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 20 of 27 for “"TRP53"”.
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P53R245W Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer
<p><em>Trp53</em> mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of <em>Trp53</em> mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with …
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p53 nuclear localization control, and p53-dependent regulation of DNA repair gene transcripts
… the cells of mice with a deletion allele for the Trp53 gene, to explore both the regulation of p53, and its downstream functions mediated by specific activation of target genes. Chapter 2 addresses the regulation of nuclear localization of the p53 protein. Previous reports in the literature had …
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Characterizing the contribution of the LXCXE binding cleft to pRB-mediated genome stability and tumor suppression
… tumor formation and more aggressive pathology in Trp53+/- and Trp53-/- mouse models, revealing a new mechanism of tumor suppression, facilitated by pRB, whereby genome stability is maintained by the proper condensation of mitotic chromosomes. Subsequent study of the mechanism by which pRB …
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Dissecting the impact of SMAD4 loss and KRAS mutations in pancreatic ductal adenocarcinoma
… models of PDAC, which focus on Kras G12D and Trp53 mutations, alongside limited consideration of CAF heterogeneity, have potentially contributed to largely inefficient treatment options for this disease. In this work, I use Trp53-mutant mouse models driven by Kras G12D or Kras G12V mutations …
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Characterizing the Impact of Specific Genetic Mutations on Chemotherapy Resistance and the Efficacy of Oncolytic Viruses for the Treatment of Ovarian Cancer
… in syngeneic tumour- bearing mice with KRas, Trp53 and Pten mutations, including one tumour model that did not respond to carboplatin. Response to VSV∆M51 in-vivo was associated with activation of CD4+ and CD8+ T lymphocytes in the peritoneal TME. In summary, VSV∆M51-based immunotherapy has …
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AXL Targeting Restores PD-1 Blockade Sensitivity of STK11/LKB1 Mutant NSCLC Through Expansion of TCF1+ CD8 T Cells
… lung adenocarcinomas driven by mutant Kras and Trp53 (KP) resulted in an ICB refractory syngeneic KPL tumor. Mechanistically, this occurred because KPL mutant NSCLCs lacked TCF1-expressing CD8 T cells, a phenotype that was recapitulated in human STK11/LKB1 mutant NSCLCs. We found that systemic …
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Pten Function in Postnatal Brain Development and Tumorigenesis
… formation. Co-deletion of <em>Pten</em> and <em>Trp53</em>, two commonly mutated tumor suppressor genes in human brain tumors, could synergize in generating high-penetrant medulloblastoma with a growth pattern centering around blood vessels and extensive neuronal differentiation. The …
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The role and function of the Ras-related protein TC21 in Neurofibromatosis type 1
… TGF-beta receptors. Conversely, growth of <i>Nf1;Trp53</i> brain tumors and <i>NF1<sup>-/-</sup></i> MPNST sarcomas were accelerated by <i>TC21</i> loss. MPNST from <i>Nf1;Trp53</i> mice and <i>NF1<sup>-/-</sup></i> MPNST xenografts had increased levels of TGF-beta mRNA and protein and blocking …
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Interlocking mechanisms regulating the circadian clock response to DNA damage
… the p53:PER2:MDM2 complex. Firstly, we generated Trp53KO (Trp53 gene encodes mouse p53) cell lines in NIH 3T3 Per2:dLuc reporter cells expressing luciferase driven by the Per2 promoter. Phase-response curves (PRCs) for Trp53WT and Trp53KO reporter cells were obtained in response to ionizing …
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Unique Transcriptional Profiles Underlie Osteosarcomagenesis Driven By Different P53 Mutants
… mutations in the DNA binding domain of the <em>Trp53</em> gene are characterized as structural (<em>p53R172H</em>) or contact (<em>p53R245W</em>) mutations based on their effect on the conformation of the protein. These mutations show gain-of-function activities such as increased metastatic …
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Notchless Interacts with Multiple Signaling Pathways during Mouse Peri-Implantation Development
… functions for NLE1 in the ribosomal biogenesis, TRP53 and WNT pathways during mammalian embryonic development.</p>
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Suppression of the Ubiquitin Ligase Function of FBXW7 Accelerates Metastatic Progression of Pancreatic Ductal Adenocarcinoma
… potential of pancreatic cancer in KrasG12D/+; Trp53-/- PDAC models, in immunocompromised and immunocompetent hosts. We explore the impact of different Fbxw7 mutants in tumorigenesis, where the hotspot mutant R465 recapitulates the phenotype seen in complete loss-of-function of Fbxw7. Finally, …
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Assessing the temporal role of miR-200 loss in murine models of NSCLC
… conditional activation of Kras<sup>G12D</sup>, Trp53<sup>R172H</sup>, and deletion of miR-200<sup>141/c</sup> autochthonously in mouse lungs, creating models with distinct metastatic potentials. Mice with loss of miR-200 had detectable distant metastases earlier than their cohorts where miR-200 …
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Y Chromosome Gene Kdm5D Epigenetically Drives Sex Differences In Colorectal Cancer
… conditional null alleles of <em>Apc</em> and <em>Trp53</em> tumor suppressors (designated iKAP), revealed higher metastases and worse outcomes specifically in males with oncogenic mutant KRAS (KRAS*) CRC. Integrated cross-species molecular and transcriptomic analyses identified Y-chromosome gene …
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Tobacco carcinogen induced mouse lung adenocarcinoma cell lines as tools to identify novel lung cancer genes
… including stemness features, Kras and Trp53 mutations. All cell lines overexpressed proliferin, a murine prolactin orthologue, functioning as a lung tumor promoter. Interestingly prolactin was found overexpressed and portended poor prognosis in human lung adenocarcinoma. In conclusion …
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Elucidating the Role of BMI1 in Lung and Colon Tumor Maintenance and Progression
… lung adenocarcinomas, with or without Trp53 deletion, genetic ablation of Bmi1 at tumor initiation induces a pronounced proliferation defect and consequently significant suppression of tumor development and thus extension of lifespan. In stark contrast, Bmi1 deletion in established lung …
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Investigating the initiation and progression of small cell lung cancer
… alleles of two tumor suppressor genes, Trp53 and Rbl. We identified frequent, high-level amplification of a novel, protooncogenic transcription factor Nuclear Factor I/B (Nfib in mouse, NFIB in human), which frequently occurred coincident with amplification of a previously characterized …
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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 mutations in …
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Myxoma Virus Therapy of Malignant Gliomas in Murine Syngeneic Models: Translating Barriers to Therapy
… syngeneic murine glioma lines derived from Nf1+/-Trp53+/- mice formed aggressive, gliosarcoma-like tumours in the brains of C57Bl/6 mice, but MYXV administration resulted in a very transient infection and no treatment efficacy. Further, a new syngeneic glioma model was created through culturing …
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Tissue adaptations to colitis influence neoplastic risk through clonal interaction
… Introduction of cancer-driver mutations in *Trp53* and *Kras* in a *Muc2<sup>KO</sup>* background had limited impact on survival and pathology, which drew interesting parallels between tissue regenerative processes and cancer initiation. Such processes were explored in depth after chemical …
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