Expresión de Proteínas Relacionadas con Resistencia a Múltiples Drogas (MDR-Proteínas) en tumores sólidos

Gaceta Medica de Bilbao - Tập 103 - Trang 163-175 - 2006
A. Paredes-Lario1, J.L. Blanco-Garda2, M. Echenique-Elizondo3
1Hospital Donostia. Departamento de Oncología. Donostia-San Sebastián. Euskadi. España UE.
2Hospital Donostia. Departamento de Radioterapia. Donostia-San Sebastián. Euskadi. España UE.
3Universidad del País Vasco. Departamento de Cirugía. Donostia-San Sebastián. Euskadi. España UE.

Tài liệu tham khảo

Beck, 1997, Mechanisms of Drug Resistance, 498 Chu, 2001, Principles of Cancer Management: Chemotherapy, 289 Skipper, 1964, Experimental evaluation of potential anticancer agents XII: on the criteria and kinetics associated With “curability” of experimental leukemia, Cancer Chem Rep, 35, I Goldie, 1979, A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate, Cancer treat Rep, 63, 1727 Skipper, 1985, Relationship Between Tumor Stem Cell Heterogeneity and Responsiveness to Chemotherapy, 63 Nishio, 1999, Drug resistance in lung cancer, Current Opinion in Oncology, 11, 109, 10.1097/00001622-199903000-00006 Miller, 1981, Reporting results of cancer treatment, Cancer, 47, 207, 10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>3.0.CO;2-6 Carney, 2000, Treatment of SCLC: Chemotherapy, 261 Shepherd, 2000, Treatment of NSCLC: Chemotherapy, 213 Doyle, 1993, Mechanisms of Drug Resistance in Human Lung Cancer Cells, Semin Oncol., 20, 326 Lehnert, 1996, Clinical Multidrug Resistance in Cancer: A Multifactorial Problem, Eur J Cancer, 32A, 912, 10.1016/0959-8049(96)00069-X Koomagi, 1999, Glucose-related protein (GRP78) and its relationship to the drug-resistance proteins P170, GST-pi, LRP56 and angio-genesis in non-small cell lung carcinomas, Anticancer Res., 19, 4333 Bradshaw, 1998, Clinical Relevance of Transmembrane Drug Efflux as a Mechanism of Multidrug Resistance, J Clin Oncol., 16, 3674, 10.1200/JCO.1998.16.11.3674 Duchesne, 1994, Fundamental bases of combined therapy in lung cancer: cell resitance to chemotherapy and radiotherapy, Lung Cancer, 10, S67, 10.1016/0169-5002(94)91668-3 Dalton, 1993, Overcoming the Multidrug-Resistant Phenotype, 2655 Simon, 1994, Cell biological mechanisms of multidrug resistance in tumors, Proc. Natl. Acad. Sci. USA, 91, 3497, 10.1073/pnas.91.9.3497 Tan, 2000, Multidrug resistance transporters and modulation, Current Opinion in Oncology, 12, 450, 10.1097/00001622-200009000-00011 Tamm, 2001, Apoptosis: implications of basic research for clinical oncology, Lancet Oncol., 2, 33, 10.1016/S1470-2045(00)00193-5 Morrow, 1993, Mechanisms of Antineoplastic Drug Resistance, 340 Ishikawa, 1993, Glutathione-Associated Cis-Diammine-Dicloroplatinum (II) Metabolism And ATP-Depedent Efflux From Leukemia Cells, J Biol Chem., 268, 20116, 10.1016/S0021-9258(20)80702-9 Borst, 2000, A Family of Drug Transporters: the Multidrug Resistance-Associated Proteins, J Natl Cancer Inst, 92, 1295, 10.1093/jnci/92.16.1295 Volm, 1991, Overexpression of P-glycoprotein and glutathione S-transferase-pi in resistant non-small-cell lung carcinomas of smokers, Br J Cancer, 64, 700, 10.1038/bjc.1991.384 Kreisholt, 1998, Inmunohistochemical detection of DNA topoisomerasa IIalpha, P-glycoprotein and multidrug resistance protein (MRP) in small-cell and non-small-cell lung cancer, Br J Cancer, 77, 1469, 10.1038/bjc.1998.241 Plasencia, 2000, Genes de quimiorresistencia, 145 Scagliotti, 1999, Multidrug resistance in non-small-cell lung cancer, Annals of Oncology, 10, 83, 10.1093/annonc/10.suppl_5.S83 Drake, 1989, Bichemical and Pharmacological properties of p170 and p180 forms of topoisomerase II, Biochemistry, 28, 8154, 10.1021/bi00446a029 Stewart, 2001, Topoisomerase Interactive Agents, 415 Giaccone, 1995, Differential expression of DNA topoisomerases in non-small-cell lung cancer and normal lung, Bichim Biophys Acta, 1264, 337, 10.1016/0167-4781(95)00171-9 Dingemans, 2001, Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer, Lung Cancer, 32, 117, 10.1016/S0169-5002(00)00224-5 Rosell, 2002, Determinants of Response and Resístance to Cytotoxics, Semin Oncol., 29, 110, 10.1053/sonc.2002.31532 Yang, 2003, Overcoming Drug Resistance In Multiple Myeloma: The Emergence Of Therapeutic Approaches To Induce Apoptosis, J Clin Oncol., 21, 4239, 10.1200/JCO.2003.06.001 Leonard, 1995, The role of p53 in cell-cycle control and apoptosis: implications for cancer, 33 Marie, 2001, Drug resistance in hematologic malignances, Current Opinion in Oncology, 13, 463, 10.1097/00001622-200111000-00008 Chin, 1992, Modulation of activity of the promoter of the human MDR1 gene by Ras and p53, Science, 2, 459, 10.1126/science.1346476 Harada, 2003, Predictive value of expression of P53, Bcl-2 and lung resistance-related protein for response to chemotherapy in non-small cell lung cancers, Cancer Science, 94, 394, 10.1111/j.1349-7006.2003.tb01453.x Kawasaki, 1998, Inmunohistochemically Detected p53 and P-glycoprotein Predict the Response to Chemotherapy in Lung Cancer, Eur J Cancer, 34, 1352, 10.1016/S0959-8049(98)00067-7 Galimberti, 1998, Multidrug resistance related genes and p53 expression in human non small cell lung cancer, Anticancer Res., 18, 2973 Schiller, 2001, Lack of Prognostic Significance of P53 and K-ras Mutations in Primary Resected Non-Small-Cell lung Cancer on E4592: A Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial Of Postoperative Adjuvant Therapy, J Clin Oncol., 19, 448, 10.1200/JCO.2001.19.2.448 Johnson, 2002, Aberrant p53 staining does not predict cisplatin resistance in locally advanced non-samall cell lung cancer, Cancer Invest., 20, 686, 10.1081/CNV-120003537 Wang, 1998, Transcriptional suppression of multidrug resistance-associated protein (MRP) gene expression by wild- type p53, Cancer Res., 58, 5762 Smyth, 1988, The drug efflux protein, P-glyco-protein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis, Proc Natl Acad Sci USA, 95, 7024, 10.1073/pnas.95.12.7024 Solary, 2000, Positive and negative regulation of apoptotic pathways by cytotoxic agents in hematologycal malignances, Leukemia, 14, 1833, 10.1038/sj.leu.2401902 Gottesman, 2002, Multidrug Resistance In Cancer : Role Of Atp-Dependent Transporters, Nature Reviews Cancer, 2, 48, 10.1038/nrc706 Dano, 1973, Active outward transport of daunomycin in resistant Ehrlich ascitis tumor cells, Biochim Biophys Acta, 323, 466, 10.1016/0005-2736(73)90191-0 Juliano, 1976, A Surface Glycoprotein Modulating Drug Permeability In Chinese Hamster Ovary Cell Mutants, Biochim Biophys Acta, 455, 152, 10.1016/0005-2736(76)90160-7 Kartner, 1983, Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines, Science, 221, 1285, 10.1126/science.6137059 Cole, 1992, Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line, Science, 258, 1650, 10.1126/science.1360704 Cordón-Cardo, 1992, El Fenotipo de Resistencia a Multiples Farmacos en el Cáncer Humano, 35 Goldstein, 1989, Expression of a Multidrug Resistance Gene in Human Cancers, JNCI, 81, 116, 10.1093/jnci/81.2.116 Zaman, 1994, The Human Multidrug Resistance-associated Protein MRP is a Plasma Membrane Drug-Efflux Pump, Proc Natl Acad Sci USA, 91, 8822, 10.1073/pnas.91.19.8822 Koomagi, 1996, Expression of resistance-related proteins in tumoral and peritumoral tissues of patients with lung cancer, Cancer Lett., 110, 129, 10.1016/S0304-3835(96)04471-0 Kitazono, 1999, Multidrug resistance and the lung resistance-related protein in human colon carcinoma SW-620 cells, J Natl Cancer Inst, 91, 1647, 10.1093/jnci/91.19.1647 Scheffer, 1995, The drug resistance-related protein LRP is the human major vault protein, Nature Med., 1, 578, 10.1038/nm0695-578 Pallis, 2000, P-glycoprotein plays a drug-efflux-independent role in augmenting cell survival in acute myeloblastic leukemia and is associated with modulation of a sphingomyelin-ceramide apoptotic pathway, Blood, 95, 2897, 10.1182/blood.V95.9.2897.009k14_2897_2904 Lincke, 1991, Structure Of The Human MDR3 Gene And Physical Mapping Of The Human MDR Locus, J Biol Chem., 266, 5303, 10.1016/S0021-9258(19)67788-4 de Vree, 1998, Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis, Proc Natl Acad Sci USA, 95, 282, 10.1073/pnas.95.1.282 Scheffer, 2002, Multidrug resistance related molecules in human and murine lung, J Clin Pathol., 55, 332, 10.1136/jcp.55.5.332 Sugawara, 1997, Lung resistance protein (LRP) expression in human normal tissues comparison with that of MDR1 and MRP, Cancer Lett., 112, 23, 10.1016/S0304-3835(96)04542-9 Godstein, 1996, MDR1 Gene Expression in Solid Tumours, Eur J Cancer, 32A, 1039, 10.1016/0959-8049(96)00100-1 Trock, 1997, Multidrug Resistance In Breast Cancer: A Meta-Analisys Of MDR1/Gp170 Expression And Its Possible Functional Significace, J Natl Cancer Inst, 89, 917, 10.1093/jnci/89.13.917 Ng, 1998, Expression of P-glycoprotein, a multidrug-resistance gene product, is induced by radiotherapy in patients with oral squamous cell carcinoma, Cancer, 83, 851, 10.1002/(SICI)1097-0142(19980901)83:5<851::AID-CNCR8>3.0.CO;2-L Rappa, 1997, Evidence that the multidrug resitance protein (MRP) functions as a co-transporter of glutathione and natural product toxins, Cancer Res., 57, 5232 Grant, 1994, Overexpression of Multidrug Resistance-Associated Protein (MRP) Increases Resistance to Natural Product Drugs, Cancer Res., 54, 357 Young, 1999, Expression of Multidrug Resistance Protein-related Genes in Lung Cancer : Correlation with Drug Response, Clin Cancer Res., 5, 673 Thomas, 1994, Expression of the Multidrug Resistance-Associated Protein (MRP) Gene in Human Lung Tumours and Normal Tissue as Determined by In Situ Hybridisation, Eur J Cancer, 30, 1705, 10.1016/0959-8049(94)00290-L Jedlitschky, 1994, ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein, Cancer Res., 54, 4833 Busse, 1998, Leukotrienes and inflammation, Am J Respir Crit Care Med., 157, S210, 10.1164/ajrccm.157.6.mar-1 Young, 2001, Multidrug Resistance Proteins MRP3, MRP1, and MRP2 in Lung Cancer : Correlation of Protein Levels with Drug Response and Messenger RNA Levels, Clin Cancer Res., 7, 1798 Oguri, 2001, Association between expression of the MRP3 gene and exposure to platinum drugs in lung cancer, Int J Cancer, 93, 584, 10.1002/ijc.1369 Scheper, 1993, Overexpression of a Mr 110.000 Vesicular Protein in Non-P-Glycoprotein-Mediated Multidrug Resistance, Cancer Res., 53, 1475 Slovak, 1995, The LRP gene encoding a major vault protein associated with drug resistance maps proximal to MRP on cromosoma 16 : Evidence that chromosoma breakage plays a key role in MRP or LRP gene amplification, Cancer Res., 55, 4214 Kedersha, 1986, Isolation and Characterization of a Novel Ribonucleoprotein Particle: Large Structures Contain a Single Species of Small RNA, J Cell Biol., 103, 699, 10.1083/jcb.103.3.699 Chugani, 1993, Evidence that Vault Ribonucleoprotein Particles Localize to The Nuclear Pore Complex, J Cell Sci., 106, 23, 10.1242/jcs.106.1.23 Dingemans, 1996, Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues, Annals of Oncology, 7, 625, 10.1093/oxfordjournals.annonc.a010681 Izquierdo, 1996, Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors, Am J Pathol., 148, 877 Izquierdo, 1996, Overlapping phenotipes of multidrug resistance among panels of human cancer-cell lines, Int J Cancer, 65, 230, 10.1002/(SICI)1097-0215(19960117)65:2<230::AID-IJC17>3.0.CO;2-H Ikeda, 1998, Lung resistance-related protein gene expression and drug sensitivity in human gastric and lung cancer cells, Anticancer Res., 18, 3077 Allikmets, 1998, A human placenta-specific ATP-binding cassette gene (ABCP) on chromosoma 4q22 that is involved in multidrug resistance, Cancer Res., 58, 5337 Miyake, 1999, Molecular cloning of cDNA which are highly overexpress in mitoxantrone-resistant cells: demostration of homology to ABC transport genes, Cancer Res., 59, 8 Ross, 1999, Atipycal multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone- selected cell lines, J Natl Cancer Inst, 91, 429, 10.1093/jnci/91.5.429 Maliepaard, 1999, Overexpression of the BCRP/MXR/ABCP gene in a topotecan selected ovarian tumor cell line, Cancer Res., 59, 4559 Ross, 1999, Expression of breast cancer resistance protein in blast cells from patients with acute leukemia, Blood, 96, 365, 10.1182/blood.V96.1.365 Kawabata, 2003, Expression and functional analyses of breast cancer resistance protein in lung cancer, Clin Cancer Res., 9, 3052 Faneyte, 2002, Expression of the breast cancer resistance protein in breast cancer, Clin Cancer Res., 8, 1068 Broxterman, 1996, How to Probe Clinical Tumour Samples for P-glycoprotein and Multidrug Resistance-associated Protein, Eur J Cancer, 32A, 1024, 10.1016/0959-8049(96)00045-7 Campling, 1997, Expression of the MRP and MDR1 multidrug resistance genes in small cell lung cancer, Clin Cancer Res., 3, 115 Duhem, 1996, What does Multidrug Resistance (MDR) Expression Mean in the Clinic?, The Oncologist, 1, 151, 10.1634/theoncologist.1-3-151 Twentyman, 1992, MDR1 (P-glycoprotein) Gene Expression. Implications for Resistance Modifier Trials, JNCI, 84, 1458, 10.1093/jnci/84.19.1458 Sonneveld, 2000, Multidrug resistance in hematological malignancies, J Intern Med., 247, 521, 10.1046/j.1365-2796.2000.t01-1-00689.x Baumforth, 1999, The Polymerase chain reaction, J Clin Pathol: Mol Pathol., 52, 1, 10.1136/mp.52.1.1 Giaccone, 1996, MRP is frequently expressed in human lung-cancer cell lines, in non-small-cell lung cancer and in normal lungs, Int J Cancer, 66, 760, 10.1002/(SICI)1097-0215(19960611)66:6<760::AID-IJC9>3.0.CO;2-Y Beck, 1996, Methods to detect P-glycoprotein-associated multidrug resistance in patients tumours: consensus recomendations, Cancer Res., 56, 3010 Scagliotti, 1991, Detection of Multidrug Resistance Associated P-170 Glycoprotein in Previously Untreated Non Small Cell Lung Cancer, Anticancer Res., 11, 2207 Wright, 1998, Inmunohistochemical detection of multidrug resistance protein in human lung cancer and normal lung, Cancer Res., 4, 2279 Xu, 1999, Expression of multidrug resistance-associated protein gene in non-small cell lung cancer, Zhonghua Yi Xue Za Zhi, 22, 268 Thomas, 2003, Overcoming Multidrug Resistance in Cancer: An Update on the Clinical Strategy of Inhibiting P-Glycoprotein, Cancer control., 10, 159, 10.1177/107327480301000207 Hendrikse, 1998, 99mTc-sestamibi is a substrate for P-glycoprotein and the multidrug resistance associated protein, Br J Cancer, 77, 353, 10.1038/bjc.1998.57 Cayre, 2002, Single static view 99m Tc-sestamibi scintimammography predicts response to neoadyuvant chemotherapy and is related to MDR expression, Int J Oncol., 20, 1049 Gorlik, 2001, Lack of Correlation of Functional Scintigraphy with 99mTechnetium-Methoxyisobutylisonitrile with Histologycal Necrosis Following Induction Chemotherpy or Measures of P-Glycoprotein Expression in High-Grade Osteosarcoma, Clin Cancer Res., 7, 3065 Kostakoglu, 1998, Association of tumor washout rates and accumulation of technetium-99m-MIBI with expression of P-glycoprotein in lung cancer, J Nucl Med., 39, 228 Kao, 2001, Technetium-99m metoxyisobutilisonitrilo chest imaging for small cell lung cancer: Relatioship to chemotherpy response (six courses of combination of cisplatin and etoposide) and p-glycoprotein or multidrug resistance related protein expression, Ann Oncol., 12, 1516, 10.1023/A:1013133801173 Zhou, 2001, Expression of multidrug resistance protein and messenger RNA correlate with (99m)Tc-MIBI imaging in patients with lung cancer, J Nucl Med., 42, 1476 Kao, 1998, Technetium-99m Methoxyisobutylisonitrile Chest Imaging of Small Cell Lung Carcinoma, Cancer, 83, 64, 10.1002/(SICI)1097-0142(19980701)83:1<64::AID-CNCR9>3.0.CO;2-E Shiau, 2001, To predict chemotherapy response using technetium-99m tetrofosmin and compare with p-glycoprotein and multidrug resistance related protein-1 expression in patients with untreated small cell lung cancer, Cancer Lett., 169, 181, 10.1016/S0304-3835(01)00519-5 Dirlik, 2002, The role of Tc-99m sestamibi imaging in predicting clinical respose to chemotherapy in lung cancer, Ann Nucl Med., 16, 103, 10.1007/BF02993712 Shi, 2002, Correlationof the uptake of techne-tium-99 methoxyisobutyl isonitrilo with expression of multidrug resistance genes mdr-1 and MRP in human lung cancer, Zhonghua Yi Xue Za Zhi, 82, 824 Kuo, 2002, To predict response chemotherapy using technetium-99m tetrofosmin chest images in patients with untreated small cell lung cancer and compare with p-glycoprotein, multidrug resistance related protein-1, and lung resistance-related protein expression, Nuclear Med Biol., 30, 627, 10.1016/S0969-8051(03)00058-1 Bates, 2002, Reversal of multidrug resistance: lessons from clinical oncology, Novartis Foundation Symposium, 243, 83, 10.1002/0470846356.ch7 Pennock, 1991, Systemic toxic effects associated with high dose verapamil infusion and chemotherapy administration, JNCI, 83, 105, 10.1093/jnci/83.2.105 Salmon, 1991, Multidrug resistant myeloma: Laboratory and clinical effects of Verapamil as a chemosensitizer, Blood, 78, 44, 10.1182/blood.V78.1.44.44 Dalton, 1995, A phase III randomized study of oral verapamil as a chemosensitizer to reverse drug resistance in pacientes with refractory myeloma. A South-West Oncology Group study, Cancer, 75, 815, 10.1002/1097-0142(19950201)75:3<815::AID-CNCR2820750311>3.0.CO;2-R Wattel, 1998, Quinina improves the results of intensive chemotheraphy in myelodysplastic syndromes expressing P-glycoprotein: results of a randomized study, Br J Haematol., 102, 1015, 10.1046/j.1365-2141.1998.00870.x Milroy, 1993, A randomized clinical study of verapamil in addition to combination chemotherapy in small-cell lung cancer, Br J Cancer, 68, 813, 10.1038/bjc.1993.433 Loo, 2000, Blockage of drug resistance in vitro by disulfiram, a drug used to treat alcoholism, JNCI, 92, 898, 10.1093/jnci/92.11.898 Baer, 2002, Phase III study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 Years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720, Blood, 100, 1224, 10.1182/blood.V100.4.1224.h81602001224_1224_1232 Rowinsky, 1998, Phase I and pharmacokinetic study of paclitaxel in combination with bricodar, a novel agent that reverses multidrug resistance conferred by overexpression of both MDR1 and MRP, J Clin Oncol., 16, 2964, 10.1200/JCO.1998.16.9.2964 Dantzig, 2001, Reversal of multidrug resistance by the P-glycoprotein modulator, LY335979, from the bench to the clinic, Curr Med Chem., 8, 39, 10.2174/0929867013373903 Petrylack, 1995, Expresión de P-glicoproteina en el carcinoma de células transicionales de vejiga primario y metástasico, AnnOncol (ed. español), 1, 68 Tada, 2002, Increased expresión of multidrug resistance-associated proteins in bladder cancer during clinical course and drug resistance to doxorrubicin, Int J Cancer, 98, 630, 10.1002/ijc.10246 Charpin, 1994, Quantitative immunocytochemical assays of P-glycoprotein in breast carcinomas: correlation to messenger RNA expression and to immunohistochemical prognostic indicators, JNCI, 86, 1539, 10.1093/jnci/86.20.1539 Levine, 1997, Evaluation of Newer prognostic Markers for adult Soft Tissue Sarcomas, J Clin Oncol., 15, 3249, 10.1200/JCO.1997.15.10.3249 Sinicrope, 1994, Relationship of P-glycoprotein and Carcinoembryonic Antigen Expression in Human Colon Carcinoma to Local Invasion, DNA Ploidy, and Disease Relapse, Cancer, 74, 2908, 10.1002/1097-0142(19941201)74:11<2908::AID-CNCR2820741104>3.0.CO;2-M Benchimol, 1994, P-glycoprotein and tumor progression, JNCI, 86, 814, 10.1093/jnci/86.11.814 Chan, 1991, P-Glycoprotein Expression As A Predictor Of The Outcome Of Therapy For Neuroblastoma, New Engl J Med., 325, 1608, 10.1056/NEJM199112053252304 Chan, 1990, Immunohistochemical Detection of P-Glycoprotein: Prognostic Correlation in Soft Tissue Sarcoma of Childhood, J Clin Oncol., 8, 689, 10.1200/JCO.1990.8.4.689 Schneider, 2001, Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary node invasion at the time of rescue mastectomy after induction chemotherapy, Breast Cancer Res., 3, 183, 10.1186/bcr293 Kamazawa, 2002, Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer, Gynecol Oncol., 86, 171, 10.1006/gyno.2002.6738 Warmann, 2002, The role of the MDR1 gene in the development of multidrug resistance in human hepatoblastoma: clinical course and in vivo model, Cancer, 95, 1795, 10.1002/cncr.10858 Hsu, 2002, Prognostic value of multidrug resistance 1, gltathione-s-transferase-pi and p53 in advanced nasopharyngeal carcinoma treated with systemic chemotherapy, Oncology, 62, 305, 10.1159/000065061 Chan, 1997, Multidrug resistance protein (MRP) expression in retinoblastoma correlates with the rare failure of chemotherapy despite cyclosporine for reversal of P-glycoprotein, Cancer Res., 57, 2325 Baldini, 1995, Expression of P-glycoprotein in hiah grade osteosarcoma in relation to dlinical out come, N Engl J Med., 333, 1380, 10.1056/NEJM199511233332103 Cheson, 2001, Miscellaneous Chemotherapeutic Agents Cancer, Principles and Practice of Oncology, 452 Choi, 2002, Expression of multidrug resistance-associated protein 1, P-glycoprotein, and thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adyuvant chemotherapy after curative resection, Br J Cancer, 86, 1578, 10.1038/sj.bjc.6600305 Oudard, 2002, Expression of genes involved in chemoresistance, proliferation and apoptosis in clinical samples of renal cell carcinoma and correlation with a clinical outcome, Anticancer Res., 22, 121 Arts, 1999, Drug Resistance-associated Markers P-Glycoprotein, Multidrug Resistance-associated Protein 1, Multidrug Resistance-associated Protein 2, and Lung Resistance Protein as Prognostic Factors in Ovarian Carcinoma, Clin Cancer Res., 5, 2798 Nakayama, 2002, Copper-transporting P-type adenosine triphosphate (ATP7B) as a cisplatin based chemoresistance marker in ovarian carcinoma: comparative analysis with expression of MDR1, MRP1, MRP2, LRPand BCRP, IntJ Cancer, 101, 488, 10.1002/ijc.10608 Wunder, 2000, MDR1 Gene Expression and Outcome in Osteosarcoma: A Prospective, Multicenter Study, J Clin Oncol., 18, 2685, 10.1200/JCO.2000.18.14.2685 Kanzaki, 2001, Expression of multidrug resistance-related transportes in human breast carcinoma, Jpn J Cancer Res., 92, 452, 10.1111/j.1349-7006.2001.tb01115.x Soini, 2001, The expression of P-glycoprotein and multidrug resistance proteins 1 and 2 (MRP1 and MRP2) in human malignant mesothelioma, Ann Oncol., 12, 1239, 10.1023/A:1012292230480