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. 1985 Apr;51(4):525–532. doi: 10.1038/bjc.1985.75

Assay of anti-cancer drugs in tissue culture: relationship of relapse free interval (RFI) and in vitro chemosensitivity in patients with malignant cerebral glioma.

D G Thomas, J L Darling, E A Paul, T J Mott, J N Godlee, J S Tobias, L G Capra, C D Collins, C Mooney, T Bozek, et al.
PMCID: PMC1977138  PMID: 3978031

Abstract

One hundred and seventeen patients with cerebral glioma (Kernohan grades III and IV) were treated with adjuvant chemotherapy using procarbazine (PCB), CCNU and vincristine (VCR) following whole head irradiation. Cell cultures were prepared from 40 patients in this series and their sensitivity to each cytotoxic drug was assessed in a mictotitration assay with 35 S-methionine incorporation as the end point. Twenty-two of forty (55%) patients responded to PCB and/or CCNU in vitro, and sensitivity to these drugs was linked with increased RFI, whilst sensitivity to VCR was not. The RFI of patients who had responded to PCB or CCNU in vitro was significantly longer than the RFI of patients whose tumours failed to respond in vitro or patients who had not been tested. There was no difference in sex ratio, extent of operation, radiation dose and degree of steroid cover between responders, non-responders and untested groups. Grade III tumours tended to be more sensitive in vitro than grade IV tumours. The age of patients also influenced in vitro chemosensitivity. Patients with chemosensitive tumours in vitro tended to be younger than patients with insensitive tumours in vitro. Further statistical analysis, taking into account these prognostic factors, indicated an association between chemosensitivity in vitro and RFI.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berranco S. C., Drewinko B., Humphrey R. M. Differential response by human melanoma cells to 1,3-bis-(2-chloroethyl)-1-nitrosourea and bleomycin. Mutat Res. 1973 Aug;19(2):277–280. doi: 10.1016/0027-5107(73)90089-4. [DOI] [PubMed] [Google Scholar]
  2. Bigner S. H., Bullard D. E., Pegram C. N., Wikstrand C. J., Bigner D. D. Relationship of in vitro morphologic and growth characteristics of established human glioma-derived cell lines to their tumorigenicity in athymic nude mice. J Neuropathol Exp Neurol. 1981 Jul;40(4):390–409. doi: 10.1097/00005072-198107000-00004. [DOI] [PubMed] [Google Scholar]
  3. Bloom H. J. Intracranial tumors: response and resistance to therapeutic endeavors, 1970-1980. Int J Radiat Oncol Biol Phys. 1982 Jul;8(7):1083–1113. doi: 10.1016/0360-3016(82)90056-6. [DOI] [PubMed] [Google Scholar]
  4. Bradley N. J., Bloom H. J., Davies A. J., Swift S. M. Growth of human gliomas in immune-deficient mice: a possible model for pre-clinical therapy studies. Br J Cancer. 1978 Aug;38(2):263–272. doi: 10.1038/bjc.1978.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bullard D. E., Bigner S. H., Bigner D. D. The morphologic response of cell lines derived from human gliomas to dibutyryl adenosine 3':5'-cyclic monophosphate. J Neuropathol Exp Neurol. 1981 May;40(3):230–246. doi: 10.1097/00005072-198105000-00002. [DOI] [PubMed] [Google Scholar]
  6. Bullard D. E., Schold S. C., Jr, Bigner S. H., Bigner D. D. Growth and chemotherapeutic response in athymic mice of tumors arising from human glioma-derived cell lines. J Neuropathol Exp Neurol. 1981 Jul;40(4):410–427. doi: 10.1097/00005072-198107000-00005. [DOI] [PubMed] [Google Scholar]
  7. Crafts D. C., Levin V. A., Edwards M. S., Pischer T. L., Wilson C. B. Chemotherapy of recurrent medulloblastoma with combined procarbazine, CCNU, and vincristine. J Neurosurg. 1978 Oct;49(4):589–592. doi: 10.3171/jns.1978.49.4.0589. [DOI] [PubMed] [Google Scholar]
  8. Durie B. G., Young L. A., Salmon S. E. Human myeloma in vitro colony growth: interrelationships between drug sensitivity, cell kinetics, and patient survival duration. Blood. 1983 May;61(5):929–934. [PubMed] [Google Scholar]
  9. Edwards M. S., Levin V. A., Wilson C. B. Brain tumor chemotherapy: an evaluation of agents in current use for phase II and III trials. Cancer Treat Rep. 1980;64(12):1179–1205. [PubMed] [Google Scholar]
  10. Freshney R. I., Paul J., Kane I. M. Assay of anti-cancer drugs in tissue culture: conditions affecting their ability to incorporate 3H-leucine after drug treatment. Br J Cancer. 1975 Jan;31(1):89–99. doi: 10.1038/bjc.1975.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gazsó L. R., Afra D. Study on the effect of actinomycins in tissue cultures from human brain tumours. Acta Neurochir (Wien) 1969;21(2):139–151. doi: 10.1007/BF01540921. [DOI] [PubMed] [Google Scholar]
  12. Kimball P. M., Brattain M. G. Isolation of a cellular subpopulation from a human colonic carcinoma cell line. Cancer Res. 1980 May;40(5):1574–1579. [PubMed] [Google Scholar]
  13. Kornblith P. L., Smith B. H., Leonard L. A. Response of cultured human brain tumors to nitrosoureas: correlation with clinical data. Cancer. 1981 Jan 15;47(2):255–265. doi: 10.1002/1097-0142(19810115)47:2<255::aid-cncr2820470209>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  14. Kornblith P. L., Szypko P. E. Variations in response of human brain tumors to BCNU in vitro. J Neurosurg. 1978 Apr;48(4):580–586. doi: 10.3171/jns.1978.48.4.0580. [DOI] [PubMed] [Google Scholar]
  15. Levin V. A., Crafts D. C., Norman D. M., Hoffer P. B., Spire J. P., Wilson C. B. Criteria for evaluating patients undergoing chemotherapy for malignant brain tumors. J Neurosurg. 1977 Sep;47(3):329–335. doi: 10.3171/jns.1977.47.3.0329. [DOI] [PubMed] [Google Scholar]
  16. Levin V. A., Edwards M. S., Wright D. C., Seager M. L., Schimberg T. P., Townsend J. J., Wilson C. B. Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors. Cancer Treat Rep. 1980 Feb-Mar;64(2-3):237–244. [PubMed] [Google Scholar]
  17. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966 Mar;50(3):163–170. [PubMed] [Google Scholar]
  18. Mealey J., Jr, Chen T. T., Shupe R. Response of cultured human glioblastomas to radiation and BCNU chemotherapy. J Neurosurg. 1974 Sep;41(3):339–349. doi: 10.3171/jns.1974.41.3.0339. [DOI] [PubMed] [Google Scholar]
  19. Morgan D., Freshney R. I., Darling J. L., Thomas D. G., Celik F. Assay of anticancer drugs in tissue culture: cell cultures of biopsies from human astrocytoma. Br J Cancer. 1983 Feb;47(2):205–214. doi: 10.1038/bjc.1983.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rosenblum M. L., Gerosa M. A., Wilson C. B., Barger G. R., Pertuiset B. F., de Tribolet N., Dougherty D. V. Stem cell studies of human malignant brain tumors. Part 1: Development of the stem cell assay and its potential. J Neurosurg. 1983 Feb;58(2):170–176. doi: 10.3171/jns.1983.58.2.0170. [DOI] [PubMed] [Google Scholar]
  21. Rosenblum M. L., Gerosa M., Dougherty D. V., Reese C., Barger G. R., Davis R. L., Levin V. A., Wilson C. B. Age-related chemosensitivity of stem cells from human malignant brain tumours. Lancet. 1982 Apr 17;1(8277):885–887. doi: 10.1016/s0140-6736(82)92154-7. [DOI] [PubMed] [Google Scholar]
  22. Rosenblum M. L., Knebel K. D., Vasquez D. A., Wilson C. B. In vivo clonogenic tumor cell kinetics following 1,3-bis(2-chloroethyl)-1-nitrosourea brain tumor therapy. Cancer Res. 1976 Oct;36(10):3718–3725. [PubMed] [Google Scholar]
  23. Rosenblum M. L., Vasquez D. A., Hoshino T., Wilson C. B. Development of a clonogenic cell assay for human brain tumors. Cancer. 1978 Jun;41(6):2305–2314. doi: 10.1002/1097-0142(197806)41:6<2305::aid-cncr2820410632>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  24. Saez R. J., Campbell R. J., Laws E. R., Jr Chemotherapeutic trials on human malignant astrocytomas in organ culture. J Neurosurg. 1977 Mar;46(3):320–327. doi: 10.3171/jns.1977.46.3.0320. [DOI] [PubMed] [Google Scholar]
  25. Shapiro J. R., Yung W. K., Shapiro W. R. Isolation, karyotype, and clonal growth of heterogeneous subpopulations of human malignant gliomas. Cancer Res. 1981 Jun;41(6):2349–2359. [PubMed] [Google Scholar]
  26. Shapiro W. R., Basler G. A., Chernik N. L., Posner J. B. Human brain tumor transplantation into nude mice. J Natl Cancer Inst. 1979 Mar;62(3):447–453. doi: 10.1093/jnci/62.3.447. [DOI] [PubMed] [Google Scholar]
  27. Shapiro W. R., Young D. F. Chemotherapy of malignant glioma with CCNU alone and CCNU combined with vincristine sulfate and procarbazine hydrochloride. Trans Am Neurol Assoc. 1976;101:217–220. [PubMed] [Google Scholar]
  28. Walker M. D., Gehan E. A. Clinical studies in malignant gliomas and their treatment with the nitrosoureas. Cancer Treat Rep. 1976 Jun;60(6):713–716. [PubMed] [Google Scholar]
  29. Yung W. K., Shapiro J. R., Shapiro W. R. Heterogeneous chemosensitivities of subpopulations of human glioma cells in culture. Cancer Res. 1982 Mar;42(3):992–998. [PubMed] [Google Scholar]

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