Pleomorphism and drug resistant cancer stem cells are characteristic of aggressive primary meningioma cell lines.

BACKGROUND: Meningioma tumors arise in arachnoid membranes, and are the most reported central nervous system (CNS) tumors worldwide. Up to 20% of grade I meningioma tumors reoccur and currently predictive cancer stem cells (CSCs) markers for aggressive and drug resistant meningiomas are scarce. METHODS: Meningioma tissues and primary cell lines were investigated using whole transcriptome microarray analysis, immunofluorescence staining of CSCs markers (including CD133, Sox2, Nestin, and Frizzled 9), and drug treatment with cisplatin or etoposide. RESULTS: Unsupervised hierarchical clustering of six meningioma samples separated tissues into two groups. Analysis identified stem cells related pathways to be differential between the two groups and indicated the de-regulation of the stem cell associated genes Reelin (RELN), Calbindin 1 (CALB1) and Anterior Gradient 2 Homolog (AGR2). Immunofluorescence staining for four tissues confirmed stemness variation in situ. Biological characterization of fifteen meningioma primary cell lines concordantly separated cells into two functionally distinct sub-groups. Pleomorphic cell lines (NG type) grew significantly faster than monomorphic cell lines (G type), had a higher number of cells that express Ki67, and were able to migrate aggressively in vitro. In addition, NG type cell lines had a lower expression of nuclear Caspase-3, and had a significantly higher number of CSCs co-positive for CD133+ Sox2+ or AGR2+ BMI1+. Importantly, these cells were more tolerant to cisplatin and etoposide treatment, showed a lower level of nuclear Caspase-3 in treated cells and harbored drug resistant CSCs. CONCLUSION: Collectively, analyses of tissues and primary cell lines revealed stem cell associated genes as potential targets for aggressive and drug resistant meningiomas.

Epidemiological trends of histopathologically WHO classified CNS tumors in developing countries: systematic review.

BACKGROUND: Many developing countries are lagging behind in reporting epidemiological data for individual central nervous system (CNS) tumors. This paper aimed to elicit patterns for the epidemiology of individual World Health Organization (WHO) classified CNS tumors in countries registered by WHO as "developing". MATERIALS AND METHODS: Cyber search was carried out through 66 cancer networks/registries and 181 PubMed published papers that reported counts of CNS tumors for the period of 2009-2012. The relationship between the natural log of incidence Age Standardized Rate (ASR) reported by Globocan and Latitude/ Longitude was investigated. RESULTS: Registries for 21 countries displayed information related to CNS tumors. In contrast tends for classified CNS tumor cases were identified for 38 countries via 181 PubMed publications. Extracted data showed a majority of unclassified reported cases [PubMed (38 countries, 45.7%), registries (21 countries, 96.1%)]. For classified tumors, astrocytic tumors were the most frequently reported type [PubMed (38 countries, 1,245 cases, 15.7%), registries (21 countries, 627 cases, 1.99%]. A significant linear regression relationship emerged between latitudes and reported cases of CNS tumors. CONCLUSIONS: Previously unreported trends of frequencies for individually classified CNS tumors were elucidated and a possible link of CNS tumors occurrence with geographical location emerged.

Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance.

Hepatitis C virus (HCV) is one of the foremost causes of chronic liver disease affecting over 300 million globally. HCV contains a positive-stranded RNA of ~9600 nt and is surrounded by the 5' and 3'untranslated regions (UTR). The only successful treatment regimen includes interferon (IFN) and ribavirin. Like many other viruses, HCV has also evolved various mechanisms to circumvent the IFN response by blocking (1) downstream signaling actions via STAT1, STAT2, IRF9 and JAK-STAT pathways and (2) repertoire of IFN Stimulatory Genes (ISGs). Several studies have identified complex host demographic and genetic factors as well as viral genetic heterogeneity associated with outcomes of IFN therapy. The genetic predispositions of over 2000 ISGS may render the patients to become resistant, thus identification of such parameters within a subset of population are necessary for management corollary. The ability of various HCV genotypes to diminish IFN antiviral responses plays critical role in the establishment of chronic infection at the acute stage of infection, thus highlighting importance of the resistance in HCV treated groups. The recently defined role of viral protein such as C, E2, NS3/NS4 and NS5A proteins in inducing the IFN resistance are discussed in this article. How the viral and host genetic composition and epistatic connectivity among polymorphic genomic sites synchronizes the evolutionary IFN resistance trend remains under investigation. However, these signals may have the potential to be employed for accurate prediction of therapeutic outcomes. In this review article, we accentuate the significance of host and viral components in IFN resistance with the aim to determine the successful outcome in patients.