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https://www.readbyqxmd.com/read/29678134/health-risk-assessment-of-volatile-organic-compounds-exposure-near-daegu-dyeing-industrial-complex-in-south-korea
#1
Jianfei Shuai, Sunshin Kim, Hyeonsu Ryu, Jinhyeon Park, Chae Kwan Lee, Geun-Bae Kim, Venecio U Ultra, Wonho Yang
BACKGROUND: Studying human health in areas with industrial contamination is a serious and complex issue. In recent years, attention has increasingly focused on the health implications of large industrial complexes. A variety of potential toxic chemicals have been produced during manufacturing processes and activities in industrial complexes in South Korea. A large number of dyeing industries gathered together in Daegu dyeing industrial complex. The residents near the industrial complex could be often exposed to volatile organic compounds...
April 20, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29676132/-inhibition-of-yiqi-jiedu-formula-on-proliferation-of-nasopharyngeal-carcinoma-cells-by-mapk-erk-signaling-pathway
#2
Jing Hu, Na Dai, Bing-Yan Xu, Fang-Liang Zhou, Ting Lin, Jing-Jing Luo, Jing-Ying Fan, Ying-Chun He
To study the effect of aqueous extracts of Yiqi Jiedu formula (YQ) on the proliferation of CNE2 cells in human nasopharyngeal carcinoma, and investigate its mechanism to provide a new theoretical basis for the clinical application of YQ. CNE2 cells were treated with different concentrations (0.125, 0.25, 0.5, 0.25 g·L⁻¹) of YQ, positive control medicine (cisplatin 4.0 mg·L⁻¹), inhibitor PD98059 (50 μmol·L⁻¹), activator isoproterenol hydrochloride (20 μmol·L⁻¹), activator isoproterenol hydrochloride (ISO)+YQ 0...
March 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29674718/tak-733-inhibits-inflammatory-neointimal-formation-by-suppressing-proliferation-migration-and-inflammation-in-vitro-and-in-vivo
#3
Jun-Hee Park, Sang Woo Kim, Min-Ji Cha, Nara Yoon, Chang Youn Lee, Jiyun Lee, Hyang-Hee Seo, Sunhye Shin, Jung-Won Choi, Seahyoung Lee, Soyeon Lim, Ki-Chul Hwang
As a potent and selective allosteric inhibitor of MEK, TAK-733 has been shown to exert anti-cancer effects for a wide range of cancers both in vitro and in vivo. However, its effects on inhibiting growth have never been investigated in the cardiovascular system, where regulation of abnormal vascular smooth muscle cell growth in neointimal hyperplasia is an important area of focus. Angiotensin II was used to mimic inflammatory neointimal hyperplasia in an in vitro environment, and balloon catheter-induced injury with an infusion of angiotensin II was used to generate an in vivo rat restenosis model under inflammatory conditions...
April 20, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29674704/mek-inhibitors-overcome-resistance-to-bet-inhibition-across-a-number-of-solid-and-hematologic-cancers
#4
Anastasia Wyce, Jeanne J Matteo, Shawn W Foley, Daniel J Felitsky, Satyajit R Rajapurkar, Xi-Ping Zhang, Melissa C Musso, Susan Korenchuk, Natalie O Karpinich, Kathryn M Keenan, Melissa Stern, Lijoy K Mathew, Charles F McHugh, Michael T McCabe, Peter J Tummino, Ryan G Kruger, Christopher Carpenter, Olena Barbash
BET inhibitors exhibit broad activity in cancer models, making predictive biomarkers challenging to define. Here we investigate the biomarkers of activity of the clinical BET inhibitor GSK525762 (I-BET; I-BET762) across cancer cell lines and demonstrate that KRAS mutations are novel resistance biomarkers. This finding led us to combine BET with RAS pathway inhibition using MEK inhibitors to overcome resistance, which resulted in synergistic effects on growth and survival in RAS pathway mutant models as well as a subset of cell lines lacking RAS pathway mutations...
April 20, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29674508/combined-braf-and-hsp90-inhibition-in-patients-with-unresectable-braf-v600e-mutant-melanoma
#5
Zeynep Eroglu, Yian Ann Chen, Geoffrey T Gibney, Jeffrey S Weber, Ragini R Kudchadkar, Nikhil I Khushalani, Joseph Markowitz, Andrew S Brohl, Leticia F Tetteh, Howida Ramadan, Gina Arnone, Jiannong Li, Xiuhua Zhao, Ritin Sharma, Lancia N F Darville, Bin Fang, Inna Smalley, Jane L Messina, John M Koomen, Vernon K Sondak, Keiran S M Smalley
PURPOSE: BRAF inhibitors are clinically active in patients with advanced BRAFV600 -mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. METHODS: Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAFV600 -mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose...
April 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29673908/mechanism-underlying-the-contractile-activity-of-utp-in-the-mammalian-heart
#6
Ulrich Gergs, Daniel Rothkirch, Britt Hofmann, Hendrik Treede, Bernard Robaye, Andreas Simm, Christa E Müller, Joachim Neumann
We previously reported that uridine 5'-triphosphate (UTP), a pyrimidine nucleoside triphosphate produced a concentration- and time-dependent increase in the contraction force in isolated right atrial preparations from patients undergoing cardiac bypass surgery due to angina pectoris. The stimulation of the force of contraction was sustained rather than transient. In the present study, we tried to elucidate the underlying receptor and signal transduction for this effect of UTP. Therefore, we measured the effect of UTP on force of contraction, phosphorylation of p38 and ERK1/2, in human atrial preparations, atrial preparations from genetically modified mice, cardiomyocytes from adult mice and cardiomyocytes from neonatal rats...
April 16, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29673198/chemoresistance-to-cancer-treatment-benzo-%C3%AE-pyrene-as-friend-or-foe
#7
Kevin Dzobo, Naseeha Hassen, Dimakatso Alice Senthebane, Nicholas Ekow Thomford, Arielle Rowe, Hendrina Shipanga, Ambroise Wonkam, M Iqbal Parker, Shaheen Mowla, Collet Dandara
Background: Environmental pollution such as exposure to pro-carcinogens including benzo-α-pyrene is becoming a major problem globally. Moreover, the effects of benzo-α-pyrene (BaP) on drug pharmacokinetics, pharmacodynamics, and drug resistance warrant further investigation, especially in cancer outpatient chemotherapy where exposure to environmental pollutants might occur. Method: We report here on the effects of benzo-α-pyrene on esophageal cancer cells in vitro, alone, or in combination with chemotherapeutic drugs cisplatin, 5-flurouracil, or paclitaxel...
April 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29669300/gzmb-gene-silencing-confers-protection-against-synovial-tissue-hyperplasia-and-articular-cartilage-tissue-injury-in-rheumatoid-arthritis-through-the-mapk-signaling-pathway
#8
Cui-Xia Bao, Hai-Xia Chen, Xue-Jie Mou, Xiang-Kui Zhu, Qi Zhao, Xin-Guang Wang
INTRODUCTION: Rheumatoid arthritis (RA) represents the most commonly occurring inflammatory type of arthritis and is a major cause of disability. Reports have placed emphasis on the potential of, granzyme B (GZMB) as a potentially valuable prognostic marker in early RA, the mechanism of which still remains largely unclear. Thus, the aim of the current study was to investigate the effects GZMB gene silencing influences synovial tissue hyperplasia and articular cartilage tissue injury of RA through the regulation of the MAPK signaling pathway...
April 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29669006/gene-signature-based-approach-identified-mek1-2-as-a-potential-target-associated-with-relapse-after-anti-tnf%C3%AE-treatment-for-crohn-s-disease
#9
Kanae Gamo, Yuumi Okuzono, Masato Yabuki, Takashi Ochi, Kyoko Sugimura, Yosuke Sato, Masaki Sagara, Hiroki Hayashi, Yoshimasa Ishimura, Yutaka Nishimoto, Yusuke Murakawa, Zenyu Shiokawa, Masayuki Gotoh, Takahiro Miyazaki, Yukihiko Ebisuno
Background: Anti-tumor necrosis factor alpha (anti-TNFα) therapy has become the mainstay of therapy for Crohn's disease (CD). However, post-therapy, the recurrence rate is still high. The aim of this study was to dissect the molecular mechanism for recurrence of CD treated with anti-TNFα therapy and investigate novel therapeutic options that could induce complete remission. Methods: We re-analyzed publicly available mucosal gene expression data from CD patients pre- and post-infliximab therapy to extract the transcriptional differences between responders and healthy controls...
April 13, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29668670/exosomes-released-by-gastric-cancer-cells-induce-transition-of-pericytes-into-cancer-associated-fibroblasts
#10
Xiaofei Ning, Hongran Zhang, Cong Wang, Xiuqi Song
BACKGROUND Cancer-associated fibroblasts (CAFs) are functionally and structurally essential for tumor progression. There are 3 main origins of CAFs: mesenchymal stem cells (MSCs), epithelial-to-mesenchymal (EMT) transition cells, and tissue-resident cells. Pericytes retain characteristics of progenitor cells and can differentiate into other cells under normal physiological conditions and into myofibroblasts under pathological conditions. Exosomes play an important role in intercellular communication by transferring membrane components and nucleic acids between different cells...
April 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29663336/melanoma-what-do-all-the-mutations-mean
#11
REVIEW
Elizabeth J Davis, Douglas B Johnson, Jeffrey A Sosman, Sunandana Chandra
Melanoma is one of the most highly mutated malignancies, largely as a function of its generation through ultraviolet light and other mutational processes. The wide array of mutations in both "driver" and "passenger" genes can present a confusing array of data for practitioners, particularly within the context of the recent revolutions in targeted and immune therapy. Although mutations in BRAF V600 clearly confer sensitivity to BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors, the clinical implications of most other mutations are less often discussed and understood...
April 17, 2018: Cancer
https://www.readbyqxmd.com/read/29662665/molecular-mechanism-of-action-and-potential-biomarkers-of-growth-inhibition-of-synergistic-combination-of-afatinib-and-dasatinib-against-gefitinib-resistant-non-small-cell-lung-cancer-cells
#12
Miao Wang, Alex Yuang-Chi Chang
Epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) is the first choice of treatment for advanced non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, single agent usually has limited efficacy due to heterogeneous resistant mechanisms of cancer cells. Thus drug combination therapy would offer more benefits by synergistic interactions and avoidance of resistance emergence. In this study, we selected 8 NSCLC cell lines with different genetic characteristics as research models to investigate the efficacy of 4 agents (gefitinib, cetuximab, afatinib and dasatinib) and their combinations...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662630/type-ii-raf-inhibitor-causes-superior-erk-pathway-suppression-compared-to-type-i-raf-inhibitor-in-cells-expressing-different-braf-mutant-types-recurrently-found-in-lung-cancer
#13
Amir Noeparast, Philippe Giron, Sylvia De Brakeleer, Carolien Eggermont, Ulrike De Ridder, Erik Teugels, Jacques De Grève
A large fraction of somatic driver BRAF mutations in lung cancer are non-V600 and impaired-kinase. Non-V600 BRAF mutations predict sensitivity to combination of a type I RAF inhibitor, Dabrafenib, and a MEK inhibitor, Trametinib. Singly, Dabrafenib only weakly suppresses mutant BRAF-induced ERK signaling and can induce ERK paradoxical activation in CRAF-overexpressing cells. The present study compared the effects of Dabrafenib and a type II RAF inhibitor, AZ628, on ERK activity in HEK293T cells expressing several tumor-derived BRAF mutants, and in a non-V600 and impaired-kinase BRAF-mutant lung cancer cell line (H1666)...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662327/spotlight-on-dabrafenib-trametinib-in-the-treatment-of-non-small-cell-lung-cancer-place-in-therapy
#14
REVIEW
Thomas C Weart, Kenneth D Miller, Charles B Simone
Advanced non-small-cell lung cancer (NSCLC) remains a challenging disease. The limited utility of chemotherapy indicates the need for additional therapeutic options. Targeted therapy continues to be an important tool in the treatment of NSCLC. Mutations within the RAS-RAF-MEK-MAPK pathway, specifically the BRAF V600E mutation, have become an important target for the subset of NSCLC patients with this mutation. This paper summarizes the clinical evidence that lead to the recent approval of the combination of dabrafenib and trametinib to treat patients with advanced NSCLC who harbor a BRAF V600E mutation...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29661693/phosphorylation-of-beta-3-adrenergic-receptor-at-serine-247-by-erk-map-kinase-drives-lipolysis-in-obese-adipocytes
#15
Shangyu Hong, Wei Song, Peter-James H Zushin, Bingyang Liu, Mark P Jedrychowski, Amir I Mina, Zhaoming Deng, Dimitrije Cabarkapa, Jessica A Hall, Colin J Palmer, Hassan Aliakbarian, John Szpyt, Steven P Gygi, Ali Tavakkoli, Lydia Lynch, Norbert Perrimon, Alexander S Banks
OBJECTIVE: The inappropriate release of free fatty acids from obese adipose tissue stores has detrimental effects on metabolism, but key molecular mechanisms controlling FFA release from adipocytes remain undefined. Although obesity promotes systemic inflammation, we find activation of the inflammation-associated Mitogen Activated Protein kinase ERK occurs specifically in adipose tissues of obese mice, and provide evidence that adipocyte ERK activation may explain exaggerated adipose tissue lipolysis observed in obesity...
March 29, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29660387/long-term-inhibition-of-pde5-ameliorates-aging-induced-changes-in-rat-testis
#16
Srdjan J Sokanovic, Ivan Capo, Marija M Medar, Silvana A Andric, Tatjana S Kostic
NO-cGMP signaling pathway has been implicated in reduction of testicular steroidogenesis during aging. Here we analyzed the effect of PDE5 inhibition on old testicular phenotype formation. The old phenotype exhibited low testosterone and increased nitrite levels in circulation, increased cGMP accumulation in testicular interstitial fluid (TIF), progressive atrophy of testicular seminiferous tubules and enlargement of interstitial area followed by rise in blood vessel density and slight increase in the number of Leydig cells and macrophages...
April 13, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29660312/the-egf-ras-pathway-controls-growth-in-drosophila-via-ribosomal-rna-synthesis
#17
Shrivani Sriskanthadevan-Pirahas, Joshua Lee, Savraj S Grewal
The Ras small G-protein is a conserved regulator of cell and tissue growth during animal development. Studies in Drosophila have shown how Ras can stimulate a Raf-MEK-ERK signaling pathway to control cell growth and proliferation in response to epidermal growth factor (EGF) stimulation. This work has also defined several transcription factors that can function as downstream growth effectors of EGF/Ras/ERK pathway by stimulating mRNA transcription. Here we report on stimulation of RNA polymerase I (Pol I)-mediated ribosomal RNA (rRNA) synthesis as a growth effector of Ras/ERK signalling in Drosophila...
April 13, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29658609/survivin-knockdown-induces-senescence-in-ttf%C3%A2-1-expressing-kras-mutant-lung-adenocarcinomas
#18
Toshiyuki Sumi, Sachie Hirai, Miki Yamaguchi, Yusuke Tanaka, Makoto Tada, Gen Yamada, Tadashi Hasegawa, Yohei Miyagi, Toshiro Niki, Atsushi Watanabe, Hiroki Takahashi, Yuji Sakuma
Survivin plays a key role in regulating the cell cycle and apoptosis, and is highly expressed in the majority of malignant tumors. However, little is known about the roles of survivin in KRAS-mutant lung adenocarcinomas. In the present study, we examined 28 KRAS-mutant lung adenocarcinoma tissues and two KRAS-mutant lung adenocarcinoma cell lines, H358 and H441, in order to elucidate the potential of survivin as a therapeutic target. We found that 19 (68%) of the 28 KRAS-mutant lung adenocarcinomas were differentiated tumors expressing thyroid transcription factor‑1 (TTF‑1) and E-cadherin...
April 11, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29656183/hispidulin-inhibits-hepatocellular-carcinoma-growth-and-metastasis-through-ampk-and-erk-signaling-mediated-activation-of-ppar%C3%AE
#19
Mei Han, Hui Gao, Ping Ju, Ming-Quan Gao, Yin-Ping Yuan, Xue-Hong Chen, Kai-Li Liu, Yan-Tao Han, Zhi-Wu Han
Hispidulin, a phenolic flavonoid, exerts potent cytotoxicity towards a variety of human cancers. However, the effects of hispidulin on hepatocellular carcinoma (HCC) and underlying molecular mechanisms of its action remain elusive. The present study investigated the effect of hispidulin on HCC in experimental models, including tumor cell lines and mouse tumor xenograft. Results demonstrated that hispidulin was cytotoxic and anti-proliferative to HCC cell lines (SMMC7721 and Bel7402). Hispidulin activated caspase-3 and triggered apoptosis in HCC cells...
April 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29656114/synergistic-action-of-dual-igf1-r-and-mek-inhibition-sensitizes-childhood-acute-lymphoblastic-leukaemia-all-cells-to-cytotoxic-agents-and-involves-down-regulation-of-stat6-and-pdap1
#20
Victoria J Weston, Wenbin Wei, Tatjana Stankovic, Pamela Kearns
Heterogeneous upregulation of multiple pro-survival pathways underlies resistance to damage-induced apoptosis in acute lymphoblastic leukaemia (ALL) cells despite normal p53 responses. Here we identify the dual combination of IGF1/R and MEK inhibition using AG1024 and U0126 can sensitise apoptosis-resistant ALL cells to ionising radiation (IR)-induced DNA damage irrespective of effect of single pathway inhibition in vitro. This AG1024+U0126 combination also significantly potentiates the ability of the core chemotherapy compounds vincristine, dexamethasone and daunorubicin to kill ALL cells in vitro...
April 12, 2018: Experimental Hematology
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