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Introduction: Directly Observed Treatment Short (DOTS) course strategy is aimed at diagnosing 70% of infectious Tuberculosis (TB) and curing 85% of it. Aim: To analyse the trend in TB treatment outcomes in the newly diagnosed patients from 2010 to 2015 in Andaman and Nicobar Islands. Materials and Methods: A retrospective cohort study was conducted among TB patients registered from 2010 to 2015 at DOTS TB State Center. Patient particulars like age, sex, TB category at the beginning, and treatment outcomes were collected from the records that were available with DOTS. Results: Incidence of TB in Andaman and Nicobar islands was about 171 per 1,00,000 population during 2010 to 2015, a total of 3917 cases were registered. The total annual new case detection rate increased from 72% to 78%, treatment success rate increased from 84.9% to 89.3%, default rate decreased from 4.1% to 1.4%. Conclusion: The present study analyses the situation of newly diagnosed TB patients in Andaman and Nicobar Islands from 2010 to 2015. Over the years there was a significant increase in the cure rate and a significant decrease in failure and defaulter rates. Over the years there was a significant transition of the treatment outcomes in these islands. [ABSTRACT FROM AUTHOR]

Objective: There is scarcity of information on the prevalence of female genital tuberculosis (FGTB) in the community. The present study was carried out to estimate the prevalence of FGTB, its risk factors and associated clinical features. Study design: Community-based cross-sectional survey. Methods: This study was carried during October 2011 and May 2014 in the Andaman Islands. A total of 13,300 women aged 20-59 years were primarily screened using a structured questionnaire. About 721 (5.4%) were found initially eligible for screening for genital tuberculosis by clinical examination and specimen collection for laboratory tests but only 460 (63.8%) expressed their willingness. Endometrial specimens were collected from 405 (88%) subjects. The association of the potential risk factors with genital tuberculosis was tested by Chi-squared test. A similar analysis was performed to identify clinical features associated with genital tuberculosis. Results: The estimated prevalence of FGTB was 45.1 cases per 100,000 women (95% confidence interval [CI]: 16.6-98.1). Infertility and oligomenorrhoea were identified as clinical features associated with FGTB. Past history of tuberculosis and history of close contact with tuberculosis cases were identified as risk factors. Conclusions: This study shows the prevalence of FGTB among the female population of the Andaman Islands. Though the estimated prevalence was close to the expected prevalence, but as only 63.8% of the eligible women could be adequately screened, a much higher prevalence of FGTB could not be ruled out. Infertility, oligomenorrhoea, past history of tuberculosis and contact with tuberculosis case were identified as factors associated with genital tuberculosis. [ABSTRACT FROM AUTHOR]

Glioblastomas (GBM) are highly radioresistant and lethal brain tumors. Ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are a risk factor for the development of GBM. In this study, we systematically examined the contribution of IR-induced DSBs to GBM development using transgenic mouse models harboring brain-targeted deletions of key tumor suppressors frequently lost in GBM, namely Ink4a, Ink4b, Arf and/or PTEN. Using low linear energy transfer (LET) X-rays to generate simple breaks or high LET HZE particles (Fe ions) to generate complex breaks, we found that DSBs induce high-grade gliomas in these mice which, otherwise, do not develop gliomas spontaneously. Loss of Ink4a and Arf was sufficient to trigger IR-induced glioma development but additional loss of Ink4b significantly increased tumor incidence. We analyzed IR-induced tumors for copy number alterations to identify oncogenic changes that were generated and selected for as a consequence of stochastic DSB events. We found Met amplification to be the most significant oncogenic event in these radiation-induced gliomas. Importantly, Met activation resulted in the expression of Sox2, a GBM cancer stem cell marker, and was obligatory for tumor formation. In sum, these results indicate that radiation-induced DSBs cooperate with loss of Ink4 and Arf tumor suppressors to generate high-grade gliomas that are commonly driven by Met amplification and activation. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR)vIII is the most common EGFR mutant found in glioblastoma (GBM). EGFRvIII does not bind ligand, is highly oncogenic and is usually coexpressed with EGFR wild type (EGFRwt). EGFRvIII activates Met, and Met contributes to EGFRvIII-mediated oncogenicity and resistance to treatment. Here, we report that addition of EGF results in a rapid loss of EGFRvIII-driven Met phosphorylation in glioma cells. Met is associated with EGFRvIII in a physical complex. Addition of EGF results in a dissociation of the EGFRvIII-Met complex with a concomitant loss of Met phosphorylation. Consistent with the abrogation of Met activation, addition of EGF results in the inhibition of EGFRvIII-mediated resistance to chemotherapy. Thus, our study suggests that ligand in the milieu of EGFRvIII-expressing GBM cells is likely to influence the EGFRvIII-Met interaction and resistance to treatment, and highlights a novel antagonistic interaction between EGFRwt and EGFRvIII in glioma cells. [ABSTRACT FROM AUTHOR]

EGFRvIII is a key oncogene in glioblastoma (GBM). EGFRvIII results from an in-frame deletion in the extracellular domain of EGFR, does not bind ligand and is thought to be constitutively active. Although EGFRvIII dimerization is known to activate EGFRvIII, the factors that drive EGFRvIII dimerization and activation are not well understood. Here we present a new model of EGFRvIII activation and propose that oncogenic activation of EGFRvIII in glioma cells is driven by co-expressed activated EGFR wild type (EGFRwt). Increasing EGFRwt leads to a striking increase in EGFRvIII tyrosine phosphorylation and activation while silencing EGFRwt inhibits EGFRvIII activation. Both the dimerization arm and the kinase activity of EGFRwt are required for EGFRvIII activation. EGFRwt activates EGFRvIII by facilitating EGFRvIII dimerization. We have previously identified HB-EGF, a ligand for EGFRwt, as a gene induced specifically by EGFRvIII. In this study, we show that HB-EGF is induced by EGFRvIII only when EGFRwt is present. Remarkably, altering HB-EGF recapitulates the effect of EGFRwt on EGFRvIII activation. Thus, increasing HB-EGF leads to a striking increase in EGFRvIII tyrosine phosphorylation while silencing HB-EGF attenuates EGFRvIII phosphorylation, suggesting that an EGFRvIII-HB-EGF-EGFRwt feed-forward loop regulates EGFRvIII activation. Silencing EGFRwt or HB-EGF leads to a striking inhibition of EGFRvIII-induced tumorigenicity, while increasing EGFRwt or HB-EGF levels resulted in accelerated EGFRvIII-mediated oncogenicity in an orthotopic mouse model. Furthermore, we demonstrate the existence of this loop in human GBM. Thus, our data demonstrate that oncogenic activation of EGFRvIII in GBM is likely maintained by a continuous EGFRwt-EGFRvIII-HB-EGF loop, potentially an attractive target for therapeutic intervention. [ABSTRACT FROM AUTHOR]