keyword
MENU ▼
Read by QxMD icon Read
search

Mek

keyword
https://www.readbyqxmd.com/read/28732393/microrna-30a-suppresses-tumor-progression-by-blocking-ras-raf-mek-erk-signaling-pathway-in-hepatocellular-carcinoma
#1
Kun Zhou, Xiaoyu Luo, Yu Wang, Dachun Cao, Gang Sun
Emerging reports suggest microRNAs (miRNAs) play a vital role in the progression of malignant tumors. MiR-30a is downregulated in a variety of cancers and acts as a tumor suppressing gene. However, the molecular mechanisms of miRNA-30a in hepatocellular carcinoma (HCC) are still unclear. Hereby, in this study, we detected that miR-30a expression was significantly down-regulated in both HCC tissues compared with adjacent non-cancerous liver tissues, and we also observed that miR-30a expression was lower in HCC cell lines than that of normal controls...
July 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28732383/radiation-alters-pd-l1-nkg2d-ligand-levels-in-lung-cancer-cells-and-leads-to-immune-escape-from-nk-cell-cytotoxicity-via-il-6-mek-erk-signaling-pathway
#2
Ming Jing Shen, Li Jun Xu, Li Yang, Ying Tsai, Peter C Keng, Yongbing Chen, Soo Ok Lee, Yuhchyau Chen
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730748/extracellular-signal-regulated-kinase-activation-in-the-spinal-cord-contributes-to-visceral-hypersensitivity-induced-by-craniofacial-injury-followed-by-stress
#3
Y-J Zhao, J-H Li, B Hu, Y Wang, X-F Chang, R J Traub, D-Y Cao
BACKGROUND: We previously developed an animal model to examine mechanisms that underlie the emergence of visceral hypersensitivity modeling pain characteristics of temporomandibular disorder (TMD) patients with comorbid irritable bowel syndrome (IBS). In ovariectomized (OVx) rats with estradiol (E2) replacement, visceral hypersensitivity developed subsequent to masseter muscle inflammation followed by repeated forced swim (FS) stress. The purpose of this study was to investigate whether activation of extracellular signal-regulated kinase (ERK) in the spinal cord contributes to visceral hypersensitivity in this overlapping pain model...
July 21, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28726203/cysteine-containing-peptides-stimulate-monocyte-migration-through-nadph-oxidase-activation
#4
T L Krasnikova, T I Arefieva, E A Pylaeva, M V Sidorova
We analyzed migration of monocytes under the effect of apocinin (NADPH inhibitor) and PD98059 (blocker of extracellular MEK/ERK kinase involved in Nox4 oxidase-mediated migration of monocytes). Migration of monocytes stimulated by cysteine-containing peptides (fragments of chemokines with free thiol group MCP-1 and fractalkine) was completely inhibited by apocinin and MEK/ERK blocker. It is assumed that the stimulating effect of cysteine-containing peptides on monocyte migration is mediated by the NADPH-oxidase system, in particular, Nox4...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28724936/an-engineered-protein-antagonist-of-k-ras-b-raf-interaction
#5
Monique J Kauke, Michael W Traxlmayr, Jillian A Parker, Jonathan D Kiefer, Ryan Knihtila, John McGee, Greg Verdine, Carla Mattos, K Dane Wittrup
Ras is at the hub of signal transduction pathways controlling cell proliferation and survival. Its mutants, present in about 30% of human cancers, are major drivers of oncogenesis and render tumors unresponsive to standard therapies. Here we report the engineering of a protein scaffold for preferential binding to K-Ras G12D. This is the first reported inhibitor to achieve nanomolar affinity while exhibiting specificity for mutant over wild type (WT) K-Ras. Crystal structures of the protein R11.1.6 in complex with K-Ras WT and K-Ras G12D offer insight into the structural basis for specificity, highlighting differences in the switch I conformation as the major defining element in the higher affinity interaction...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724666/braf-inhibitors-amplify-the-pro-apoptotic-activity-of-mek-inhibitors-by-inducing-er-stress-in-nras-mutant-melanoma
#6
Heike Niessner, Tobias Sinnberg, Corinna Kosnopfel, Keiran S M Smalley, Daniela Beck, Christian Praetorius, Marion Mai, Stefan Beissert, Dagmar Kulms, Martin Schaller, Claus Garbe, Keith T Flaherty, Dana Westphal, Ines Wanke, Friedegund Meier
<p>NRAS mutations in malignant melanoma are associated with aggressive disease requiring rapid antitumor intervention, but there is no approved targeted therapy for this subset of patients. In clinical trials, the MEK inhibitor (MEKi) binimetinib displayed modest antitumor activity, making combinations a requisite. In a previous study, the BRAF inhibitor (BRAFi) vemurafenib was shown to induce endoplasmic reticulum (ER) stress that together with inhibition of the RAF-MEK-ERK (MAPK) pathway amplified its pro-apoptotic activity in BRAF-mutant melanoma...
July 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28724663/pd-l1-expression-and-immune-escape-in-melanoma-resistanceto-mapk-inhibitors
#7
Hojabr Kakavand, Robert V Rawson, Gulietta M Pupo, Jean Y H Yang, Alexander M Menzies, Matteo S Carlino, Richard F Kefford, Julie R Howle, Robyn Saw, John F Thompson, James S Wilmott, Georgina V Long, Richard A Scolyer, Helen Rizos
Purpose: To examine the relationship between immune activity, PD-L1 expression and tumor cell signaling, in metastatic melanomas prior to and during treatment with targeted MAPK inhibitors. <p>Experimental design: Thirty-eight tumors from 17 patients treated with BRAF inhibitor (n=12) or combination BRAF/MEK inhibitors (n=5) with known PD-L1 expression were analyzed. RNA expression arrays were performed on all pre-treatment (PRE, n=17), early during treatment (EDT, n=8) and progression (PROG, n=13) biopsies...
July 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28724429/the-noncoding-rna-hoxd-as1-is-a-critical-regulator-of-the-metastasis-and-apoptosis-phenotype-in-human-hepatocellular-carcinoma
#8
Shan Lu, Jiansheng Zhou, Yimin Sun, Nan Li, Mingyong Miao, Binghua Jiao, Huan Chen
BACKGROUND: Despite accumulating evidence that long noncoding RNAs (lncRNAs) are associated with cancer development in multiple types of cancer, the biological roles of many lncRNAs in human hepatocellular carcinoma (HCC) metastasis have not been well characterized. METHODS: A lncRNA+ mRNA human gene expression microarray analysis was used to identify differentially expressed lncRNAs in metastatic HCC tissues compared to non-metastatic tissue. RESULTS: We observed remarkable overexpression of HOXD-AS1 in metastatic cancer tissues...
July 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28724377/combination-therapy-for-melanoma-with-braf-mek-inhibitor-and-immune-checkpoint-inhibitor-a-mathematical-model
#9
Xiulan Lai, Avner Friedman
BACKGROUND: The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years...
July 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28721890/the-prognostic-value-of-braf-c-kit-and-nras-mutations-in-melanoma-patients-with-brain-metastases
#10
Paul W Sperduto, Wen Jiang, Paul D Brown, Steve Braunstein, Penny Sneed, Daniel A Wattson, Helen A Shih, Ananta Bangdiwala, Ryan Shanley, Natalie A Lockney, Kathryn Beal, Emil Lou, Thomas Amatruda, William A Sperduto, John P Kirkpatrick, Norman Yeh, Laurie E Gaspar, Jason K Molitoris, Laura Masucci, David Roberge, James Yu, Veronica Chiang, Minesh Mehta
PURPOSE: Brain metastases are a common problem in patients with melanoma, but little is known about the effect of gene mutations on survival in these patients. METHODS AND MATERIALS: We created a retrospective multi-institutional database of 823 patients with melanoma and brain metastases diagnosed between 2006 and 2015. Clinical parameters, gene mutation status (BRAF, C-KIT, NRAS), and treatment were correlated with survival. Treatment patterns and outcomes were compared with a prior era (1985-2005)...
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28720574/fructose-1-6-bisphosphatase-inhibits-erk-activation-and-bypasses-gemcitabine-resistance-in-pancreatic-cancer-by-blocking-iqgap1-mapk-interaction
#11
Xin Jin, Yunqian Pan, Liguo Wang, Tao Ma, Lizhi Zhang, Amy H Tang, Daniel D Billadeau, Heshui Wu, Haojie Huang
Dysregulation of the mitogen-activated protein kinase (MAPK) pathway correlates with progression of pancreatic ductal adenocarcinoma (PDAC) progression. IQ motif containing GTPase activating protein 1 (IQGAP1) is a MAPK scaffold that directly regulates the activation of RAF, MEK, and extracellular signaling-regulated kinases (ERK). Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, is transcriptionally downregulated in various cancers, including PDAC. Here we demonstrate that FBP1 acts as a negative modulator of the IQGAP1-MAPK signaling axis in PDAC cells...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28720543/involvement-of-the-bh3-only-pro-apoptotic-bik-nbk-in-braf-mek-inhibitor-induced-apoptosis-in-melanoma-cell-lines
#12
Andreas Borst, Sebastian Haferkamp, Johannes Grimm, Manuel Rösch, Guannan Zhu, Sen Guo, Chunying Li, Tianwen Gao, Svenja Meierjohann, David Schrama, Roland Houben
In patients with BRAF-mutated melanoma specific inhibitors of BRAF(V600E) and MEK1/2 frequently induce initial tumor reduction, frequently followed by relapse. As demonstrated previously, BRAF(V600E)-inhibition induces apoptosis only in a fraction of treated cells, while the remaining arrest and survive providing a source or a niche for relapse. To identify factors contributing to the differential initial response towards BRAF/MEK inhibition, we established M14 melanoma cell line-derived single cell clones responding to treatment with BRAF inhibitor vemurafenib and MEK inhibitor trametinib predominantly with either cell cycle arrest (CCA-cells) or apoptosis (A-cells)...
July 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28718440/selective-targeting-of-rsk-isoforms-in-cancer
#13
REVIEW
Kimberly A Casalvieri, Christopher J Matheson, Donald S Backos, Philip Reigan
The p90 ribosomal S6 kinase family (RSK1-4) is a group of highly conserved Ser/Thr kinases that act as downstream effectors of the Ras/Raf/MEK/ERK signaling pathway. The RSKs phosphorylate a range of substrates involved in transcription, translation, cell cycle regulation, and cell survival. Although the RSKs have a high degree of sequence homology, their functional differences in cancer are of great interest. Current RSK inhibitors target more than one RSK isoform, and this may limit their efficacy as anticancer agents...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716954/synaptically-driven-phosphorylation-of-ribosomal-protein-s6-is-differentially-regulated-at-active-synapses-versus-dendrites-and-cell-bodies-by-mapk-and-pi3k-mtor-signaling-pathways
#14
Patricia Salgado Pirbhoy, Shannon Farris, Oswald Steward
High-frequency stimulation of the medial perforant path triggers robust phosphorylation of ribosomal protein S6 (rpS6) in activated dendritic domains and granule cell bodies. Here we dissect the signaling pathways responsible for synaptically driven rpS6 phosphorylation in the dentate gyrus using pharmacological agents to inhibit PI3-kinase/mTOR and MAPK/ERK-dependent kinases. Using phospho-specific antibodies for rpS6 at different sites (ser235/236 versus ser240/244), we show that delivery of the PI3-kinase inhibitor, wortmannin, decreased rpS6 phosphorylation throughout the somatodendritic compartment (granule cell layer, inner molecular layer, outer molecular layer), especially in granule cell bodies while sparing phosphorylation at activated synapses (middle molecular layer)...
August 2017: Learning & Memory
https://www.readbyqxmd.com/read/28714990/an-approach-to-suppress-the-evolution-of-resistance-in-braf-v600e-mutant-cancer
#15
Yaohua Xue, Luciano Martelotto, Timour Baslan, Alberto Vides, Martha Solomon, Trang Thi Mai, Neelam Chaudhary, Greg J Riely, Bob T Li, Kerry Scott, Fabiola Cechhi, Ulrika Stierner, Kalyani Chadalavada, Elisa de Stanchina, Sarit Schwartz, Todd Hembrough, Gouri Nanjangud, Michael F Berger, Jonas Nilsson, Scott W Lowe, Jorge S Reis-Filho, Neal Rosen, Piro Lito
The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAF(amp)) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or in combination with other ERK signaling inhibitors. Single-cell sequencing and multiplex fluorescence in situ hybridization analyses mapped the emergence of extra-chromosomal amplification in parallel evolutionary trajectories that arose in the same tumor shortly after treatment...
July 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28713009/aeromonas-hydrophila-induced-alterations-in-cytosolic-calcium-activate-pro-apoptotic-cpkc-mek1-2-tnf%C3%AE-axis-in-infected-headkidney-macrophages-of-clarias-gariepinus
#16
Asha Shelly, Chaitali Banerjee, Gunjan Kumar Saurav, Atish Ray, Vipin Singh Rana, Rajagopal Raman, Shibnath Mazumder
Alterations in intracellular-calcium (Ca(2+))i homeostasis is critical to Aeromonas hydrophila-induced headkidney macrophages (HKM) apoptosis of Clarias gariepinus, though the implications are poorly understood. Here, we describe the role of intermediate molecules of Ca(2+-)signaling pathway that are involved in HKM apoptosis. We observed phosphoinositide-3-kinase/phospholipase C is critical for (Ca(2+))i release in infected HKM. Heightened protein kinase-C (PKC) activity and phosphorylation of MEK1/2-ERK1/2 was noted which declined in presence of 2-APB, Go6976 and PD98059, inhibitors to IP3-receptor, conventional PKC isoforms (cPKC) and MEK1/2 respectively implicating Ca(2+)/cPKC/MEK-ERK1/2 axis imperative in A...
July 14, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28711906/oxidative-stress-mediates-an-increased-formation-of-vascular-endothelial-growth-factor-in-human-hepatocarcinoma-cells-exposed-to-erlotinib
#17
Nataliya Rohr-Udilova, Florian Klinglmüller, Martha Seif, Hubert Hayden, Martin Bilban, Matthias Pinter, Klaus Stolze, Wolfgang Sieghart, Markus Peck-Radosavljevic, Michael Trauner
The tyrosine kinase inhibitor erlotinib targets the receptor of epidermal growth factor (EGFR) involved in development of hepatocellular carcinoma (HCC). Although inefficient in established HCC, erlotinib has been recently proposed for HCC chemoprevention. Since Cyp3A4 and Cyp1A2 enzymes metabolize erlotinib in the liver, the insights into the mechanisms of erlotinib effects on liver cells with maintained drug metabolizing activity are needed. We applied erlotinib to both commercially available (SNU398, Huh7) and established in Austria HCC cell lines (HCC-1...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28709702/clinical-and-morphologic-characteristics-of-mek-inhibitor-associated-retinopathy-differences-from-central-serous-chorioretinopathy
#18
Jasmine H Francis, Larissa A Habib, David H Abramson, Lawrence A Yannuzzi, Murk Heinemann, Mrinal M Gounder, Rachel N Grisham, Michael A Postow, Alexander N Shoushtari, Ping Chi, Neil H Segal, Rona Yaeger, Alan L Ho, Paul B Chapman, Federica Catalanotti
PURPOSE: To investigate the clinical and morphologic characteristics of serous retinal disturbances in patients taking mitogen-activated protein kinase kinase (MEK) inhibitors. PARTICIPANTS: A total of 313 fluid foci in 50 eyes of 25 patients receiving MEK inhibitors for treatment of their metastatic cancer, who had evidence of serous retinal detachments confirmed by optical coherence tomography (OCT). DESIGN: Single-center, retrospective cohort study...
July 12, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28708582/tumor-specific-hepatic-stellate-cells-thscs-induces-digr2-expression-in-dendritic-cells-to-inhibit-t-cells
#19
Yun-Hong Xia, Zhen Lu, Min Zhao, Wen-Ting Dai, Lu Ding, Li-Xia Hu, Guo-Lin Jiang
Tumor-specific hepatic stellate cells (tHSCs) contributes to tumorigenesis and progression of hepatocellular carcinoma (HCC). The potential function of tHSCs on dendritic cells (DCs) was studied here. We discovered that tHSCs co-culture induced upregulation of DIgR2 (dendritic cell-derived immunoglobulin receptor 2) in bone marrow-derived DCs (mDCs). Activation of MEK-ERK is required for DIgR2 expression in mDCs. MEK-ERK inhibitors or shRNA-mediated silence of MEK1/2 in mDCs inhibited tHSCs-induced DIgR2 expression...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705928/miniaturized-radiochemical-purity-testing-for-99m-tc-hmpao-99m-tc-hmdp-and-99m-tc-tetrofosmin
#20
Ana de la Fuente, Roberta Zanca, Angela Gabriella Cataldi, Roberto Boni, Martina Sollini, Elena Lazzeri, Giuliano Mariani, Paola Anna Erba
Quick methods are functional in clinical practice in order to ensure the fastest availability of radiopharmaceuticals. For this purpose, we investigated the radiochemical purity of the widely used (99m)Tc-HMDP (hydroxymethylene diphosphonate), (99m)Tc-HMPAO (hexamethylpropyleneamine oxime) and (99m)Tc-Tetrofosmin by reducing time as compared to the manufacturer's method. Methods: We applied a miniaturized chromatographic method with a reduced strip development from 18 cm to 9 cm for all three radiopharmaceuticals...
July 13, 2017: Journal of Nuclear Medicine Technology
keyword
keyword
111027
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"