Multidrug resistance in leukemias and its reversal

Leukemia and Lymphoma

Volumn 23, Issue 5-6, 1996, Pages 451-458

  Malayeri, R ^a   Filipits, M ^a   Suchomel, R W ^a   Zochbauer S ^a   Lechner, K ^a   Pirker, R ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Acute leukemia; Clinical trial; MDR1 gene; MRP; Multidrug resistance; P glycoprotein; Resistance modifier; Reversal

Indexed keywords

AMSACRINE; ANTHRACYCLINE DERIVATIVE; DNA TOPOISOMERASE (ATP HYDROLYSING); GLUTATHIONE TRANSFERASE; GLYCOPROTEIN P; MITOXANTRONE;

ACUTE GRANULOCYTIC LEUKEMIA; BLAST CELL CRISIS; CHRONIC MYELOID LEUKEMIA; GENE EXPRESSION; HUMAN; MULTIDRUG RESISTANCE; PRIORITY JOURNAL; REVIEW;

EID: 0030463181     PISSN: 10428194     EISSN: None     Source Type: Journal    
DOI: 10.3109/10428199609054853     Document Type: Review

References (89)

1. Pastan, I. and Gottesman, M. (1987) Multiple-drug resistance in human cancer. New Engl. J. Med., 316, 1388-1393.
2. Simon, S. M and Schindler, M. (1994) Cell biological mechanisms of multidrug resistance in tumors. Proc Natl. Acad. Sci. USA, 91, 3497-3504.
3. Cole, S P. C., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. V., Duncan, A. M. V and Deeley, R. G. (1992) Overexpression of a transporter gene in a multidrug-resistant human cancer cell line. Science, 258, 1650-1654.
4. Scheffer, G. L., Wijngaard, P. L. J., Flens, M. J., Izquierdo, M. A., Slovak, M. L., Pinedo, H. M., Meijer, C. J. L. M., Clevers, H. C. and Scheper, R. J. (1995) The drug resistance-related protein LRP is the human major vault protein. Nature Medicine, 1, 578-582.
5. Tew, K. D. (1994) Glutathione-associated enzymes in anticancer drug resistance. Cancer Res , 54, 4313-4320.
6. Beck, W T. (1989) Unknotting the complexities of multidrug resistance: the involvement of DNA topoisomerases in drug action and resistance. J. Natl. Cancer Inst., 81, 1683-1685.
7. Fojo, A. T., Ueda, K. Slamon, D. J., Poplack, D G., Gottesman, M. M. and Pastan, I. (1987) Expression of a multidrug-resistance gene in human rumors and tissues. Proc Natl. Acad. Sci. USA, 84, 265-269.
8. Goldstein, L. J., Galski, H., Fojo, A., Willingham, M., Lai, S. L , Gazdar, A., Pirker, R., Green, A., Crist, W., Brodeur, G. M., Lieber, M., Cossman, J., Gottesman, M. M. and Pastan, I. (1989) Expression of a multidrug resistance gene m human cancers. J. Natl. Cancer Inst., 81, 116-124.
9. Pirker, R., Wallner, J., Gsur, A , Götzl, M., Zöchbauer, S., Scheithauer, W. and Depisch, D. (1993) MDR1 gene expression in primary colorectal carcinomas. Br. J. Cancer, 68, 691-694.
10. Wallner, J., Depisch, D., Hopfner, M., Haider, K., Spona, J., Ludwig, H. and Pirker, R. (1991) MDR1 gene expression and prognostic factors in primary breast carcinomas. Eur. J. Cancer, 11, 1352-1355.
11. Wallner, J., Depisch, D., Gsur, A., Götzl, M., Haider, K. and Pirker, R. (1993) MDR1 gene expression and its clinical relevance in primary gastric carcinomas. Cancer, 71, 667-671.
12. Baldini, N., Scotlandi, K., Barbanti-Brodano, G., Manara, M. C., Maurici, D., Bacci, G., Bertoni, F., Picci, P , Scottili, S., Campanacci, M. and Serra, M. (1995) Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. New Engl. J. Med. 333, 1380-1385.
13. Hipfner, D. R., Gauldie, S. D., Deeley, R. G. and Cole, S. P. C. (1994) Detection of the Mr 190,000 Multidrug resistance protein, MRP, with monoclonal antibodies. Cancer Res., 54, 5788-5792.
14. Flens, M. J., Izquierdo, M. A., Scheffer, G. L., Fritz, J. M., Meijer, C. J. L. M., Scheper, R. J. and Zaman, G. J. R (1994) Immunochemical detection of the multidrug resistance-associated protein MRP in human multidrug-resistant tumor cells by monoclonal antibodies. Cancer Res., 54, 4557-4563.
15. Nooter, K., Westerman, A. M., Flens, M. J., Zaman, G. J R., Scheper, R. J., van Wingerden, K. E., Burger, H., Oostrum, R., Boersma, T., Sonneveld, P., Gratama, J. W., Kok, T., Eggermont, A. M. M., Bosman, F. and Stoter, G. (1995) Expression of the multidrug-resistance associated protein (MRP) gene in human cancers. Clinical Cancer Res., 1, 1301-1310.
16. Harnada, S., Kamada, M., Furumoto, H , Hirao, T. and Aono, T. (1994) Expression of glutathione S-transferase-π in human ovarian cancer as an indicator of resistance to chemotherapy. Gynecol. Oncol., 52, 313-319.
17. Goerges, E., Bradley, G., Gariepy, J. and Ling, V. (1990) Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies. Proc. Natl. Acad. Sci. USA, 87, 152-156.
18. Herzog, C., Trepel, J., Mickley, L., Bates, S. and Fojo, A (1992) Various methods of analysis of mdr-I/p-glycoprotein in human colon cancer cell lines. J. Natl. Cancer Inst., 84, 711-716.
19. Filipits, M , Suchomel, R W., Dekan, G., Haider, K., Valdimarsson, G. Depisch, D. and Pirker, R. MRP and MDR1 gene expression in primary breast carcinomas. Clin Cancer Res, in press (1996).
20. Charpin, C , Vielh , P , Duffaud, F , Devictor, B., Andrac, L., Lavaut, M., Allasia, C., Horschowski, N. and Piana, L. (1994) Quantitative immunocytochemical assays of P-glycoprotein in breast carcinomas: correlation to messenger RNA expression and to immunohistochemical prognostic indicators J. Natl Cancer Inst., 86, 1539-1546.
21. Marie, J. P., Faussat-Suberville, A. M , Zhou, D. and Zittoun, R. (1993) Daunorubicin uptake by leukemic cells: correlation with treatment outcome and mdr1 expression. Leukemia, 7, 825-831
22. Ludescher, C , Thaler, J., Drach, D., Drach, J , Spitaler, M., Gattringer, C., Huber, H. and Hofmann, J. (1992) Detection of activity of P-glycoprotein in human tumour samples using rhodamine 123. Br. J. Haematol., 82, 161-168.
23. Twentyman, P., Rhodes, T. and Rayner, S. (1994) A comparison of rhodamine 123 accumulation and efflux in cells with P-glycoprotein-mediated and MRP-associated multidrug resistance phenotypes. Eur. J Cancer, 30A, 1360-1369.
24. Kuwazuru, Y., Yoshimura, A., Hanada, S., Utsunomiya, A., Makino, T., Ishibashi, K , Kodama, M., Iwahashi, M., Arima, T. and Akiyama, S. (1990) Expression of the multidrug transporter, P-glycoprotein, in acute leukemia cells and correlation to clinical drug resistance. Cancer, 66, 868-873.
25. Sato, H., Preisler, H , Day, R., Raza, A., Larson, R., Browman, G., Goldberg, J., Vogler, R., Grunwald, H , Gottlieb, A , Bennet, J., Gottesman, M. and Pastan, I. (1990) MDR1 transcript levels as an indication of resistant disease in acute myelogenous leukaemia. Br. J. Haematol., 75, 340-345.
26. Pirker, R., Wallner, J., Geissler, K., Linkesch, W., Haas, O. A., Bettelheim, P., Hopfner, M., Scherrer, R., Valent, P , Havelec, L., Ludwig, H. and Lechner, K. (1991) MDR1 gene expression and treatment outcome in acute myeloid leukemia. J. Natl. Cancer Inst., 83, 708-712
27. Marie, J. P., Zittoun, R. and Sikic, B. I. (1991) Multidrug resistance (mdr1) gene expression in adult acute lekemias: correlations with treatment outcome and in vitro drug sensitivity. Blood, 78, 586-592.
28. Campos, L., Guyotat, D., Archimbaud, E., Calmard-Oriol, P., Tsuruo, T., Troncy, J , Treille, D. and Fiere, D. (1992) Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood, 79, 473-476.
29. te Boekhorst, P. A. W., de Leeuw, K., Schoester, M., Wittebol, S., Nooter, K., Hagemeijer, A., Löwenberg, B. and Sonneveld, P. (1993) Predominance of functional multidrug resistance (MDR-1) phenotype m CD 34+ acute myeloid leukemia cells. Blood, 82, 3157-3162.
30. Hegewisch-Becker, S., Fliegener, M , Tsuruo, T., Zeller, W. and Hossfeld, D. (1993) Multidrug resistance (mdr1) in adult acute leukemia at diagnosis: correlation with response to induction chemotherapy. Onkologie, 16, 264-269.
31. Zöchbauer, S., Gsur, A., Brunner, R , Kyrle, P , Lechner, K. and Pirker, R (1994) P-glycoprotein as unfavorable prognostic factor in acute myeloid leukemia. Leukemia, 6, 974-977.
32. Wood, P., MacGregor, B. A. and Liu Yin, J. A. (1994) P-glycoprotein expression on acute myeloid leukaemia blast cells at diagnosis predicts response to chemotherapy and survival Br. J. Haematol., 87, 509-514.
33. Guerci, A., Merlin, J. L., Missoum, N , Feldmann, L., Marchal, S., Witz, F., Rose, C. and Guerci, O. (1995) Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry. Blood, 85, 2147-2153.
34. Gruber, A., Vitols, S., Norgren, S., Arestrom, I., Peterson, C., Björkholm, M., Reizenstein, P. and Luthman, H. (1992) Quantitative determination of mdr1 gene expression in leukemic cells from patients with acute leukemia. Br. J. Cancer, 66, 266-272.
35. Hart, S. M., Ganeshaguru, K., Lyttelton, M. P. A., Prentice, H G., Hoffbrand, A. V. and Mehta, A. B (1993) Flow cytometric assessment of multidrug resistance (MDR) phenotype in acute myeloid leukaemia. Leuk Lymph , 11, 239-248.
36. Zöchbauer, S., Haas, O. A., Schwarzinger, I., Lechner, K. and Pirker, R. (1994) Multidrug resistance in acute myeloid leukaemia with inversion in chromosome 16 or FAB M4Eo subtype. Lancet, 344, 894.
37. Ludescher, C., Eisterer, W., Hilbe, W., Gotwald, W., Hofmann, J., Zabernigg, A., Cianfriglia, M and Thaler, J. (1995) Low frequency of activity of P-glycoprotein (P-170) in acute lymphoblastic leukemia compared to acute myeloid leukemia. Leukemia, 9, 350-356.
38. Holmes, J., Jacobs, A., Carter, G., Janowska-Wieczorek, A. and Padua, R. A. (1989) Multidrug resistance in haemapoietic cell lines, myelodysplastic syndromes and acute myeloblastic leukaemia. Br. J Haematol., 72, 40-44.
39. Musto, P., Melillo, L., Lombardi, G., Matera, R., Di Giorgio, G., and Carotenuto, M. (1991) High risk of early relapse for leukaemic patients with presence of multidrug resistance associated P-glycoprotein positive cells in complete remission. Br. J. Haematol., 77, 50-53
40. Drach, D., Zhao, S., Drach, J. and Andreeff, M. (1995) Low incidence of MDR1 expression in acute promyelocytic leukaemia Br. J. Haematol., 90, 369-374.
41. Holmes, J. A. and West, R. R. (1994) The effect of MDR-1 gene expression on outcome in acute myeloid leukemia. Br. J. Cancer, 69, 382-384.
42. List, A. F. and Spier, C. M. (1992) Multidrug resistance in acute leukemia: a conserved physiologic function. Leuk. Lymph., 8, 9-14.
43. Lamy, T., Goasguen, J. E., Mordelet, E., Grulois, I., Dauriac, C., Drenou, B., Chaperon, J., Fauchet, R. and le Prise, P. Y. (1994) P-glycoprotein (P-170) and CD34 expression in adult acute myeloid leukemia (AML). Leukemia, 8, 1879-1883.
44. Rothenberg, M. L., Mickley, L. A., Cole, D. E., Balis, F. M , Tsuruo, T., Poplack, D. G. and Fojo, A. T. (1989) Expression of the mdr-1/P-170 gene in patients with acute lymphoblastic leukemia. Blood, 74, 1388-1395.
45. Kuwazuru, Y., Hanada, S., Furukawa, T., Yoshimura, A., Sumizawa, T. Utsunomiya, A., Ishibashi, K., Saito, T., Uozumi, K., Maruyama, M., Ishizawa, M., Arima, T. and Akiyama, S. (1990) Expression of P-glycoprotein in adult T-cell leukemia cells. Blood, 76, 2065-2071
46. Goasguen, J. E., Dossot, J.-M., Fardel, O., Le Mee, F., Le Gall, E., Leblay, R., LePrise, P. Y., Chaperon, J. and Fauchet, R. (1993) Expression of the multidrug resistance-associated P-glycoprotein (P-170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implications Blood, 81, 2394-2398.
47. Pirker, R., Goldstein, L., Ludwig, H., Linkesch, W., Lechmer, C., Gottesman, M and Pastan, I. (1989) Expression of a multidrug resistance gene in blast crisis of chronic myelogenous leukemia. Cancer Communications, 1, 141-144.
48. Weide, R., Dowding, C., Paulsen, W. and Goldman, J. (1990) The role of the MDR-1/P-170 mechanism in the development of multidrug resistance in chronic myeloid leukemia. Leukemia, 4, 695-699.
49. Kuwazuru, Y., Yoshimura, A., Hanada, S., Ichikawa, M , Saito, T., Uozumi, K., Utsunomiya, A., Arima, T. and Akiyama, S. (1990) Expression of the multidrug transporter, P-glycoprotein, in chronic myelogenous leukaemia cells in blast crisis. Br. J. Haemat., 74, 24-29
50. Holmes, J., Jacobs, A., Carter, G., Whittaker, J., Bentley, D. and Padua, R. A. (1990) Is the mdr 1 gene relevant in chronic lymphocytic leukemia? Leukemia, 4, 216-218
51. Wallner, J., Gisslinger, H., Gisslinger, B., Gsur, A., Götzl, M., Zöchbauer, S. and Pirker, R. (1994) MDR1 gene expression in chronic lymphocytic leukemia. Leuk. Lymph., 13, 333-338.
52. Sonneveld, P., Nooter, K., Burghouts, J. T. M., Herweijer, H., Adriaansen, H. J. and van Dongen, J. J. M. (1992) High expression of the mdr3 multidrug-resistance gene in advanced-stage chronic lymphocytic leukemia. Blood, 79, 1496-1500.
53. Ludescher, C., Hilbe, W., Eisterer, W., Preuss, E., Huber, C., Gotwald, M., Hofmann, J. and Thaler, J. (1993) Activity of P-glycoprotein in B-cell chronic lymphocytic Ieukemia determined by a flow cytometric assay. J. Natl. Cancer Inst., 85, 1751-1758
54. El Rouby, S., Thomas, A., Costin, D., Rosenberg, C. R., Potmesil, M., Silber, R. and Newcomb, E. W. (1993) P53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression. Blood, 82, 3452-3459.
55. Zochbauer, S., Gsur, A., Götzl, M., Wallner, J., Lechner, K. and Pirker, R. (1994) MDR1 gene expression in myelodysplastic syndrome and in acute myeloid leukemia evolving from myelodysplastic syndrome. Anticancer Res., 14, 1293-1296.
56. Burger, H., Nooter, K., Zaman, G. J. R., Sonneveld, P., van Wingerden, K. E., Oestrum, R G. and Stoter, G. (1994) Expression of the multidrug resistance-associated protein (MRP) in acute and chronic leukemias Leukemia, 8, 990-997.
57. Zhou, D. C., Zittoun, R. and Marie, J. P. (1995) Expression of multidrug resistance-associated protein (MRP) and multidrug resistance (MDR1) genes in acute myeloid leukemia. Leukemia, 9, 1661-1665.
58. Schneider, E., Cowan, K. H., Bader, H., Toomey, S., Schwartz, G. N., Karp, J. E., Burke, P. J. and Kaufmann, S. H. (1995) Increased expression of the multidrug resistance-associated protein gene in relapsed acute leukemia. Blood, 85, 186-193.
59. Hart, S. M., Ganeshaguru, K., Hoffbrand, A. V., Prentice, H. G. and Mehta, A. B. (1994) Expression of the multidrug resistance-associated protein (MRP) in acute leukemia. Leukemia, 8, 2163-2168.
60. Kuss, B. J., Deeley, R. G., Cole, S. P. C., Willman, C. L., Kopecky, K. J., Wolman, S. R., Eyre, H. J., Lane, S. A., Nancarrow, J. K., Whitmore, S. A and Callen, D F. (1994) Deletion of gene for multidrug resistance in acute myeloid leukemia with inversion in chromosome 16: prognostic implications. Lancet, 343, 1531-1534.
61. List, A F., Spier, C. S., Abbaszadegan, M., Grogan, T. M., Greer, J. P., Wolff, S. N., Scheper, R. J. and Dalton, W. S. (1993) Non-P-glycoprotein (PGP) mediated multidrug resistance (MDR): Identification of a novel drug resistance phenotype with prognostic relevance in acute myeloid leukemia (AML). Blood, 83, Suppl. 1, 443a.
62. Tiirikainen, M. I., Elonen, E., Syrjälä, M. T., Jansson, S.-E. and Krusius, T. (1994) Flow cytometric analysis of glutathione-S-transferase-π in acute leukemia. Leukemia, 8, 978-984.
63. Tidefelt, U., Elmhorn-Rosenborg, A., Paul, C., Hao, X.-Y., Mannervik, B. and Eriksson, L. C. (1992) Expression of glutathione transferase π as a predictor for treatment results at different stages of acute nonlymphoblastic leukemia. Cancer Res., 52, 3281-3285.
64. McKenna, S. L., West, R. R., Whittaker, J. A., Padua, R. A. and Holmes, J. A. (1994) Topoisomerase II α expression in acute myeloid leukemia and its relationship to clinical outcome. Leukemia, 8, 1498-1502.
65. Kaufmann, S. H., Karp, J. E., Jones, R. J., Miller, C. B., Schneider, E., Zwelling, L. A., Cowan, K., Wendel, K. and Burke, P. J. (1994) Topoisomerase II levels and drug sensitivity in adult acute myelogenous leukemia. Blood, 83, 517-530.
66. Sela, S., Husain, S. R., Pearson, J. R., Longo, D. L. and Rahman, A. (1995) Reversal of multidrug resistance in human colon cancer cells expressing the human MDR1 gene by liposomes in combination with monoclonal antibody or verapamil. J. Natl. Cancer Inst., 87, 123-128.
67. Petrini, M., Mattii, L., Valentini, P., Sabbatini, A. R., Grassi, B. and Grandi, M. (1993) Idarubicin is active on MDR cells: evaluation of DNA synthesis inhibition on P388 cell lines. Annals Haematol., 67, 227-230.
68. Michieli, M., Damiani, D., Michellutti, A., Candoni, A., Masolini, P., Scaggiante, B., Quadrifoglio, F. and Baccarani, M. (1994) Restoring uptake and retention of daunorubicin and idarubicin in P170-related multidrug resistance cells by low concentration D-verapamil, cyclosporine A and SDZ PSC 833. Haematologica, 79, 500-507.
69. Tsuruo, T , Iida, H., Tsukagoshi, S. and Sakurai, Y. (1981) Overcoming of vincristine resistance in p388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res., 41, 1967-1972.
70. Stewart, D. and Evans, W. (1989) Non-chemotherapeutic agents that potentiate chemotherapy efficacy. Cancer Treatment Rev., 16, 1-40.
71. Müller, M. R., Lennartz, K., Boogen, C., Nowrousian, M. R., Rajewsky, M. F. and Seeber, S. (1992) Cytotoxicity of adriamycin, idarubicin and vincristine in acute myeloid leukemia: chemosensitization by verapamil in relation to P-glycoprotein expression. Annals Hematol , 65, 206-212.
72. Ross, D. D., Wooten, P. J., Sidhara, R., Ordonez, J. V., Lee, E. J. and Schiffer, C. A. (1993) Enhancement of daunorubicin accumulation, retention and cytotoxicity by verapamil or cyclosporin A in blast cells from patients with previously untreated acute myeloid leukemia. Blood, 82, 1288-1299
73. - cases. Blood, 86, 2329-2342.
74. Pirker, R., Keilhauer, G., Raschack, M., Lechner, C. and Ludwig, H. (1989) Reversal of multi-drug resistance in human KB cell lines by structural analogs of verapamil. Int. J. Cancer, 45, 916-919.
75. Pirker, R., Zöchbauer, S., Kupper, H., Lassmann, A., Gsur, A., Frass, M., Krajnik, G., Knobl, P. and Lechner, K. Dexverapamil as resistance modifier in acute myeloid leukemia. In: Drug resistance in leukemia and lymphoma, edited by R. Pieters. London: Harwood Academic Publishers, 1996 in press.
76. Twentyman, P. R. and Bleehen, N M (1991) Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporine A. Eur. J. Cancer, 27, 1639-1642.
77. Jiang, X.-R., Kelsey, S. M., Wu, Y.-L. and Newland, A. C. (1995) Circumvention of P-glycoprotein-mediated drug resistance in human leukaemic cells by non-immunosuppressive cyclosporin D analogue, SDZ PSC 833. Br. J. Haematol., 90, 375-383.
78. Lum, B. L., Kaubisch, S., Yahanda, A. M., Adler, K. M., Jew, L., Ehsan, M. N., Brophy, N. A., Halsey, J., Gosland, M. P. and Sikic, B. I. (1992) Alteration of etoposide pharmatokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J. Clin. Oncol., 10, 1635-1642.
79. Yahanda, A. M , Adler, K. M., Fisher, G. A., Brophy, N. A., Halsey, J., Hardy, R. L. Gosland, M. P., Lum, B. L. and Sikic, B. I. (1992) Phase I trial of etoposide with cyclosporine as a modulator of multidrug resistance. J. Clin. Oncol., 10, 1624-1634.
80. List, A. F., Spier, C., Greer, J., Wolff, S., Hutter, J., Dorr, R., Salmon, S., Futscher, B., Baier, M. and Dalton, W. (1993) Phase I/II trial of cyclosporine as a chemotherapy resistance modifier in acute leukemia. J. Clin. Oncol., 11, 1652-1660.
81. Sonneveld, P., Durie, B. G. M., Lockhorst, H. M., Marie, J. P., Solbu, G., Suciu, S., Zittoun, R., Löwenberg, B. and Nooter, K. (1992) Modulation of multidrug-resistant multiple myeloma by cyclosporine. Lancet, 340, 255-259.
82. Miller, T. P., Grogan, T M., Dalton, W. S., Spier, C. M., Scheper, R. J. and Salmon, S. E. (1991) P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. J. Clin. Oncol., 9, 17-24.
83. Ozols, R. F., Cunnion, R. E., Klecker, Jr., R. E., Hamilton, T. C., Ostchega, Y., Parillo, J E. and Young, R. C. (1987) Verapamil and adriamycin in the treatment of drug resistant ovarian cancer patients. J. Clin. Oncol., 5, 641.
84. Rodenburg, C. J., Nooter, K., Herweijer, H., Seynaeve, C., Oosterum, R., Stoter, G and Verweij, J. (1991) Phase II study of combining vinblastine and cyclosporine-A to circumvent multidrug resistance in renal cell cancer. Annals Oncol., 2, 305-306.
85. Lehnert, M , Dalton, W. S., Roe, D., Emerson, S. and Salmon, S. E. (1991) Synergistic inhibition by verapamil and quinine of P-glycoprotein-mediated multidrug resistance in human myeloma cell lines. Blood, 77, 348-354.
86. Lehnert, M., Emerson, S., Kunke, K., Dalton, W. S. and Salmon, S. E. (1991) Combined chemosensitization for reversing MDR-1: Synergism of verapamil and quinine but antagonism with quinidine. Proc. Am. Assoc. Cancer Res., 32, 2244.
87. Lehnert, M. (1994) Reversal of P-glycoprotein-associated multidrug resistance: From bench to bedside. Onkologie, 17, 8-15.
88. Lum, B. L., Fisher, G. A., Brophy, N. A., Yahanda, A. M., Adler, K. M., Kaubisch, S., Halsey, J and Sikic, B. I. (1993) Clinical trials of modulation of multidrug resistance Cancer, 72, 3502-3504.
89. Marie, J. P., Bastie, J., Coloma, F., Faussat Suberville, A., Delmer, A., Rio, B., Delmas-Marsalet, B., Leroux, G., Casassus, P., Baumelou, E., Catalin, J and Zittoun, R. (1993) Cyclosporine A as a modifier agent in the salvage treatment of acute leukemia. Leukemia, 7, 821-824