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.

Multipronged quantitative proteomic analyses indicate modulation of various signal transduction pathways in human meningiomas.

Abstract: Meningiomas (MGs) are frequent tumors of the CNS originating from the meningeal layers of the spinal cord and the brain. In this study, comparative tissue proteomic analysis of low and high grades of MGs was performed by using iTRAQ-based quantitative proteomics in combination with ESI-quadrupole-TOF and Q-Exactive MS, and results were validated by employing ELISA. Combining the results obtained from two MS platforms, we were able to identify overall 4308 proteins (1% false discover rate), among which 2367 exhibited differential expression (more than and equal to 2 peptide and ≥ 1.5-fold in at least one grade) in MGs. Several differentially expressed proteins were found to be associated with diverse signaling pathways, including integrin, Wnt, Ras, epidermal growth factor receptor, and FGR signaling. Proteins, such as vinculin or histones, which act as the signaling activators to initiate multiple signaling pathways, were found to be upregulated in MGs. Quite a few candidates, such as protein S-100A6, aldehyde dehydrogenase mitochondrial, AHNAK, cytoskeleton-associated protein 4, and caveolin, showed sequential increase in low- and high-grade MGs, whereas differential expressions of collagen alpha-1 (VI), protein S100-A9, 14 kDa phosphohistidine phosphatase, or transgelin-2 were found to be grade specific. Our findings provide new insights regarding the association of various signal transduction pathways in MG pathogenesis and may introduce new opportunities for the early detection and prognosis of MGs.

Effect of short-term vs prolonged nasogastric decompression on major postesophagectomy complications: a parallel-group, randomized trial.

Abstract: Hypothesis Controversy exists over the need for prolonged nasogastric decompression after esophagectomy. We hypothesized that early removal of the nasogastric tube would not adversely affect major pulmonary complications and anastomotic leak rates. Design Single-center, parallel-group, open-label, randomized (1:1) trial. Setting A tertiary referral cancer center with high esophagectomy volume. Patients One hundred fifty patients undergoing esophagectomy with gastric tube reconstruction. Interventions Either conventional nasogastric decompression for 6 to 10 days (75 patients) or early removal (48 hours) of nasogastric tube (75 patients) with stratification for pyloric drainage and anastomotic technique. Main Outcome Measures The primary (composite) end point was the occurrence of major pulmonary complications and anastomotic leaks. Secondary end points were the need for nasogastric tube reinsertion and patient discomfort scores. Analysis was performed on an intent-to-treat basis. Results No significant differences were seen in the occurrence of the composite primary end point of major pulmonary and anastomotic complications between the delayed (14 of 75 patients [18.7%]) and early (16 of 75 patients [21.3%]) removal groups, respectively (P = .84). Nasogastric tube reinsertion was required more often (23 of 75 patients [30.7%] vs 7 of 75 patients [9.3%]) in the early group (P = .001). Mean patient discomfort scores were significantly higher in the delayed (+1.3; 95% CI, 0.4-2.2; P = .006) than in the early removal group. Significantly more patients in the delayed removal group (26 of 75 patients [34.7%] vs 10 of 75 patients [13.3%] in the early removal group; P = .002) identified the nasogastric tube as the tube causing the most discomfort. Conclusions Early removal of nasogastric tubes does not increase pulmonary or anastomotic complications after esophagectomy. Patient discomfort can be significantly reduced by early removal of the nasogastric tube. Trial Registration Clinical Trials Registry of India Identifier: CTRI/2010/091/003023

Surgical pathology of squamous carcinoma of the oral cavity: its impact on management.

Abstract: Squamous carcinoma of the oral cavity is relatively common in India. The anterior tongue and buccal mucosa are the two common sites. A retrospective analysis of various histological parameters in surgically treated patients with carcinoma of the anterior tongue (57 cases) and buccal mucosa (71 cases) was undertaken to evaluate their role in prognosis and management. The main findings of this study are the strong correlation between high tumour grade, infiltrative tumour margins, perineural invasion, and tumour size >2 cm and lymph node metastasis at presentation, for both groups of patients. Tumour thickness >5 mm was an additional variable associated with both overt and occult nodal metastases for anterior tongue lesions. All tumours thicker than 5 mm recurred in the untreated N0 neck. Clinically palpable nodes (N1) were falsely positive in 63% of patients with T4 buccal mucosa carcinoma. Grade I histology on biopsy can be used to predict which patients will have negative lymph nodes. Patients with pathologically proven nodal metastases have a poor prognosis. However, the mode of invasion and the presence of perineural invasion in the resected specimen determines the subsequent recurrence of histologically staged N0 cases, most of whom will relapse at the primary site. The low incidence of neck node metastases even in large, buccal mucosa tumours and the virtual absence of “skip” metastases to low nodal sites has made a supraomohyoid lymph node dissection after intraoperative staging a logical alternative to a conventional neck dissection for T3 and T4 buccal mucosa tumours. Finally, carcinoma of the oral cavity in India can be said to be at least two diseases. Cancer of the buccal mucosa and alveolus differs widely in its biological behaviour from carcinoma of the anterior tongue and floor of the mouth.

Genome-wide expression and copy number analysis identifies driver genes in gingivobuccal cancers.

Abstract: The molecular mechanisms contributing to the development and progression of gingivobuccal complex (GBC) cancers–a sub-site of oral cancer, comprising the buccal mucosa, the gingivobuccal sulcus, the lower gingival region and the retromolar trigone-remain poorly understood. Identifying the GBC cancer-related gene expression signature and the driver genes residing on the altered chromosomal regions is critical for understanding the molecular basis of its pathogenesis. Genome-wide expression profiling of 27 GBC cancers with known chromosomal alterations was performed to reveal differentially expressed genes. Putative driver genes were identified by integrating copy number and gene expression data. A total of 315 genes were found differentially expressed (P≤0.05, logFC>2.0) of which eleven genes were validated by real-time quantitative reverse transcriptase-PCR (qRT-PCR) in tumors (n=57) and normal GBC tissues (n=18). Overexpression of LY6K, in chromosome band 8q24.3, was validated by immunohistochemical (IHC) analysis. We found that 78.5% (2,417/3,079) of the genes located in regions of recurrent chromosomal alterations show copy number dependent expression indicating that copy number alteration has a direct effect on global gene expression. The integrative analysis revealed BIRC3 in 11q22.2 as a candidate driver gene associated with poor clinical outcome. Our study identified previously unreported differentially expressed genes in a homogeneous subtype of oral cancer and the candidate driver genes that may contribute to the development and progression of the disease.

Unexpected case of aplastic anemia in a patient with glioblastoma multiforme treated with Temozolomide

Abstract: We report the case of a 30-year-old woman with glioblastoma multiforme (GBM) treated with surgery followed by concomitant Temozolomide (TMZ) and external beam radiation, which she tolerated well without any interruptions. However, when she was being evaluated for adjuvant Temozolomide, she developed progressive decline in leukocyte counts and platelet counts and subsequently, febrile neutropenia with bleeding manifestations. A bone marrow aspiration and biopsy done showed a gross hypocellular bone marrow with very few erythriod and myeloid cells and no suggestion of progenitor cells, consistent with aplastic anemia.