Response of short-term cultures derived from human malignant glioma to aziridinylbenzoquinone, etoposide and doxorubicin: an in vitro phase II trial.

2.50
Hdl Handle:
http://hdl.handle.net/2436/29812
Title:
Response of short-term cultures derived from human malignant glioma to aziridinylbenzoquinone, etoposide and doxorubicin: an in vitro phase II trial.
Authors:
Darling, John L.; Thomas, David G.
Abstract:
The 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.
Citation:
Anti-cancer Drugs, 12 (9): 753-760
Publisher:
Lippincott Williams & Wilkins, Inc.
Journal:
Anti-cancer Drugs
Issue Date:
2001
URI:
http://hdl.handle.net/2436/29812
PubMed ID:
11593057
Additional Links:
http://www.anti-cancerdrugs.com/pt/re/anticd/abstract.00001813-200110000-00007.htm;jsessionid=LTWhTW6qcGpXJWyLzKtJVTbLqjDGV1l7TlZhXc2h2KJHmTcrgQyr!-471255264!181195629!8091!-1
Type:
Article
Language:
en
ISSN:
0959-4973
Appears in Collections:
Cancer Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorDarling, John L.-
dc.contributor.authorThomas, David G.-
dc.date.accessioned2008-06-10T15:15:35Z-
dc.date.available2008-06-10T15:15:35Z-
dc.date.issued2001-
dc.identifier.citationAnti-cancer Drugs, 12 (9): 753-760en
dc.identifier.issn0959-4973-
dc.identifier.pmid11593057-
dc.identifier.urihttp://hdl.handle.net/2436/29812-
dc.description.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.en
dc.language.isoenen
dc.publisherLippincott Williams & Wilkins, Inc.en
dc.relation.urlhttp://www.anti-cancerdrugs.com/pt/re/anticd/abstract.00001813-200110000-00007.htm;jsessionid=LTWhTW6qcGpXJWyLzKtJVTbLqjDGV1l7TlZhXc2h2KJHmTcrgQyr!-471255264!181195629!8091!-1en
dc.subjectMalignant tumoursen
dc.subjectBrain Tumoursen
dc.subjectOncologyen
dc.subjectCancer treatmenten
dc.subjectChemotherapeutic targetsen
dc.subjectCytotoxic drugsen
dc.subject.meshAntineoplastic Agentsen
dc.subject.meshAziridinesen
dc.subject.meshBenzoquinonesen
dc.subject.meshDoxorubicinen
dc.subject.meshDrug Screening Assays, Antitumoren
dc.subject.meshEtoposideen
dc.subject.meshGliomaen
dc.subject.meshHumansen
dc.subject.meshTumor Cells, Cultureden
dc.titleResponse of short-term cultures derived from human malignant glioma to aziridinylbenzoquinone, etoposide and doxorubicin: an in vitro phase II trial.en
dc.typeArticleen
dc.identifier.journalAnti-cancer Drugsen

Related articles on PubMed

All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.