A multicenter phase I trial of combination therapy with interferon-β and temozolomide for high-grade gliomas (INTEGRA study): the final report.

Our previous study demonstrated that interferon-β markedly enhanced chemosensitivity to temozolomide; one of the major mechanisms is downregulation of O(6)-methylguanine DNA-methyltransferase transcription via p53 induction. This effect was also observed in an experimental animal model. The results of these studies suggest that compared to temozolomide-based chemotherapy performed concomitantly with radiotherapy, chemotherapy with interferon-β and temozolomide and concomitant radiotherapy might further improve the clinical outcomes of patients with malignant gliomas.

A free-radical scavenger protects the neural progenitor cells in the dentate subgranular zone of the hippocampus from cell death after X-irradiation.

It has been elucidated that cognitive dysfunction following cranial radiotherapy might be linked to the oxidative stress-induced impairment of hippocampal neurogenesis that is mediated by proliferating neural stem or progenitor cells. The novel free-radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been clinically used to reduce neuronal damage following ischemic stroke. Previously, we reported that the free-radical scavenger, edaravone, which is currently used to treat patients with brain ischemia, protected cultured human neural stem cells (NSCs) from radiation-induced cell death; the protective effect was observed more significantly in NSCs than in brain tumor cells.

p16 promoter methylation in the serum as a basis for the molecular diagnosis of gliomas.

Objective: Deoxyribonucleic acid (DNA) methylation of tumor origin can be detected in the serum/plasma of cancer patients. The aim of this study was to detect aberrant p16 promoter methylation as a potential diagnostic marker in the serum of patients with diffuse glioma to differentiate between gliomas and, particularly, to differentiate those in the brainstem from others; this was done by using the modified methylation-specific polymerase chain reaction technique.

Methods: The methylation-specific polymerase chain reaction was used to detect p16 methylation in the DNA extracted from 20 astrocytic tumors and 20 oligodendroglial tumors and the corresponding serum samples.

A multicenter phase I trial of interferon-beta and temozolomide combination therapy for high-grade gliomas (INTEGRA Study).

A multicenter phase I clinical trial, namely, Integrated Japanese Multicenter Clinical Trial: A Phase I Study of Interferon-beta and Temozolomide for Glioma in Combination with Radiotherapy (INTEGRA Study), is being conducted for patients with high-grade glioma in order to evaluate the safety, feasibility and preliminary clinical effectiveness of the combination of interferon-beta and temozolomide. The primary endpoint is incidence of adverse events. The secondary endpoints are progression-free survival time and overall survival time.