Summary
In this study we assessed the influence of patient- and drug-specific parameters in the short-term MTT-chemosensitivity assay in 150 primary cell cultures derived from human brain tumors. In 45 patients the MTT assay was directly compared with the CFA (Colony Forming Assay). Resistance was 10–20% higher in the MTT assay than in the CFA, but there was a good agreement in both assays, that more malignant gliomas had a higher in vitro chemosensitivity against ACNU and BCNU. Overall the results demonstrate, that there is no uniform correlation between the in vitro chemosensitivity and the histopathological classification of the tumors, which corresponds well to the clinical situation. On the basis of this study we suggest prospective clinical trials with the MTT assay in human brain tumors.
Parts of this paper have been presented at the 63th annual meeting of the ‘Deutsche Gesellschaft für Neurologie’, September 13–15, 1990, in Darmstadt, Germany
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Nazzaro JM, Neuwelt EA: The role of surgery in the management of supratentorial intermediate and high-grade astrocytomas in adults. J Neurosurg 73: 331–344, 1990
Neuwelt EA, Nazzaro JM, Gumerlock MK: Is there a role for biopsy in the treatment of supratentorial high-grade glioma? Clin Neurosurg 36: 384–407, 1990
North CA, North RB, Epstein JA, Piantadosi S, Wharam MD: Low-grade cerebral astrocytomas. Cancer 66: 6–14, 1990
Marchese MJ, Chang CH: Malignant astrocytic gliomas in children. Cancer 65: 2771–2778, 1990
Schiffer D, Chiò A, Giordana MT, Leone M, Soffietti R: Prognostic value of histologic factors in adult cerebral astrocytoma. Cancer 61: 1386–1393, 1988
Kornblith PL, Walker M: Chemotherapy for malignant gliomas. J Neurosurg 68: 1–17, 1988
Paoletti P, Butti G, Knerich R, Gaetani P, Assietti R: Chemotherapy for malignant gliomas of the brain: a review of ten-years experience. Acta Neurochir (Wien) 103: 35–46, 1990
Stewart DJ: The role of chemotherapy in the treatment of gliomas in adults. Cancer Treat Rev 16: 129–160, 1989
Kimmel DW, Shapiro JR, Shapiro WR: In vitro drug sensitivity testing in human gliomas. J Neurosurg 66: 161–171, 1987
Yung WKA: In vitro chemosensitivity testing and its clinical application in human gliomas. Neurosurg Rev 12: 197–203, 1989
Nikkhah G, Darling JL, Thomas DGT: The application of the MTT chemosensitivity assay to short-term cell lines derived from gliomas: characterization and comparison with a 35 S-methionine uptake assay. Reg Cancer Treat 2: 112–118, 1989
Nikkhah G, Tonn JC, Hoffmann O, Kraemer HP, Darling JL, Schönmayr R, Schachenmayr W: The MTT assay for chemosensitivity testing of human tumors of the central nervous system. Part I: Evaluation of test variables* specific variables. J Neurooncol 13: 297–307, 1990
Tonn JC, Schönmayr R, Braun R, Seuffer R: Plasma levels of ACNU in humans and tissue concentrations in the rat brain. J Chemotherapy 1: 1183–1184, 1989
Yoshida J, Shibuya N, Kobayashi T, Kageyama N: Sensitivity to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2 chloroethyl)-3-nitrosourea hydro-chloride (ACNU) of glioma cells in vivo and in vitro. Cancer 50: 410–418, 1982
Bogdahn U: Chemosensitivity of malignant human brain tumors. J Neurooncol 1: 149–166, 1983
Kornblith PL, Smith BH, Leonard LA: Response of cultured human brain tumors to nitrosoureas. Cancer 47: 255–265, 1981
Tonn JC, Schönmayr R, Kraemer H-P: Sensitivity of human malignant intracranial tumors against MCNU in vitro in comparison to ACNU and BCNU. J Neurooncol 8: 41–45, 1990
Chinoin: DIAL DAG. Drugs of the future 9 (No 6): 466–469, 1984
Chinoin: DIAC DAG. Drug of the future 10 (No 6): 504–505, 1985
Tonn JC, Schönmayr R, Aigner KR, Kraemer H-P: Mitomycin C-Gewebespiegelmessung in einer zerebralen Karzinommetastase. Tumor Diagnostik & Therapie 2: 60–63, 1989
Stewart DJ, Green RM, Mikhael NZ, Monpetit V, Thibault M, Maroun JA: Human autopsy tissue concentrations of mitoxantrone. Cancer Treat Rep 70: 1255–1261, 1986
Tonn JC, Schönmayr R, Braun R, Kraemer HP, Ehninger G: Brain tissue concentration of mitoxantrone in the rat in relation to in vitro chemosensitivity of malignant human intracranial tumors — preliminary results. J Chemother 1: 1181–1182,. 1989
Hamburger AW, Salmon SE: Primary bioassay of human tumor stem cells. Science 192: 461–463, 1977
Salmon SE, Hamburger AW, Soehnlen B, Durie BGM, Alberts DS, Moon TE: Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. N Engl J Med 298: 1321–1327, 1978
Bertelsen CA, Sondak VK, Mann BD, Korn EL, Kern DH: Chemosensitivity testing of human solid tumors. Cancer 53:1240–1245, 1984
Moon TE: Quantitative and statistical analysis of the association between in vitro and in vivo studies. In: Salmon SE, Soehnlen BJ, Young L, Chen H-SG, Moon TE (eds) Cloning of human tumor stem cells. Alan R Liss, New York, 1980, pp 209–221
Moon TE, Salmon SE, White CS, Chen H-SG, Meyskens FL, Durie BGM, Alberts DS: Quantitative association between the in vitro human tumor stem cell assay and clinical response to cancer chemotherapy. Cancer Chemother Pharmacol 6: 211–218, 1981
Harms V: Biomathematik, Statistik und Dokumentation. Harms Verlag, Kiel, 1988, pp 158–187
Bowles AP, Pamazis CG, Wansley W: Use of verapamil to enhance the antiproliferative activity of BCNU in human glioma cells: an in vitro and in vivo study. J Neurosurg 73: 248–253, 1990
Couldwell WT, Antel JP, Apuzzo MLJ, Yong VW: Inhibition of growth of established human glioma cell lines by modulators of the protein kinase-C system. J Neurosurg 73: 594–600, 1990
Sargent JM, Taylor CG: Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia. Br J Cancer 60: 206–210, 1989
Wilson JK, Sargent JM, Elgie AW, Hill JG, Taylor CG: A feasibility study of the MTT assay for chemosensitivity testing in ovarian malignancy. Br J Cancer 62: 189–194, 1990
Roosen N, Kiwit JCW, Lins E, Schirmer M, Bock WJ: Adjuvant intraarterial chemotherapy with nimustine in the management of world health organization grade IV gliomas of the brain. Cancer 64: 1984–1994, 1989
Yung WKA, Shapiro JR, Shapiro WR: Heterogeneous chemosensitivities of subpopulations of human glioma cells in culture. Cancer Res 42: 992–998, 1982
Weisenthal LM, Lippman ME: Clonogenic and nonclonogenic in vitro chemosensitivity assays. Cancer Treat Rep 69 (No 6): 615–632, 1985
Green RM, Stewart DJ, Hugenholtz H, Richard MT, Thibault M, Montpetit V: Human central nervous system and plasma pharmacology of mitoxantrone. J Neurooncol 6: 75–83, 1988
Stewart DJ, Hugenholtz H, Green R, Richard M, Benoit B, Russell N, Maroun J, Thibault M: Mitoxantrone hydrochloride: Uptake into human brain tumors and phase II study in gliomas. J Neurooncol 4 (abstract): 114, 1986
Woodman RJ: NSC-132313. Drugs of the future 3 (No 6): 459–461, 1978
Levin VA, Wheeler KT: Chemotherapeutic approaches to brain tumors. Cancer Chemother Pharmacol 8: 125–131, 1982
Thomas DGT, Darling JL, Paul EA, Mott TJ, Godlee JN, Tobias JS, Capra LG, Collins CD, Mooney C, Bozek T, Finn GP, Arigbabu SO, Bullard DE, Shannon N, Freshney RI: Assay of anti-cancer drugs in tissue culture: Relationship of relapse free interval (RFI) and in vitro chemosensitivity in patients with malignant cerebral glioma. Br J Cancer 51: 525–532, 1985
Shapiro JR, Shapiro WR: The subpopulations and isolated cell types of freshly resected high grade human gliomas: Their influence on the tumor's evolution in vivo and behavior and therapy in vitro. Cancer Met Reviews 4: 107–124, 1985
Watts ME, Roberts IJ, Woodcock M: A comparison of colorimetric and clonogenic assays for hypoxic-specific toxins with hamster and human cells. Int J Radiation Oncology Biol Phys 16 (No 4): 939–942, 1989
Stratford IJ, Stephens MA: The differential hypoxic cytotoxicity of bioreductive agents determined in vitro by the MTT assay. Int J Radiation Oncology Biol Phys 16 (No 4): 973–976, 1989
Kuratsu JI, Ushio Y: Antiproliferative effect of trapidil, a platelet-derived growth factor antagonist, on a glioma cell line in vitro. J Neurosurg 73: 436–440, 1990
Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55–63, 1983
Shimoyama Y, Kubota T, Watanabe M, Ishibiki K, Abe O: Predictability of in vivo chemosensitivity by in vitro MTT assay with reference to the clonogenic assay. J Surg Oncol 41:12–18, 1989
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This paper is part of G. Nikkhah's thesis.
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Nikkhah, G., Tonn, J.C., Hoffmann, O. et al. The MTT assay for chemosensitivity testing of human tumors of the central nervous system. J Neuro-Oncol 13, 13–24 (1992). https://doi.org/10.1007/BF00172942
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DOI: https://doi.org/10.1007/BF00172942