Chava S.,Bhagawan Mahavir Hospital and Research Center |
Chava S.,Vasavi Medical and Research Center |
Kaliq D.,Vasavi Medical and Research Center |
Nagarjuna P.,Kamineni Life science |
And 8 more authors.
International Journal of Cancer Research | Year: 2011
Among three epigenetic mechanisms, DNA methylation is a distinct and crucial mechanism to regulate a variety of genes in tissue specific manner in pathophysiology of cancer. Methylation status of four selected genes which include tumor suppressor genes like p53 and FHIT as well as oncogenes, Aurora-A and IGF2 was assessed to find the association with esophageal cancer by performing methylation specific restriction assay in both blood and tissue of patients who had undergone diagnostic endoscopy and results were correlated with the exogenous factors like tobacco, alcohol, hot beverages and diet. Individuals with all four types of exposure were found in a higher percentage in the cancer group when compared to normals and esophagitis, however, those exposed to tobacco and alcohol were significantly more in cancer (p<0.05). The methylation status of p53, FHIT and IGF2 did not show difference between cancer and normal samples whereas Aurora (p = 0.0002). But methylation was increased in p53, FHIT and Aurora-A gene and decreased in IGF2 in cancer tissue if the individuals were exposed to tobacco and alcohol. MDR analysis indicated that the four genes evaluated were acting independently whereas there was a stronger interaction between non vegetarian diet and hot beverages as well as tobacco and alcohol for the development of esophageal cancer. In conclusion it can be stated that exogenous factors affect the methylation status of genes in tissues which may act as an early step in esophageal carcinogenesis. © 2011 Academic Journals Inc.
Shetty P.J.,Kamineni Hospital |
Shetty P.J.,Vasavi Medical and Research Center |
Pasupuleti N.,Kamineni Life science |
Chava S.,Bhagwan Mahavir Medical Research Center |
And 4 more authors.
Breast Disease | Year: 2011
Breast cancer (BC) is the commonest cancer in women worldwide with a widely variable incidence between countries and regions. BC is either familial or sporadic. Mutations in tumor suppressor gene, PTEN has been associated with syndromic BC and in a subset of sporadic BCs. The present study was carried out in archival formalin fixed paraffin embedded samples. Immunohistochemistry and quantitative RTPCR indicated a reduced expression/transcription of PTEN in tumor as compared to adjacent non-tumorous tissue. However, the promoter methylation evaluated by Methylation Specific Restriction Assay indicated that only 20% of the tumors showed PTEN methylation and could not account for the rest of the samples with reduced expression. Overall evidence from literature and our present findings indicate that: (i) Loss of Heterozygosity at PTEN gene locus (ii) germline and somatic gene mutations of PTEN (iii) epigenetic silencing by methylation in PTEN promoter CpG cluster (iv)protein interactions which reduce PTEN transcription and (v) PTEN protein degradation together play an important role in the etiology of BC. © 2011/2012-IOS Press and the authors. All rights reserved.
Shetty P.J.,Vasavi Medical and Research Center |
Movva S.,Vasavi Medical and Research Center |
Pasupuleti N.,Kamineni Life science |
Vedicherlla B.,Vasavi Medical and Research Center |
And 5 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2011
Purpose: Breast Cancer is one of the leading causes of cancer deaths among women worldwide. The role of epigenetics as a distinct mechanism to alter gene expression in a tissue-specific manner has emerged as an important mechanism in the pathophysiology of cancer. Present study was carried out to assess the role of methylation in regulating transcription and protein expression of Insulin-like growth factor 2 (IGF2), an oncogene with parental imprinting. Methods: Paraffin-embedded archival breast tumor and adjacent normal tissue samples were used for carrying out PCR-based methylation assay, genomic PCR, immunohistochemistry and Real-Time Reverse transcriptase PCR. Results: A significant loss of methylation in exon 9 CpG cluster of IGF2 in breast tumor tissues was observed when compared to normal tissue (P < 0.0001). Expression of IGF2 by immunohistochemistry exhibited a mean twofold increase correlating with the hypomethylation of this specific CpG. Real-Time RT PCR showed increased transcripts in the tumor tissue supporting the IHC and methylation results. A total of 33% of tumor samples heterozygous for the ApaI IGF2 polymorphism exhibited biallelic IGF2 expression due to loss of imprinting; this was not seen in any of the normal breast tissues. Conclusions: Altered methylation of exonic CpG plays an important role in the enhanced transcription/expression of IGF2 in breast tumors. Methylation analysis of exon 9 CpG can be used as a biomarker for upregulation of IGF2 in breast tumor tissue and maybe developed as a diagnostic test in future. © 2010 Springer-Verlag.
Apoorva G.,Kamineni Institute of Medical Sceinces |
Lavanya K.,Kamineni Institute of Medical Sceinces |
Vidisha V.,Kamineni Institute of Medical Sceinces |
Pavani P.,Kamineni Life science |
And 3 more authors.
Proceedings of the International Conference on "Advanced Nanomaterials and Emerging Engineering Technologies", ICANMEET 2013 | Year: 2013
We investigated the genotoxic effects of 10-20 nm silver (Ag) and Titanium dioxide (TiO2) nanoparticles (NPs) by evaluating chromosome aberrations and polyploidy status and micronucleus (MN) assay. Methods Before testing, we confirmed that the Ag-NPs were completely dispersed in the experimental medium by sonication (three times in 1 minute) and filtration (0.2 μm pore size filter), and then we measured their size in a zeta potential analyzer. After that the genotoxicity was measured. Results After incubation with the defined concentration and size of the Silver and TiO2 nanoparticles, 100 metaphases were analyzed under microscope, 9%, 12% structural aberrations and 3%, 2% numerical aberrations were observed respectively. There was no aberration found in the control sample. After incubation with the defined concentration and size of the Ag & TiO2 nanoparticles, 1000 bi-nucleated cells were analyzed under microscope, 3% and 1% of these cells were observed with micronuclei respectively.Conclusions All of our findings indicate that Ag-and TiO2 NPs show genotoxic effects in mammalian cell system. In addition, present study suggests that the genotoxicity effect of Ag and TiO2 nanoparticles is concentration and size dependent. © 2013 IEEE.
Ramakrishna D.,Kamineni Institute of Medical science |
Roy S.,Kamineni Life science |
Reddy G.C.,Kamineni Institute of Medical science |
Subhash M.N.,National Institute of Mental Health and Neuro Sciences
International Journal of Pharma and Bio Sciences | Year: 2011
Background: Heterotrimeric G proteins play a pivotal role in post receptor information transduction. These proteins have been implicated in the pathophysiology, diagnosis, and treatment of depression. Aims and Objectives: The aim of the present study was to examine the effect of chronic antidepressants treatment on the Gqα-protein levels in rat brain. Materials & Methods: Density of G qα/11α-protein levels was measured in cortex and cerebellum of rats treated with amitriptyline (AMI), desipramine (DMI) and fluoxetine (FLX) and imipramine (10 mg/Kg body wt), for 30 days, using Sodium Dodecyl Sulphate - Polyacrylamide Gel Electrophoresis (SDS-PAGE) and western blotting. Results:In cortex, a significant decrease was observed after AMI treatment (28%, p<0.0001), followed by DMI (17%, p<0.0001) and CMI (19%, p<0.0001). In contrast a significant increase was observed after IMI treatment (14%, p<0.001) but there was no change in fluoxetine treatment. In cerebellum, a significant increase in G q-protein levels was observed after treatment with all the above drugs. A very high increase was observed after CMI treatment (114%, p<0.0001) as compared to AMI (59%, p<0.0001), DMI (45%, p<0.0001) fluoxetine (28%, p<0.0001) and IMI (42%, p<0.0001). Conclusion: The results suggest that chronic antidepressant (AD) treatment decreases the expression of cortical G qα/11α-protein levels in contrast to cerebellum where these proteins are showed increased expression. However IMI treatment in cortical G qα/11αprotein levels predominantly over expressed by IMI treatment. The region-specific expression of G qα/11α-protein levels which occurs after prolonged AD treatment, may underline the therapeutic mechanism of action.