Differential chemosensitivity in human intracerebral gliomas measured by flow cytometric DNA analysis.
The present study was designed to investigate the chemosensitivity of human intracerebral gliomas using the flow cytometric (FCM) analysis of DNA integrity as an in vitro drug sensitivity testing. We also correlated the in vitro results and the clinical responses to chemotherapy. Forty-one fresh tumor specimens were obtained at surgery, and exposed to 30 currently-available anticancer agents. Drug-induced nuclear damage such as chromatin condensation or DNA degradation were assessed both by morphological observation and FCM analysis of DNA integrity. The FCM assay could be performed in all the cases (100% success rate). The chemosensitivities of anaplastic astrocytoma, oligodendroglial tumors, and medulloblastoma were generally higher than those of glioblastoma multiforme and ependymoma. The in vitro chemosensitivity was markedly heterogeneous among patients with the same histological tumor. Clinical sensitivity was predicted in 86% of all evaluable patients and clinical resistance in 81%; the overall accuracy of the FCM assay was 82%. The FCM analysis of DNA integrity proved to be feasible and sufficiently reliable as a routine clinical examination for the purpose of screening new chemotherapeutic agents and individualizing chemotherapy regimens for patients with intracerebral gliomas.
Iwadate
Yasuo
Y
Department of Neurological Surgery, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. iwadate@med.m.chiba-u.ac.jp
Fujimoto
Shuichi
S
Yamaura
Akira
A
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001254:Astrocytoma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D001932:Brain Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D002843:Chromatin / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis* / Q000187:drug effects; D003955:Diagnostic Tests, Routine; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004806:Ependymoma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D005240:Feasibility Studies; D005434:Flow Cytometry; D005909:Glioblastoma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D005910:Glioma / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008527:Medulloblastoma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D009837:Oligodendroglioma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D011446:Prospective Studies; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D002843:Chromatin; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors