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 43 for “"MEK1/2"”.
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U0126, MEK1/2 inhibitor, Induces Adhesion Molecules Expression in Human Blood Cells
… the expression of adhesion molecule by MEK1/2 inhibotors such as U0126 in human blood cells, U937 cells. Cell viability was determined by MTT assay. The expression of adhesion molecule was observed by flow cytometry. Adhesion molecules were time- and dose-dependently incresed by U0126. …
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Exploiting tumour cell dependency on pro-survival BCL2 proteins with BH3 mimetics
The RAS-RAF-MEK1/2-ERK1/2 signalling pathway is one of the most frequently deregulated pathways in human cancer, with mutations in KRAS and BRAF commonly occurring in cancers of the pancreas, skin, and colon, among others. Indeed, BRAF and MEK1/2 inhibitors are approved for the treatment of …
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Regulation von MAPK Signalwegen durch die Sein/Threonin Kinase MLK3
… phosphoryliert MLK3 die dualspezifischen Kinasen MEK1/2 direkt in vitro und in vivo an den für die Aktivierung wichtigen Serinen 217/221. Wohingegen dies nur zu einer ERK Aktivierung in Überexpressionssystemen führte, demonstrieren die Analysen überzeugend, dass endogenes MEK1/2, welches von MLK3 …
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Therapeutic Targeting Of Bmp2 In Nf1-Deficient Malignant Peripheral Nerve Sheath Tumors (mpnsts)
… target in MPNSTs, independent of the NRAS and MEK1/2 regulation. The overall goal of my research was to validate the significance of BMP2 in MPNSTs in novel cellular models, study the combinatorial effects of BMP2 and MEK1/2 inhibition, and use the regulation of BMP2 transcriptional control to …
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Leveraging copper chelators as targeted therapy for BRAFV600E mutant thyroid cancer
… 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 clinical adaption of these inhibitors, as the financial and …
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ERK1/2 signalling and protein ubiquitylation in the control of apoptosis
… undergo BIM-dependent cell death in response to MEK1/2 inhibitors when combined with BH3-mimetics such as ABT263, small molecules that inhibit pro-survival proteins of the apoptotic pathway. The RSK1/2 protein kinases, immediate downstream targets of ERK1/2, have also been implicated in the …
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Evaluation of inhibitors of histone deacetylases as potential neurotrophic agents
… were interrogated with selective inhibitors of MEK1/2 (PD98059/U0126) PI3K (LY294002) and TrkA (GW441756) and phosphorylation of target kinases. Associated factors namely, acetylation of histones (H3/H4) and α-tubulin, role of cAMP, and cell- cycle analysis with flowcytometry were also studied. …
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Identification of transcriptional mechanisms downstream of nf1 gene defeciency in malignant peripheral nerve sheath tumors
… 2012).</p> <p>In this study, we modulated NRAS, MEK1/2 and neurofibromin levels in MPNST cell lines and determined the global gene expression changes that were associated with each experimental condition. Furthermore, gene expression changes due to neurofibromin deficiency but independent of NRAS …
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Design, Synthesis, & Biological Evaluation of Novel Het-Aromatic/Aromatic Analogs for the Treatment of HIV, Cancer, & Cognitive Dysfunctions
… Using the x-ray crystal structure of known MEK1/2 inhibitors bound to MEK1/2 (PDB ID: 3EQC and 3SLS) the homology model of MEK5 was built, and along with medicinal chemistry approaches, it was utilized for the design of diphenylamine and 2-amino-3-carboxythiophene derivatives as selective …
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Genomweite Suche neuer Modulatoren der Signaltransduktion in kardialer Hypertrophie und Herzinsuffizienz
… der Ratte, zu einer signifikanten Reduktion der Mek1/2 Phosphorylierung führt. Dies wurde sowohl in den unstimulierten Kardiomyocyten, als auch in den durch Phenylephrin stimulierten Kardiomyocyten sichtbar. Auf Grundlage dieser Ergebnisse ist anzunehmen, dass es sich bei B-Raf um die RAF-Isoform …
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The Role of the Mitogen Activated Protein Kinase Pathway in Cisplatin and Noise-Induced Hearing Loss
… consists of a phosphorylation cascade with RAF, MEK1/2, ERK1/2 as the main three kinases that effect a multitude of cellular processes. The MAPK pathway has been associated with hearing loss; however, its exact role was not elucidated. This dissertation explores the exact role that MAPK …
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Investigation into the role of HMGb1 in relation to myofibroblasts and cancer cells exposed to various conditions
… myofibroblasts cells via activation of PI3K and MEK1/2. Conditioned medium collected from glucose deprived HT29 cells was shown to stimulate migration and invasion of colonic myofibroblasts, and these processes were significantly inhibited by immunoneutralising antibodies to HMGb1, RAGE and …
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Staphylococcus aureus의 Lipoteichoic acid(LTA)에 의한 사람의 정상 코 점막 상피세포에서의 MMP와 TIMP의 발현
… 1. LTA 처리, 단백질 정량 2. 단백질의 전기영동, Antibody 반응 H. MEK1/2 inhibitor에 의한 MMP-9의 발현 억제 확인 Ⅲ. 결과 A. LTA에 의한 코 점막 상피세포의 세포독성 확인 B. MMP-9와 TIMP-1, -2 유전자의 발현 차이 C. MMP-9와 TIMP-1, -2의 분비량 차이 D. 분비 된 MMP-9(gelatinase B)의 활성 확인 E. ERK1/2, STAT3의 발현 F. ERK1/2를 매개로 MMP-9 발현 Ⅳ. 고찰 Ⅴ. 결론 참고문헌 ABSTRACT "
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Lipoteichoic acid from Staphylococcus aureus induced expression of MMP-9 in human middle ear epithelial cells
… (MAPK) pathway was activated by LTA. And the MEK1/2 inhibitor prevented the expression of MMP-9 by LTA.LTA increased the activity of MMP-9, not TIMPs in middle ear epithelia, suggesting that disturbed balance between MMP-9 and TIMPs could play an active role in LTA-induced otitis media.
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Circumventing Cisplatin Resistance In Ovarian Cancers Through Reactivation of P53 By Non-Cross-Resistant Platinum Analogs
… using targeted inhibitors have identified MEK1/2, but not ERK1/2, as a novel biomarker important to mediate p53-Ser20 phosphorylation by oxali-Pt. Overall, the findings gathered in this research project have revealed Ser20 of p53 as a key site that induces cis-Pt resistance when its …
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Serine 910 Phosphorylation of Focal Adhesion Kinase Is Critical for Costamere Assembly
… activation of PKCδ and Src via parallel Raf-1→MEK1/2→ERK1/2 and MEK5→ERK5 signaling pathways. Using co-immunoprecipitation, TIRF-microscopy and FRAP, ET-1 stimulation of NRVM expressing a nonphosphorylatable, S910A-FAK mutant decreased the interaction of paxillin and vinculin within costameres. …
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The innate response to fungal infection
… activation. For most stimuli, Raf-1 activates MEK1/2 which activates ERK1/2, however in response to TLR signalling the kinase Tpl2 is required to activate MEK1/2. I show that the kinase responsible for ERK1/2 activation downstream of Dectin-1 is not Tpl2, but is an unidentified off target …
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Procaspase-3 activation as a strategy to overcome resistance to targeted anticancer therapies
… two of the identified substrates of caspase-3, MEK1 and MEK2, are critical gatekeeper kinases in the mitogen-activated protein kinase (MAPK) pathway. Next, I will discuss the prevalence of oncogenic drivers in the MAPK pathway and the development of inhibitors as targeted anticancer …
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Neutrophil Regulation of Colitis
… IEC functions. Neutrophil-derived TGFβ activates MEK1/2 signaling in IECs enhancing the production of amphiregulin (AREG), a member of EGFR ligand family. Upon the induction of an intestinal inflammatory state, AREG signals through the EGFR pathway to induce epithelial junction formation, as a way …
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A NOVEL BRAF SIGNALING CASCADE THROUGH p-21 ACTIVATED KINASES REGULATES THYROID CANCER CELL MOTILITY
… induced by the BRAF siRNA. In addition, because MEK1/2 is a well-established BRAF downstream effector, we verified using rescue experiments that it also plays a role in BRAF-mediated migration. We inhibited both MEK1/2 and group I PAKs and showed a lack of synergy. To determine whether one …
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