Summary
Samples of 38 human renal cell carcinomas (RCC) were subjected to routine histopathological examination but also to in vitro sensitivity testing with mitomycin C, vinblastine and interferon Alpha-2a at various concentrations corresponding to serum titers recommended to be effective in vivo, employing a monolayer assay. Extending earlier in vitro studies, both tumor cell kill rates (TCKR) and proliferation rates (PR) were assessed. Following in vitro preparation the tumor cell cultures were simultaneously exposed to the anticancer drugs listed above. The proliferation rates were determined immunocytochemically using the monoclonal antibody Ki-67. Nine (23.7%) of the tumors investigated revealed temporary and limited response with respect to either TCKR or PR. Improvement of this percentage could only be obtained by increasing drug concentration to titers with toxicity intolerable for in vivo administration. The in vivo data presented correspond to clinical temporary and limited remissions in patients with metastatic RCC ranging up to 25%.
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References
Albrecht M, Simon WE, Hölzel F (1985) Individual chemosensitivity of in vitro proliferation mammary and ovarian carcinoma cells in comparison to clinical results of chemotherapy. J Cancer Res Clin Oncol 109:210
Bergerat JP, Herbrecht R, Dufour P, Jacqmin D, Bollack C, Prevot G, Bailly G, de Garis S (1988) Combination of recombinant interferon alpha-2a and vinblastine in advanced renal cell cancer. Cancer 62:2320
Buzaid AC, Todd MB (1989) Therapeutic options in renal cell carcinoma. Semin Oncol 16:12
Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, MacDonald S (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexe of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219
Davis WH (1989) Study of recombinant interferon in advanced renal cell carcinoma. J Urol 141:140
Fossa SD (1988) Interferon with or without vinblastine in treatment of metastatic renal cell carcinoma. Semin Surg Oncol 4:178
Gerdes J (1985) An immunochistological method for estimating cell growth fractions in rapid histopathological diagnosis during surgery. Int J Cancer 35:169
Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13
Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710
Gutterman JU, Fine S, Quesada JR (1982) Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance and biologic effects in cancer patients. Ann Intern Med 96:549
Hamburger AW, Salmon SE (1977) Primary bioassay of human stem cells. Science 197:461
Hanauske AR, von Hoff DD (1985) Clinical correlations with the human tumor cloning assay. Cancer Invest 3:541
Harris DT (1983) Hormonal therapy and chemotherapy of renal cell carcinoma. Semin Oncol 10:422
Hrushesky WJ, Murphy GP (1977) Current status of the therapy of advanced renal carcinoma. J Surg Oncol 9:277
de Kernion JB (1986) Renal tumors. In: Walsh PC, Gittes AD, Perlmutter AD, Stamey TA (eds) Campbell's urology. Saunders, Philadelphia, p 1319
Kovacs G, Szücs S, de Riese W, Baumgärtel H (1987) Specific chromosome aberration in human renal cell carcinoma. Int J Cancer 40:171
Leder LD, Richter HJ (1987) Renal and adrenal tumors. In: Loehr E, Leder LD (eds). Pathology of renal neoplasms. Springer, Berlin Heidelberg New York, p 15
Lieber MM (1984) Soft agar colony formation assay for in-vitro chemotherapy sensitivity testing of human renal cell carcinoma. J Urol 131:391
de Mulder PHM, Geboers ADH, Debruyne FMJ (1988) Recombinant interferons alfa and gamma in patients with metastatic renal cell carcinoma (RCC). Proc Am Soc Clin Oncol 7:126
Muss HB (1988) Interferon therapy of metastatic renal cell cancer. Sem Surg Oncol 4:199
Oliver RT (1987) Unexplained spontaneous regression and its relevance to the clinical behaviour of renal cell carcinoma and its response to interferon. Proc Ann Meet Am Soc Clin Oncol 6:383
de Riese W, Allhoff E, Pohl U, Lenis G, Liedke S, Atay Z, Jonas U, Warnaar SO (1989)Comparison of human normal renal cells and malignant renal cells (RCC) in vivo and in vitro using cytological cytochemical and immunocytochemical methods. Invest Urol 3:8
de Riese W, Szücs S, Hoene E, Lenis G, Kovacs G (1987) Shortterm in-vitro sensitivity testing of human renal cell carcinoma. Invest Urol 2:81
Rinehart J, Young D, La Forge J (1987) Trial of interferon in patients with metastatic renal cell carcinoma: immunological and biological effects. Cancer Res 47:2481
Von Hoff DD (1987) In vitro predictive testing. Int J Cell Cloning 5:179
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de Riese, W., Allhoff, E., Stief, C.G. et al. In vitro sensitivity testing of human renal cell carcinoma with cytostatic agents and interferon alpha-2a. Urol Res 19, 87–90 (1991). https://doi.org/10.1007/BF00368182
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DOI: https://doi.org/10.1007/BF00368182