How immunotherapies are targeting the glioblastoma immune environment.

The diagnosis of glioblastoma remains one of the most dismal in medical practice, with current standard care only providing a median survival of 14.6 months. The need for new therapies is desperately clear. Components of the tumour microenvironment are demonstrating growing importance in the field, given they allow the tumour to utilise pathways involved in autoimmune prevention, something that enables the tumour's establishment and growth. As with many different cancers, the search for a new standard has progressed to the design of immunotherapies, which aim to counteract the immune changes within this microenvironment. Serotherapy, adoptive lymphocyte transfer, peptide and dendritic cell vaccines and a range of other methods are currently under investigation, while intracranial infection has also been researched for its capacity to reverse glioblastoma mediated immunosuppression. Some of these new therapies have shown promise, but it is a long road ahead before their incorporation into glioblastoma standard therapy.

Is neuroglial antigen 2 a potential contributor to cilengitide response in glioblastoma?

BACKGROUND: Determining the expression levels of neuroglial antigen 2 (NG2) in glioma cell lines and to evaluate the potential contribution of NG2 to cilengitide response were aimed. MATERIALS AND METHODS: Endogenous expression level of NG2 was determined using quantitative reverse transcription polymerase chain reaction and immunoblotting. Cilengitide responses of the cells were monitored to determine half maximal inhibitory concentration values. Whether the suppression of NG2 expression alters the response of A172 cells to cilengitide was examined. RESULTS: The effect of cilengitide on inducing apoptosis of the cells was determined by TUNEL staining. High mRNA and protein expression of NG2 was detected in A172 and U-87MG cells, while T98G, M059K and M059J cells demonstrated low levels of NG2. A172, U-87MG and positive control MG-63 were relatively sensitive to cilengitide compared to T98G, M059K and M059J. MG-63, A172 and U-87MG were unexpectedly found to be more susceptible to cilengitide. In addition, NG2 knock-down showed no significant difference in cell death between small interfering RNA (siRNA)-transfected and cilengitide-treated groups. The results showed that cilengitide caused detachment and subsequently initiated apoptosis. Glioma cell lines express variable levels of NG2 and differ in their responses to cilengitide. Although increased numbers of apoptotic cells were found in untransfected cells compared to siRNA-transfected cells upon exposed to cilengitide, the difference was not documented to be significant between two groups. CONCLUSION: It may be proposed that the combination therapy of NG2 suppression and cilengitide treatment showed no considerable effect on glioblastoma compared to cilengitide therapy alone. Response to therapy may be further improved by targeting other factors act in concert in this signaling pathway.

Current progress for the use of miRNAs in glioblastoma treatment.

Glioblastoma (GBM) is a highly aggressive brain cancer with the worst prognosis of any central nervous system disease despite intensive multimodal therapy. Inevitably, glioblastoma is fatal, with recurrence of treatment-resistant tumour growth at distal sites leading to an extremely low median survival rate of 12-15 months from the time of initial diagnosis. With the advent of microarray and gene profiling technology, researchers have investigated trends in genetic alterations and, in this regard, the role of dysregulated microRNAs (highly conserved endogenous small RNA molecules) in glioblastoma has been studied with a view to identifying novel mechanisms of acquired drug resistance and allow for development of microRNA (miRNA)-based therapeutics for GBM patients. Considering the development of miRNA research from initial association to GBM to commercial development of miR-based therapeutics in less than a decade, it is not beyond reasonable doubt to anticipate significant advancements in this field of study, hopefully with the ultimate conclusion of improved patient outcome. This review discusses the recent advancements in miRNA-based therapeutic development for use in glioblastoma treatment and the challenges faced with respect to in vivo and clinical application.