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Chavan S.S.,Kempegowda Institute of Medical science | Ravindra S.,Kempegowda Institute of Medical science | Prasad M.S.N.,Sri Shankara Cancer Hospital and Research Center
Journal of Clinical and Diagnostic Research | Year: 2017

Introduction: Estrogen Receptor (ER), Progesterone Receptor (PR) and Her2/neu are routinely studied markers for breast carcinoma. Analysis of these biomarkers is traditionally done by Immunohistochemistry (IHC) on whole sections. These markers can also be studied on Tissue Microarray (TMA) sections. Tissue microarray is a technique where core samples from different paraffin blocks are arrayed on a single recipient block which can then be cut to yield a single section with multiple cores in it. Aim: To compare ER, PR and Her2/neu on TMA sections with whole sections and to determine the concordance of results between the two methods. Materials and Methods: A TMA block was constructed by punching out 2 mm cores from appropriately marked paraffin blocks of 53 breast carcinoma cases and embedding them in the recipient block. Immunostaining of TMA sections and whole sections were performed for ER, PR and Her2/neu and the results were compared. Statistical analysis was done using chi square test/Fisher-Exact test. Kappa co-efficient, Jaccard Index and G-Index were computed. Results: Infiltrating Ductal Carcinoma-No Special Type (IDC-NST) was the predominant type of carcinoma and most of the tumours were of Grade II and III. Majority, 38/53 (71.7%) were ER/PR positive and Her2 negative and 9/53 (17%) cases were triple negative. Good concordance between whole sections and TMA sections were noted with kappa value for ER, PR and Her2/neu being 0.671, 0.754, 1.000 respectively which was statistically significant. Conclusion: Immunostaining for ER, PR and Her2/neu done on TMA section using single 2 mm core were comparable with conventional whole section scores. Thus, TMA is a reliable method for evaluating these biomarkers with the advantage of being time and cost effective. © 2017, Journal of Clinical and Diagnostic Research. All rights reserved.


Wells J.,University of Chicago | Srinath A.,Sri Shankara Cancer Hospital and Research Center | Free C.,London School of Hygiene and Tropical Medicine | Forde G.,Michigan State University | Forde C.,University of South Florida
University of Toronto Medical Journal | Year: 2012

Objective: To examine the cost-effectiveness of a mobile phone SMS text-based smoking cessation intervention of young adult smokers in the United Kingdom. Design: A Markov model was constructed to examine data from British and international literature. The SMS text-based intervention is compared with a NHS behavioral modification smoking cessation program. Setting: Community setting in the United Kingdom. Participants: 200 people, average age of 37, in the London metropolitan area. Main Outcome Measures: Cost per life years gained. Results: The SMS text-based smoking intervention is more advantageous from the health care payer and societal viewpoints. Sensitivity analyses illustrate robust results. The incremental cost-effectiveness ratio (ICER) is £1.86 per life year gained, far below the NICE willingness to pay cost-effectiveness threshold of £20,000. Discussion: Cost-effectiveness modeling for smoking cessation intervention programs is a daunting challenge. However, even with the limitations of SMS text-based smoking cessation interventions, further research should be conducted with this burgeoning, innovative mode of facilitating behavioral modification through the use technology.


Janardhan B.,Kidwai Memorial Institute of Oncology | Vaderhobli S.,Kidwai Memorial Institute of Oncology | Bhagat R.,Kidwai Memorial Institute of Oncology | Srinivasamurthy P.C.,Kidwai Memorial Institute of Oncology | And 4 more authors.
PLoS ONE | Year: 2015

Epithelial ovarian cancer is one of the increasingly incident malignancies that is notorious because of its evasiveness for early diagnosis and high mortality rates. Epithelial ovarian cancers are highly dependent on pathologic vasculature and Vascular Endothelial Growth Factor is known to be one of the most efficient angiogenic factors. Polymorphisms of the VEGF gene, in this study, were assessed for association with the malignancy and other clinico-pathological factors. 300 case samples and 320 age and mensus status matched controls were inculcated into the study. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were the six single nucleotide polymorphisms that were scrutinized. Genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism. rs 3025039 showed immense promise as a marker for disease aggression and recurrence and a factor for poor prognosis. rs699947 showed least association with the disease and clinico-pathologic factors studied. rs833061, rs 1570360 showed significant association with some clinico-pathological factors such as bilateral affliction of ovaries and post operative CA-125 levels. rs2010963 associated with presence of ascites in higher volumes. The SNPs under consideration showed no formidable linkage in our study samples. A haplotype analysis (excluding rs699947 and rs1413711) revealed 5 frontrunners being present in >85% of the population with TGGC and CGCC associating significantly as protective and risk factors respectively. These haplotypes showed a dose dependent additive effect of their seeming functionality. This study is unique and a first of its kind carried out in the Indian population of South-east Asia. Copyright: © 2015 Janardhan et al.


Murthy R.S.,Sri Shankara Cancer Hospital and Research Center
Current Opinion in Psychiatry | Year: 2016

PURPOSE OF REVIEW: Understand recent developments in psychosocial and behavioral aspects of populations affected by humanitarian emergencies. The review covers the prevalence, longitudinal course, risk factors, posttraumatic growth, biological basis and interventions to address the needs. RECENT FINDINGS: Populations living in humanitarian emergencies, over 50 million worldwide, have higher risk of developing a range of mental disorders. There is evidence of persistence of these disturbances over long periods of time. There is growing body of knowledge to indicate the biological pathways to the occurrence of mental disorders. A proportion of population report posttraumatic growth. There is new focus on identifying the characteristics of risk factors, resilience at the individual, family, community and societal levels. Range of interventions to address the mental health needs is in use from strengthening the coping of individuals, parenting, school-based interventions and use of cognitive behavior therapy. Biological basis is becoming clear. SUMMARY: The most important message of the review is the high mental health needs of individuals living in emergency situations and the urgent need to work toward adequate preparedness for natural disasters, integrate psychosocial interventions as part of relief, rehabilitation and reconstruction and work toward preventing situations of conflict, war, migration and refugee situations. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Korlimarla A.,St Johns Research Institute | Prabhu J.S.,St Johns Research Institute | Remacle J.,St Johns Research Institute | Rajarajan S.,St Johns Research Institute | And 8 more authors.
PLoS ONE | Year: 2016

Purpose: Apart from germ-line BRCA1-mutated breast cancers, a significant proportion of women with sporadic triple negative breast cancer (TNBC) sub-type are known to harbour varying levels of BRCA1-dysfuction. There is currently no established diagnostic method to identify these patients. Methods: The analysis was performed on 183 primary breast cancer tumor specimens from our longitudinal case-series archived as formalin-fixed-paraffin-embedded (FFPE) blocks comprising 71 TNBCs and 112 Hormone receptor positive HER2 negative (HR+HER2-) tumors. Transcript levels of BRCA1 and two of its repressors ID4 and microRNA182 were determined by TaqMan quantitative PCR. BRCA1 protein was detected immunohistochemically with the MS110 antibody. Results: The representation of BRCA1 and its repressor ID4 as a ratio led to improved separation of TNBCs from HR+HER2- compared to either measure by itself. We then dichotomised the continuous distribution of each of the three measurements (Protein, MIRNA and transcript: repressor ratio) into categories of deficient (0) and adequate (1). A composite BRCA1 Deficiency Score (BDS) was computed by the addition of the score for all three measures. Samples deficient on 2 or more measures were deemed to be BRCA1 deficient; and 40% of all TNBCs met this criterion. Conclusion: We propose here a simple multi-level assay of BRCA1 deficiency using the BRCA1:ID4 ratio as a critical parameter that can be performed on FFPE samples in clinical laboratories by the estimation of only 3 bio-markers. The ease of testing will hopefully encourage adoption and clinical validation. © 2016 Korlimarla et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Bhagat R.,Kidwai Memorial Institute of Oncology | Kumar S.S.,Kidwai Memorial Institute of Oncology | Vaderhobli S.,Kidwai Memorial Institute of Oncology | Premalata C.S.,Kidwai Memorial Institute of Oncology | And 3 more authors.
Tumor Biology | Year: 2014

Silencing of tumor suppressor and tumor-related genes by promoter hypermethylation is one of the major events in ovarian carcinogenesis. In this study, we analyzed aberrant promoter methylation of p16 and RAR-β genes in 134 epithelial ovarian carcinomas (EOCs), 23 low malignant potential (LMP) tumors, 26 benign cystadenomas, and 15 normal ovarian tissues. Methylation was investigated by methylation-specific PCR (MSP), and the results were confirmed by bisulfite DNA sequencing. Relative gene expression of p16 and RAR-β was done using quantitative reverse transcriptase PCR (qRT-PCR) on 51 EOC cases, 9 LMP tumors, and 7 benign cystadenomas with 5 normal ovarian tissues. Aberrant methylation for p16 and RAR-β was present in 43 % (58/134) and 31 % (41/134) in carcinoma cases, 22 % (05/23) and 52 % (12/23) in LMP tumors, and 42 % (11/26) and 69 % (18/26) in benign cystadenomas. No methylation was observed in any of the normal ovarian tissues. The mRNA expression level of p16 and RAR-β was significantly downregulated in EOC and LMP tumors than the corresponding normal tissues whereas the expression level was normal in benign cystadenomas for p16 and slightly reduced for RAR-β. A significant correlation of p16 promoter methylation was observed with reduced gene expression in EOC. For RAR-β, no significant correlation was observed between promoter methylation and gene expression. Our results suggest that epigenetic alterations of p16 and RAR-β have an important role in ovarian carcinogenesis and that mechanism along with methylation plays a significant role in downregulation of RAR-β gene in ovarian cancer. © 2014, International Society of Oncology and BioMarkers (ISOBM).


Shilpa V.,Kidwai Memorial Institute of Oncology | Bhagat R.,Kidwai Memorial Institute of Oncology | Premalata C.S.,Kidwai Memorial Institute of Oncology | Pallavi V.R.,Kidwai Memorial Institute of Oncology | And 3 more authors.
Tumor Biology | Year: 2014

Mounting evidences suggest that aberrant methylation of CpGislands is amajor pathway leading to the inactivation of tumour suppressor genes and the development of cancer. The aim of the current study was to examine the prevalence of the promoter hypermethylation and protein expression of the BRCA1 gene in epithelial ovarian carcinoma (EOC) to understand the role of epigenetic silencing in ovarian carcinogenesis. We studied the promoter methylation of the BRCA1 gene by methylation-specific PCR in a cohort of 88 patients with EOC, 14 low malignant potential (LMP) tumours and 20 patients with benign tumours of the ovary. The expression of the BRCA1 protein by immunohistochemical analysis was carried out in a subset of 64 EOCs, 10 LMP tumours, 10 benign tumours and 5 normal ovarian tissues. The frequencies of methylation in EOCs and LMP tumours were 51.2 and 57%, respectively, significantly higher (p=0.000 and p=0.001) in comparison to benign tumours and normal ovarian tissue where no methylation was seen. Expression of BRCA1 was significantly lower in EOCs (p=0.003). Lack of protein expression correlated with tumour grade and type. The methylation status correlated well with downregulation of BRCA1 expression. Our results clearly demonstrate that hypermethylation of BRCA1 promoter is a frequent event in ovarian cancer. These data support the hypothesis that BRCA1 promoter methylation plays an important role in the functional inactivation of BRCA1. Follow-up clinical data will reveal the impact of BRCA1 methylation on survival. © International Society of Oncology and BioMarkers (ISOBM) 2014.


Bhaskari J.,Kidwai Memorial Institute of Oncology | Premalata C.S.,Kidwai Memorial Institute of Oncology | Shilpa V.,Kidwai Memorial Institute of Oncology | Rahul B.,Kidwai Memorial Institute of Oncology | And 4 more authors.
Tumor Biology | Year: 2015

In this study, we have analyzed six genetic polymorphisms of the VEGF-A gene and correlated the genetic data with plasma and tissue expression of VEGF-A in epithelial ovarian carcinomas. A total of 130 cases including 95 malignant carcinomas, 17 low malignant potential and 18 benign tumours were studied. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were studied by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma levels of VEGF-A were estimated by enzyme-linked immunosorbent assay (ELISA) and tissue expression of VEGF-A by immunohistochemistry (IHC). Four polymorphisms of the above excluding rs699947 and rs3025039 showed significant association with malignancy, and we observed the presence of positive correlation between haplotype CCGGCC and increased expression of VEGF-A in both plasma and tissues which also correlated with poor prognosis and recurrence suggesting a probable increase in resistance to treatment in such carriers. Highly upregulated tissue expression of VEGF-A was seen in all epithelial ovarian carcinomas with intensity of expression increasing from benign to malignant cases. ELISA data from our study showed an increase in circulating levels of VEGF-A in malignancies. VEGF-A plasma levels can be employed as a biomarker for high-grade malignancy in epithelial ovarian cancers alongside tissue expression and CA-125 levels. This study is unique due to the fact that a simultaneous analysis of plasma and tissue expression has been demonstrated and is a first such study in epithelial ovarian cancers and representing the Indian population (South-east Asian) synchronized with genetic polymorphism data as well. © 2015 International Society of Oncology and BioMarkers (ISOBM)


Thippeswamy R.,Sri Shankara Cancer Hospital and Research Center | Patil S.,Bangalore Institute of Oncology Speciality Center | Shashidara H.P.,Bangalore Institute of Oncology Speciality Center | Satheesh C.T.,Bangalore Institute of Oncology Speciality Center | And 2 more authors.
Indian Journal of Cancer | Year: 2015

BACKGROUND: Eribulin mesylate is the latest addition in the armamentarium of management of metastatic breast cancer (MBC) with a unique mechanism of action. Although the multicentric EMBRACE trial suggests significant overall survival benefit from this novel drug, its effectiveness in Indian population is yet to be evaluated. MATERIALS and METHODS: Presented here is a single center experience of eight patients who were administered eribulin for MBC. Patients had received a median of 3 prior chemotherapies before eribulin administration. The median dose of eribulin therapy was 5 cycles (range: 2-6 cycles). Results: The objective response rate was 75% (CR in one and PR in five out of eight patients). Response was seen across all subtypes of patients. Eribulin was well tolerated. No serious adverse events were reported. CONCLUSION: Eribulin conferred good response rates with satisfactory tolerability profile in Indian patients. Its use in earlier lines and in combination with other drugs may achieve deeper and longer responses.

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