Browsing by Author "Sharna, Ansley"
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Item Investigating the mechanism of action of metformin and tolfenamic acid in medulloblastoma cells(2024-03-21) Sharna, Ansley; Mata, Fernanda; Sankpal, UmeshPurpose: Medulloblastoma, a highly malignant CNS tumor primarily diagnosed in children, presents a complex challenge in the field of medicine. While current multimodal treatment approaches, including total excision, chemotherapy, and radiation, yield relatively high survival rates, they are often accompanied by a range of significant adverse effects in adulthood, including neurological and motor deficits, endocrine dysfunction, hearing loss, and secondary tumors. Thus, more recent studies have shifted their focus to developing alternative, more precisely targeted anti-tumor therapies to mitigate the toxicity associated with existing therapies and enhance patient quality of life. An approach to address this problem involves investigating the synergistic potential of drug combination therapy using FDA-approved drugs to treat medulloblastoma. Among the drugs being investigated are Metformin (Met), an antidiabetic medication, and Tolfenamic Acid (TA), a nonsteroidal anti-inflammatory drug (NSAID) used for migraine treatment. Both drugs have been shown to exhibit anti-cancer activity. Previous work conducted in our laboratory has provided evidence of TA’s anticancer activity being mediated through the downregulation of pro-cancer Sp1 and survivin protein expression. The objective of this study was to enhance understanding of the mechanisms of action of metformin and tolfenamic acid by assessing their cell cycle-associated effects on DAOY human medulloblastoma cancer cells using Western blotting and flow cytometry techniques. Methods: The efficacies of Met and TA in terms of their anticancer effects were evaluated by determining the IC50 values of each drug using CellTiter-Glo and CCK-8 cell viability assays. The cell cycle effects of TA and Met were studied by Western blot analysis using protein extracts from treated DAOY cells. In addition, a cell cycle analysis of treated cells was performed using flow cytometry. Results: In our studies, both TA and Met were found to demonstrate anti-proliferative effects on DAOY cells. As demonstrated by Western blotting and flow cytometry analysis, the antiproliferative effects of both TA and Met were mediated through cell cycle arrest. Conclusion: This study suggests the significant potential of utilizing Met and TA in novel drug combination therapy for medulloblastoma. Their effects on protein expression open possibilities for enhancing cell cycle arrest or inducing apoptosis while decreasing the use of toxic therapies. Given the importance of minimizing long-term effects in children being treated for medulloblastoma and enhancing their quality of life, the mechanisms of Tolfenamic Acid and Metformin can be further explored.Item Survivin as a Prognostic Marker in Breast Cancer(2024-03-21) Khosla, Aishani; Sharna, Ansley; Sankpal, UmeshPurpose: Breast cancer is the second leading cause of cancer-related death for women in the United States and continues to pose a threat to millions of women globally. Incidence rates of breast cancer continue to rise across ethnic/ racial groups and survival rates continue to increase with the development of screening protocols and targeted therapeutics. However, despite the advances in disease diagnosis and management a racial disparity continues to be evident. Even with advanced therapeutics and the development of various prognostic markers, Black women continue to have higher rates of breast cancer mortality when compared to other racial groups. Mortality is also correlated with the status of metastasis, as advanced disease points to poor outcomes and survival rates. The evident racial disparity and advanced staging reflect the need for new and more efficient prognostic markers to be developed to better manage and treat breast cancer. Existing prognostic factors include immunohistochemical markers such as estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor-2. One potential immunohistochemical marker is the Inhibitor of Apoptosis Protein (IAP), survivin, with elevated levels of expression found in various cancer types, including breast cancer. Previous research has linked elevated levels of survivin expression with increased resistance to therapeutics like chemotherapy and radiation. However, there remains some question of the true clinical significance of survivin as a prognostic factor. The objective of this literature review is to provide an overview of research on the use of survivin expression as a clinically useful prognostic marker in breast cancer. Methods: Relevant research articles were collected mainly through the PubMed database. Studies investigating survivin expression alone or with other prognostic markers of breast cancer using immunohistochemistry or PCR analysis of breast tumor tissue were selected. Results: Review of this literature showed that the majority of studies found a significant correlation between levels of survivin expression and poor prognosis. Fourteen studies from the total seventeen analyzed identified various established prognostic markers to be correlated with survivin expression. Increased levels of survivin were associated with poor prognosis through findings of higher grade, greater lymph node metastasis, increased proliferation, and other indicators. Conclusion: These findings suggest that survivin has the potential to be used clinically in combination with other biomarkers to bolster diagnostics. In addition, the results indicate that survivin may be used as a marker in disease management as well as a unique focus of targeted therapy.