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 14 of 14 for “"MCL1"”.
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Molecular Mechanisms Regulating Neonatal Oocyte Survival and Primordial Follicle Formation in the Mouse Ovary
… from the BCL2 family of proteins, BCL2 and MCL1, may be responsible for regulating neonatal oocyte survival. To elucidate the effects of BCL2 in the neonatal ovary, we examined ovaries of both <em>Bcl2</em> overexpressing and knockout transgenic mice. When compared to wild-type mice, neither …
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Exploiting tumour cell dependency on pro-survival BCL2 proteins with BH3 mimetics
… we determined that melanoma cells had a high MCL1:BCL-XL ratio, and as a result were biased towards MCL1 due to low expression of BCL-XL. Consequently, melanoma cells were uniquely dependent on MCL1 to restrain the pro-apoptotic BH3-only proteins induced by ERK1/2 pathway inhibition. The BH3 …
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Dissecting The Mechanisms of Venetoclax Resistance In Myelodysplastic Syndromes
… therapy. Our preliminary data reveal that MCL1 is one of the determinants of venetoclax resistance in MDS patients and that combining MCL1 inhibition and venetoclax can synergistically eradicate venetoclax-resistant MDS blasts and HSPCs <em>in vitro</em> and reduce tumor burden in …
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Preclinical Development of Therapeutic Strategies Against Triple-Negative and Inflammatory Breast Cancer
… inhibition of the anti-apoptotic protein MCL1 following inhibition of histone deacetylases (HDAC) in combination with inhibition of the oncogenic MEK pathway. In breast cancer patients, low NOXA/high MCL1 tumor expression is indeed associated to poor survival outcomes, supporting the …
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Therapeutic Vulnerabilities of Venetoclax Resistant Chronic Lymphocytic Leukemia and Novel Treatment Strategies Targeting BCL2/BCL-XL
… targets <em>BCL2A1</em>/BFL1 and <em>MCL1</em>. Other 2 minor clusters were gained at relapse by two independent <em>TP53</em>-mutated CLL samples, with high co-expression of <em>BCL2</em>, <em>MCL1,</em> and the pro-apoptotic binding partner of MCL1, <em>PMAIP1</em>/NOXA, suggesting …
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TRP75-Mediated STAT3 Activation Promotes Anti-Apoptotic Signaling and Ehrlichia chaffeensis Infection
… target genes, including the anti-apoptotic gene MCL1. Pharmacological inhibition of STAT3 significantly reduced MCL1 expression and increased caspase cleavage, implicating STAT3 as a regulator of anti-apoptotic signaling during infection. Furthermore, both pharmacological inhibition and genetic …
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Single Cell Proteogenomics Analysis of AML Samples Treated with Decitabine and Venetoclax Reveals Divergent Treatment Escape Mechanisms
… shift. Furthermore, we confirmed the upregulated MCL1 in the monocytic compartments of two patients with monocytic shifts. In one of these patients, scRNAseq additionally revealed a considerable presence of erythroid compartment upregulated with BCL2L1. Importantly, BCL2 was downregulated in all …
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The Heme-Regulated Inhibitor Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics
<p>Anti-apoptotic MCL1 is one of the most frequently amplified genes in human cancers and its elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes …
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Ehrlichia chaffeensis E3 Ligase TRP120 Ubiquitinates Tumor Suppressor FBW7 for Degradation to Promote Infection
… network of oncoproteins (Notch, cyclin E, c-Jun, MCL1 and cMYC). In this study, we demonstrate that TRP120 and FBW7 colocalize strongly in the nucleus by confocal immunofluorescent microscopy and interactions between TRP120 and FBW7 FBOX and WD40 domains were demonstrated by ectopic expression and …
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"Ανάλυση έκφρασης μεταγράφων γονιδίων της οικογένειας BCL2 σε ανθρώπινα λευχαιμικά κύτταρα"
… αποπτωτικών μορίων τη οικογένειας BCL-2, όπως το MCL1, καθώς και απορρύθμιση της ενεργοποίησης των κασπασών, συμβάλλοντας στην ανθεκτικότητα των κακοήθων κλώνων και στην αντίσταση στη θεραπεία. Παράλληλα, η απόπτωση αποτελεί βασικό μηχανισμό δράσης πολλών θεραπευτικών παραγόντων, γεγονός που …
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Loss of Gprc5A Enhances Survival In Normal and Malignant Lung Epithelial Cells By Eliciting Persistent Stat3 Activation Induced By Autocrine Lif
… anti-apoptotic genes Bcl-XL, Cryab, Hapa1a, and Mcl1 were higher in the <em>Gprc5a</em><sup>-/-</sup> than in <em>Gprc5a</em><sup>+/+</sup> cells. In addition, their responses to Lif were different; Stat3 activation was persistent by Lif treatment in the <em>Gprc5a</em><sup>-/-</sup> cells, but …
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The Novel Upstream Regulator of Fbxw7
… oncoproteins such as Cyclin E, c-Myc, c-Jun and MCL1. The deregulation of these proteins often leads to the proliferation of cancer cells. Thus, intracellular stability and functional activity of FBXW7 is critical for regulating cancer. However, there is a gap of knowledge about the intracellular …
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Androgen receptor-mediated growth suppression and apoptosis of human prostate epithelial cells
… whereas pro-survival genes (BCL2L1/BCL-XL and MCL1) are androgen-repressed. Hence, we propose that the net effect of these AR-mediated expression changes shifts the balance of BCL2-family proteins in a manner that sensitizes mitochondria to apoptotic signaling and thus renders HPr-1AR more …
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Molecular Effects of the Nampt Inhibitor FK866 on Leukemia Cells
… reduced the levels of the anti-apoptotic protein MCL1 and impacted on the endoplasmic reticulum homeostasis. In addition, we established and characterized an FK866-resistant model derived from the T-ALL cell line Jurkat. Target-specific acquired resistance has been described after several …