In Sweden, with a population of 9 million, there are approximately 300 new those GBM cases per year. Histolo gically, GBM is characterized by the presence of necrotic areas in the brain tissue surrounded by anaplastic cells and hyperplastic blood vessels, and a disparate genetic signature, which illustrates the heterogeneity of this tumor. Inhibitors,Modulators,Libraries Current treatments such as surgical resec tion, radiation, and chemotherapy are relatively ineffec tive due to the aggressive nature of GBM. Despite increasing molecular knowledge of GBM tumors, few new therapeutic strategies have been offered these patients during the past decades and these patients still have a poor prognosis with a median survival of 12 15 months. Recent studies have reported the presence of an active Human Cytomegalovirus infection in 90 100% of GBM tumors.

HCMV belongs to the herpesviridea Inhibitors,Modulators,Libraries family and main tains latency in pre monocytic cells after a primary infection. Viral reactivation can occur when latently infected monocytes undergo differentiation to macro phages or dendritic cells, which involves stimulation with inflammatory cytokines. Thus, it is possible that the inflammatory environment in the glioblastoma tumor triggers reactivation of latent HCMV. Although there is compelling evidence that the HCMV protein US28 may be oncogenic, this virus has not been considered to be oncogenic. Rather, HCMV proteins confer a variety of biological functions that potentially affect tumor biology and contribute to cancer progression.

HCMV proteins for example interact with p53, Rb and PTEN and influence cell cycle regulation, induce chromosomal Inhibitors,Modulators,Libraries aberrations, cellular differentiation, migration, angiogenesis and confer immune evasion mechanisms. Recent studies have demonstrated that HCMV US28 induces cyclo oxygenase 2 expression, production of vascular endothelial growth factor and tumor formation in vivo, via activa tion of nuclear factor kappa B, STAT3 phos phorylation and accumulation of beta cathenin in the cell nucleus. Furthermore, we found that phosphorylated STAT 3 was correlated with poor survival of GBM patients. Thus, this virus may either be an epi phenomenon of glioblastomas or may through its sophisticated Inhibitors,Modulators,Libraries strategies that affect tumor biology and provide immune evasion strategies contribute to cancer progression.

We recently demonstrated that targeting HCMV infection in medulloblastoma tumors with an anti viral drug Inhibitors,Modulators,Libraries and a COX 2 inhibitor prevented tumor growth by 72% in an animal www.selleckchem.com/products/ABT-888.html model. These observa tions suggest that HCMV may contribute to the tumor genesis of medulloblatsoma tumors, and that the virus may be a novel target for cancer therapy. We hypothe sized that if the virus affects tumor progression, a low grade HCMV infection in glioblastomas may be asso ciated with longer patient survival. In this case control study, we investigated if the grade of HCMV infection in GBM tumors was associated with survival over 18 months.