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 18 of 18 for “"MEK inhibitors"”.
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Pharmacological effect of MEK inhibitors on plasmodium falciparum
… modules comprising the MAPK and upstream MAPKKs (MEKs) and MAPKKKs (MEKKs). Surprisingly, experimental and in silico analyses have demonstrated P. falciparum does not possess any MEK homologues, even though its kinome comprises two members of the MAP kinase family. Prior to the finding that the …
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Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma
… membership defines sensitivity to clinical MEK inhibitors versus TBK1/IKBKE inhibitors. Importantly, subtype membership can be predicted using a robust quantitative 5-feature genetic biomarker. This biomarker, or the mechanistic relationships linked to it, can identify a cohort of best …
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Angiotensin Type-2 (At2) Receptor Modulation of Nmda-Mediated Current, Signaling and Apoptosis
… treatment with NMDA. Inhibition of ERK with MEK inhibitors (PD98059 and U0126) significantly decreased PARP cleavage (cPARP), while inhibition of PP2A with 10 nM okadaic acid, significantly increased NMDA-mediated cPARP expression. Further, we demonstrate that the AT2 receptor attenuates …
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The Role of The Epithelial-To-Mesenchymal Transition (Emt) In Lung Cancer Progression
… downstream effector proteins of KRAS, such as MEK inhibitors, have failed to produce significant clinical benefits. Previous studies by our group on the metastatic process revealed that malignant lung cancer cells undergo an epithelial-to-mesenchymal transition (EMT) that is regulated by a …
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Dissecting Tumor Heterogeneity In Lung Cancer
… a combinatorial approach of utilizing CDK4 and MEK inhibitors to effectively control tumor growth by targeting distinct tumor subpopulations within lung cancer and prevented emergent resistance to either single agent.</p>
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Assessment of the clinical validity of ctDNA Analysis for melanoma management
… of targeted therapy and immune-checkpoint inhibitors has improved the clinical management of melanoma, but durable survival benefit is only seen in a minority of patients. The use of these very expensive systemic therapies on all appropriate patients also poses a high economic burden on …
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Preclinical Development of Therapeutic Strategies Against Triple-Negative and Inflammatory Breast Cancer
… 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 induction of NOXA expression, and subsequent inhibition of MCL1, for the treatment against TNBC and IBC.</p> …
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A metabolic perturbation by U0126 identifies a role for glutamine in resveratrol-induced cell death
… downstream pro-survival signaling with the MEK inhibitor U0126 rescued the C4-2 cells from resveratrol-induced death, however other MEK inhibitors did not recapitulate this response. In fact, U0126 acted independently of MEK, inhibiting mitochondrial function and shifting cells to aerobic …
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Integrative Cancer Immunogenomic Analysis of Serial Melanoma Biopsies Reveals Correlates of Response and Resistance to Sequential Ctla-4 and Pd-1 Blockade Treatment
… is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic …
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Systems modeling of quantitative kinetic data identifies receptor tyrosine kinase-specific resistance mechanisms to MAPK pathway inhibition in cancer
… cell lines up-regulate many RTKs in response to Mek inhibition, although reported with conflicting mechanisms. Upon integrated analysis, we find both Axl and Her2 have increased lysate levels after Mek inhibition with 3 Mek inhibitors, Selumetinib, Binimetinib, and PD0325901. Axl changes are …
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Investigating the role of the Hippo pathway in epithelial-mesenchymal transition and drug resistance
… and identified a significant resistance to MEK inhibition (MEKi) in YAP-driven cells. This resistance was robust; YAP-driven cells survived MEKi treatment even with a combined inhibition of common compensatory signaling through pro-survival kinase, AKT and receptor tyrosine kinase, AXL. …
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Low grade gliomas treated at the University of Cape Town Academic Hospital complex: 2001-2017
… targeted, novel biologic therapy such as BRAF/MEK inhibitors. The outcome of children with LGGs in our institution was assessed. Methods: A retrospective analysis was performed on all children < 15 years of age diagnosed with a LGG at Red Cross War Memorial Children's Hospital (RCWMCH) between …
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P4HB TARGETING HALTS TUMOR GROWTH AND RE-SENSITIZES RESISTANT MELANOMA CELLS TO DABRAFENIB AND TRAMETINIB STANDARD-OF-CARE THERAPY VIA IRE1-⍺ ACTIVATION AND AKT DOWNMODULATION
… the introduction of targeted therapy (BRAF and MEK inhibitors) and immune checkpoints inhibitors (anti-PD1, anti-CTLA4). However, a significant proportion of BRAF-mutant patients develop secondary resistance to targeted therapies, while others exhibit even primary resistance. To either prevent …
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The Oncogenic Map Kinase Signaling Pathway Modulates Mhc-I Surface Expression In Melanoma
… melanoma patient survival. Two MAPK targeted inhibitors, vemurafenib and dabrafenib, have produced positive results in clinical trials thus far, but they are not without limitations. Recent studies have shown that oncogene activation in tumor cells can affect the level of expression of major …
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Signaling crosstalk in cancers
… signaling in pancreatic cancer cells through RAF/MEK/MAPK subpathway, but not PI3K/AKT subpathway. Inactivation of KRAS/MEK pathway activity by a KRAS specific siRNA or MEK inhibitors inhibits GLI transcriptional activity and GLI1 expression, and promotes GLI1 protein degradation in pancreatic …
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Leveraging copper chelators as targeted therapy for BRAFV600E mutant thyroid cancer
… in recurrent/persistent disease. Excitingly, inhibitors against this mutant kinase or its substrates, the MEK1/2 kinases, can prolong progression free survival or stabilize disease in radioiodine-refractory thyroid cancer patients. However, the indolent nature of PTC may be a challenge to the …
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Role of the Leukotriene B4 Metabolic Pathway in Human Pancreatic Cancer
… and transient phosphorylation and activation of MEK and ERK1/2 kinases. The MEK inhibitors, PD98059 and U0126 as well as the selective LTB, receptor antagonist LY293111 all blocked LI B,-induced ERR 1/2 activation and cell proliferation. LTB, also induced phosphorylation and activation of p38 …
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An investigation on role of the ATP-binding cassette B5 (ABCB5) transporter as potential mediator of melanoma resistance to BRAF inhibition
… deaths. Targeted therapies, in the form of BRAF inhibitors (BRAFis), have been effective at treating BRAFV600 mutant melanomas. However, majority of the melanoma patients fail to respond to BRAFis due to intrinsic or acquired resistance within one year of treatment commencement. Multiple …