Browsing by Author "Thakur, Sanjeev"

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Evaluation of breast cancer cell lines (MCF-7 & T47D) : Influence of insulin and metformin on growth parameters
(Central University of Punjab, 2016) Sharma, Prateek; Thakur, Sanjeev
Breast cancer is the complex and heterogenous malignancy caused as a result of interaction of hormonal, environmental and genetic factors. Major advances made in the field of breast cancer research have emanated from studies involving human breast cancer cell lines MCF-7 and T47D. Insulin act as a potent mitogen in normal mammary tissue and breast cancer cells in culture. Insulin receptor is overexpressed in several human breast cancers and this overexpression results in transformed phenotype in human mammary epithelial cells. Experimental study has shown that Insulin induces significant mitogenic effect in MCF-7 and T47D cells in dose-dependent manner. 100nM concentration of Insulin enhances the growth of MCF-7 and T47D cells by ? 7.3 and ? 5 folds respectively in comparison to control. The antidiabetic drug metformin lowers risk of breast cancer via direct action (Insulin independent) and indirect action (Insulin dependent). The treatment of the hyperinsulinemia with the metformin will lower the circulating levels of insulin and improve insulin sensitivity, thus results into potential decrease in the incidence of breast cancer. The results show that MCF-7 and T47D cells growth inhibited over control at high doses (10 mM concentration) of metformin. MCF-7 and T47D cells also show decrease in insulin induced cell proliferation at higher doses of metformin.
Histopathological staging in putative prostate cancer tissues and reviewing litearture of correlation between prostate specific antigen levels and prostate cancer inci. 2012.
(Central University of Punjab, 2012) Thakur, Shweta; Thakur, Sanjeev
Prostate cancer (PCa) remains the most significant cause of cancer specific mortality in elderly men. Asymptomatic behavior, non-modifiable risk factors and metastatic nature is the main problem of PCa. It remains clinically silent and presents itself only at advanced stage. Thus, diagnosing PCa at an early stage can result in increased chances of better treatment and hence, increased survival rate. An accurate biomarker can detect the cancer at an early stage and hence, at curable stage. Clinical parameters can only suspect prostate cancer. Whereas, histopathological examination can establish definite diagnosis of PCa. Various histological patterns are associated with cancer aggressiveness. Therefore, better understanding of clinical relevance of these histopathological findings can help to evaluate a robust biomarker for early detection of PCa. Present study was divided into two parts. First part was aimed to study the histopathology of putative prostate cancer tissue specimens. In second part, the literature of association of pre-operative serum prostate specific antigen levels with cancer detection and aggressiveness was reviewed. Protocol for histopathology of prostate tissues was established. Results of histopathological findings in putative PCa specimens were evaluated. Prevalence of histological PCa was not found in putative PCa tissues. Image library of results of the study was prepared for future analysis. Review of literature of correlation of serum PSA levels with PCa incidence suggests that PSA screening for PCa is a two-sided debate. No doubt that PSA holds the probability of detecting early PCa before development of symptoms; certain v limitations are associated with it. First, it is not reported to be 100% accurate. Second, it generates false positive and false negative results. A false positive result leads to over-treatment whereas a false negative result generates false sense of security against PCa in patient, both affects quality of life. Another main concern with PSA screening is its inability to differentiate between indolent and aggressive cancer. Therefore; accurate and economical molecular biomarkers for early detection and distinction of indolent versus aggressive cancer are urgently required. Until such biomarkers are developed and more convincing evidences regarding efficacy of PSA screening becomes available, research should focus on improving the diagnostic clinical utility of PSA by utilizing novel PSA isoforms. Identifying and validating correlation of serum PSA with tissue PSA and histological grade would be beneficial in terms of requirement of less invasive diagnostic methods to be used to measure PSA expression level as well as to confirm PCa. Future research may focus on evaluating the histological expression of other putative biomarkers and comparative serum proteomic profiling in different PCa stages.
To Study the Dose and Time Dependent Effect of Human Insulin and Metformin on the Growth of Breast Cancer Cells
(Central University of Punjab, 2012) Cholia, Ravi Prakash; Thakur, Sanjeev
Cancer and diabetes, both are leading causes of mortality globally. Both the diseases are multifactorial and share number of common risk factors. Hyperglycemia and hyperinsulinemia which are the characteristic features of diabetes influences the growth rate and proliferation of tumor cells directly or indirectly. Type 2 diabetes shows stronger association with various cancers. Breast cancer is one of the malignancy affecting females worldwide. This study demonstrates that glucose not only acts as energy source in tumor cell but also acts as mitogen. Insulin not only regulates the blood glucose level but also induces growth and proliferation in MCF 7 and MDA MB 231 breast cancer cell lines independently and in combination with glucose. Metformin inhibit proliferation of MCF 7 and MDA MB 231 breast cancer cell lines independently and also in presence of glucose and insulin, but shows more inhibitory effect in presence of insulin as compare to glucose. Recently discovered insulin receptor antagonist S961 did not showed any significant response in breast cancer cell lines MCF 7 and MDA MB 231. The ineffectiveness is probably due to blocking effect of higher insulin dose. So with this investigation it can be concluded that metabolic alteration leads to proliferation of breast cancer cell lines.