Expression of mdr-1 in refractory lymphoma: quantitation by polymerase chain reaction and validation of the assay [published erratum appears in Blood 1995 Dec 15;86(12):4710]

作者: Yoon-Koo Kang , Zhirong Zhan , Joanna Regis , M Alvarez , R Robey

DOI: 10.1182/BLOOD.V86.4.1515.BLOODJOURNAL8641515

关键词:

摘要: Measurement of P-glycoprotein and the gene that encodes it, mdr-1, is an important tool for assessing impact multidrug resistance in clinical cancer. We evaluated mdr-1 expression by a quantitative polymerase chain reaction (PCR) assay 78 biopsy samples from 48 patients with refractory lymphoma enrolled on trial infusional chemotherapy (EPOCH) which R-verapamil was added as antagonist subset whose tumors were unresponsive to treatment. Expression detectable all biopsies at time enrollment study, fourfold or greater increase mdr- 1 noted 42% treatment failure. also diagnosis lymphoma. An endogenous control gene, beta 2-microglobulin, quantitated normalization values. The use 2-microglobulin validated comparing Northern blots detecting actin, GAPDH expression. Immunoblot analysis suggested no major discrepancy present between mRNA protein level. Immunophenotyping lymphomatous lymph nodes showed infiltration tumor cells ranged 8% 95% normal T 1% 83%. monocytes shown be low. levels patient independent T- cell contamination, suggesting presence has best small measurements. can PCR, wide variations observed. Increased disease supports role Pgp drug These studies will aid design interpretation trials

参考文章(47)
Cynthia E. Herzog, Susan E. Bates, Molecular diagnosis of multidrug resistance. Cancer treatment and research. ,vol. 73, pp. 129- 147 ,(1994) , 10.1007/978-1-4615-2632-2_7
Casassus P, Marie Jp, Delmer A, Leroux G, Faussat Suberville Am, Coloma F, Delmas-Marsalet B, Baumelou E, Bastie Jn, Rio B, Cyclosporin A as a modifier agent in the salvage treatment of acute leukemia (AL). Leukemia. ,vol. 7, pp. 821- 824 ,(1993)
Sonja Kaubisch, Michael P. Gosland, Branimir I. Sikic, Bert L. Lum, Bert L. Lum, Molecular Targets in Oncology: Implications of the Multidrug Resistance Gene Pharmacotherapy. ,vol. 13, pp. 88- 109 ,(1993) , 10.1002/J.1875-9114.1993.TB02695.X
Thomas C. Thomas, Mark G. McNamee, Purification of membrane proteins. Methods in Enzymology. ,vol. 182, pp. 499- 520 ,(1990) , 10.1016/0076-6879(90)82040-9
L A Mickley, S E Bates, N D Richert, S Currier, S Tanaka, F Foss, N Rosen, A T Fojo, Modulation of the expression of a multidrug resistance gene (mdr-1/P-glycoprotein) by differentiating agents Journal of Biological Chemistry. ,vol. 264, pp. 18031- 18040 ,(1989) , 10.1016/S0021-9258(19)84675-6
B I Sikic, Modulation of multidrug resistance: at the threshold. Journal of Clinical Oncology. ,vol. 11, pp. 1629- 1635 ,(1993) , 10.1200/JCO.1993.11.9.1629
T P Miller, T M Grogan, W S Dalton, C M Spier, R J Scheper, S E Salmon, P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. Journal of Clinical Oncology. ,vol. 9, pp. 17- 24 ,(1991) , 10.1200/JCO.1991.9.1.17
W H Wilson, G Bryant, S Bates, A Fojo, R E Wittes, S M Steinberg, D R Kohler, E S Jaffe, J Herdt, B D Cheson, EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. Journal of Clinical Oncology. ,vol. 11, pp. 1573- 1582 ,(1993) , 10.1200/JCO.1993.11.8.1573
Y. Mizuno, T. Hara, M. Nagata, A. Tawa, T. Tsuruo, K. Ueda, Detection of multidrug-resistant protein, P-glycoprotein in childhood leukaemia and lymphoma. European Journal of Pediatrics. ,vol. 150, pp. 416- 418 ,(1991) , 10.1007/BF02093722