Modulation of Cytotoxicity by Nitric Oxide Donors during Treatment of Glioma with Anticancer Drugs

OBJECTIVE: Nitric oxide(NO) is implicated in a wide range of biological processes in tumors and is produced in glioma. To investigate the role of NO and its interaction with the tumoricidal effects of anticancer drugs, we study the antitumor activities of NO donors, with or without anticancer drugs, in human glioma cell lines. METHODS: U87MG and U373MG cells were treated with the NO donors sodium nitroprusside(SNP) and S-nitroso-N-acetylpenicillamine(SNAP), alone or in combination with the anticancer drugs 1, 3-bis(2-chloroethyl)-1-nitrosourea(BCNU) and cisplatin. Cell viability, cell proliferation, DNA fragmentation, nitrite level, and the expression of Bcl-2 and Bax were determined. RESULTS: NO was markedly increased after treatment with SNP or SNAP; however, the addition of the anticancer drugs did not significantly affect NO production. NO donors or anticancer drugs reduced glioma cell viability and, in combination, acted synergistically to further decrease cell viability in a dose- and time-dependent manner. Cell proliferation was inhibited and apoptosis were enhanced by combined treatment. Bax expression was increased by combined treatment, whereas Bcl-2 expression was reduced. The antitumor cytotoxicity of NO donors and anticancer drugs differed according to cell type. CONCLUSION: BCNU or cisplatin can inhibit cell viability and proliferation of glioma cells and can induce apoptosis. These effects are further enhanced by the addition of a NO donor which modulates the antitumor cytotoxicity of chemotherapy depending on cell type. Further biological, chemical, and toxicological studies of NO are required to clarify its mechanism of action in glioma.

A Clinical Analysis of Anaplastic Oligodendroglioma

OBJECTIVE: The author evaluate the efficacy of surgery, radiation therapy and chemotherapy as a treatment methods for anaplastic oligodendroglioma patients to provide the standardized treatment option. METHODS: A retrospective analysis of ten pathologically proven cases of anaplastic oligodendroglioma was performed. RESULTS: The ten patients comprised four males and six females. The mean age at diagnosis was 34.4 year (8-70). The mean follow-up was 40.5 months, and two patients died of tumor progression during the follow-up (70, 86 months, respectively). All patients had craniotomy and the tumors were removed as much as possible. The tumos were resected totally in five cases, only subtotally in the rest. Radiation therapy was applied to seven patients, and PCV (procarbazine-CCNU-vincristine) based chemotherapeutic agent was administered to five patients. In the group with PCV therapy, complete remission was observed in two, partial remission was in one, stable disease in one, and disease progression in one who were died of tumor extension. During the follow-up, tumor recurrences were observed in four patients, and they were treated with additional operation and/or chemotherapy. CONCLUSION: Anaplastic oligodendrogliomas respond to the surgical and radiological treatment and especially to the chemotherapy, and have a relatively good prognosis. PCV is an effective and safe regimen for suppressing tumor growth, and is feasible for recurrent cases. PCV chemotherapy should be considered for primary treatment method for anaplastic oligodendroglioma patients.