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https://www.readbyqxmd.com/read/28323857/myocardial-ischemia-reperfusion-enhances-transcriptional-expression-of-endothelin-1-and-vasoconstrictor-etb-receptors-via-the-protein-kinase-mek-erk1-2-signaling-pathway-in-rat
#1
Gry Freja Skovsted, Lars Schack Kruse, Lukas Adrian Berchtold, Anne-Sofie Grell, Karin Warfvinge, Lars Edvinsson
BACKGROUND: Coronary artery remodelling and vasospasm is a complication of acute myocardial ischemia and reperfusion. The underlying mechanisms are complex, but the vasoconstrictor peptide endothelin-1 is suggested to have an important role. This study aimed to determine whether the expression of endothelin-1 and its receptors are regulated in the myocardium and in coronary arteries after experimental ischemia-reperfusion. Furthermore, we evaluated whether treatment with a specific MEK1/2 inhibitor, U0126, modified the expression and function of these proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28323848/7%C3%AE-hydroxycholesterol-induces-monocyte-macrophage-cell-expression-of-interleukin-8-via-c5a-receptor
#2
Hyok-Rae Cho, Yonghae Son, Sun-Mi Kim, Bo-Young Kim, Seong-Kug Eo, Young Chul Park, Koanhoi Kim
We investigated effects of 7-oxygenated cholesterol derivatives present in atherosclerotic lesions, 7α-hydroxycholesterol (7αOHChol), 7β-hydroxycholesterol (7βOHChol), and 7-ketocholesterol (7K), on IL-8 expression. Transcript levels of IL-8 and secretion of its corresponding gene product by monocytes/macrophages were enhanced by treatment with 7αOHChol and, to a lesser extent, 7K, but not by 7βOHChol. The 7-oxygenated cholesterol derivatives, however, did not change transcription of the IL-8 gene in vascular smooth muscle cells...
2017: PloS One
https://www.readbyqxmd.com/read/28323504/pembrolizumab-use-for-the-treatment-of-advanced-melanoma
#3
Pol Specenier
Until recently, overall long term survival in patients with stage IV melanoma was lower than 10 %. However, the treatment of melanoma has evolved rapidly over the last few years, with the advent of inhibitors of BRAF and MEK and of immunotherapeutic agents including ipilimumab, nivolumab, and pembrolizumab. Areas covered: This is a comprehensive review of the literature on the role of pembrolizumab in melanoma. Pembrolizumab is a Programmed Death Receptor 1 (PD-1) directed monoclonal antibody which is approved by FDA and EMA for the treatment of patients with metastatic melanoma...
March 21, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28314720/rechallenge-with-braf-and-mek-inhibitors-has-antitumor-activity
#4
(no author information available yet)
Resistance to BRAF plus MEK inhibitors may be reversible in patients with BRAF(V600)-mutant melanoma.
March 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28314119/a-combined-in-vitro-assay-for-evaluation-of-neurotrophic-activity-and-cytotoxicity
#5
Narayan D Chaurasiya, Surabhi Shukla, Babu L Tekwani
Neurotrophic assays are phenotypic methods to identify molecules that stimulate differentiation of neuronal cells. Bioactive small molecules with neurotrophic actions hold great promise as therapeutic agents for the treatment of neurodegenerative diseases and neuronal injuries by virtue of their ability to stimulate neuritic outgrowth. A combined in vitro method, which measures neurotrophic activity and cytotoxicity in a single assay, has been described. This assay, performed in 96-well microplates with PC12 and Neuroscreen-1 (NS-1; a subclone of PC12) cells, is a simple tool for identification of new neurotrophic agents...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28302530/regorafenib-overcomes-chemotherapeutic-multidrug-resistance-mediated-by-abcb1-transporter-in-colorectal-cancer-in-vitro-and-in-vivo-study
#6
Yi-Jun Wang, Yun-Kai Zhang, Guan-Nan Zhang, Sweilem B Al Rihani, Meng-Ning Wei, Pranav Gupta, Xiao-Yu Zhang, Suneet Shukla, Suresh V Ambudkar, Amal Kaddoumi, Zhi Shi, Zhe-Sheng Chen
Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1...
March 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28301591/in-vivo-and-ex-vivo-cetuximab-sensitivity-assay-using-three-dimensional-primary-culture-system-to-stratify-kras-mutant-colorectal-cancer
#7
Takahiro Tashiro, Hiroaki Okuyama, Hiroko Endo, Kenji Kawada, Yasuko Ashida, Masayuki Ohue, Yoshiharu Sakai, Masahiro Inoue
In clinic, cetuximab, an anti-EGFR antibody, improves treatment outcomes in colorectal cancer (CRC). KRAS-mutant CRC is generally resistant to cetuximab, although difference of the sensitivity among KRAS-mutants has not been studied in detail. We previously developed the cancer tissue-originated spheroid (CTOS) method, a primary culture method for cancer cells. We applied CTOS method to investigate whether ex vivo cetuximab sensitivity assays reflect the difference in sensitivity in the xenografts. Firstly, in vivo cetuximab treatment was performed with xenografts derived from 10 CTOS lines (3 KRAS-wildtype and 7 KRAS mutants)...
2017: PloS One
https://www.readbyqxmd.com/read/28300835/geranylgeranyl-diphosphate-synthase-inhibition-induces-apoptosis-that-is-dependent-upon-ggpp-depletion-erk-phosphorylation-and-caspase-activation
#8
Sherry S Agabiti, Jin Li, Andrew J Wiemer
Bisphosphonates are diphosphate analogs that inhibit the intermediate enzymes of the mevalonate pathway. Here, we compared the effects of a farnesyl diphosphate synthase inhibitor, zoledronate, and a geranylgeranyl diphosphate synthase (GGDPS) inhibitor, digeranyl bisphosphonate (DGBP), on lymphocytic leukemia cell proliferation and apoptosis. Both zoledronate and DGBP inhibited proliferation with DGBP doing so more potently. DGBP was markedly less toxic than zoledronate toward the viability of healthy human peripheral blood mononuclear cells...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28299583/braf-plus-mek-targeted-drugs-a-new-standard-of-treatment-for-braf-mutant-advanced-melanoma
#9
Paola Queirolo, Francesco Spagnolo
BRAF plus MEK-targeted drugs have out-performed BRAF inhibitor monotherapy in three randomized phase 3 studies, and such combinations have become a new standard of treatment for BRAF-mutant advanced melanoma. With an overall response rate of about 70%, no other therapy in melanoma has shown a better response rate in late-phase clinical trials than combined BRAF and MEK inhibitors; the rapid kinetics of response make them the ideal front-line treatment for symptomatic, BRAF-mutant advanced melanoma patients...
March 15, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28299358/a-novel-potentially-targetable-tmem106b-braf-fusion-in-pleomorphic-xanthoastrocytoma
#10
Susan J Hsiao, Matthias A Karajannis, Daniel Diolaiti, Mahesh M Mansukhani, Julia Glade Bender, Andrew L Kung, James H Garvin
Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization (WHO) Grade II glioma occurring primarily in children and young adults. Most PXAs harbor the known activating mutation BRAF V600E. We report a case of locally recurrent PXA with anaplastic features in a 10-yr-old female. The PXA was negative by immunohistochemical (IHC) staining for BRAF V600E mutation. Whole-exome and transcriptome sequencing of the tumor confirmed the absence of BRAF V600E, but identified copy-number alterations (including loss of the tumor suppressor CDKN2A) and a novel TMEM106B-BRAF fusion...
March 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28298334/erythropoietin-facilitates-definitive-endodermal-differentiation-of-mouse-embryonic-stem-cells-via-activation-of-erk-signaling
#11
Taku Kaitsuka, Kohei Kobayashi, Wakako Otsuka, Takuya Kubo, Farzana Hakim, Fan-Yan Wei, Nobuaki Shiraki, Shoen Kume, Kazuhito Tomizawa
Artificially generated pancreatic β-cells from pluripotent stem cells are expected for cell replacement therapy for type 1 diabetes. Several strategies are adopted to direct pluripotent stem cells toward pancreatic differentiation. However, a standard differentiation method for clinical application has not been established. It is important to develop more effective and safer methods for generating pancreatic β-cells without toxic or mutagenic chemicals. In the present study, we screened several endogenous factors involved in organ development to identify the factor, which induced the efficiency of pancreatic differentiation and found that treatment with erythropoietin (EPO) facilitated the differentiation of mouse embryonic stem cells (ESCs) into definitive endoderm...
March 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28297625/genomics-of-hairy-cell-leukemia
#12
Enrico Tiacci, Valentina Pettirossi, Gianluca Schiavoni, Brunangelo Falini
Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28293123/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cancer-patient-selection-and-perspectives
#13
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28293067/syndecan-1-acts-as-an-important-regulator-of-cxcl1-expression-and-cellular-interaction-of-human-endometrial-stromal-and-trophoblast-cells
#14
Dunja Maria Baston-Buest, Olga Altergot-Ahmad, Sarah Jean Pour, Jan-Steffen Krüssel, Udo Rudolf Markert, Tanja Natascha Fehm, Alexandra Petra Bielfeld
Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28291381/selimetry-a-multicentre-i-131-dosimetry-trial-a-clinical-perspective
#15
Jonathan Wadsley, Rebecca Gregory, Glenn Flux, Kate Newbold, Yong Du, Laura Moss, Andrew Hall, Louise Flanagan, Sarah R Brown
Treatment options for patients with thyroid cancer that is no longer sensitive to iodine therapy are limited. Those treatments which currently exist are associated with significant toxicity. The SELIMETRY trial (EudraCT No 2015-002269-47) aims to investigate the role of the MEK inhibitor Selumetinib in re-sensitising advanced iodine refractory differentiated thyroid cancer to radioiodine therapy. Patients deemed to have sufficient iodine uptake in previously iodine refractory lesions after 4 weeks of Selumetinib therapy will be given an empirical activity of 5...
March 14, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28288968/depletion-of-tcf3-and-lef1-maintains-mouse-embryonic-stem-cell-self-renewal
#16
Shoudong Ye, Tao Zhang, Chang Tong, Xingliang Zhou, Kan He, Qian Ban, Dahai Liu, Qi-Long Ying
Mouse and rat embryonic stem cell (ESC) self-renewal can be maintained by dual inhibition of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase kinase (MEK). Inhibition of GSK3 promotes ESC self-renewal by abrogating T-cell factor 3 (TCF3)-mediated repression of the pluripotency network. How inhibition of MEK mediates ESC self-renewal, however, remains largely unknown. Here, we show that inhibition of MEK can significantly suppress lymphoid enhancer factor 1 (LEF1) expression in mouse ESCs...
March 13, 2017: Biology Open
https://www.readbyqxmd.com/read/28288818/3-o-z-coumaroyloleanolic-acid-overcomes-cks1b-induced-chemoresistance-in-lung-cancer-by-inhibiting-hsp90-and-mek-pathways
#17
He Wang, Mingna Sun, Jiayi Guo, Lei Ma, Hui Jiang, Liang Gu, Huaying Wen, Siyan Liao, Jingqi Chen, Bohang Zeng, Yongmei Li, Yueshan Li, Xiyong Yu, Yinghong Feng, Yi Zhou
Expression of CDC28 protein kinase regulatory subunit 1 (Cks1), an adaptor for cyclin-dependent kinases, is tightly regulated at transcriptional and posttranslational levels. Increased expression of Cks1 has been documented to be attributable to cancer progression, chemoresistance, and chemosensitivity. Here we report that ectopic overexpression of Cks1b in human lung cancer cells (Cks1b-OE) induces chemoresistance of the cells to cisplatin (CDDP) and doxorubicin (DOX) through mechanisms independent of its canonical Skp2-p27 pathway...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28287251/cisplatin-induced-apoptosis-of-ovarian-cancer-a2780s-cells-by-activation-of-erk-p53-puma-signals
#18
Hao Song, Mei Wei, Wenfen Liu, Shulin Shen, Jiaqun Li, Liming Wang
Cisplatin (CDDP) is one of the most effective anticancer agents widely used in the treatment of solid tumors, including ovarian cancer. It is generally considered as a cytotoxic drug which kills cancer cells by causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, the underlying mechanisms leading to cell apoptosis remain obscure. In this study, the signaling pathways involved in CDDP -induced apoptosis were examined using CDDP-sensitive ovarian cancer A2780s cells. A2780s cells were treated with CDDP (1...
March 13, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28286738/tsc2-rheb-signaling-mediates-erk-dependent-regulation-of-mtorc1-activity-in-c2c12-myoblasts
#19
Mitsunori Miyazaki, Tohru Takemasa
The enhanced rate of protein synthesis in skeletal muscle cells results in a net increase in total protein content that leads to skeletal muscle growth/hypertrophy. The mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent regulation of the activity of mechanistic target of rapamycin (mTOR) and subsequent protein synthesis has been suggested as a regulatory mechanism; however, the exact molecular processes underlying such a regulation are poorly defined. The purpose of this study was to investigate regulatory mechanisms involved in the MEK/ERK-dependent pathway leading to mTORC1 activation in skeletal muscle cells...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28286121/high-glucose-enhances-camp-level-and-extracellular-signal-regulated-kinase-phosphorylation-in-chinese-hamster-ovary-cell-usage-of-br-camp-in-foreign-protein-%C3%AE-galactosidase-expression
#20
Hsiao-Hsien Lin, Tsung-Yih Lee, Ting-Wei Liu, Ching-Ping Tseng
Glucose is a carbon source for Chinese hamster ovary (CHO) cell growth, while low growth rate is considered to enhance the production of recombinant proteins. The present study reveals that glucose concentrations higher than 1 g/L reduce the growth rate and substantially increase in cAMP (∼300%) at a high glucose concentration (10 g/L). High glucose also enhances the phosphorylation of extracellular signal-regulated kinase (ERK) and p27(kip) by Western blot analysis. To determine whether the phosphorylation of ERK is involved in the mechanism, a cyclic-AMP dependent protein kinase A (PKA) inhibitor (H-8) or MEK (MAPKK) inhibitor (PD98059) was added to block ERK phosphorylation...
March 9, 2017: Journal of Bioscience and Bioengineering
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