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 24 for “"mTOR inhibitors"”.
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Characterization of mTOR Inhibition and Autophagy Inhibition in Non-Small Cell Lung Cancer
… has been to characterize NSCLC response to mTOR inhibition and determine whether there are any molecular biomarkers that can predict response. mTOR is a central regulator of several pro-oncogenic signaling pathways and plays a role in cell growth, proliferation, metabolism, and inhibition of …
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Role of Manganese Superoxide Dismutase in Chemotherapy-induced Oxidative Stress
… with the use of mammalian target of rapamycin inhibitors. I hypothesize that the anti-tumor effect of mTOR inhibitors in mantle cell lymphoma is mediated by an increase in manganese superoxide dismutase (MnSOD) protein expression and accumulation of hydrogen peroxide (H₂O₂). Findings indicate …
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Understanding the nutrient sensing branch upstream of mTORC1
mTORC1 is a master regulator of cell growth that responds to diverse environmental inputs and is deregulated in human diseases, such as cancer and epilepsy. One important input to this system is amino acids, such as leucine, which require the Rag GTPases and its regulators, including GATOR1 and …
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Pi3K- and Mtor-Dependent Mechanisms of Lapatinib Resistance and Resulting Therapeutic Opportunities
… and/or upregulation. In a third LapR cell line, mTOR activation was enhanced in a manner independent of its usual PI3K/Akt-mediated activation or other known mTOR activators. Thus, all three cell lines possessed increased activation of the PI3K/mTOR pathway, suggesting the use of PI3K and/or mTOR …
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The impact of supplemental vitamin D on motor learning and seizures in mice with hyperactive mTOR induced epilepsy and ataxia.
Genetic mutations that cause hyperactive mTOR signaling in the cerebellum lead to disrupted cerebellar growth, debilitating motor impairments, and may contribute to the development of epilepsy. mTOR inhibitors can reduce seizures and may prevent behavioral impairments but are associated with …
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Análisis obsevacional para evaluar la eficacia y seguridad de los mTORi en la esfera oncológica en el paciente trasplantado hepático
… the immune tumor surveillance. The appearance of mTOR inhibitors (mTORi, sirolimus, everolimus) within the immunosuppressive arsenal as non-nephrotoxic agents may represent an advance in the tumor control of these patients, since they are basically used in the area of oncology as antiproliferative …
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A Phase I Dose-Escalation Study of The Braf Inhibitor Vemurafenib In Combination With The Mtor Inhibitor Everolimus In Subjects With Advanced Cancer
… to cell proliferation in many human cancers. The mTOR inhibitors are well known to exert profound anticancer effects across malignancies through inhibition of the PTEN/PI3K/AKT/mTOR (mTOR) pathway. We hypothesize that the toxicity profile of the combination of vemurafenib and everolimus will be …
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TRANSLATIONAL RESEARCH TARGETING BILIARY TRACT CANCER
… combined with genetic ablation of members of the mTOR pathway. This combination effect was validated using multiple pharmacological BET and mTOR inhibitors, accompanied by increased levels of apoptosis and cell cycle arrest. In a xenograft model, combined BET degradation and mTOR inhibition …
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The Role of LKBI Tumor Suppressor in Endometrial Cancer
… but also suggest that clinical responses to mTOR inhibitors may be linked to LKB1 inactivation.
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The identification of the mTOR-regulated phosphoproteome and a mediator of feedback inhibition to P13K-Akt
The mTOR protein kinase nucleates two complexes, mTORC1 and mTORC2. Collectively, the two complexes regulate processes important for cell growth and proliferation, including protein synthesis, autophagy, metabolism, and cytoskeletal maintenance. Despite this diverse array of cellular functions, few …
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Determining S6K1 localisation and interactions with mTORC1 in live cells using fluorescence lifetime imaging microscopy
The S6K1 kinase functions downstream within the mTORC1 pathway to regulate cell proliferation, aging and adiposity. Using GFP technology and advanced imaging, localisation of S6K1 has been established (47% nucleus and 53% cytoplasm). S6K1 strongly (Δτ=200 ps) interacts with the complex scaffold …
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Crosstalk Signaling Between cAMP and mTORC1
The mammalian target of rapamycin complex 1 (mTORC1) senses multiple stimuli to regulate anabolic and catabolic processes. G-protein-coupled receptors (GPCRs) paired to Gs proteins increase cyclic adenosine 3'5' monophosphate (cAMP) to activate protein kinase A (PKA), which phosphorylates Raptor …
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Histone Lysine Demethylase KDM4A as a Therapeutic Target for Small Cell Lung Cancer
… phenotypes of etoposide and three JmjC KDM inhibitors using a panel of SCLC cell lines representing all the SCLC transcription factor subtypes and found that SCLC responses to JmjC KDM inhibitors did not correlate with their responses to etoposide. Furthermore, I found that upon treatment …
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Autophagy and Inflammation During Rickettsial Infection
… I examined the mammalian target of rapamycin (mTOR), a master regulator of autophagy, during infection of BMMs with R. australis. Rickettsiae induced mTOR phosphorylation and activation of the downstream protein P70S6K, a measurement of mTORC1 activation. Furthermore, treatment with mTOR …
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Characterization of Notch1 and Pi3K-Pten-Akt/Mtor Pathway Interaction In Head and Neck Squamous Cell Carcinoma
… mutations are sensitive to PI3K and dual PI3K/mTOR inhibitors, leading us to investigate the interaction of these pathways in HNSCC. The NOTCH pathway plays key roles in cell proliferation, differentiation, and apoptosis. With inactivating mutations in 18% of 510 HNSCC patient samples, …
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The Role of the Mammalian Target of Rapamycin (mTOR) in Cytotoxic T Lymphocytes
… kinase mammalian target of rapamycin (mTOR) is an important integrator of nutrient, cytokine and growth factor sensing in T cells and controls transcriptional programs that determine CD8+ cytotoxic T cell fate and trafficking. mTORC1 is inhibited by the drug rapamycin which is a …
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Identifying and Targeting Adaptive Changes to Bet Inhibition In Ovarian Cancer
… Bromodomain and Extra-Terminal Domain (BET) inhibitors in a mechanism driven fashion to maximize anti-tumor activity, and to determine the efficacy of BET inhibitor combinations in pre-clinical ovarian cancer mouse models.</p> <p><strong>Experimental Design: </strong>We used a novel, …
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Direct Effects of Metformin On Pi3K and Ras Signaling In Endometrial Cancer
… EC cells with metformin in combination with PI3K inhibitors resulted in a significant decrease in proliferation than either agent or metformin alone.</p> <p>While metformin exerts antineoplastic effects by activation of AMPK and decreased PI3K signaling, our data suggest that metformin may also …
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Sleep Disturbances in Adults with TSC: Influences of Treatment and Clinical Features
… respectively). Those who self-reported taking mTOR inhibitors, antiepileptic drugs, or antidepressants were also more likely to have severe sleep problems (<em>p</em><sub>AD</sub>=0.016, <em>p</em><sub>mTORi</sub><0.001, <em>p</em><sub>AEDs</sub>=0.045). Epilepsy was not found to be a risk …
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The signalling pathways allowing hormonal regulation of Na+ transport in murine collecting duct cells
… (Ieq). Selective inhibition of PI3-kinase, mTORC2 and SGK1 left ~80 % of the current intact, indicating these signalling molecules are not required for basal Na+ transport. Acute addition of insulin stimulated Ieq and this occurred with a concomitant increase in mTORC2, SGK1 and Akt …
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