Ferroptosis Involvement in Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is one of the deadliest brain tumors. Current standard therapy includes tumor resection surgery followed by radiotherapy and chemotherapy. Due to the tumors invasive nature, recurrences are almost a certainty, giving the patients after diagnosis only a 12-15 months average survival time. Therefore, there is a dire need of finding new therapies that could potentially improve patient outcomes. Ferroptosis is a newly described form of cell death with several implications in cancer, among which GBM. Agents that target different molecules involved in ferroptosis and that stimulate this process have been described as potentially adjuvant anti-cancer treatment options. In GBM, ferroptosis stimulation inhibits tumor growth, improves patient survival, and increases the efficacy of radiation and chemotherapy. This review provides an overview of the current knowledge regarding ferroptosis modulation in GBM.

Proteomic Advances in Glial Tumors through Mass Spectrometry Approaches.

Being the fourth leading cause of cancer-related death, glial tumors are highly diverse tumor entities characterized by important heterogeneity regarding tumor malignancy and prognosis. However, despite the identification of important alterations in the genome of the glial tumors, there remains a gap in understanding the mechanisms involved in glioma malignancy. Previous research focused on decoding the genomic alterations in these tumors, but due to intricate cellular mechanisms, the genomic findings do not correlate with the functional proteins expressed at the cellular level. The development of mass spectrometry (MS) based proteomics allowed researchers to study proteins expressed at the cellular level or in serum that may provide new insights on the proteins involved in the proliferation, invasiveness, metastasis and resistance to therapy in glial tumors. The integration of data provided by genomic and proteomic approaches into clinical practice could allow for the identification of new predictive, diagnostic and prognostic biomarkers that will improve the clinical management of patients with glial tumors. This paper aims to provide an updated review of the recent proteomic findings, possible clinical applications, and future research perspectives in diffuse astrocytic and oligodendroglial tumors, pilocytic astrocytomas, and ependymomas.

High dose vs low dose irradiation of the subventricular zone in patients with glioblastoma-a systematic review and meta-analysis.

PURPOSE: The published data indicate that the irradiation of the subventricular zone (SVZ) might play a role in the treatment of patients with glioblastoma (GBM). We aimed to determine whether radiation treatment doses (high vs low) applied to the SVZ can lead to an increase in progression free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: We undertook a systematic review and meta-analysis according to the PICOS research criteria of patients with glioblastoma which received high doses compared to low doses in order to determine if they have a better survival in observational and experimental studies. RESULTS: Our survey of the literature yielded 2573 unique records. After screening, 17 were assessed for eligibility, and in the end 8 were included in the qualitative and 4 in the quantitative analysis. Subjects who received higher doses of ipsilateral SVZ (iSVZ) irradiation had a statistically significant better PFS than those receiving lower doses (HR 0.58 [95% CI 0.42-0.82], p=0.002). Subjects receiving higher doses of contralateral SVZ (cSVZ) irradiation did not have a statistically significant better PFS than those receiving lower doses (HR =0.89 [95% CI 0.35-2.26], p=0.81). Also for OS the subjects receiving higher doses to the iSVZ did not have a statistically significant better survival than those receiving lower doses (HR =0.75 [95% CI 0.51-1.11], p=0.15). CONCLUSION: The data indicate a possible involvement of the SVZ in the onset and progression of the GBM, as well as a possible role of the SVZ in radiation therapy.

The role of p-Stat3 Y705 immunohistochemistry in glioblastoma prognosis.

BACKGROUND: In spite of the multimodal treatment used today, glioblastoma is still the most aggressive and lethal cerebral tumour. To increase survival in these patients, novel therapeutic targets must be discovered. Signal transducer and activator of transcription 3 (Stat3), a transcription factor that controls normal cell differentiation and survival is also involved in neoplastic celltransformation. In this study we evaluated the immunohistochemical expression of pY705-Stat3 in patients with primary glioblastoma and determined its prognostic role by correlating it with survival. METHODS: This retrospective study included 94 patients diagnosed with glioblastoma. We determined the localization, number of positive cells, and marker intensity for pY705-Stat3 in these patients with the use of immunohistochemistry. The prognostic role was determined by correlating pY705-Stat3 expression on formalin-fixed paraffin-embedded tumour tissues with the patient's survival in univariate and multivariate COX regressions. RESULTS: We found a statistically significant difference in survival between the patients with more than 20% pY705-Stat3 positive cells and those with less than 20% pY705-Stat3 positive cells (8.9 months median survival versus 13.7 months medial survival, p <  0.001). On multivariate analyses with the COX proportional hazards regression model including pY705-Stat3 expression, age and relapse status, pY705-Stat3 status was an independent prognostic factor in glioblastoma (P <  0.001). CONCLUSION: The results obtained show that the immunohistochemical expression of pY705-Stat3 correlates with survival in glioblastoma. This study identifies Stat3 as a possible target for existing or new developed Stat3 inhibitors.