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 23 for “"MEK inhibitor"”.
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Investigating the Anti-Melanoma Activity of Combinatorial Paclitaxel and MEK Inhibitor
Melanoma has increased considerably over the past forty years. Traditional and newly-developed anti-melanoma drugs do not produce a satisfactory therapeutic response for the treatment of late stage melanoma. Nanomedicine is a potent tool for clinicians to circumvent many of the existing …
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The Kras/Mapk Pathway and Ligand Independent Activation of Erα: Implications For The Treatment of Endometrial Cancer
… which was restored following treatment with a MEK inhibitor.</p> <p>To address the functional consequence of differential estrogen signaling expression of estrogen induced genes and cell viability assays were evaluated. Following treatment with a MEK inhibitor, mutant KRas cells had increased …
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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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Activation of Ca<sup>2+</sup>-activated K<sup>+</sup> Channels and Cell Migration by Hepatocyte Growth Factor/Scatter Factor in Madin-Darby Canine Kidney Cells.
… induced ERK phosphorylation, and addition of the MEK inhibitor PD98059 inhibited ERK phosphorylation, as well as HGF/SF stimulation of Ca<sup>2+</sup>-activated K<sup>+</sup> currents and cell migration in MDCK II cells. Taken together, HGF/SF induces phosphorylation of ERK, which plays a role in …
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The SYK tyrosine kinase suppresses autolysosome biogenesis via activation of mTORC1 in pancreatic cancer cell lines
… PDAC cell lines. Furthermore, combined SYKi and MEK inhibitor (MEKi) treatment promotes additive effects on suppression of PDAC cell proliferation and clonogenic growth. Mechanistically, SYK activates the mTORC1 kinase complex as shown by reduced phosphorylation of ribosomal S6 protein and its …
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Approaches to Reduce Selection of Genomic Variants in Human Pluripotent Stem Cell Culture
… medium devoid of bFGF containing LIF plus two inhibitors, MEK inhibitor (PD0325901) and p38 inhibitor (SB203580), we demonstrate that hPSCs are LIF responsive and can be stably maintained in naive pluripotent culture conditions. Based on their clonal viability, we propose that naive hPSCs are a …
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A chemical genetic approach to identify new treatments for melanoma
… drugs, it was tested in combination with the MEK inhibitor selumetinib. This combination showed a synergistic effect in the majority of the cell lines tested. The M375 melanoma cell line produced strong synergy values across all of the combinations of leflunomide and selumetinib tested. This …
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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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A Mechanistic Evaluation of how Melatonin Enhances Alkaline Phosphatase Activity in Human Adult Mesenchymal Stem Cells
… Conversely, co-incubation with melatonin and the MEK inhibitor PD98059 prevented the melatonin-mediated enhancement in ALP activity in hAMSCs. Taken together, these findings indicate melatonin enhances ALP activity via activation of the mitogen activated protein kinase (MAP-K) cascade. Protein …
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Modulation of the response to cisplatin by nitric oxide and reactive oxygen species in melanoma cells
… p53, it also increased the expression of the p53 inhibitor MDM2, which may have counteracted p53-induced apoptosis upon cisplatin treatment. Also, likely via ERK1/2 activation, NO favored phosphorylation of MiTF, which is associated with survival signals. Furthermore, NO displayed the remarkable …
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Regulation of acid-stimulated H+ secretion by Pyk2 and MAPK signaling pathways in the outer medullary collecting duct
… knockdown Pyk2 expression levels, the Src kinase inhibitor PP 1 to inhibit Src phosphorylation, and the MEK inhibitor U0126 to inhibit ERK1/2 phosphorylation. Furthermore, we used adenoviral-gene transfer of AdCRNK, a dominant-interfering truncated Pyk2 construct, to block Pyk2 phosphorylation at …
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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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PROGRAMMED DEATH LIGAND 1 (PD-L1) IMMUNE CHECKPOINT-MEDIATED STIMULATION OF MALIGNANT PHENOTYPES IN TUMOUR CELLS
… autophagosome formation. Using autophagy inhibitors, we showed that drug resistance induced by reverse PD-1/PD-L1 signaling is causally linked to increased autophagy. In addition, results of our studies demonstrated a role for extracellular signal-related kinase (ERK) signaling in …
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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 Effect of Resveratrol on Lipopolysaccharide-induced Dopaminergic Deficits and BV-2 Cell Activation
… pretreatment. Interestingly, at 6 hours the MEK inhibitor U0126 decreased LPS-mediated ERK1/2 activation and TNF-α release. ERK5 was not activated by LPS, but preliminary data suggest that the MEK5 inhibitor BIX02189 inhibited LPS-induced TNF-α release. Therefore, BIX02189 may be inhibiting a …
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The molecular pathways mediating the role of cyclooxygenase enzymes and prostaglandins in cervical neoplasias
… inhibited by co-treatment of cells with chemical inhibitors of MEK (PD98059), epidermal growth factor receptor tyrosine kinase (AGI478) or EP4-selective receptor antagonist (ONO-AE2-227). We next investigated the target genes activated by seminal plasma or prostaglandin E2-EP4 ligand-receptor …
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Aberrant Ras/MAPK signaling in skeletal development
… time window, where in utero treatment with MEK inhibitor is sufficient to completely rescue the bone phenotype. The Osx1-Cre;K-rasG12D mutant mice allowed us to activate expression of hyperactive K-ras in the osteoblast population at different times during the development of the organism. …
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Role of the LPA2 Receptor in Protecting Against Apoptosis
… effects were completely blocked by the MEK inhibitor PD98059 and the PI3K inhibitor LY294002. Pertussis toxin partially abolished OTP-induced ERK1/2 and apoptotic protection. In RH7777 cells lacking LPA receptors, OTP selectively protected LPA<sub>2</sub> but not LPA<sub>1</sub> and …
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Role of Extracellular Signal-Regulated Kinase (ERK) in Regulation of Intestinal Epithelial Tight Junctions
… hydrogen peroxide. Studies using pharmacological inhibitors have shown that EGF increases Thr-phosphorylation of occludin by a MAP kinase-dependent mechanism. This study aimed at looking at the role of ERK in regulation of tight junctions using pharmacological and molecular techniques.</p> …
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Studies on the Roles of PDGFRA and EGFR in the Classification and Identification of Therapeutic Targets for Human Gliomas
… corresponding tumor samples. We also found that MEK inhibitor U0126 treatment can decrease the surface PDGFRA expression and result in deviation of PDGFRA from endosomal trafficking and recycling compartment to the Golgi network in a reversible, dose- and time-dependent manner without affecting …
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