Response of short-term cultures derived from human malignant glioma to aziridinylbenzoquinone, etoposide and doxorubicin: an in vitro phase II trial.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe relative resistance of malignant glioma to chemotherapy makes the identification of new cytotoxic drugs critically important. The use of short-term cultures derived from these tumors to screen drugs at doses that can be attained within human intracranial tumors provides a model system that should be capable of identifying effective drugs suitable for clinical evaluation. The sensitivity of a panel of short-term cultures derived from 22 malignant astrocytoma and four malignant oligodendroglioma was assessed to aziridinylbenzoquinone (AZQ), etoposide and doxorubicin (DOX) using a [(35)S] methione uptake assay. The ID(50) of each culture was compared to the levels of drug which could be achieved in the tumor using standard doses. There was marked heterogeneity between cultures in response to each drug. Whilst there was no evidence that cultures derived from grade III astrocytoma were more sensitive to any of the drugs than cultures derived from grade IV astrocytoma, cultures derived from oligodendroglioma tended to be more sensitive to the alkylating agent AZQ, but not to either of the other drugs. The sensitivity of these short-term cultures at concentrations that can be achieved in situ corresponded well with the clinical efficacy of AZQ and etoposide. Although DOX appeared to be toxic to human gliomas cells in vitro, its limited penetration into the intact brain would seem to preclude its use i.v., but it is likely to be effective if local drug delivery techniques could be employed. The study suggests that short-term cultures derived from malignant glioma should be used to screen investigational agents for potential clinical efficacy.
CitationAnti-cancer Drugs, 12 (9): 753-760
PublisherLippincott Williams & Wilkins, Inc.
- Phase II study of aziridinylbenzoquinone (AZQ: NSC-182986) in the treatment of malignant gliomas recurrent after radiation. Preliminary report.
- Authors: Decker DA, Al Sarraf M, Kresge C, Austin D, Wilner HI
- Issue date: 1985
- Response variability of human brain tumors to AZQ in tissue culture.
- Authors: Kornblith PL, Rosa L, Bona JD, Edwards JA, Matuzic N, Hirschfeld A, Hawkins C
- Issue date: 1986
- Aziridinylbenzoquinone (AZQ) in the treatment of recurrent pediatric brain and other malignant solid tumors. A Pediatric Oncology Group phase II study.
- Authors: Castleberry RP, Ragab AH, Steuber CP, Kamen B, Toledano S, Starling K, Norris D, Burger P, Krischer JP
- Issue date: 1990 Nov
- Response rate and toxicity with aziridinylbenzoquinone in patients with recurrent gliomas. A progress report.
- Authors: Tapazoglou E, Kish J, Ensley J, Al-Sarraf M
- Issue date: 1988 Aug
- Sensitivity of short-term cultures derived from human malignant glioma to the anti-cancer drug temozolomide.
- Authors: Sankar A, Thomas DG, Darling JL
- Issue date: 1999 Feb