. Alternative ubiquitin activation\u002Fconjugation cascades interact with N-end rule ubiquitin ligases to control degradation of RGS proteins. Mol Cell. 2011;43:392–405.",{"doi":3209},"10.1016\u002Fj.molcel.2011.05.034",{"id":18,"text":3211,"url":18,"identifiers":3212},"Jiang Y, Choi WH, Lee JH, Han DH, Kim JH, Chung YS, et al. A neurostimulant para-chloroamphetamine inhibits the arginylation branch of the N-end rule pathway. Sci Rep. 2014;4:6344.",{"doi":3213},"10.1038\u002Fsrep06344",{"id":18,"text":3215,"url":18,"identifiers":3216},"Raveh A, Schultz PJ, Aschermann L, Carpenter C, Tamayo-Castillo G, Cao S, et al. Identification of protein kinase C activation as a novel mechanism for RGS2 protein upregulation through phenotypic screening of natural product extracts. Mol Pharmacol. 2014;86:406–16.",{"doi":3217},"10.1124\u002Fmol.114.092403"]