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Showing 1 to 15 of 15 for “"KRASG12D"”.
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Functional contribution of epithelial to mesenchymal transition program on KRASG12D targeting efficacy in pancreatic cancer
<p><strong>Functional contribution of epithelial to mesenchymal transition program on KRAS<sup>G12D</sup> targeting efficacy in pancreatic cancer</strong></p> <p>Ana S. Maldonado, BS</p> <p>Advisory Professor: Raghu Kalluri, M.D., Ph.D. </p> <p>Pancreatic Ductal Adenocarcinoma (PDAC), a highly …
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Absence of Enhancer of Zeste Homolog 2 Promotes the Progression of KRAS-Driven Pancreatic Ductal Adenocarcinoma
… studies showed constitutive activation of KRAS (KRASG12D) is a key genetic driver of PDAC, accelerated by deletion of the epigenetic regulator Enhancer of Zeste Homologue 2 (EZH2). However, contradictory findings suggest multiple roles for EZH2. The goal of this study was to define EZH2’s …
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The origin and properties of pro-oncogenic fields in the intestinal epithelium
… the cell of origin and stem cell behaviour of KrasG12D fields and to develop new tools to recapitulate sequential mutations in vivo. Cre mediated lineage tracing of Atoh1 expressing early secretory progenitors carrying KrasG12D mutations demonstrated that KrasG12D expression does not change …
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Suppression of the Ubiquitin Ligase Function of FBXW7 Accelerates Metastatic Progression of Pancreatic Ductal Adenocarcinoma
… Fbxw7 mutations and loss cooperate with KrasG12D to accelerate PDAC formation with a high frequency, showing that Fbxw7 is an important tumor suppressor in Kras-driven pancreatic cancer. However, studies on the impact of Fbxw7 expression and its substrates in pancreatic cancer progression …
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Role of Il-17/Il-17Ra Signaling In The Pancreatic Tumor Microenvironment
… a transgenic mouse model with pancreatic KrasG12D activation and selective deletion of IL-17RA in the epithelial vs. immune component using either genetic manipulation or bone marrow transplantation. Deletion of IL17RA from the pancreatic epithelial compartment delayed premalignant lesion …
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Investigating the role of the basic helix-loop-helix transcription factor MIST1 in pancreatic diseases
… generated that contained a mutated oncogenic <em>KrasG12D</em> allele. Direct comparison between embryonic <em>Mist1</em> null mice with conditional <em>Mist1</em> null mice in the context of KRASG12D activity demonstrated that embryonic <em>Mist1</em> null mice are more susceptible to PanIN …
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The Regulation of Oncogenic MAP Kinase Signalling by Dual-Specificity MAP Kinase Phosphatases
… show that the endogenous expression of mutant KRasG12D in murine fibroblasts induces the expression of both DUSP5 and DUSP6/MKP-3, suggesting these proteins are involved in the negative feedback response, which constrains ERK activity following constitutive pathway activation. Finally, using …
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Ο ρόλος του επιθηλιακού πυρηνικού παράγοντα -κΒ στη χημική και γενετική καρκινογένεση πνεύμονα
… αναπνευστικής επιθηλιακής έκφρασης ογκογόνου KRASG12D. . Για το σκοπό αυτό, ιχνηλατήσαμε την ενεργότητα του NF-κΒ στους πνεύμονες κατά τη διάρκεια γενετικά επαγόμενης καρκινογένεσης και βρήκαμε δύο διακριτές πρώιμες και όψιμες φάσεις ενεργοποίησής του, οι οποίες χαρακτηρίζονται από πυρηνική …
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Catalytic-Independent And Subtype-Specific Roles Of Fructose-1,6-Bisphosphatase 2 In Sarcoma Growth
… to promote tumor growth in an autochthonous LSL-KrasG12D/+;Trp53fl/fl (KP) model of undifferentiated pleiomorphic sarcoma (UPS), reflecting human epidemiological data. Collectively, these findings reveal FBP2 as a context-dependent regulator of metabolic signaling and sarcoma progression, …
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Modulation of the tumor microenvironment by the CXCR4 antagonist AMD3100 in pancreatic and colorectal adenocarcinoma
… tumour microenvironment (TME) of PDAC. In the KRasG12D; p53R172H; Pdx1-Cre (KPC) genetically engineered mouse model of PDAC, T cells are excluded from tumour nests and this effect is related to the chemokine CXCL12 produced by FAP+ stromal cells. Targeting the CXCL12/CXCR4 pathway with AMD3100, …
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Stromal Fibroblasts Restrain The Rate of Colon Cancer Progression and Metastasis By Suppressing Regulatory T Cells and Colon Cancer Stem Cells
… APCflox/flox; p53flox/flox; tetO-LSL-KrasG12D; Rosa26-LSL-Luc; Rosa26-LSL-rtTA- eGFP. These mice were bred with αSMA-TK and αSMA-RFP transgenic mice for selective targeting and monitoring of myofibroblasts in the tumor microenvironment in these eight allelic transgenic mice.</p> …
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Inhibition of Discoidin Domain Receptor 1 Reduces Collagen-Mediated Tumorigenicity in Pancreatic Ductal Adenocarcinoma
… mice were crossed with a GEMM of PDA, KIC (LSL KrasG12D/+; Ink4aArflox/lox; p48Cre/+). Survival was reduced and tumors were more aggressive in Sparc-/-; KIC mice. Tumors from these animals also displayed elevated Ddr1-mediated signaling. Human PDA, and primary PDA cell lines isolated from …
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Alveolar stem cell dynamics and regulatory mechanisms in homeostasis and early oncogenesis
… model to simultaneously trace wildtype and *KrasG12D* mutant AT2 cells in the same mouse. Clonal analysis of the mutant compartment revealed a heterogeneous response to oncogenic activation where only one AT2 subset underwent significant clonal expansion. By leveraging single cell …
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An Oxanthroquinone Derivative Disrupts Ras Plasma Membrane Localization and Function By Inhibition of Acylpeptide Hydrolase and Perturbation of Sphingomyelin Metabolism
… (MEFs) expressing oncogenic mutant KRASG12V or KRASG12D but not RAS-less MEFs expressing oncogenic mutant BRAFV600E. Consistent with these effects, G01 inhibited the proliferation of KRAS-transformed pancreatic, colon, and endometrial cancer cells. Taken together, these results suggest that G01 …
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Structure Based Drug Design of High Affinity Kras Inhibitors
… on a molecular dynamics simulation-derived KRASG12D structure. The in silico predicted hits were then validated with a battery of cell-based and biophysical assays. Specifically, the hits effects on KRAS signaling, binding affinities for KRAS and mechanisms of activity were evaluated. We …