Tata Memorial Hospital

About: Tata Memorial Hospital is a healthcare organization based out in Mumbai, India. It is known for research contribution in the topics: Cancer & Breast cancer. The organization has 3187 authors who have published 4636 publications receiving 109143 citations.

Altered keratin expression in buccal mucosal squamous cell carcinoma

Abstract: Cytokeratin pattern was analyzed in 14 moderately differentiated and 12 well-differentiated squamous cell carcinomas of buccal mucosa by SDS-PAGE, immunoblotting and two dimensional electrophoresis. These were compared with patterns of normal buccal mucosa and surrounding areas whenever possible. Normal buccal mucosa expresses keratin No. 4 (59Kd), 5 (58Kd), 13 (54Kd) and 14 (50Kd). Keratin No. 4 (59Kd) and 14 (50Kd) were expressed by 20 of 26 tumors studied, while many of the tumors did not express keratins No. 5 (58Kd) and 13 (54Kd). Keratin No. 1 (67Kd) and 16 (48Kd) were aberrantly expressed by 9 well-differentiated tumors. Keratin No. 17 (46Kd) and 18 (45Kd) were expressed by 10 and 8 tumors of 14 moderately differentiated tumors. Six tumors which showed involvement of alveolar mucosa, expressed some keratins expressed by its normal counterpart. Their altered expression was consistent with the differentiation pattern as stated earlier. Non-expression of keratins 5 and 13 seems to be the result of malignant transformation and is seen in the majority of tumors, while appearance of aberrant keratins seems to be related more to the degree of differentiation of the tumor.

Molecular targeted therapy in recurrent glioblastoma: current challenges and future directions.

Abstract: Introduction: The survival of patients with glioblastoma (GBM), which is the most common primary brain malignancy, remains poor with current treatment modalities. However, an enhanced understanding of gliomagenesis is supporting the development of targeted molecular therapies with the potential for improving clinical outcomes. Areas covered: Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) initiate key signaling pathways in GBM; however, trials with anti-EGFR agents have failed to show improved outcomes. Bevacizumab, a monoclonal antibody targeting VEGF, remains the only FDA-approved molecular drug in GBM; yet its use has only improved progression-free survival without any improvement in overall survival. We review the evidence supporting the continued evaluation of targeted molecular therapies in recurrent GBM. In addition, newer potential therapies targeting other signaling pathways, heat shock proteins and proteosomes, as well as the concept of targeting g...

Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study

Abstract: Summary Background Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. The aim of this study was to identify common genetic susceptibility alleles for gallbladder cancer. Methods In this case-control genome-wide association study (GWAS), we did a genome-wide scan of gallbladder cancer cases and hospital visitor controls, both of Indian descent, followed by imputation across the genome. Cases were patients aged 20–80 years with microscopically confirmed primary gallbladder cancer diagnosed or treated at Tata Memorial Hospital, Mumbai, India, and enrolled in the study between Sept 12, 2010, and June 8, 2015. We only included patients who had been diagnosed less than 1 year before the date of enrolment and excluded patients with any other malignancies. We recruited visitor controls aged 20–80 years with no history of cancer visiting all departments or units of Tata Memorial Hospital during the same time period and frequency matched them to cases on the basis of age, sex, and current region of residence. We estimated association using logistic regression, adjusting for age, sex, and five eigenvectors. We recruited samples for a replication cohort from patients visiting Tata Memorial Hospital between Aug 4, 2015, and May 17, 2016, and patients visiting the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, between July, 2010, and May, 2015. We used the same inclusion and exclusion criteria for the replication set. We examined three of the most significant single-nucleotide polymorphisms (SNPs) in the replication cohort and did a meta-analysis of the GWAS discovery and replication sets to get combined estimates of association. Findings The discovery cohort comprised 1042 gallbladder cancer cases and 1709 controls and the replication cohort contained 428 gallbladder cancer cases and 420 controls. We observed genome-wide significant associations for several markers in the chromosomal region 7q21.12 harbouring both the ABCB1 and ABCB4 genes, with the most notable SNPs after replication and meta-analysis being rs1558375 (GWAS p=3·8 × 10 −9 ; replication p=0·01; combined p=2·3 × 10 −10 ); rs17209837 (GWAS p=2·0 × 10 −8 ; replication p=0·02; combined p=2·3 × 10 −9 ), and rs4148808 (GWAS p=2·4 × 10 −8 ; replication p=0·008; combined p=2·7 × 10 −9 ). Combined estimates of per-allele trend odds ratios were 1·47 (95% CI 1·30–1·66; p=2·31 × 10 −10 ) for rs1558375, 1·61 (1·38–1·89; p=2·26 × 10 −9 ) for rs17209837, and 1·57 (1·35–1·82; p=2·71 × 10 −9 ) for rs4148808. GWAS heritability analysis suggested that common variants are associated with substantial variation in risk of gallbladder cancer (sibling relative risk 3·15 [95% CI 1·80–5·49]). Interpretation To our knowledge, this study is the first report of common genetic variation conferring gallbladder cancer risk at genome-wide significance. This finding, along with in-silico and biological evidence indicating the potential functional significance of ABCB1 and ABCB4 , underlines the likely importance of these hepatobiliary phospholipid transporter genes in the pathology of gallbladder cancer. Funding The Tata Memorial Centre and Department of Biotechnology.

Giant cell tumor of bone in children and adolescents.

Abstract: Background: There are very few series that document giant cell tumor of bone (GCT) in the immature skeleton, and the reported incidence in literature varies from 1.8% to 10.6%. The purpose of this study was to document the incidence of GCT in patients with open physis in the Indian population and study the course of the disease with respect to its adult counterpart to see if it behaved any differently. Methods: Between January 2000 and December 2005, 17 (6%) of 285 surgically treated patients with histologically proven GCT had open physis on imaging. Treatment was directed toward local control without sacrificing joint function, with most lesions treated with intralesional curettage. Results: Fourteen (82%) patients were girls. The most common site was around the knee (53%). Of 15 lesions in tubular bones, 13 were epiphysiometaphyseal in location. An open physis did not prevent GCT from penetrating the epiphyseal cartilage. Histologically, the tumors were typical of GCT. Of 15 patients available for follow-up, 3 (20%) developed local recurrence. Conclusions: Although the overall incidence of GCT may be higher in the Asian population, the percentage of skeletally immature patients or those nearing skeletal maturity is similar to that described in literature. The biological behavior of the disease is similar to that seen in adults, except a marked female preponderance, principles of treatment, recurrence patterns, and course of the disease mirror the behavior of its adult counterpart. Level of Evidence: Level IV, case series.

Glioblastoma-Derived Epidermal Growth Factor Receptor Carboxyl-Terminal Deletion Mutants Are Transforming and Are Sensitive to EGFR-Directed Therapies

Abstract: Genomic alterations of the epidermal growth factor receptor (EGFR) gene play a crucial role in pathogenesis of glioblastoma multiforme (GBM). By systematic analysis of GBM genomic data, we have identified and characterized a novel exon 27 deletion mutation occurring within the EGFR carboxyl-terminus domain (CTD) in addition to identifying additional examples of previously reported deletion mutations in this region. We show that the GBM-derived EGFR CTD deletion mutants are able to induce cellular transformation in vitro and in vivo in the absence of ligand and receptor autophosphorylation. Treatment with the EGFR-targeted monoclonal antibody, cetuximab, or the small molecule EGFR inhibitor, erlotinib, effectively impaired tumorigenicity of oncogenic EGFR CTD deletion mutants. Cetuximab in particular prolonged the survival of intracranially xenografted mice with oncogenic EGFR CTD deletion mutants, compared to untreated control mice. Therefore, we propose that erlotinib and especially cetuximab treatment may be a promising therapeutic strategy in GBM patients harboring EGFR CTD deletion mutants.