Department of Life Sciences

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Browsing Department of Life Sciences by Author "Ghosh, Amlan"

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    Identification of candidate tumor suppressor genes’ loci on chromosome 9 associated with the development of arsenic induced urinary bladder cancer in West Bengal, India
    Ghosh, Amlan
    The etiological link of arsenic with bladder cancer (BC) is well established across the globe. The molecular pathogenesis of arsenic induced BC should be explored to identify potential markers of clinical importance for better disease management. Arsenic toxicity is a burning health issue along Gangetic belt of West Bengal and higher BC incidence was recorded in affected areas of the state than safe areas. On this background, present hospital-based study aimed to analyse the association of arsenic with development/progression/prognosis of BC in West Bengal and, explore molecular pathogenesis of arsenic-induced BC targeting candidate tumor suppressor genes (TSGs) of chromosome-9 due to previous reports of alteration of the chromosome in BC. In this hospital-based study, majority of BC patients were documented from arsenic affected areas of the state and in these patients, concordantly high tumor arsenic level (AsH, >100 ppb) was detected. High tumor arsenic level was found to be associated with higher proliferation potential (assessed by immunohistochemical analysis of ki67) and pathological stages of tumor and poor patient survival. Thus, in exposed individuals, arsenic accumulates in bladder tissue to influence tumorigenesis and favour acquisition of aggressive tumor phenotypes that affect disease outcome. To explore molecular pathogenesis, 9p22-21 and 9q22.3 were selected based on previous report and candidate TSGs deleted in these regions in AsH tumors were detected by analysing whole genome CGH+SNP array data of our previous study. In 9p22 region, SH3GL2 (SH3 domain containing GRB2 like 2) showed molecular alteration (deletion & promoter methylation) preferably in AsH tumors similar to array based data and, concordant reduced expression. SH3GL2 inactivation seemed to affect receptor mediated endocytosis of active EGFR as evident from overexpression of the later without any amplification of gene in same sample set. SH3GL2 inactivation and associated dysregulation in “negative regulation of ERBB signalling pathway” was seen to have prognostic significance. In 9q22.3 region, deletion, promoter methylation, and concordant reduced expression of PHF2 was seen preferentially in AsH tumors. PHF2 (PHD finger protein 2) involves in “histone lysine (H3K9me2) demethylation pathway” essential for p53 functioning. In present study, PHF2 inactivation might affect p53 mediated transcription as evident from reduced p21 expression in same set of tumors over- expressing p53 protein. CDKN2A and CDKN2B loci from 9p21 region, FANCC and PTCH1 loci from 9q22.3 region were also analysed in this study. As evident from comparable and high frequency of molecular alteration in AsH and AsL (arsenic low; ≤100 ppb) tumors, the gene loci did not seem to have important contribution in pathogenesis of arsenic induced BC. The information on association of arsenic with disease progression, prognosis and related molecular pathogenesis will have implementation in designing preventive and management strategies for arsenic induced bladder cancer in future.
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    Identification of Molecular Markers associated with Development and clinical outcome of Gestational Diabetes Mellitus in West Bengal, India
    Ghosh, Amlan
    Gestational diabetes mellitus (GDM) is considered as health hazard with respect to short and long term adverse effect on maternal and neonatal health. On the background of fragmented knowledge, present study aimed to analyze prevalence, population specific risk factor, pathogenesis and adverse disease outcome of GDM on case control basis in a Kolkata based population of West Bengal, India. Prevalence of GDM in Kolkata was 17.2%. Older maternal age, presence of acanthosis nigricans and diabetic family history was found as major risk factors. Association of oxidative stress and related inflammation with GDM indicated incidence of insulin resistance in disease pathogenesis. Genetic predisposition seemed to play major role in development of GDM of our studied population; this was evident from significant association of genetic variants of type-2 diabetes from insulin synthesis/ processing (rs7903146, rs4132670 and rs12255372 of TCF7L2 and rs2269023 of PCSK2) and secretion pathways (rs5219 of KCNJ11, rs757110 of ABCC8, rs10830963 of MTNR1B) with disease condition. As disease specific adverse neonatal outcome, macrosomia (newborn with excess birth weight) and neonatal hypoglycaemia (abnormally low blood glucose level of newborn) were highlighted in studied population. In GDM pregnancy, phenomenon of intrauterine hypoxia was evident from higher incidence of placental histological anomalies like villous edema, increased syncytial knots, chorangiosis, and thickening of basement membrane than normal one. Over-expression of GLUT1 and GLUT3 in GDM placenta was found than normal one, indicating enhanced glucose transport to fetus and was predicted as consequence of hypoxic condition. In logistic regression, villous edema, chorangiosis and placental GLUT1 were established as independent predictors for both macrosomia and neonatal hypoglycaemia and increased syncytial knots for neonatal hypoglycaemia; this indicated importance of intrauterine hypoxia and enhanced fetal glucose transport in pathogenesis of GDM associated neonatal health.