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 23 for “"Oncogenic KRAS"”.
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Oncogenic Kras and Telomere Biology In Crc Progression
… to advanced CRC. </p> <p>Human CRCs carrying oncogenic mutations in the <em>KRAS</em> oncogene, henceforth referred to as KRAS*, exhibit a 25% higher propensity for developing liver metastases. Similarly, in our CRC mouse model, engineered with an inducible <em>Kras</em>* transgene and …
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Targeting Plasma Membrane Phosphatidylserine Content to Inhibit Oncogenic Kras Function
<p>The small GTPase KRAS, which is frequently mutated in human cancers, must be localized to the plasma membrane (PM) for biological activity. We recently showed that the KRAS C-terminal membrane anchor exhibits exquisite lipid-binding specificity for select species of phosphatidylserine (PtdSer). …
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Cd47+ Exosomes Facilitate Effective Targeting of Oncogenic Kras In Pancreatic Cancer
… of PDAC show that mutations in the GTPase KRAS are encountered in the majority of patients that present with the disease, and are key drivers of cancer initiation, progression and metastasis. However, while it is recognized that the Ras mediated signaling pathway is a key mediator of PDAC …
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Investigating the Role of Oncogenic KRAS G12 Mutations in Cell Signalling
… most frequently mutated oncogene in cancer is KRAS, encoding a small GTPase protein involved in controlling the activity of critical signalling pathways that regulate normal cellular proliferation, such as the PI3K and ERK pathways. The prevalence of different codon substitutions in the KRAS …
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Identification of Oncogenic KRAS-Associated Vulnerabilities in Non-Small Cell Lung Cancer
Activating mutations in KRAS are frequently involved in the pathogenesis of non-small cell lung cancer (NSCLC), the disease responsible for the most cancer-related deaths in the US. Despite intensive efforts to develop drugs that directly interfere with KRAS activity over the past decade, no …
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Targeting Stromal-Mediated Resistance Mechanisms in Oncogenic KRAS-Driven Pancreatic Ductal Adenocarcinoma
… one of the most lethal malignancies, with oncogenic KRAS mutations driving both tumor initiation and maintenance. Despite recent breakthroughs in KRAS-targeted therapies, the rapid emergence of resistance mechanisms limits their clinical efficacy. This dissertation investigates three …
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Oncogenic KRAS drives heterogeneity in metabolic and signalling pathways through genetic and non-genetic mechanisms
… activating mutation in key cell signalling hub KRAS. Despite extensive research into PDAC and KRAS, the impact of both genetic and non-genetic variability during the earliest steps of carcinogenesis are scantly described. We hypothesise that both forms of heterogeneity might alter the efficiency …
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The Functional Contribution of Adaptive Immunity In The Biology of Pancreatic Cancer and Therapeutic Targeting of Oncogenic Kras
… Pancreatic Cancer And Therapeutic Targeting Of Oncogenic Kras</p> <p>Krishnan K. Mahadevan M.B.B.S*</p> <p>Advisory professor: Dr. Raghu Kalluri</p> <p>Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer related deaths in the …
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Oncogene-driven post-transcriptional regulation in lung cancer
… in the RAS family, with somatic mutation of the KRAS gene occurring in ~30% of lung adenocarcinoma tumors. A gene of the same family, RIT1, is mutated or amplified in 10-15% of lung adenocarcinomas. Although therapies targeting some KRAS-mutated tumors have begun to enter the clinic, a …
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Epithelial Memory of Resolved Inflammation Limits Tissue Damage While Promoting Pancreatic Tumorigenesis
… in the context of pancreatitis, mutations of KRAS accelerate tumor development. We discovered that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, …
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Involvement of The Receptor For Advanced Glycation End Products (Rage) In Progression of Pancreatic Cancer
<p>Oncogenic<strong> </strong><em>KRAS</em> is central to several cancer types including pancreatic ductal adenocarcinoma (PDAC), but has been determined to be “undruggable”. Recent studies have indicated that oncogenic <em>KRAS</em> is not constitutively active but relies on a feed-forward …
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Signaling crosstalk in cancers
… cancer. In this dissertation, cross-talk among oncogenic signaling pathways was investigated in two common human cancers. \r\n Pancreatic cancer has a well known spectrum of genetic alterations, among which KRAS mutation is the most prominent component with a detection frequency as high as 90%. …
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An integrated approach to understanding the metabolic rewiring of cancer cells
… and signaling pathways that give rise to oncogenic transformation. However, the field of oncology has only relatively recently begun to appreciate the extent of metabolic rewiring required to sustain the uncontrolled growth of tumors. Cancer metabolism is now an active area of research, …
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Machine Learning Methods for Cancer Immunology
… basis of transcription factor regulators of an oncogenic KRAS signature. Next, gene expression tools are used to resolve the leukocyte subset mixing proportions, stromal contamination, immune checkpoint expression and immune pathway dysregulation from the data. Finally, partial correlations are …
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Elucidating the Role of BMI1 in Lung and Colon Tumor Maintenance and Progression
… engineered mouse models, we determine that in oncogenic KRAS-driven 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 …
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Roles for the polycomb group protein BMI1 in lung adenocarcinoma progression and maintenance
… in mind, in this thesis I used mouse models of oncogenic Kras driven lung cancer to explore the potential dependence of lung adenocarcinoma, among the deadliest of cancers, on Bmil for tumor initiation, progression, and maintenance. Specifically, I demonstrate that Bmil is dispensable for tumor …
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An Oxanthroquinone Derivative Disrupts Ras Plasma Membrane Localization and Function By Inhibition of Acylpeptide Hydrolase and Perturbation of Sphingomyelin Metabolism
<p>Oncogenic RAS proteins are commonly expressed in human cancer. To be functional, RAS proteins must undergo post-translational modification and localize to the plasma membrane (PM). Therefore, compounds that prevent RAS PM targeting have potential as putative RAS inhibitors. Here we examined the …
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Modulation of Kras Structure and Dynamics By Kras Ubiquitination and Membrane Depolarization
<p>KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS …
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