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Dutta, Anand,Girotra, Mohit,Merchant, Nipun,Nair, Padmanabhan,Dutta, Sudhir Kumar Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10
Background: Heat-shock protein70 (HSP70) are intracellular protein chaperones, with emerging evidence of their association with various diseases. We have previously reported significantly elevated plasma-HSP70 (pHSP70) in pancreatic cancer. Current methods of pHSP70 isolation are ELISA-based which lack specificity due to cross-reactivity by similarities in the amino-acid sequence in regions of the protein backbone resulting in overestimated HSP70 value. Materials and Methods: This study was undertaken to develop a methodology to capture all isoforms of pHSP70, while further defining their tyrosine and serine phosphorylation status. Results: The methodology included gel electrophoresis on centrifuged supernatant obtained from plasma incubated with HSP70 antibody-coupled beads. After blocking non-specific binding sites, blots were immunostained with monoclonal-antibody specific for human-HSP70, phosphoserine and phosphotyrosine. Conclusions: Our novel immunocapture approach has distinct advantages over the commercially available methods of pHSP70 quantification by allowing isolation of molecular aggregates of HSP70 with additional ability to precisely distinguish phosphorylation state of HSP70 molecules at serine and tyrosine residues.
Isolated Renal Mucormycosis in a Healthy Immunocompetent Patient: Atypical Presentation and Course
Mrinal Pahwa,Archna R. Pahwa,Mohit Girotra,Arun Chawla 대한비뇨의학회 2013 Investigative and Clinical Urology Vol.54 No.9
Isolated renal mucormycosis is rarely identified and has been described in only a handful of cases. We hereby report a case of isolated renal mucormycosis with an atypical presentation in an immunocompetent patient with no identifiable risk factors. A 30-year-old nondiabetic male presented with a poorly functioning right kidney with minimal constitutional symptoms. The patient underwent a right simple nephrectomy. Histopathology revealed necrotizing xanthogranulomatous pyelonephritis with mucormycosis. The postoperative period was uneventful and the patient was managed without any antifungal administration. We hereby emphasize that renal mucormycosis can affect immunocompetent healthy adults without any previously known risk factors and that asymptomatic patients with no evidence of fungemia or disseminated disease can be managed without administration of intravenous amphotericin.
Dutta, Sudhir K.,Agrawal, Kireet,Girotra, Mohit,Fleisher, A. Steven,Motevalli, Mahnaz,Mah'moud, Mitchell A.,Nair, Padmanabhan P. Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12
Introduction: Epidemiological studies suggest a protective role for ${\beta}$-carotene with several malignancies. Esophageal adenocarcinoma frequently arises from Barrett's esophagus (BE). We postulated that ${\beta}$-carotene therapy maybe protective in BE. Materials and Method: We conducted a prospective study in which 25 mg of ${\beta}$-carotene was administered daily for six-months to six patients. Each patient underwent upper endoscopy before and after therapy and multiple mucosal biopsies were obtained. Additionally, patients completed a gastroesophageal reflux disease (GERD) symptoms questionnaire before and after therapy and severity score was calculated. To study the effect of ${\beta}$-carotene at molecular level, tissue extracts of the esophageal mucosal biopsy were subjected to assessment of heat-shock protein 70 (HSP70). Results: A significant (p<0.05) reduction in mean GERD symptoms severity score from $7.0{\pm}2.4$ to $2.7{\pm}1.7$ following ${\beta}$-carotene therapy was noted. Measurement of Barrett's segment also revealed a significant reduction in mean length after therapy. In fact, two patients had complete disappearance of intestinal metaplasia. Furthermore, marked enhancement of HSP70 expression was demonstrated in biopsy specimens from Barrett's epithelium in four cases that were tested. Conclusions: Long-term ${\beta}$-carotene therapy realizes amelioration of GERD symptoms along with restitution of the histological and molecular changes in esophageal mucosa of patients with BE, associated with concurrent increase in mucosal HSP70 expression.
Evidence for Enhanced Telomerase Activity in Barrett's Esophagus with Dysplasia and Adenocarcinoma
Merchant, Nipun B.,Dutta, Sudhir K.,Girotra, Mohit,Arora, Manish,Meltzer, Stephen J. Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2
Background: Dysplasia and adenocarcinoma developing in Barrett's esophagus (BE) are not always endoscopically identifiable. Molecular markers are needed for early recognition of these focal lesions and to identify patients at increased risk of developing adenocarcinoma. The aim of the current study was to correlate increased telomerase activity (TA) with dysplasia and adenocarcinoma occurring in the setting of BE. Materials and Methods: Esophageal mucosal biopsies were obtained from patients (N=62) who had pathologically verified BE at esophagogastroduodenoscopy (EGD). Mucosal biopsies were also obtained from the gastric fundus as controls. Based on histopathology, patients were divided into three groups: 1) BE without dysplasia (n=24); 2) BE with dysplasia (both high grade and low grade, n=13); and 3) BE with adenocarcinoma (n=25). TA was measured by a PCR-based assay (TRAPeze$^{(R)}$ ELISA Telomerase Detection Kit). Statistical analyses were performed using one-way ANOVA and post-hoc Bonferroni testing. Results: TA was significantly higher in biopsies of BE with dyplasia and BE with adenocarcinoma than in BE without dysplasia. Subgroup analyses did not reveal any significant correlations between TA and patient age, length of BE, or presence of gastritis. Conclusions: Telomerase activity in esophageal mucosal biopsies of BE may constitute a useful biomarker for the early detection of esophageal dysplasia and adenocarcinoma.