Hypoxia helps glioma to fight therapy

Despite major improvements in the surgical management the prognosis for patients bearing malignant gliomas is still dismal. Malignant gliomas are notoriously resistant to treatment and the survival time of patients is between 3-8 years for low-grade and anaplastic gliomas and 6 - 12 month for glioblastoma. Increasing malignancy of gliomas correlates with an increase in cellularity and a poorly organized tumour vasculature leading to insufficient blood supply, hypoxic areas and ultimately to the formation of necrosis, a characteristic of glioblastoma. Hypoxic/necrotic tumours are more resistant to chemotherapy and radiation. Hypoxia induces either directly or indirectly (through the activation of transcription factors) changes in the biology of a tumour and its microenvironment leading to increased aggressiveness and tumour resistance to chemotherapy and radiation. This review is focused on hypoxia-induced molecular changes affecting glioma biology and therapy

Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors

Aim: The aim of the study was to assess the prognostic performance of a 6-gene molecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade. Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM. The prognostic value for distant recurrence-free survival (DRFS) and invasive disease-free survival (IDFS) was assessed using Cox proportional hazards models and Kaplan-Meier analysis. All statistical tests were two-sided ones. Results: OMm and OM (both with likelihood ratio statistic [LRS] P Discussion: Both OncoMasTR scores were significantly prognostic for DRFS and IDFS and provided additional prognostic information to the molecular and clinicopathological risk factors/tools assessed. OM was also the most accurate risk classification tool for identifying DR. A concise 6-gene signature with superior risk stratification was shown to increase prognosis reliability, which may help clinicians optimise treatment decisions. Trial registration: ClinicalTrials.gov NCT02050750 NCT00310180.</p