SACM - United Kingdom
Permanent URI for this collectionhttps://drepo.sdl.edu.sa/handle/20.500.14154/9667
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Item Restricted Investigating resistance mechanisms to chemotherapy and targeted therapy in a model of BRCA2-mutated breast cancer(University of the West of England, 2024-07) Almuafi, Mashael; Ordonez, LilianaIntroduction Breast cancer ranks as the most frequently occurring cancer in the UK. Although there have been promising advancements in survival rates, it remains the second leading cause of cancer-related death among women in the UK. BRCA2 mutations predispose individuals to breast cancer and affect DNA repair mechanisms. While targeted therapies such as olaparib (PARP inhibitors) and carboplatin (platinum-based chemotherapies) have shown efficacy, resistance remains a significant challenge. This study aims to investigate the mechanisms underlying resistance to carboplatin and olaparib in BRCA2-mutated breast cancer, focusing on epithelial-mesenchymal transition (EMT) as a potential pathway contributing to therapy resistance. Methods Using a previously genetically engineered mouse model with BRCA2/TP53 mutations, tumour samples were analysed using hematoxylin and eosin (H&E) for morphological characteristics and expression of key markers (E-cadherin, vimentin, Ki67) via immunohistochemistry (IHC). Tumours were categorised into untreated, olaparib-resistant and carboplatin-resistant groups. Statistical analysis was performed to compare marker expression and morphological features across these groups. Results H&E analysis revealed interestingly that carboplatin-resistant tumours showed an equal distribution of epithelial and mesenchymal features, not significantly different from untreated and Olaparib-resistant tumours. IHC analysis of EMT markers showed that carboplatin-resistant tumours maintained moderate E-cadherin levels. Vimentin expression showed no significant differences in carboplatin-resistant tumours compared to untreated and Olaparib-resistant tumours. Notably, Ki67 expression analysis revealed no significant differences in proliferation rates across all three cohorts, challenging the assumption that resistant tumours would exhibit increased proliferation. These findings suggest distinct resistance mechanisms between olaparib and carboplatin in BRCA2-mutated breast cancer. EMT appears to play a crucial role in olaparib-resistance but not in carboplatin-resistance. These findings underscore the need for tailored treatment strategies and further research into the diverse mechanisms of therapy resistance. Future studies should focus on developing EMT-targeted therapies and exploring their efficacy in combination with existing treatments to improve patient outcomes.13 0Item Restricted Orofacial Development Changes in Children Following Cancer Treatment: A Comprehensive Review of Literature and Analysis of Current Data in Leeds Dental Institute.(University of Leeds, 2024) Alghamdi, Talal; Drummond, BernadetteIntroduction: Childhood cancer survivors often experience various side effects after treatment, including dental and orofacial developmental conditions. According to the literature, the treatment for cancer in children can affect the development of teeth, the function of salivary glands, the development of facial structures, and the operation of the temporomandibular joint [TMJ]. Leeds Dental Institute [LDI] has accumulated a wealth of data while providing dental healthcare for cancer survivors. This extensive data has not been thoroughly explored or published. Thus, this study aims to investigate the long-term effects of cancer treatment on dental and orofacial structures from the literature and the available records in children at Leeds Dental Institute. Methods: This research is structured into two sections. The first is a comprehensive literature review of existing studies on the adverse effects of cancer treatments on oral and facial structures in children by searching six databases to establish a foundation for understanding the broader context of the issue. The second section is a retrospective data collection and analysis of paediatric patient data from the electronic records in LDI using a list of appointments attended by cancer patients in LDI. Results: Fifty-one articles were included in the comprehensive literature review following the database search and the inclusion criteria. Numerous studies concluded that chemotherapy and other anticancer treatments in children are linked to increased dental anomalies like microdontia and enamel defects, especially when treatment occurs at a young age. The findings have been summarised in tables. Of the 806 registered appointments identified, the clinical records of 85 childhood cancer survivors who met the inclusion criteria were included. The post-treatment identified conditions included microdontia, hypodontia and enamel hypoplasia. Demographics, cancer diagnosis and type of treatment, in addition to dental findings, were summarised in tables. The data were also categorised according to age at the cancer treatment time and type of treatment provided. Conclusions: The literature review and LDI patient data revealed that childhood cancer survivors commonly face serious long-term dental issues due to their treatments. These findings highlight the importance of a better understanding of cancer therapy's impact on orofacial development, requiring more attention and support from healthcare professionals, particularly dentists.37 0Item Restricted The Role of an online health forum for Women with Breast Cancer Treated by Chemotherapy(Saudi Digital Library, 2023-11-03) Aljehani, Shroog; Bath, PeterBreast cancer, which affects more women than men, is among the global death-leading chronic conditions that have triggered the need for online health forums as interventions to help meet various healthcare goals. Women with breast cancer treated with chemotherapy have diverse needs, some of which can be met through these forums. Therefore, this dissertation is a systematic review that evaluates evidence from different journal publications to investigate the role of an online health forum for women with breast cancer treated by chemotherapy. The PICO framework was the preferred method for developing the study’s research question, while the Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was the selected methodology for presenting results for this systematic review. This study is important because the findings will inform the relevance and usage of online health forums, informational needs, and the perceptions and information-seeking behaviours of women with breast cancer treated by chemotherapy.10 0