Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents

A series of bifunctional alkylators were tested against the genotypically and phenotypically heterogeneous continuous human medulloblastoma cell lines, TE-671, Daoy, and D283 Med in vitro and against TE-671 and Daoy growing as s.c. and intracranial xenografts in athymic mice. Drugs tested included m...

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Published inCancer research (Chicago, Ill.) Vol. 48; no. 15; pp. 4189 - 4195
Main Authors FRIEDMAN, H. S, COLVIN, O. M, SKAPEK, S. X, LUDEMAN, S. M, ELION, G. B, SCHOLD, S. C. JR, JACOBSEN, P. F, MUHLBAIER, L. H, BIGNER, D. D
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 01.08.1988
Subjects
Alkylating Agents - therapeutic use
Animals
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Brain Neoplasms - drug therapy
Cell Line
Cross-Linking Reagents
Dose-Response Relationship, Drug
Female
General aspects
Humans
Male
Medical sciences
Medulloblastoma - drug therapy
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Pharmacology. Drug treatments
Antineoplastic agent
Neurospongioma
Rodentia
Bifunctional agent
In vitro
In vivo
Clonogenic assay
Vertebrata
Alkylating agent
Chemotherapy
Mammalia
Cell line
Mouse
Animal
Transplanted tumor
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Summary:A series of bifunctional alkylators were tested against the genotypically and phenotypically heterogeneous continuous human medulloblastoma cell lines, TE-671, Daoy, and D283 Med in vitro and against TE-671 and Daoy growing as s.c. and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, thiotepa, 1,3-bis(2-chloroethyl)-1-nitrosourea (in vivo), and busulfan (in vivo). Melphalan and phenylketocyclophosphamide were the most active agents in vitro with drug doses at which there is a 90% reduction in the number of colonies in comparison to controls of 2.13, 5.29, and 4.72 microM for melphalan and 4.60, 5.01, and 4.34 microM for phenylketocyclophosphamide against TE-671, D283 Med, and Daoy, respectively. Melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, and thiotepa produced significant growth delays against s.c. TE-671 and Daoy xenografts, while no activity could be demonstrated for 1,3-bis(2-chloroethyl)-1-nitrosourea or busulfan. Melphalan, cyclophosphamide, iphosphamide, and thiotepa also produced significant increases in median survival in mice bearing intracranial TE-671 and Daoy xenografts. These results extend our previous studies demonstrating the antitumor activity of nitrogen and phosphoramide mustard-based bifunctional alkylating agents in the treatment of human medulloblastoma continuous cell lines and transplantable xenografts, and support the continued use of these agents in clinical trials.
ISSN:0008-5472
1538-7445