Sirtuins belong to the family of class III histone deacetylases; its role in neoplasia is controversial as both tumor-suppressive and promoting functions have been reported. There are very few reports available, where expressions of sirtuin isoforms are comprehensively analyzed during neoplasia. Therefore, in the present study, the expression of SIRT1, SIRT2, and SIRT7 during different stages of cervical cancer progression was analyzed. The normal cervical epithelium showed feeble expression of sirtuin isoforms, SIRT1, SIRT2, and SIRT7. A significant increase in SIRT1 expression was noted in the cytoplasm as well as in the nucleus of proliferative layers of cervical epithelium in squamous intraepithelial lesions (SIL); however, in the squamous cell carcinomas (SCC), a heterogeneous pattern of SIRT1 expression varying from low to high was noted. A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal < preneoplasia < cancer. Cervical cancer cell lines, HeLa and SiHa, showed higher levels of SIRT1 and SIRT2 in comparison to the immortalized cell counterpart, HaCaT. Specific inhibitors of SIRT1 (Ex527) and SIRT2 (AGK2) impaired the growth of the cervical cancer cells, SiHa, but not of the HaCaT cells. SIRT1 inhibition caused cell death, while SIRT2 inhibition resulted in cell cycle arrest. In conclusion, we report the overexpression of SIRT2 and SIRT7 proteins in cervical cancer and suggest probable application of sirtuin inhibitors as therapeutic targets. Further, a specific increase in the levels of SIRT1 in intraepithelial lesion makes it a promising candidate for identification of preneoplastic changes.
Smartphone-based telestroke services may be a much cheaper alternative to video-conferencing-based telestroke services and are more portable with less technical glitches. To the best of our knowledge, this is the first telestroke model being reported from India. It seems to be the way forward in providing timely treatment in acute ischemic stroke in underserved and resource poor settings.
Exposure to pollutants in the environment, tobacco and alcohol consumption, poor oral hygiene and opportunistic viral infections are important aetiological factors in head and neck cancers. In this study, we evaluate the complex interrelationships between these factors and molecular events such as p53 overexpression in causation of head and neck cancers. Tissue samples from 110 patients with histopathologically confirmed carcinoma of head and neck were analyzed from our tissue biorepository with patient consent. Data pertaining to their dietary habits, tobacco and alcohol consumption were abstracted. P53 overexpression was analysed by immunohistochemistry and HPV (high-risk genotype) were studied by Chromogenic in situ Hybridization using an ultra sensitive DNA probe. Chi-square analysis was done to determine relationships between proportions of dependent and independent variables. Bivariate relationships were determined between these variables using Spearman's rank correlation. Linear regression analysis was used to determine the best predictor variable influencing p53 expression. Tobacco consumption especially smoking cigarettes and all forms of tobacco consumption put together and HPV infection significantly influenced p53 overexpression. Forty-five percent of the studied cohort was positive for HPV. Regression analysis showed interaction between tobacco and HPV infection to be a primary predictor (β = 0.31, p = 0.02) for p53 expression. Tobacco in any form: chewing, smoking and snuffing, along with HPV infection is significantly associated with p53 overexpression. There is a high prevalence of HPV infection (45%) in Indian patients suggesting its possible role in the aetiology of head and neck cancer.
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