Hasan T.N.,Bharathiar University |
Leena Grace B.,Vinayaka Missions University |
Shafi G.,Institute of Genetics |
Syed R.,Mahavir Hospital and Research Center
Clinical and Translational Oncology | Year: 2013
Objective: Breast cancer is the most common cancer and the main cause of cancer morbidity for women worldwide and is manifestation of abnormal genetic as well as epigenetic changes. Therefore, our aim was to study the association of BRCA1 promoter methylation with rs11655505 (c.-2265C/T) variants and gene expression in sporadic breast cancer. Methods: Twenty-nine sporadic breast cancer tissues and 26 normal biopsies were used for this study. Genomic DNA and total RNA were extracted from paraffin-embedded tissue and SNP analysis performed. Methylation status of the BRCA1 promoter region was determined by methylation-specific PCR after sodium bisulfite modification of DNA. Results: Among all clinical-pathological parameters only estrogen receptor -ve and +ve samples were significantly different for methylation status (P = 0.04). The genotypic (CC, CT and TT), allelic frequencies and methylation status had not been found to be significantly different from that of healthy controls (P = 0.67, 0.71 and 0.17, respectively). Similarly, methylated BRCA1 promoter was not found to be significantly different in different genotypes from unmethylated promoters between patients and controls. Interestingly, only heterozygous (CT) genotypes with low and normal expression of BRCA1 were significantly different for the differential expression of BRCA1 compared to controls (P = 0.004). However, in tumor samples decreased expression of gene is associated with methylated state of BRCA1 promoter [OR (95 % CI) = 25.09 (2.17-29.75); P = 0.01]. Conclusions: Our data suggest that both single nucleotide variations rs11655505 (c.-2265C/T) and the methylation status of BRCA1 are not associated significantly with the occurrence of sporadic breast cancer in studied population. However, decreased expression of gene is associated with the CT genotypes and the disease. But, in case of tumor samples, an association of methylation of the promoter to the decreased expression of BRCA1 gene suggests the possible role of methylation in gene silencing. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).
Ehtesham N.Z.,University of Hyderabad |
Ehtesham N.Z.,National Institute of Nutrition |
Nasiruddin M.,National Institute of Nutrition |
Alvi A.,University of Hyderabad |
And 7 more authors.
Tuberculosis | Year: 2011
Treatment of tuberculosis (TB), which takes one human life every 15 s, globally, requires a prolonged (>6 months) antitubercular treatment (ATT) which, is known to have hepatotoxic side effects. This study was designed to explore the utility of human resistin, a proinflammatory hormone, as a sensitive biomarker to determine TB treatment end points. Patients for pulmonary tuberculosis enrolled under the directly observed treatment, short-course (DOTS) program were followed-up for six months and were monitored by sputum analysis, body weight and ELISA-based serum resistin and C-reactive protein (CRP) levels at 0, 2, 4 and 6 months, along with close family contacts of TB patients and healthy controls. The mean circulating resistin levels were found to be significantly higher (P < 0.001) in patients (n = 48, 25.74 ± 9.45 ng/ml) reporting for the first time for treatment (T0) as compared to healthy subjects (n = 45, 7.18 ± 2.40 ng/ml). Resistin levels in contacts (n = 48, 19.61 ± 7.88 ng/ml) also were found to be significantly (P < 0.001) elevated as compared to healthy controls. Significant increase in body weight after four months (P = 0.006) and at 6 months (P < 0.001) of treatment inversely correlated with resistin levels. Our data suggest resistin could be a surrogate marker for TB treatment in addition to its utility as an early prognostic biomarker for monitoring TB disease onset. © 2011 Elsevier Ltd. All rights reserved.
Alam K.,DNA Diagnostics Center |
Ghousunnissa S.,DNA Diagnostics Center |
Nair S.,DNA Diagnostics Center |
Valluriand V.L.,Mahavir Hospital and Research Center |
Mukhopadhyay S.,DNA Diagnostics Center
Journal of Immunology | Year: 2010
The glutathione-redox balance, expressed as the ratio of intracellular reduced glutathione (GSH) and oxidized glutathione, plays an important role in regulating cellular immune responses. In the current study, we demonstrate that alteration of glutathione-redox balance in macrophages by GSH donors like cell-permeable glutathione ethyl ester reduced or N-acetyl-L-cysteine (NAC) can differentially regulate production of IL-12 cytokine in macrophages. A low concentration of NAC increased IL-12 p40/p70 production, whereas at high concentration, IL-12 production was inhibited due to increased calmodulin expression that binds and sequesters c-rel in the cytoplasm. Although NAC treatment increased the IκBα phosphorylation, it failed to increase TNF-α levels due to enhanced expression of suppressor of cytokine signaling 1, which specifically prevented nuclear translocation of p65 NF-κB. We demonstrate that NAC at 3 mM concentration could increase bacillus Calmette-Guérin-induced IFN-γ production by PBMCs from patients with active tuberculosis and shifts the anti-bacillus Calmette-Guérin immune response toward the protective Th1 type. Our results indicate that redox balance of glutathione plays a critical role in regulating IL-12 induction in native macrophages, and NAC can be used in tailoring macrophages to induce enhanced Th1 response that may be helpful to control tuberculosis and other pathophysiological disorders. Copyright © 2010 by The American Association of Immunologists, Inc.
Chava S.,Mahavir Hospital and Research Center |
Chava S.,Vasavi Medical and Research Center |
Mohan V.,Tapadia Diagnostics Services |
Shetty P.J.,Vasavi Medical and Research Center |
And 8 more authors.
Diseases of the Esophagus | Year: 2012
The aim of the study was to evaluate the expression of tumor suppressor genes p53, fragile histidine triad gene (FHIT), and an oncogene insulin-like growth factor 2 (IGF2) as prognostic markers in the etiology of esophageal cancer. Immunohistochemistry (IHC) was performed in 39 archival tissue samples of different esophageal pathologies for the three genes. Abnormal p53 expression was maximum in all the cases of squamous cell carcinoma, while IGF2 expression was enhanced in squamous cell carcinoma (81%), adenocarcinoma (100%), and dysplasia of squamous epithelium (75%) samples when compared with normals (50%). To our surprise, 75% of normal tissues did not show FHIT expression, which was also not seen in 40% of dysplasias of squamous epithelium, 33.3% of adenocarcinoma, and 41% of squamous cell carcinoma. To the best of our knowledge, this is the first study evaluating IGF2 by IHC, as well as, correlating it with the expression of the two tumor suppressor genes, p53 and FHIT, in esophageal tissue. p53 expression was threefold higher than normal in dysplasias of squamous epithelium and adenocarcinoma, while it was eightfold higher in squamous cell carcinoma. IGF2 expression was low in normal and dysplasia tissue but was increased 1.97-fold in both types of malignancy. FHIT and p53 expression were well correlated in squamous cell carcinoma, supporting the observation that FHIT regulates and stabilizes p53. Altered/lowered FHIT levels may be a result of exposure to various exogenous agents; however, this could not be assessed in the present study as it was carried out on archival samples. A larger prospective study is warranted to establish the role of exogenous factors in FHIT expression. © 2011 the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.
Jamil K.,Bhagwan Mahavir Medical Research Center |
Jamil K.,Jawaharlal Nehru Institute of Advanced Studies JNIAS |
Jayaraman A.,Jawaharlal Nehru Institute of Advanced Studies JNIAS |
Ahmad J.,Osmania University |
And 2 more authors.
Saudi Journal of Biological Sciences | Year: 2016
Several reports document the role of tumor necrosis factor alpha (TNF-α) and lipid metabolism in the context of acute inflammation as a causative factor in obesity-associated insulin resistance and as one of the causative parameter of type 2 diabetes mellitus (T2DM). Our aim was to investigate the association between -308G/A and -238G/A polymorphisms located in the promoter region of the TNF-α gene in T2DM in the Indian population with bioinformatics analysis of TNF-α protein networking with an aim to find new target sites for the treatment of T2DM. Demographics of 100 diabetes patients and 100 healthy volunteers were collected in a structured proforma and 3 ml blood samples were obtained from the study group, after approval of Institutional Ethics Committee of the hospital (IEC). The information on clinical parameters was obtained from medical records. Genomic DNA was extracted; PCR-RFLP was performed using TNF-α primers specific to detect the presence of SNPs. Various bioinformatics tools such as STRING software were used to determine its network with other associated genes. The PCR-RFLP studies showed that among the -238G/A types the GG genotype was 87%, GA genotype was 12% and AA genotype was 1%. Almost a similar pattern of results was obtained with TNF-α -308G/A polymorphism. The results obtained were evaluated statistically to determine the significance. By constructing TNF-α protein interaction network we could analyze ontology and hubness of the network to identify the networking of this gene which may influence the functioning of other genes in promoting T2DM. We could identify new targets in T2DM which may function in association with TNF-α. Through hub analysis of TNF-α protein network we have identified three novel proteins RIPK1, BIRC2 and BIRC3 which may contribute to TNF-mediated T2DM pathogenesis. In conclusion, our study indicated that some of the genotypes of TNF-α -308G/A, -238G/A were not significantly associated to type 2 diabetes mellitus, but TNF-α -308G/A polymorphism was reported to be a potent risk factor for diabetes in higher age (>45) groups. Also, the novel hub proteins may serve as new targets against TNF-α T2DM pathogenesis. © 2016 The Authors.