BACKGROUND: Glioma, including anaplastic astrocytoma and glioblastoma multiforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is a highly invasive and angiogenic tumor, resulting in a 12 to 15 months median survival. The treatment of GBM is multimodal and includes surgical resection, followed by adjuvant radio-and chemotherapy. We have previously reported that short-term starvation (STS) enhances the therapeutic index of chemo-treatments by differentially protecting normal cells against and/or sensitizing tumor cells to chemotoxicity.
To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications.
CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective.
Glioblastoma stem cells (GSC) are a significant cell model for explaining brain tumor recurrence. However, mechanisms underlying their radiochemoresistance remain obscure. Here we show that most clonogenic cells in GSC cultures are sensitive to radiation treatment (RT) with or without temozolomide (TMZ). Only a few single cells survive treatment and regain their self-repopulating capacity.
BACKGROUND AND OBJECTIVE: Epigenetic silencing of the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), is associated with the therapeutic response to methylating agents. This study was to assess the value of detecting the promoter methylation of MGMT gene in chemotherapy for glioma. METHODS: Methylation-specific PCR (MSP) was employed to detect MGMT promoter CpG island methylation in 39 samples of glioma taken from surgery. Western blot and immunohistochemistry were used to detect protein expression.
Gliomatosis confined to the cerebellum is most unusual. We report such a case in a 20-month-old male who presented with unsteadiness. Magnetic resonance imaging revealed a diffuse area of abnormal signal intensity within both cerebellar hemispheres, which did not enhance after contrast administration. The patient underwent a biopsy, which revealed a diffuse glioma infiltrating the cerebellum. Overall, the tumor cells had oligodendroglioma-like features and exhibited only focal vimentin immunoreactivity.