ABSTRACT
Glioblastoma multiforme is one of the most aggressive malignant brain tumours with limited therapeutics options. Standard therapy is maximal surgical resection and adjuvant concurrent chemo-radiotherapy and maintenance therapy with temozolomide. This approach improves median and 5-year survival in comparison with postsurgical radiotherapy alone. Additional predictive and prognostic biomarkers are necessary, especially due to the development of targeted therapy--antibodies and tyrosine kinase inhibitors. These new therapeutic approaches are under intensive investigation. The most promising data currently available are for anti-angiogenic therapies, such as bevacizumab and cediranib. This review presents a summary of the possible role of targeted therapy in the treatment of glioblastoma multiforme.
Subject(s)
Brain Neoplasms/therapy , Glioblastoma/therapy , Combined Modality Therapy , HumansABSTRACT
Free fatty acids (FFAs) are natural ligands of the PPARgamma2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32+/-11 years; BMI 23.9+/-4.0 kg/m(2)) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels - the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARgamma2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes.