Nitric oxide and glioma: a target for novel therapy?

The biological activities of nitric oxide (NO) include vasodilatation, inhibition of platelet aggregation, neurotransmission, neural plasticity, and modulation of inflammatory and immunological functions. NO synthase (NOS), which is the enzyme that produces NO, has been detected in resected human glioma specimens, and both human and rodent glioma cell lines. NO production in gliomas can alter several important pathophysiological processes, such as local host immune response, tumour cell apoptosis, tumour invasion/metastasis, free radical injury to tumour cells and adjacent normal brain tissues, tonic vasodilatation of tumour vessels, vascular permeability and neovascularization. Recently, some therapeutic strategies for gliomas using NO manipulation have been proposed, and evaluated both experimentally and indirectly in preliminary clinical trials. These include NO manipulation designed to modify tumour cell oncogenesis, tumour blood flow and disposition of anti-cancer drugs in tumour tissue. This review will discuss the biological role of NO in the central nervous system and gliomas and its current and future possibilities in neuro-oncology.