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.

Chronic arsenic poisoning: a global health issue -- a report of multiple primary cancers.

Abstract: Chronic arsenic (As) poisoning is a worldwide public health problem. Effects of prolonged exposure to high levels of As in drinking water have been observed and documented in various epidemiological studies from all over the world. The non-malignant cutaneous effects of chronic exposure to inorganic As are well known. A case presenting with multiple cutaneous cancers as well as an internal lung primary in a patient exposed to toxic levels of As in the drinking water is discussed along with a review of literature.

MiR-148a, a microRNA upregulated in the WNT subgroup tumors, inhibits invasion and tumorigenic potential of medulloblastoma cells by targeting Neuropilin 1.

Abstract: Medulloblastoma, a common pediatric malignant brain tumor consists of four molecular subgroups viz. WNT, SHH, Group 3 and Group 4. MiR-148a is over-expressed in the WNT subgroup tumors, which have the lowest incidence of metastasis and excellent survival among all medulloblastomas. MiR-148a was expressed either in a transient manner using a synthetic mimic or in a stable doxycycline inducible manner using a lentiviral vector in non-WNT medulloblastoma cell lines. Expression of miR-148a to levels comparable to that in the WNT subgroup tumors was found to inhibit proliferation, clonogenic potential, invasion potential and tumorigenicity of medulloblastoma cells. MiR-148a expression in medulloblastoma cells brought about reduction in the expression of NRP1, a novel miR-148a target. Restoration of NRP1 expression in medulloblastoma cells was found to rescue the reduction in the invasion potential and tumorigenicity brought about by miR-148a expression. NRP1 is known to play role in multiple signaling pathways that promote tumor growth, invasion and metastasis. NRP1 expression in medulloblastomas was found to be associated with poor survival, with little or no expression in majority of the WNT tumors. The tumor suppressive effect of miR-148a expression accompanied by the down-regulation of NRP1 makes miR-148a an attractive therapeutic agent for the treatment of medulloblastomas.

Establishment of 3D Co-Culture Models from Different Stages of Human Tongue Tumorigenesis: Utility in Understanding Neoplastic Progression

Abstract: To study multistep tumorigenesis process, there is a need of in-vitro 3D model simulating in-vivo tissue. Present study aimed to reconstitute in-vitro tissue models comprising various stages of neoplastic progression of tongue tumorigenesis and to evaluate the utility of these models to investigate the role of stromal fibroblasts in maintenance of desmosomal anchoring junctions using transmission electron microscopy. We reconstituted in-vitro models representing normal, dysplastic, and malignant tissues by seeding primary keratinocytes on either fibroblast embedded in collagen matrix or plain collagen matrix in growth factor-free medium. The findings of histomorphometry, immunohistochemistry, and electron microscopy analyses of the three types of 3D cultures showed that the stratified growth, cell proliferation, and differentiation were comparable between co-cultures and their respective native tissues; however, they largely differed in cultures grown without fibroblasts. The immunostaining intensity of proteins, viz., desmoplakin, desmoglein, and plakoglobin, was reduced as the disease stage increased in all co-cultures as observed in respective native tissues. Desmosome-like structures were identified using immunogold labeling in these cultures. Moreover, electron microscopic observations revealed that the desmosome number and their length were significantly reduced and intercellular spaces were increased in cultures grown without fibroblasts when compared with their co-culture counterparts. Our results showed that the major steps of tongue tumorigenesis can be reproduced in-vitro. Stromal fibroblasts play a role in regulation of epithelial thickness, cell proliferation, differentiation, and maintenance of desmosomalanchoring junctions in in-vitro grown tissues. The reconstituted co-culture models could help to answer various biological questions especially related to tongue tumorigenesis.

Mammary analogue secretory carcinoma of parotid: Is preoperative cytological diagnosis possible?

Abstract: Mammary analogue secretory carcinoma is a recently recognized tumor of salivary gland with characteristic t(12;15)(q13;q25) that results in ETV6-NTRK3 fusion product. Distinguishing mammary analogue secretory carcinoma from other salivary gland tumors is important. Present study highlights cytologic findings in three cases of mammary analogue secretory carcinoma of parotid which facilitate preoperative diagnosis with the aid of ancillary diagnostic techniques. Fine needle aspiration cytology of parotid was performed on three cases after clinical examination. Immunocytochemistry for mammoglobin and S100 were performed. Parotidectomy was done in all cases. The corresponding hematoxylin and eosin stained slides and blocks of all cases were studied. Molecular analysis was done in one of the cases. Cases 1 and 3 revealed uniform atypical epithelial cells arranged in branching papillary pattern with few cells in microcystic pattern. Case 2 showed atypical cells arranged mainly in loose clusters and few singly dissociated. Individual cells revealed round nuclei, vesicular chromatin, prominent nucleoli and abundant finely vacuolated cytoplasm with metachromasia prominent in May-Grunwald-Giemsa smear (case 3). Characteristic hob-nail cells covering papillae were observed in cases 1 and 3. Immunocytochemistry showed strong positivity for mammoglobin and S100 thereby confirming the diagnosis of mammary analogue secretory carcinoma preoperatively. The diagnosis was in concordance with surgical specimen. Also, characteristic ETV6-NTRK3 translocation was confirmed in case 1. Increased awareness and high index of suspicion is necessary for the upfront diagnosis, more so for the papillary variant of mammary analogue secretory carcinoma. Immunocytochemistry aids in confirming this preoperative diagnosis, based on which treatment can be planned. Diagn. Cytopathol. 2016;44:519-525. © 2016 Wiley Periodicals, Inc.