However, these approaches do not benefit all patients equally. Adverse effects of these approaches even dramatically deteriorate the quality-of-life of some patients. Therefore, individualized therapy should be considered
as a valuable approach for patients GDC-0068 mouse with high-grade gliomas. Molecular profiling of gliomas may define the critical genetic alterations that underlie glioma pathogenesis and their marked resistance to therapy . So elucidation of these critical molecular events will improve therapy and individualize therapeutic interventions for patients with gliomas. Mothers against decapentaplegic homologue 4 (SMAD4), learn more expressed ubiquitously in different human organ systems, was initially isolated as a tumor suppressor gene on chromosome 18q21.1 in pancreatic ductal adenocarcinomas . The SMAD4 protein is the downstream mediator of transforming growth factor beta (TGF-β), which is an important multifunctional cytokine that regulates cell proliferation, differentiation and extracellular matrix production . Conflicting data exist about the influence of SMAD4 on the development
and progression of various human tumors. Papageorgis et al. reported that SMAD4 inactivation promotes malignancy and drug resistance of colon cancer . The study of Sakellariou et al. found that SMAD4 may behave as a tumor promoter in low grade gastric cancer and the survival rates were significantly higher for Staurosporine concentration patients with reduced SMAD4 Metformin molecular weight expression, in cases of well- or moderately differentiated tumors . In pancreatic cancer, inactivation of the SMAD4 gene through mutation occurs frequently in association with malignant progression . In non-small-cell lung carcinoma, immunohistochemistry revealed that SMAD4 was expressed at high level in normal broncho-tracheal epithelium, but at low level in tumor tissues, and closely correlated with tumor lymph node metastasis . Lv et
al. also demonstrated that the hypo-expression level of SMAD4 was associated with the pathological stage, and lymph node metastasis of the patients with esophageal squamous cell carcinoma, however, it might not be the independent prognostic factor . On the other hand, Sheehan et al. indicated that SMAD4 protein expression persists in prostatic adenocarcinomas compared with benign glands, with both nuclear and cytoplasmic overexpression correlating with prognostic variables indicative of aggressive tumor behavior . Hiwatashi et al. also concluded that strong SMAD4 expression in hepatocellular carcinoma is likely to suggest poor prognosis of patients . However, little is known about the expression level of SMAD4 or its prognostic significance in human gliomas.