Saudi Cultural Missions Theses & Dissertations
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Item Restricted Repurposing Approved-Chemotherapeutics for Head and Neck Squamous Cell Carcinoma(Saudi Digital Library, 2022) Alkurdi, Khlood; Tappuni, Anwar; Muy, Teck- TehThe advancement in head and neck squamous cell carcinoma (HNSCC) therapy necessitates the acquisition of a superior understanding of cancer molecular biology and the capability to use this knowledge to adapt the therapy to achieve best patient outcome. HNSCC is heterogeneous in its basis, mechanism, and behaviour, and its biomarkers are considered greatly important in identifying the tumorigenesis mechanism that is involved in therapy resistance to increase patient survival. Resistance to chemotherapy is a major cause of treatment failure in HNSCC patients; the long-term assessment of a patient’s compliance with chemotherapy is key to overcoming treatment resistance and controlling cancer. FOXM1 is a known oncogene and plays an important role in conferring chemoresistance. The objective of the current study was to investigate candidate approved-chemotherapeutic drugs to inhibit FOXM1 in HNSCC cells in the aim to counteract chemoresistance. Methods: Dose-response assay was performed to investigate the potency of 16 candidate drugs using crystal violet cell viability assay in 11 human cell lines consisting of normal oral keratinocytes, oral fibroblasts, normal skin keratinocytes, premalignant oral buccal mucosa and 7 HNSCC cell lines. The most potent drugs with least toxicity towards normal control cells were selected to investigate their effect on FOXM1 gene expression using reverse transcription quantitative PCR. Results: Vincristine, lanatoside A and topotecan were found to be the most potent drugs with least toxicity across the 11 cell lines. Lanatoside A was the only effective drug for a paclitaxel resistant cell line (CaLH2-PTX). All three drugs significantly suppressed FOXM1 gene expression levels in all 7 HNSCC cell lines. Conclusion: This study identified 3 existing candidate approved chemotherapeutic drugs demonstrating potent anti-proliferation effects against a panel of HNSCC cell lines and with low toxicity towards normal cells. Further investigations are needed to understand their mechanisms and their effects on FOXM1 in HNSCC cells.7 0Item 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-2.12 0