Saudi Cultural Missions Theses & Dissertations
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Item Restricted Role of Cancer Stem Cells in Oral Squamous Cell Carcinoma – A Systematic-Like Review(Saudi Digital Library, 2023-08-07) Aldossary, Razan; Delaney, ChristopherBackground: Oral squamous cell carcinoma (OSCC), is a serious global concern due to its high mortality rate and the deformation and functional defects associated with the disease. Limited studies in the literature have discussed the most common cancer stem cell (CSC) markers expressed in OSCC. This study aims identify all the papers that discussed markers in OSCC and to identify which of those markers might be the most likely cause of cancer progression, metastasis and resistance to therapy. Methods: A Systematic-like review was conducted by searching PubMed, Scopus, Google and Google Scholar for articles published from 2015 to 2023 using variety of terms: ‘oral cancer’, ‘cancer stem cells’ and ‘cancer treatment resistance’. Studies that examined cancer stem cell markers in OSCC and were published in English were included. Excluded articles were the studies discussed tumors other than OSCC, opinions, editorials, book chapters, and abstracts only. Forty-two articles containing a total of 19 stem cell markers were included. Results: CD44, CD133 and Sry related HMG-Box 2 (SOX2) were the most common CSC markers in OSCC and were responsible for chemoresistance, self-renewal and tumourigenicity. Aldehyde dehydrogenase (ALDH), CD24, B-cell specific Moloney murine leukemia virus integration site 1 (BMI1) and NANOG were involved in metastasis. Conclusion: CSC markers are contributors to metastasis, progression, and treatment resistance in OSCC. Determination of CSC markers involved in OSCC is crucial to developing therapies that target OSCC. Additional studies are needed to accurately identify the role of these markers and to enhance the effectiveness of developed treatments for OSCC. Keywords: Cancer stem cells, OSCC, therapy resistance, ALDH, CD133, CD44, NANOG, SOX-2.13 0Item Restricted Effects of MDM2 and HMG-CoA Reductase Inhibition on Epithelial to Mesenchymal Transition in Prostate Cancer(2023-07-27) Alsubhi, Samia Mekheer; Rathinavelu, AppuAccording to the American Cancer Society, prostate cancer is the second leading cause of cancer death among men. Aggressive growth and metastasis are the main reasons for high mortality among prostate cancer patients. The proto-oncogene MDM2 controls multiple signaling pathways that are involved in cell cycle regulation and survival. MDM2 also has a major role in imparting stemness and Epithelial to Mesenchymal Transition (EMT) abilities to prostate cancer cells that are inherently less aggressive. During cancer growth, lipid metabolism also plays a pivotal role in cellular reprogramming, which eventually leads to the induction of EMT and the acquisition of stemness. It has been well documented that the intermediates of mevalonate metabolism can significantly affect gene expressions in cancer and influence the tumor microenvironment to support tumor growth and survival. At present, there is a lack of comprehensive knowledge about the use of MDM2 inhibitor RG7388 in cancers with p53 mutation, since most studies report that it is most effective in cancers with wild-type p53. Therefore, our study was designed to investigate the effects of RG7388 in p53 mutant or p53 null prostate cancer cells. Our study also explored the effect of RG7388 in combination with simvastatin, which blocks the mevalonate pathway by inhibiting the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase enzyme. Simvastatin has been reported to have anticancer effects in several cancers but, so far, there is no data available regarding its use in combination with RG7388. Therefore, our study aimed to analyze the effects of RG7388, individually or in combination with simvastatin, on EMT and cancer stemness. Our experiments were conducted using DU145 and PC3 prostate cancer cells which have p53 mutant and null status respectively. Our experimental results showed a decrease in the viability of PC3 and DU145 cells, in a time and concentration-dependent manner, after treatment with RG7388 or simvastatin. The mesenchymal and stem cell markers were also downregulated after RG7388 and simvastatin combination treatment. In addition, individual and combination treatments with the above-mentioned drugs induced the disintegration of spheroids and eventually a reduction in the total number of spheroids. Immunofluorescence staining of spheroids revealed a downregulation of cancer stem cell markers among all treated groups. Furthermore, the scratch assay showed inhibition of migration of the DU145 and PC3 cells, particularly after the combination treatment. Our results have confirmed that RG7388, simvastatin, and their combination treatments can reverse EMT, inhibit migration, and reduce cancer stemness in p53 mutant or null prostate cancer cells. Our study also suggests that RG7388 and simvastatin combination can be effective for treating prostate cancers that are aggressive due to MDM2 expression.18 0