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 13 of 13 for “"venetoclax"”.
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Dissecting The Mechanisms of Venetoclax Resistance In Myelodysplastic Syndromes
… clinical response to BCL2 inhibition by venetoclax-based 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 …
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Therapeutic Vulnerabilities of Venetoclax Resistant Chronic Lymphocytic Leukemia and Novel Treatment Strategies Targeting BCL2/BCL-XL
… remains a major challenge. CLL resistant to venetoclax (VEN) have limited available therapeutic options, especially when the leukemic cells have dysfunctional p53 and have relapsed on Bruton’s tyrosine kinase inhibitors (BTKi). The broad hypothesis of this thesis is that VEN-relapsed CLL …
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Single Cell Proteogenomics Analysis of AML Samples Treated with Decitabine and Venetoclax Reveals Divergent Treatment Escape Mechanisms
<p> Venetoclax is a small molecule inhibitor targeting BCL-2. Since its approval, the combination therapy of hypomethylating agents and Venetoclax (HMA+Ven) has become a standard of care for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. Nonetheless, clinical challenges …
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Investigating the metabolic impact of Metformin and Berberine in combination with Venetoclax for Acute Myeloid Leukaemia treatment
… is overexpressed in AML. The BCL-2 antagonist Venetoclax inhibits OXPHOS and induces apoptosis in AML cells, which is potentiated when combined with Metformin an anti-hyperglycaemic agent used to treat type 2 diabetes, which also has anti-cancer properties. This study explored the effects of …
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Die therapieabhängige Kinetik der Neubesiedlung des T-Zellkompartiments im peripheren Blut von Patienten mit rezidivierender chronischer lymphatischer Leukämie
… der Therapiearme (Chlorambucil/Obinutuzumab vs. Venetoclax/Obinutuzumab) anhand prätherapeutischer Parameter und ihres Ansprechens kategorisiert und anschließend untersucht. CLL-Patienten zeigten ein deutlich reduziertes T-Zellrepertoire mit oligoklonalen Expansionen. Die CDR3-Länge sowie die V- …
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Molecular Characterisation and Therapeutic Targeting of NPM1-mutant Acute Myeloid Leukaemia
… D (ActD). The combination of ActD and Venetoclax inhibited the growth and colony forming ability of pre-leukaemic and leukaemic NPM1c+ cells and low-dose ActD treatment was able to re-sensitise Venetoclax-resistant NPM1c+ models. Next, using data from clustered regularly interspaced …
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Preclinical Studies of A Novel Idh1 Inhibitor In Acute Myeloid Leukemia (Aml)
… acute myeloid leukemia in combination with Venetoclax (ABT-199).</strong></p> <p>Acute myeloid Leukemia (AML) is an aggressive neoplastic blood disorder characterized by proliferation of poorly differentiated cells of myeloid lineage. IDH1 is a cytoplasmic enzyme that catalyze the oxidative …
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Modelling the effect of loss of function CREBBP mutations in the evolution and treatment of B cell acute lymphoblastic leukaemia (B-ALL)
… in B cells. A new potential use of Venetoclax in CREBBP mutated B-ALL cell lines or in combination with CREBBP inhibitors (Inobrodib) was discovered widening the use of Venetoclax to B-ALL. The hypothesised mechanism relies on the intrinsic ferroptosis sensitivity of CREBBP mutated …
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An Investigation into the Potential of Cell Therapies for Acute Myeloid Leukemia (AML) Treatment
… AML therapies cytarabine, gilteritinib, and venetoclax, the apoptotic effect induced by iPSC-NKs increased in an E:T and dose-dependent manner, with iPSC-NK viability unaffected by cytarabine. Similarly, we observed donor-derived Vγ9Vδ2 T cells induced E:T-dependent apoptosis on AML cell …
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Concomitant Inhibition of Flt3 and Mcl-1 In Flt3 Mutated Acute Myeloid Leukemia
… because resistance to the BCL-2 inhibitor venetoclax is characterized diminished by upregulation of MCL-1 we also studied the impact of the combination of venetoclax resistant FLT3-ITD AML cells. Overall, our results indicate sensitivity towards the combination of midostaurin and S63845 in …
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Mitochondrial Unfolded Protein Response Regulator Atf5 In Mitochondrial Targeted Therapies In Aml
… agents were combined with the BCL2 inhibitor venetoclax, suggesting that venetoclax combination may overcome the cell-protective response of UPR<sup>mt</sup>. However, tetracycline-inducible shRNA against ATF5 did not sensitize AML cells to any of the above treatments. Similarly, …
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Exploring the utility of the pig model for predicting bioavailability in humans
… formulations of the model drugs fenofibrate and venetoclax. In addition, the ability of predicting food dependent bioavailability was assessed for both compounds. The formulations were evaluated in vivo in landrace (LR) pigs. Followed by a post-mortem assessment of the gastrointestinal (GI) …
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The role of type I interferon in chronic lymphocytic leukemia
… such as ibrutinib and Bcl-2 inhibitors such as venetoclax. The final section of this thesis described the results of a phase I clinical trial of the recombinant interleukin-1 (IL-1) receptor antagonist anakinra in CLL patients. Anakinra was found to upregulate IFN-signaling, decrease oxidative …