Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 13 of 13 for “"p53 mutations"”.
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Uncovering p53 Mutations and Abnormal Gene Expression in Pediatric Adrenocortical Cancer
… it is well-known that the tumor suppressor p53, which is mutated in over 50% of all human cancers, is commonly mutated in pediatric adrenocortical cancer. In addition, evidence strongly suggests that if a child has adrenocortical cancer, it indicates a germline p53 mutation exists.</p> <p>In …
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Gain-of-function and dominant-negative effects of distinct p53 mutations in lung tumours
… limited therapeutic benefit in most cases. TP53 (Trp53, p53) mutations occur in approximately 50% of lung adenocarcinoma cases and are associated with poor prognosis and so novel therapies that target these p53 mutant lung tumours are urgently needed. Despite the high frequency of p53 …
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Of Apoptosomes and Oncogenes: Repurposing a Death Machine & Deconstructing the Action of P53 Mutations
… driving human disease. The tumor suppressor p53 is mutated more than any other gene in human cancer, but unlike other tumor suppressors, it acquires missense mutations which encode oncogenic variants. These gain-of-function mutants promote more aggressive and metastatic cancers in vivo but …
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The relationship between p53 mutations and differential sensitivity to anti-cancer drugs in oesophageal cancer cell lines
… (P-gp) and glutathione-S-transferase (GST), and p53 mutations were investigated. Chemosensitivity of the WHCO1, WHC03 and HCu-13 cell lines to 7 anti-cancer agents was determined. WHC03 was relatively resistant to cisplatin and transplatin, but sensitive to vinblastine, vincristine, …
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Targeting The Mdm2-P53 Axis For The Treatment of Dedifferentiated Liposarcoma
… and the most known negative regulator of p53. <em>MDM2</em> amplification is considered the “hallmark” of DDLPS. Additionally, these tumors are known to harbor wild-type p53. We sought to take advantage of this knowledge and evaluate the role of SAR405838, a novel small molecule inhibitor …
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A Cell-Based Model to Study Factors that Drive Diffuse Astrocytoma Development
… an IDH1R132H mutation, resulting in neomorphic mutations, which catalyze isocitrate to the oncometabolite D-2-hydroxyglutarate (2-HG) instead of alpha-ketoglutarate (α-KG). As 2-HG accumulates, it induces a hypermethylator phenotype that prevents the cells from differentiating. Acquisition of …
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The germline- and tissue-specific effects of endogenous point-mutant p53
p53 is frequently altered in human tumors through missense mutations that result in accumulation of mutant p53 protein. These mutations may confer dominant-negative or gain-of- function properties to p53. To ascertain the physiological effects of tumor-associated point- mutations in p53, the …
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Investigation of the p53-dependent apoptosis versus arrest decision through analysis of Prep gene regulation
The p53 tumor suppressor gene is thought to play a critical role in the maintenance of genetic integrity by virtue of its ability to check the growth of abnormal or damaged cells through initiation of the cell cycle arrest and apoptosis pathways. p53 itself is mutated in roughly half of all human …
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Synthetic Lethality of Cdk Inhibition and Doxorubicin In Triple-Negative Breast Cancer Requires P53 Inactivation
… patients. A majority of TNBC tumors carry p53 mutations, enabling them to bypass the G1 checkpoint and complete the cell cycle even in the presence of DNA damage. Therefore, we <strong>hypothesized that TNBC cells are sensitive to cell cycle targeted combination therapy, which leaves …
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Interplay Between P53 and Epigenetic Pathways in Cancer
The human TP53 gene encodes the most potent tumor suppressor protein p53. More than half of all human cancers contain mutations in the TP53 gene, while the majority of the remaining cases involve other mechanisms to inactivate wild-type p53 function. In the first part of my dissertation research, I …
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Roles for the polycomb group protein BMI1 in lung adenocarcinoma progression and maintenance
… independent of a canonical target, the pl9ARF-p53 tumor suppressive axis. This creates a large potential therapeutic window, as half of all lung adenocarcinoma patients display p53 mutations. My gene expression analyses further establishes a critical role for Bmil in the repression of …
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Molecular changes involved in oral cancer progression and their relevance to keratinocyte immortalisation
… (RAR)-b and the cell cycle inhibitor, p16INK4a, p53 mutations and increased levels of telomerase/hTERT mRNA. In contrast, increased expression of the EGF receptor (EGF-R), known to be a characteristic of oral cancer, does not occur until after the dysplasia stage in squamous cell carcinomas …
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Assessment of immunological responses to tumour antigens relevant to the development of therapeutic cancer vaccines
P53 protein that has been referred to as the "guardian of genome". It acts to suppress tumour development through mechanisms involving cell cycle arrest, DNA repair, senescence and apoptosis. Loss of the tumour-suppressive activity in p53 is a frequent event, occurring in more than 50% of all types …