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      • Association of a Newly Identified Variant of DNA Polymerase Beta (polβΔ<sub>63-123, 208-304</sub>) with the Risk Factor of Ovarian Carcinoma in India

        Khanra, Kalyani,Bhattacharya, Chandan,Bhattacharyya, Nandan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

        Background: DNA polymerase is a single-copy gene that is considered to be part of the DNA repair machinery in mammalian cells. The encoded enzyme is a key to the base excision repair (BER) pathway. It is evident that pol beta has mutations in various cancer samples, but little is known about ovarian cancer. Aim: Identification of any variant form of $pol{\beta}$ cDNA in ovarian carcinoma and determination of association between the polymorphism and ovarian cancer risk in Indian patients. We used 152 samples to isolate and perform RT-PCR and sequencing. Results: A variant of polymerase beta (deletion of exon 4-6 and 11-13, comprising of amino acid 63-123, and 208-304) is detected in heterozygous condition. The product size of this variant is 532 bp while wild type pol beta is 1 kb. Our study of association between the variant and the endometrioid type shows that it is a statistically significant factor for ovarian cancer [OR=31.9 (4.12-246.25) with p<0.001]. The association between variant and stage IV patients further indicated risk (${\chi}^2$ value of 29.7, and OR value 6.77 with 95% CI values 3.3-13.86). The correlation study also confirms the association data (Pearson correlation values for variant/stage IV and variant/endometrioid of 0.44 and 0.39). Conclusion: Individuals from this part of India with this type of variant may be at risk of stage IV, endometrioid type ovarian carcinoma.

      • Exon 8-9 Mutations of DNA Polymerase β in Ovarian Carcinoma Patients from Haldia, India

        Khanra, Kalyani,Panda, Kakali,Mitra, A.K.,Sarkar, Ranu,Bhattacharya, Chandan,Bhattacharyya, Nandan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

        Background: Ovarian cancer is the number one killer among all the gynecological cancers. We undertook association study to identify potential alterations in the genomic DNA of a DNA repair gene, DNA polymerase beta ($pol{\beta}$), involved in base excision repair (BER), in ovarian carcinomas of patients from Haldia, India. Mutations, splice variants have been reported earlier in different tumors other than ovarian tumors. Aim: In this study we explored the possibility of association of any mutation of $pol{\beta}$ (Exon 8) with prognosis in 152 ovarian cancer samples. Results: Alteration in the exon 8 region (Exon 8:468, $A{\rightarrow}C$; 15.1%) was noted among fifty seven polymorphism positive samples. Alteration in the intervening sequence 8 (IVS8, -25, $A{\rightarrow}C$; 3.9%) was also noted. All alterations are heterozygous in nature. Conclusions: We found no significant association among the samples from serous type, stage IV, and the $pol{\beta}$ mutations ($P{\leq}0.01$). Only a slight tendency of association was evident between IVS8, -25, A to C; and stage III. Further analysis with a larger number of samples is needed.

      • Association of Two Polymorphisms of DNA Polymerase Beta in Exon-9 and Exon-11 with Ovarian Carcinoma in India

        Khanra, Kalyani,Panda, Kakali,Bhattacharya, Chandan,Mitra, A.K.,Sarkar, Ranu,Bhattacharyya, Nandan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

        Background: DNA polymerase beta ($pol{\beta}$) is a key enzyme in the base excision repair pathway. It is 39kDa protein, with two subunits, one large subunit of 31 kDa having catalytic activity between exon V to exon XIV, and an 8 kDa smaller subunit having single strand DNA binding activity. Exons V to VII have double strand DNA binding activity, whereas exons VIII to XI account for the nucleotidyl transferase activity and exons XII to XIV the dNTP selection activity. Aim: To examine the association between $pol{\beta}$ polymorphisms and the risk of ovarian cancer, the present case control study was performed using 152 cancer samples and non-metastatic normal samples from the same patients. In this study, mutational analysis of $pol{\beta}$ genomic DNA was undertaken using primers from exons IX to XIV - the portion having catalytic activity. Results: We detected alteration in DNA polymerase beta by SSCP. Two specific heterozygous point mutations of $pol{\beta}$ were identified in Exon 9:486, A->C (polymorphism 1; 11.18%) and in Exon 11:676, A->C (polymorphism 2; 9.86%). The correlation study involving polymorphism 1 and 4 types of tissue showed a significant correlation between mucinous type with a Pearson correlation value of 4.03 (p=0.04). The association among polymorphism 2 with serous type and stage IV together have shown Pearson ${\chi}^2$ value of 3.28 with likelihood ratio of 4.4 (p=0.07) with OR =2.08 (0.3-14.55). This indicates that there is a tendency of correlation among polymorphism 2, serous type and stage IV, indicating a risk factor for ovarian cancer. Conclusion: Hence, the results indicate that there is a tendency for $pol{\beta}$ polymorphisms being a risk factor for ovarian carcinogenesis in India.

      • HeLa Cells Containing a Truncated Form of DNA Polymerase Beta are More Sensitized to Alkylating Agents than to Agents Inducing Oxidative Stress

        Khanra, Kalyani,Chakraborty, Anindita,Bhattacharyya, Nandan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.18

        The present study was aimed at determining the effects of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta ($pol{\beta}{\Delta}_{208-304}$) specific for ovarian cancer. $Pol{\beta}{\Delta}_{208-304}$ has a deletion of exons 11-13 which lie in the catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT, colony forming and apoptosis assays. $Pol{\beta}{\Delta}_{208-304}$ cells exhibited greater sensitivity to an alkylating agent and less sensitivity towards $H_2O_2$ and UV when compared with HeLa cells alone. It has been shown that cell death in $Pol{\beta}{\Delta}_{208-304}$ transfected HeLa cells is mediated by the caspase 9 cascade. Exon 11 has nucleotidyl selection activity, while exons 12 and 13 have dNTP selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. The lack of this part may adversely affect catalytic activity of DNA polymerase beta so that the variant may act as a dominant negative mutant. This would represent clinical significance if translated into a clinical setting because resistance to radiation or chemotherapy during the relapse of the disease could be potentially overcome by this approach.

      • 7,7,8,8-Tetracyanoquinodimethane-assisted one-step electrochemical exfoliation of graphite and its performance as an electrode material.

        Khanra, Partha,Lee, Chang-No,Kuila, Tapas,Kim, Nam Hoon,Park, Min Jun,Lee, Joong Hee RSC Pub 2014 Nanoscale Vol.6 No.9

        <P>A green approach for the preparation of water-dispersible functionalized graphene via one-step electrochemical exfoliation of graphite using 7,7,8,8-tetracyanoquinodimethane (TCNQ) anions as surface modifiers and electrolytes was described. TCNQ is an organic charge-transfer complex with electron accepting and noteworthy electrical properties. The exfoliation of graphite to a few-layer graphene sheets was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM) image analysis. The chemical state, surface functional groups and chemical compositions of bulk graphite as well as TCNQ-functionalized graphene sheets were investigated by Fourier-transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) analysis. Adsorption of TCNQ onto the surface of graphene sheets was confirmed by the appearance of the N1s peak at 399.4 eV in the XPS of TCNQ-functionalized graphene. Exfoliation of bulk graphite to functionalized graphene sheets was further confirmed by the appearance of a sharp single peak at 2695 cm(-1) along with increased intensity ratios of the D-band to the G-band. Electrochemical performance of a TCNQ-functionalized graphene sheet was investigated using 1 M Na2SO4 and 1 M KOH aqueous solutions. Cyclic voltammetry (CV) and galvanometric charge-discharge experiments revealed that TCNQ-functionalized graphene could be used as a supercapacitor electrode material. The specific capacitance values of TCNQ-modified graphene measured with electrolytes (1 M KOH and 1 M Na2SO4) were 324 and 140 F g(-1), respectively, at a current density of 1 A g(-1). Impedance spectroscopic analysis revealed that the charge transfer process was dependent on surface functionalization and interaction between the electrode and the electrolyte.</P>

      • KCI등재
      • KCI등재

        A Network Meta-Analysis Comparing Osteoporotic Fracture among Different Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Atrial Fibrillation

        Dibbendhu Khanra,Anindya Mukherjee,Saurabh Deshpande,Hassan Khan,Sanjeev Kathuria,Danesh Kella,Deepak Padmanabhan 대한골대사학회 2021 대한골대사학회지 Vol.28 No.2

        Background: There are limited studies comparing the risk of osteoporosis and fractures between different direct oral anticoagulants (DOACs) and vitamin K antagonists (VKA) in non-valvular atrial fibrillation (AF). Using a network meta-analysis (NMA), we compared osteoporotic fractures among 5 different treatment arms, viz. dabigatran, rivaroxaban, apixaban, edoxaban, and VKA. Methods: Ten studies, including 5 randomized control trials and 5 population-based studies, with a total of 321,844 patients (148,751 and 173,093 in the VKA and DOAC group, respectively) with a median follow-up of 2 years, were included. A Bayesian random-effects NMA model comparing fractures among the treatment arms was performed using MetInsight V3. Sensitivity analysis excluded studies with the highest residual deviances from the NMA model. Results: The mean age of the patients was 70 years. The meta-analysis favored DOACs over VKA with significantly lower osteoporotic fracture (odds ratio [OR], 0.77; 95% credible interval [CrI], 0.70-0.86). The NMA demonstrated that fractures were significantly lower with apixaban compared with dabigatran (OR, 0.64; 95% CrI, 0.44-0.95); however, fractures were statistically similar between apixaban and rivaroxaban (OR, 0.84; 95% CrI, 0.58-1.24) and dabigatran and rivaroxaban (OR, 1.32; 95% CrI, 0.90-1.87). Based on the Bayesian model of NMA, the probability of osteoporotic fracture was highest with VKA and lowest with apixaban, followed by rivaroxaban, edoxaban, and dabigatran. Conclusions: The decision to prescribe anticoagulants in elderly patients with AF should be made not only based on thrombotic and bleeding risks but also on the risk of osteoporotic fracture; these factors should be considered and incorporated in contemporary cardiology practice.

      • KCI등재

        An Unusual Case of Delirium after Restarting Clozapine

        Sourav Khanra,Rati Ranjan Sethy,Sanjay Kumar Munda,Christoday Raja Jayant Khess 대한정신약물학회 2016 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.14 No.1

        Clozapine is a gold standard medication and drug of choice in refractory schizophrenia. Among many of its fatal side effects, delirium is less reported and inconsistently recognized by clinicians. We here present a case of delirium which emerged during retreatment with clozapine in a patient of paranoid schizophrenia. A patient diagnosed with paranoid schizophrenia, was restarted on clozapine after he left medications and became symptomatic. He was delirious on 22nd day after clozapine was restarted. Clozapine was stopped and the patient was managed with standard treatment for delirium. After one week interval, clozapine was restarted. Delirium was not noted till 6 weeks of his hospital stay. Clozapine induced central anticholinergic toxicity or clozapine induced seizure might cause delirium in index case. Limited literature exist delirium with clozapine. Clinicians must have high index of suspicion to detect delirium during clozapine therapy. More researches should focus to explore the association between delirium and clozapine.

      • KCI등재

        Mirtazapine Is Effective in Steroid Withdrawal Syndrome Related Depression: A Case Report

        Sourav Khanra,Sourav Das 대한정신약물학회 2017 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.15 No.1

        Steroid withdrawal syndrome (SWS) following steroid dependence is becoming a common clinical condition. It may be associated with body image disorder. Though selective serotonin reuptake inhibitors (SSRIs) are found to be effective SWS associated depression, data for this clinical condition is limited. We present a case of SWS associated with body image disorder which improved with mirtazapine. Mirtazapine might be better option than SSRIs in this subgroup of patients for its noradrenergic property and better gastrointestinal profile. More research should explore its efficacy in this clinical condition.

      • One-step electrochemical synthesis of 6-amino-4-hydroxy-2-napthalene-sulfonic acid functionalized graphene for green energy storage electrode materials

        Kuila, Tapas,Khanra, Partha,Kim, Nam Hoon,Choi, Sung Kuk,Yun, Hyung Joong,Lee, Joong Hee IOP Pub 2013 Nanotechnology Vol.24 No.36

        <P>A green approach for the one-step electrochemical synthesis of water dispersible graphene is reported. An alkaline solution of 6-amino-4-hydroxy-2-naphthalene-sulfonic acid (ANS) serves the role of electrolyte as well as surface modifier. High-purity graphite rods are used as electrodes which can be exfoliated under a constant electrical potential (∼20 V) to form ANS functionalized graphene (ANEG). The aqueous dispersion of ANEG obeyed Beer’s law at moderate concentrations, as evidenced from ultraviolet–visible spectroscopy analysis. X-ray diffraction analysis suggests complete exfoliation of graphite into graphene. Fourier transform infrared and x-ray photoelectron spectroscopy not only confirm the functionalization of graphene with ANS, but also suggest the formation of oxygen containing functional groups on the surface of ANEG. Raman spectra analysis indicates the presence of defects in ANEG as compared to pure graphite. Cyclic voltammetry and charge–discharge measurements of ANEG using three electrode systems show a specific capacitance of 115 F g<SUP>−1</SUP> at a current density of 4 A g<SUP>−1</SUP>. The ANEG electrode exhibits 93% retention in specific capacitance after 1000 charge–discharge cycles, confirming its utility as a green energy storage electrode material.</P>

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