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However, their effects on mammary glands remain unclear. We investigated the effects of acetate and butyrate on antimicrobial component production in mammary epithelial cells (MECs) or leukocytes cultured in vitro and in mammary glands of lactating Tokara goats in vivo. Our results showed that butyrate enhanced the production of β-defensin-1 and S100A7 in MECs. Additionally, the infusion of butyrate into mammary glands through the teats enhanced β-defensin-1 and S100A7 concentrations in milk. The infusion of acetate also increased β-defensin-1 and S100A7 concentrations along with those of cathelicidin-2 and interleukin-8, which are produced by leukocytes. Furthermore, acetate promoted cathelicidin-2 and interleukin-8 secretion in leukocytes in vitro. 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J Dairy Sci. 2019;102:4674–81.",{"doi":323},{"id":319,"text":382,"url":321,"identifiers":383},"Tsugami Y, Matsunaga K, Suzuki T, Nishimura T, Kobayashi K. Isoflavones and their metabolites influence the milk component synthesis ability of mammary epithelial cells through prolactin\u002FSTAT5 signaling. Mol Nutr Food Res 2017, 61.",{"doi":323},{"id":319,"text":385,"url":321,"identifiers":386},"Tsugami Y, Suzuki N, Kawahara M, Suzuki T, et al. Establishment of an in vitro culture model to study milk production and the blood-milk barrier with bovine mammary epithelial cells. Anim Sci J. 2020;91:e13355.",{"doi":323},{"id":319,"text":388,"url":321,"identifiers":389},"Purba FY, Ueda J, Nii T, Yoshimura Y, Isobe N. Effects of intrauterine infusion of bacterial lipopolysaccharides on the mammary gland inflammatory response in goats. Vet Immunol Immunopathol. 2020;219:109972.",{"doi":323},{"id":319,"text":391,"url":321,"identifiers":392},"Kuwahara K, Yoshimura Y, Isobe N. Effect of steroid hormones on the innate immune response induced by Staphylococcus aureus in the goat mammary gland. Reprod Domest Anim. 2017;52:579–84.",{"doi":323},{"id":319,"text":394,"url":321,"identifiers":395},"Zhao Y, Yan S, Chen L, Shi B, Guo X. Effect of interaction between leucine and acetate on the milk protein synthesis in bovine mammary epithelial cells. Anim Sci J. 2019;90:81–9.",{"doi":323},{"id":397,"text":398,"url":399,"identifiers":400},"c142a1fa-9410-4dda-854e-7d283e58b3a1","Chen J, Wu Y, Sun Y, Dong X, et al. Bacterial endotoxin decreased histone H3 acetylation of bovine mammary epithelial cells and the adverse effect was suppressed by sodium butyrate. BMC Vet Res. 2019;15:267.","https:\u002F\u002Fbmcvetres.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs12917-019-2007-5",{"doi":401},"10.1186\u002Fs12917-019-2007-5",{"id":319,"text":403,"url":321,"identifiers":404},"Sharmin MM, Mizusawa M, Hayashi S, Arai W, et al. 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Cancer Res. 2005;65(14):6130–8.",{"doi":919},"10.1158\u002F0008-5472.CAN-04-1408",{"id":22,"text":921,"url":22,"identifiers":922},"Kuperwasser C, Chavarria T, Wu M, et al. Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA. 2004;101(14):4966–71.",{"doi":923},"10.1073\u002Fpnas.0401064101",{"id":925,"createTime":926,"updateTime":927,"relativeEntities":928,"slug":929,"properties":930,"entityType":194,"verifyStatus":195,"verifyTime":941,"verifyNote":197,"languages":22,"translateLanguages":22,"viewCount":23,"primaryUrl":942,"fullTextUrl":22,"authors":943,"publicationType":257,"publisherRelationship":1031,"citationCount":23,"citationInfo":1083,"publishDate":1086,"publishYear":1084,"citationAnalyzeStatus":314,"lastCitationAnalyze":1087,"indexDatabases":1088,"openAccess":22,"references":22,"isForceReanalyzing":483},"000d6e69-7b45-42c3-80ee-e048233da4c5","2023-12-24T19:10:28.056+00:00","2026-07-22T03:21:10.620+00:00",[],"Targeting-Inhibitors-of-Apoptosis-Proteins-IAPs-For-New-Breast-Cancer-Therapeutics",{"abstract":931,"title":933,"gsPaper":935,"references":937,"doi":939},{"EN":932},"Apoptosis resistance is a hallmark of human cancer. Research in the last two decades has identified key regulators of apoptosis, including inhibitor of apoptosis proteins (IAPs). These critical apoptosis regulators have been targeted for the development of new cancer therapeutics. In this article, we will discuss three members of IAP proteins, namely XIAP, cIAP1 and cIAP2, as cancer therapeutic targets and the progress made in developing new cancer therapeutic agents to target these IAP proteins.",{"EN":934},"Targeting Inhibitors of Apoptosis Proteins (IAPs) For New Breast Cancer Therapeutics",{"VOID":936},"[\"14145645998084010854\"]",{"VOID":938},"Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis. 2000;21:485–95.\nNicholson DW. From bench to clinic with apoptosis-based therapeutic agents. Nature. 2000;407:810–6.\nReed JC. Apoptosis-based therapies. Nat Rev Drug Discov. 2002;1:111–21.\nHanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.\nFulda S, Debatin K-M. 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LRIG1 modulates cancer cell sensitivity to Smac mimetics by regulating TNFalpha expression and receptor tyrosine kinase signaling. Cancer Res. 2012;72:1229–38.\nhttp:\u002F\u002Fclinicaltrials.gov\u002F\nInfante JR, Claire Dees EC, Burris IHA, Zawel L, Sager JA, Stevenson C, Clarke K, Dhuria S, Porter D, Sen SK, Zannou E, Sharma S, Cohen RB. A phase I study of LCL161, an oral IAP inhibitor, in patients with advanced cancer. Abstract # 2775, AACR 101st Annual Meeting 2010, April 17–21, 2010, Washington, DC; 2010.\nGraham MA, Mitsuuchi Y, Burns J, Chunduru S, Benetatos C, McKinlay M, Weng D, Wick MJ, Tolcher AW, Papadopoulos K, Amaravadi R, Schilder RJ, Adjei A, LoRusso P. In Abstract A25: Phase 1 PK\u002FPD analysis of the Smac-mimetic TL32711 demonstrates potent and sustained cIAP1 suppression in patient PBMCs and tumor biopsies, AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, San Francisco, CA, Nov 12–16, 2011, 2011; San Francisco, CA; 2011.\nSikic BI, Eckhardt SG, Gallant G, Burris HA, Camidge DR, Colevas AD, Jones SF, Messersmith WA, Wakelee HA, Li H, Kaminker PG, Morris S, Infante JR. In Safety, pharmacokinetics (PK), and pharmacodynamics (PD) of HGS1029, an inhibitor of apoptosis protein (IAP) inhibitor, in patients (Pts) with advanced solid tumors: results of a phase I study, 2011 ASCO Annual Meeting 2011; 2011.\nWu YT, Wagner KW, Bursulaya B, Schultz PG, Deveraux QL. Development and characterization of nonpeptidic small molecule inhibitors of the XIAP\u002Fcaspase-3 interaction. Chem Biol. 2003;10:759–67.\nSchimmer AD, Welsh K, Pinilla C, Wang Z, Krajewska M, Bonneau MJ, Pedersen IM, Kitada S, Scott FL, Bailly-Maitre B, Glinsky G, Scudiero D, Sausville E, Salvesen G, Nefzi A, Ostresh JM, Houghten RA, Reed JC. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Canc Cell. 2004;5:25–35.\nNikolovska-Coleska Z, Xu L, Hu Z, Tomita Y, Li P, Roller PP, Wang R, Fang X, Guo R, Zhang M, Lippman ME, Yang D, Wang S. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. J Med Chem. 2004;47:2430–40.",{"VOID":940},"10.1007\u002Fs10911-012-9265-1","2024-05-16T00:34:26.366+00:00","https:\u002F\u002Flink.springer.com\u002Farticle\u002F10.1007\u002Fs10911-012-9265-1",[944,961,976,989,1002,1018],{"id":945,"sortIndex":23,"researcher":22,"roles":946,"affiliations":947,"properties":956,"displayName":958,"givenName":22,"familyName":22},"f34b9144-c7ba-409c-975b-84d577f2597a",[203],[948],{"id":949,"sortIndex":23,"affiliation":950,"properties":22},"6d2f9461-2678-4027-84b1-db8f2dcc8b3d",{"id":949,"createTime":22,"updateTime":22,"relativeEntities":951,"slug":22,"properties":952,"entityType":22,"verifyStatus":22,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":22,"url":22,"parentIds":955,"statistic":22},[],{"title":953},{"VI":954},"Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, Ann Arbor, USA",[],{"title":957,"gsAuthor":959},{"VI":958},"Shaomeng 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the Scenes of the Human Breast Cell Atlas Project",{"VOID":1099},"[\"12919285517792801509\"]",{"VOID":1101},"Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature [Internet]. 2001;409:860–921. Available from: http:\u002F\u002Fwww.nature.com\u002Farticles\u002F35057062.\nVenter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science [Internet]. 2001;291:1304–51. Available from: https:\u002F\u002Fwww.sciencemag.org\u002Flookup\u002Fdoi\u002Fhttps:\u002F\u002Fdoi.org\u002F10.1126\u002Fscience.1058040.\nSnyder MP, Gingeras TR, Moore JE, Weng Z, Gerstein MB, Ren B, et al. Perspectives on ENCODE. Nature [Internet]. 2020;583:693–8. Available from: http:\u002F\u002Fwww.nature.com\u002Farticles\u002Fs41586-020-2449-8.\nAmit I, Bader G, Campbell P, Carninci P, Clevers H, Eils R, et al. The human cell atlas [Internet]. arXiv. 2018. Available from: https:\u002F\u002Farxiv.org\u002Fabs\u002F1810.05192.\nDegnim AC, Visscher DW, Hoskin TL, Frost MH, Vierkant RA, Vachon CM, et al. Histologic findings in normal breast tissues: comparison to reduction mammaplasty and benign breast disease tissues. Breast Cancer Res Treat [Internet]. 2012;133:169–77. Available from: http:\u002F\u002Flink.springer.com\u002Fhttps:\u002F\u002Fdoi.org\u002F10.1007\u002Fs10549-011-1746-1.\nBhat-Nakshatri P, Gao H, McGuire P, Xuei X, Sheng L, Wan J, et al. A Single Cell Atlas of the Healthy Breast Tissues Reveal Clinically Relevant Clusters of Breast Epithelial Cells. bioRxiv. 2020.\nBach K, Pensa S, Grzelak M, Hadfield J, Adams DJ, Marioni JC, et al. Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing. Nat Commun [Internet]. 2017;8:2128. Available from: http:\u002F\u002Fwww.nature.com\u002Farticles\u002Fs41467-017-02001-5.\nTwigger AJ, Engelbrecht LK, Bach K, Schultz-Pernice I, Petricca S, Scheel CH, et al. Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk. bioRxiv. bioRxiv; 2020.\nCooper A. On the anatomy of the breast. London: Longman; 1840.",{"VOID":1103},"10.1007\u002Fs10911-021-09482-7","2024-06-26T16:21:45.077+00:00","https:\u002F\u002Flink.springer.com\u002Farticle\u002F10.1007\u002Fs10911-021-09482-7",[1107],{"id":1108,"sortIndex":23,"researcher":22,"roles":1109,"affiliations":1110,"properties":1119,"displayName":1121,"givenName":22,"familyName":22},"ae26751b-5597-4153-b612-bed3e697c2ff",[203],[1111],{"id":1112,"sortIndex":23,"affiliation":1113,"properties":22},"afe15fad-2ebe-47e7-b483-7e2af86b2e82",{"id":1112,"createTime":22,"updateTime":22,"relativeEntities":1114,"slug":22,"properties":1115,"entityType":22,"verifyStatus":22,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":22,"url":22,"parentIds":1118,"statistic":22},[],{"title":1116},{"EN":1117},"Developmental, Stem Cell and Cancer Biology, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands",[],{"title":1120,"gsAuthor":1122},{"VI":1121},"Renée van Amerongen",{"VOID":1123},"[\"zdq7fBIAAAAJ\"]",{"url":1105,"publisher":1125,"properties":1171},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1126,"slug":10,"properties":1127,"entityType":20,"verifyStatus":21,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":23,"subjectFields":1131,"manageAffiliations":1140,"indexDatabases":1151,"url":22,"thumbnailPath":22,"statistic":1166,"gsStatistic":22,"type":174,"analyzePriority":22},[],{"issn":1128,"title":1129,"eissn":1130},{"VOID":15},{"EN":17},{"VOID":13},[1132,1136],{"id":26,"createTime":22,"updateTime":22,"relativeEntities":1133,"label":1134,"description":1135,"parentId":22,"standard":22,"scholarHubFieldId":22},[],{"EN":29},{},{"id":32,"createTime":22,"updateTime":22,"relativeEntities":1137,"label":1138,"description":1139,"parentId":22,"standard":22,"scholarHubFieldId":22},[],{"EN":35},{},[1141,1146],{"id":39,"createTime":22,"updateTime":22,"relativeEntities":1142,"slug":22,"properties":1143,"entityType":22,"verifyStatus":22,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":22,"url":22,"parentIds":1145,"statistic":22},[],{"title":1144},{"EN":43},[45],{"id":47,"createTime":22,"updateTime":22,"relativeEntities":1147,"slug":22,"properties":1148,"entityType":22,"verifyStatus":22,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":22,"url":22,"parentIds":1150,"statistic":22},[],{"title":1149},{"EN":51},[45],[1152,1159],{"id":55,"indexDatabase":1153,"url":66,"indexYears":67,"academicFieldIds":1158,"indexDatabaseRanking":71},{"id":57,"createTime":22,"updateTime":22,"relativeEntities":1154,"label":1155,"description":1156,"key":63,"publicationTags":1157,"standard":22},[],{"EN":60,"VI":60},{"EN":60,"VI":62},[65],[69,70],{"id":73,"indexDatabase":1160,"url":86,"indexYears":22,"academicFieldIds":1165,"indexDatabaseRanking":22},{"id":75,"createTime":22,"updateTime":22,"relativeEntities":1161,"label":1162,"description":1163,"key":82,"publicationTags":1164,"standard":22},[],{"EN":78,"VI":78},{"EN":80,"VI":81},[84,85],[88,89,90],{"impactFactor":23,"impactFactorByYear":1167,"i10Index":105,"i10IndexLast5Year":106,"totalPublication":107,"totalPublicationByYear":1168,"totalCitation":128,"totalCitationByYear":1169,"totalCitationPerPublication":149,"totalCitationPerPublicationByYear":1170,"hindexLast5Year":173,"hindex":173},{"2012":93,"2013":94,"2014":95,"2015":96,"2016":97,"2017":98,"2018":99,"2019":100,"2020":101,"2021":102,"2022":103,"2023":104},{"1996":109,"1997":110,"1998":111,"1999":110,"2000":112,"2001":113,"2002":114,"2003":113,"2004":115,"2005":116,"2006":115,"2007":117,"2008":118,"2009":119,"2010":111,"2011":120,"2012":121,"2013":122,"2014":116,"2015":123,"2016":116,"2017":124,"2018":121,"2019":125,"2020":126,"2021":121,"2022":125,"2023":127,"2024":106},{"1996":130,"2003":131,"2004":132,"2005":133,"2006":134,"2007":135,"2008":136,"2009":137,"2010":138,"2011":139,"2012":121,"2013":140,"2014":141,"2015":142,"2016":143,"2017":144,"2018":145,"2019":146,"2020":117,"2021":147,"2022":124,"2023":148},{"1996":151,"2003":152,"2004":153,"2005":154,"2006":155,"2007":156,"2008":157,"2009":158,"2010":159,"2011":160,"2012":161,"2013":162,"2014":163,"2015":164,"2016":165,"2017":166,"2018":167,"2019":168,"2020":169,"2021":170,"2022":171,"2023":172},{"pages":1172,"volume":1174},{"VOID":1173},"67-70",{"VOID":1175},"26",{"total":23,"publishYear":1177,"statisticByYear":1178},2021,{},"2021-04-29","DONE_ANALYZE_CITATION","2026-07-20T08:51:34.485+00:00",[84,71],{"id":1184,"createTime":1185,"updateTime":1186,"relativeEntities":1187,"slug":1188,"properties":1189,"entityType":194,"verifyStatus":195,"verifyTime":1202,"verifyNote":197,"languages":22,"translateLanguages":22,"viewCount":23,"primaryUrl":1203,"fullTextUrl":22,"authors":1204,"publicationType":257,"publisherRelationship":1252,"citationCount":23,"citationInfo":1299,"publishDate":1302,"publishYear":1300,"citationAnalyzeStatus":1180,"lastCitationAnalyze":1303,"indexDatabases":1304,"openAccess":22,"references":22,"isForceReanalyzing":483},"24108df6-2ea9-4277-8152-1b4af4af8cbc","2024-04-07T02:22:14.904+00:00","2026-07-13T17:18:20.837+00:00",[],"Recent-Advances-in-Experimental-Models-of-Breast-Cancer-Exosome-Secretion-Characterization-and-Function",{"abstract":1190,"title":1192,"gsPaper":1194,"keywords":1196,"references":1198,"doi":1200},{"EN":1191},"Breast cancer (BC) is responsible for 15% of all the cancer deaths among women in the USA. The tumor microenvironment (TME) has the potential to act as a driver of breast cancer progression and metastasis. The TME is composed of stromal cells within an extracellular matrix and soluble cytokines, chemokines and extracellular vesicles and nanoparticles that actively influence cell behavior. Extracellular vesicles include exosomes, microvesicles and large oncosomes that orchestrate fundamental processes during tumor progression through direct interaction with target cells. Long before tumor cell spread to future metastatic sites, tumor-secreted exosomes enter the circulation and establish distant pre-metastatic niches, hospitable and permissive milieus for metastatic colonization. Emerging evidence suggests that breast cancer exosomes promote tumor progression and metastasis by inducing vascular leakiness, angiogenesis, invasion, immunomodulation and chemoresistance. Exosomes are found in almost all physiological fluids including plasma, urine, saliva, and breast milk, providing a valuable resource for the development of non-invasive cancer biomarkers. Here, we review work on the role of exosomes in breast cancer progression and metastasis, and describe the most recent advances in models of exosome secretion, isolation, characterization and functional analysis. We highlight the potential applications of plasma-derived exosomes as predictive biomarkers for breast cancer diagnosis, prognosis and therapy monitoring. We finally describe the therapeutic approaches of exosomes in breast cancer.",{"EN":1193},"Recent Advances in Experimental Models of Breast Cancer Exosome Secretion, Characterization and Function",{"VOID":1195},"[\"8641620179712807400\"]",{"EN":1197},"",{"VOID":1199},"Feng Y, et al. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis. 2018;5(2):77–106.\nRadisky DC, et al. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature. 2005;436(7047):123–7.\nGudjonsson T, et al. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J Cell Sci. 2002;115(Pt 1):39–50.\nBhowmick NA, et al. TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science. 2004;303(5659):848–51.\nFinak G, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008;14(5):518–27.\nIngthorsson S, et al. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture. BMC Res Notes. 2010;3:184.\nKraman M, et al. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science. 2010;330(6005):827–30.\nPsaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat Rev Cancer. 2009;9(4):285–93.\nHoshino A, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329–35.\nWortzel I, et al. Exosome-Mediated Metastasis: Communication from a Distance. Dev Cell. 2019;49(3):347–60.\nCocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 2009;19(2):43–51.\nKalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020. 367(6478).\nMathieu M, et al. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9–17.\nSkotland T, et al. An emerging focus on lipids in extracellular vesicles. Adv Drug Deliv Rev, 2020.\nvan Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–28.\nZhang H, et al. 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Russo and I. H. Russo (1987). In The Mammary Gland, M. C. Neville, and C. W. Daniel (eds.), Plenum Press, New York.",{},{"id":22,"text":1688,"url":22,"identifiers":1689},"T. Sakakura (1987). In The Mammary Gland, M. C. Neville, and C. W. Daniel (eds.), Plenum Press, New York, pp. 37–66.",{},{"id":22,"text":1691,"url":22,"identifiers":1692},"C. W. Daniel and G. B. Silberstein (1987). In The Mammary Gland, M. C. Neville, and C. W. Daniel (eds.), Plenum Press, New York, pp. 3–36.",{},{"id":319,"text":1694,"url":321,"identifiers":1695},"C. Brisken, S. Park, T. Vass, J. P. Lydon, B. W. O'Malley, and R. A. Weinberg (1998). A paracrine role for the epithelial progesterone receptor in mammary gland development. Proc. Natl. Acad. Sci. U.S.A. 95:5076–5081.",{"doi":323},{"id":319,"text":1697,"url":321,"identifiers":1698},"C. D. Roskelley and M. J. Bissell (1995). 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