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 19 of 19 for “"PKM2"”.
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Elucidating the roles of endothelial PTBP1 and PKM2 in Pulmonary Arterial Hypertension: implications for therapy
… the glycolytic enzyme Pyruvate Kinase M2 (PKM2). Moreover, normal EC function and metabolism is restored by PTBP1 silencing, highlighting the therapeutic potential of targeting PTBP1 and PKM2. In this thesis, I have explored the therapeutic potential of pharmacological and genetic …
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Examining the roles of the pyruvate kinase isoforms, PKMI1 and PKM2, in systemic metabolism and tumor development
… of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase, and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. PKM1 expression, on the other hand, is restricted mostly to skeletal muscle, heart, and brain. To interrogate the functional …
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The role of pyruvate kinase regulation in tumor growth and metabolism
… sought to determine the role and importance of PKM2 in cancer. The activity of pyruvate kinase M2 (PKM2) is down-regulated by pro-proliferative signaling in the cell, and reduced PK activity appears to be important for proliferative metabolism. Because oncogenic signaling reduces PKM2 activity, …
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Coordinated regulation of glycolysis and the folate one-carbon cycle
… glycolysis, all proliferating cells express the PKM2 isoform of PK that is unique in having regulated activity which is decreased in the context of cellular proliferation. The simultaneous requirement for increased aerobic glycolysis and expression of the PKM2 isoform that is inhibited by growth …
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Studies on mammalian pre-mRNA splicing : connections to transcription and cancer
… spliced to produce to produce the PKM1 or PKM2 isoforms, which contain exons 9 or 10 respectively. Adult tissues express predominantly the PKM1 isoform, which is universally reverted to the embryonic PKM2 isoform in cancer cells. PKM2 expression promotes aerobic glycolysis. In Chapter 3, I …
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Regulation of alternative splicing and its connections to cancer
… is alternatively spliced to produce the PKM1 or PKM2 isoforms, which contain exons 9 or 10 respectively. Adult tissues, such as skeletal muscle and brain, express predominantly the PKM1 isoform, which is universally reverted to the embryonic PKM2 isoform in cancer cells. PKM2 expression promotes …
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Novos híbridos cumarínicos como protótipos para terapia de carcinoma de Células escamosas de boca: caracterização de atividade biológica e molecular e implicação da via de PKM2
… desses híbridos na via de piruvato quinase M2 (PKM2) in vitro acessada por meio da avaliação da atividade de PKM2 acoplada a lactato desidrogenase e produção de ATP. Além disso foi realizado ensaio de toxicidade aguda in vivo utilizando camundongos C57BL/6. Das substâncias testadas neste …
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Regulation of cellular glucose metabolism by HIV-1 infection
… (G6PD) and pyruvate kinase muscle type 2 (PKM2) that facilitates viral replication and biogenesis, and long-term survival of macrophages. We then focused on infected monocyte macrophages to identify if glycolytic components such as HK and G6PD were regulated by HIV-1 infection/replication. …
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The role of NEDD9 in TGFβ mediated tumour initiating cell dynamics in the Claudin-low breast cancer subtype
… in this subtype is the metabolic isoenzyme PKM2. Through a variety of techniques, I explore the known roles of PKM2 in the regulation of oncogenic metabolic reprogramming and demonstrate how these processes are influenced by its association with NEDD9. Finally, I investigate potential …
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Local effects of Linoorbitides and enterolactone On intestinal epithelial functions
… triggered the evaluation of pyruvate kinase M-2 (PKM2) as a possible biomarker of IBD. Lastly, we evaluated the effect of lignans on cholesterol metabolism in a human intestinal epithelial cell line (Caco-2). Our barrier integrity assessments of LOBs and ENL in the monoculture system identified …
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The relationship between docohexanoic acid (DHA) and L-serine, providing an insight into the biochemistry of meningioma
… expressions of pyruvate kinase isoform 2 (PKM2) and phosphoglycerate dehydrogenase (PHGDH) were shown. Therefore, the results demonstrated that within meningioma tissues, serine can allosterically regulate the flux through glycolysis. The association that serine presence alone can alter the …
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Defining the contributors to mammalian cell mass
… enolase. Although pyruvate kinase isoform M2 (PKM2) expression enables proliferation in some contexts, we demonstrate that this is not because of its putative activity as a protein kinase. We additionally characterize a novel modification of enolase by its substrate, phosphoenolpyruvate, which …
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Anti-Insulin Resistance Treatments Suppress Her2+ Breast Cancer Growth Via Altering Metabolism
… and reduced the downstream key glycolysis enzyme PKM2. Moreover, anti-insulin resistance treatments dramatically change the microenvironment by reducing serum insulin levels and this systematic effect attenuated the mTOR/AKT signaling pathway in tumor samples from MMTV-ErbB2/<em>Lepr …
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Integrative analysis of the metastatic neuroblastoma transcriptome
… down PTBP1, HNRNPA1 and their downstream target PKM2, a pro-tumor-growth isoform, resulted in repression of NBL cell growth. Second, I used whole transcriptome sequencing in a cohort of 150 patients to assess expressed mutations, fusion genes, and gene expression including long non-coding genes …
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Therapeutic Effects and Targeted Delivery of Eupenifeldin in Castration-Resistant Prostate Cancer
… regulators, including GLUT-1, HK2, and PKM2, which are critical for glucose uptake and metabolism. This metabolic stress was accompanied by a substantial increase in reactive oxygen species (ROS) production, further contributing to cellular damage and apoptosis. The addition of a ROS …
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Characterization of Mechanisms That Mediate Cancer Metastatic Colonization
… PKL negatively regulates pyruvate kinase M2 (PKM2) enzymatic activity. By inhibiting cellular pyruvate kinase activity, PKLR allows for the diversion of metabolites towards glutathione generation—allowing for the maintenance of glutathione levels. Adequate glutathione levels appears critical …
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Sunitinib-Induced Cardiotoxicity Exposes Microvascular and Metabolic Derangements In The Failing Heart
<p>Cardiac dysfunction is one of the largest obstacles to effective cancer treatment. Not only do a growing number of cancer patients have significant cardiovascular risk factors at the time of diagnosis, but a number of targeted therapies can themselves cause cardiac dysfunction. These newer …
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TUMOR PROMOTING FUNCTIONS FOR THE METABOLIC REGULATOR SIRT5
… dehydrogenase (GAPDH), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase complex (PDH), isocitrate dehydrogenase 2 (IDH2) and succinate dehydrogenase (SDH). SIRT5 also controls glutamine metabolism by targeting glutaminase (GLS), and fatty acid metabolism by activating very long-chain …
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PHYTOCHEMICAL AND SYNTHETIC INVESTIGATIONAL COMPOUNDS AS MODULATORS OF CYTOMETABOLIC AND CYTOSKELETAL DYNAMICS FOR PRE-CLINICAL TARGETING OF PROSTATE CANCER
… and glucose metabolism (SREBP1/2, INSIG1, FASN, PKM2, PPARα/γ, mTOR, MAF, PDK1, LDLR, and SRB1), induced ER stress by elevating key targets in ER stress signaling (CHOP, ATF4, GRP94, GRP58, GADD 34, and PGC1α), increased glucose uptake and glycolysis due to severe nutrient and energy reduction in …