Browsing by Author "Pravas Kumar Misra"

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Dysregulated expression and subcellular localization of base excision repair (BER) pathway enzymes in gallbladder cancer
(Babol University of Medical Sciences, 2018) Manoj Kumar; Vijay Kumar Shukla; Pravas Kumar Misra; Mercy Jacob Raman
Base excision repair (BER) pathway is one of the repair systems that has an impact on radiotherapy and chemotherapy for cancer patients. The molecular pathogenesis of gallbladder cancer is not known extensively. In the present study we investigated whether the expression of AP endonuclease 1 (APE1) and DNA polymerase β (DNA pol β), key enzymes of BER pathway has any clinical significance with gallbladder carcinogenesis. 41 gallbladder cancer, 27 chronic cholecystitis, and 3 normal gallbladder specimens were analyzed for the expression of APE1 and DNA polymerase β by western blotting, and subcellular localization studied by immunohistochemistry. The enzymatic activity of APE1 was also studied. The correlations with expression of the above proteins with clinicalpathological characteristics of gallbladder cancer patients were analyzed. The integrated density value ratio (relative expression) of total APE1 (37 kDa + 35 kDa variant) analyzed in the three groups of tissues, was 0.76±0.03 in normal gallbladder, 0.91±0.08 in chronic cholecystitis, and 1.12±0.05 in gallbladder cancer. APE1 was found to be up-regulated in 80% of gallbladder carcinoma samples (P = 0.01). A positive trend of APE1 expression with tumor stage and lymph node positivity was observed. The enzymatic activity of APE1 was found higher in gallbladder cancer samples in comparison with chronic cholecystitis. The integrated density value ratio of DNA polymerase β for normal gallbladder, chronic cholecystitis and gallbladder cancer tissue samples were 0.46±0.03, 0.7±0.06 and 1.33±0.1, respectively. DNA polymerase β was found to be upregulated in almost all gallbladder carcinoma samples (P =0.0001), and its expression was negatively correlated with age (P=0.02). DNA polymerase β expression showed a positive trend with tumor stage and nuclear differentiation of gallbladder cancer. It may be concluded that alteration of these BER pathway proteins may be the causal factors for carcinogenesis of gallbladder, and has targeted therapeutic potential. © 2018 Babol University of Medical Sciences.
P53 gene: Mutation and immunohistochemical analysis in patients with invasive ductal carcinoma of breast
(2013) Shinjini Singh; Sandeep Kumar Rajput; Mritunjai Singh; Pravas Kumar Misra; Gyanendra Mohan; Mohan Kumar; Rakesh Kumar Singh; Indrajeet Singh Gambhir
The p53 tumor suppressor gene is the most commonly mutated gene in cancer. In breast cancer, the presence of p53 gene alterations has been associated with worse prognosis. This study was attempted to associate p53 gene mutations with its protein expression in North Eastern Indian population. We used single-stranded conformation polymorphism to screen samples for mutations in five conserved regions, exons 4, 5, 6, 7 and 8, of the p53 gene. Mutations were confirmed by direct DNA sequencing. Samples were also analyzed for expression of p53 immunohistochemically. We found two critical mutations in the exon 4. A well known missense mutation at codon 72 (pro to arg) with a frequency of 47% was found which was significantly correlated with the immunohistochemical analysis of p53 protein in such patients. A novel nonsense mutation at codon 107 which leads to stop codon was also found. Although the occurrence of this mutation was very less, we did not find expression of p53 protein immunohistochemicaly. We support that mutation in p53 gene can be exploited as a prognostic marker for the early diagnosis of breast cancer, although more clinical and epidemiological data is required to establish this claim. © 2013 Science Publication.