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https://www.readbyqxmd.com/read/28641665/-research-progress-of-ras-raf-mek-erk-signaling-pathways-in-leukemia-review
#1
Jing Liu, Na Lv, Yong-Hui Li, Li Yu
Ras/Raf/MEK/ERK signaling pathway plays an important role in the occurrence and development of leukemia. Using the inhibitors of key signaling components in the signaling pathway is new strategy for the treatment of leukemia. In recent years, the screening of these inhibitors and their in vitro and in vivo researches have become a hot spot in the field of treatment. In vivo and in vitro experiments and early clinical studies have shown that these inhibitors have good effect and application prospects in the treatment of leukemia...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641490/preserved-imitation-in-contrast-to-limited-free-application-of-comfortable-hand-actions-in-intellectually-able-young-adults-with-an-autism-spectrum-disorder
#2
Caroline Beelen, Koen Cuypers, Lise van Schuerbeeck, Marijke Braeken, Veerle Ross, Ellen Jongen, Raf Meesen, Marleen Vanvuchelen
Imitation problems are commonly reported in children with an autism spectrum disorder. However, it has not yet been determined whether imitation problems persist into young adulthood. In this study, we investigated imitation skills of 20 intellectually able young adults with autism spectrum disorder relative to 19 age-matched neurotypical adults. For this purpose, we used a bar-transport task, which evokes the application of the end-state comfort principle. Specifically, we examined whether young adults with autism spectrum disorder imitated the means-end structure of a demonstrator's bar-transport action with and without application of the end-state comfort principle (imitation task)...
June 1, 2017: Autism: the International Journal of Research and Practice
https://www.readbyqxmd.com/read/28640847/heart-rate-lowering-treatment-leads-to-a-reduction-in-vulnerable-plaque-features-in-atherosclerotic-rabbits
#3
Raf H M van Hoof, Evelien Hermeling, Judith C Sluimer, Julie Salzmann, Arnold P G Hoeks, Jérôme Roussel, Mat J A P Daemen, Harry Struijker-Boudier, Joachim E Wildberger, Sylvia Heeneman, M Eline Kooi
OBJECTIVE: To investigate the effect of a heart rate (HR) lowering agent (Ivabradine) on features of atherosclerotic plaque vulnerability with magnetic resonance imaging (MRI), ultrasound imaging, and histology. APPROACH AND RESULTS: Atherosclerosis was induced in the abdominal aorta of 19 rabbits. Nine rabbits were treated with Ivabradine (17 mg/kg/day) during the entire study period. At week 14, imaging was performed. Plaque size was quantified on contrast-enhanced T1-weighted MR images...
2017: PloS One
https://www.readbyqxmd.com/read/28638488/a-look-inside-of-the-complex-pathogenesis-of-b-raf-v600e-driven-cancer
#4
EDITORIAL
Emilia Caputo
Cancer is a very complex disease, where cell alterations (i.e. gene mutations, dysregulated signaling pathway(s) and epigenetic modifications) contribute to its development and progression. Elucidating the connections among these cell modifications is a critical challenge, in order to understand the mechanisms which are activated from cancer cells to survive and proliferate. Interesting, Prof. Peng Hou and colleagues, at the First Affiliated Hospital of Xi'an Jiaotong University in China, identified unknown epigenetic mechanisms and their involvement in the tumorigenesis of B-RAF(V600E)-driven cancer...
2017: Theranostics
https://www.readbyqxmd.com/read/28637716/modulation-of-plasma-metabolite-biomarkers-of-mapk-pathway-with-the-mek-inhibitor-ro4987655-pharmacodynamic-and-predictive-potential-in-metastatic-melanoma
#5
Joo Ern Ang, Akos Pal, Yasmin J Asad, Alan T Henley, Melanie Valenti, Gary Box, Alexis de Haven Brandon, Victoria Revell, Debra J Skene, Miro Venturi, Ruediger Rueger, Valerie Meresse, Suzanne A Eccles, Johann S de Bono, Stanley B Kaye, Paul Workman, Udai Banerji, Florence I Raynaud
<p>MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based metabolomics, we identified in preclinical models 21 plasma metabolites including amino acids, propionylcarnitine, phosphatidylcholines and sphingomyelins that were significantly altered in two B-RAF mutant melanoma xenografts and that were reversed following a single dose of the potent and selective MEK inhibitor RO4987655...
June 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28634209/genetic-evidence-that-%C3%AE-arrestins-are-dispensable-for-the-initiation-of-%C3%AE-2-adrenergic-receptor-signaling-to-erk
#6
Morgan O'Hayre, Kelsie Eichel, Silvia Avino, Xuefeng Zhao, Dana J Steffen, Xiaodong Feng, Kouki Kawakami, Junken Aoki, Karen Messer, Roger Sunahara, Asuka Inoue, Mark von Zastrow, J Silvio Gutkind
The β2-adrenergic receptor (β2AR) has provided a paradigm to elucidate how G protein-coupled receptors (GPCRs) control intracellular signaling, including the discovery that β-arrestins, which bind to ligand-activated GPCRs, are central for GPCR function. We used genome editing, conditional gene deletion, and small interfering RNAs (siRNAs) to determine the roles of β-arrestin 1 (β-arr1) and β-arr2 in β2AR internalization, trafficking, and signaling to ERK. We found that only β-arr2 was essential for β2AR internalization...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28634120/highly-reproducible-improved-label-free-quantitative-analysis-of-cellular-phosphoproteome-by-optimization-of-lc-ms-ms-gradient-and-analytical-column-construction
#7
Nagib Ahsan, Judson Belmont, Zhuo Chen, James G Clifton, Arthur R Salomon
Expanding the sequencing depth of the peptides with a statistically significant quantitative change derived from a biological stimulation is critical. Here we demonstrate that optimization of LC gradient and analytical column construction can reveal over 30,000 unique peptides and 23,000 phosphopeptides at high confidence. The quantitative reproducibility of different analytical workflows was evaluated by comparing the phosphoproteome of CD3/4 stimulated and unstimulated T-cells as a model system. A fritless, 50cm-long column packed with 1...
June 17, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28631187/serine-peptidase-inhibitor-kazal-type-1-spink1-as-novel-downstream-effector-of-the-cadherin-17-%C3%AE-catenin-axis-in-hepatocellular-carcinoma
#8
Felix H Shek, Ruibang Luo, Brian Y H Lam, Wing Kin Sung, Tak-Wah Lam, John M Luk, Ming Sum Leung, Kin Tak Chan, Hector K Wang, Chung Man Chan, Ronnie T Poon, Nikki P Lee
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Previously, we reported that cadherin-17 (CDH17) and its related CDH17/β-catenin axis may be responsible for inducing HCC in a subset of patients exhibiting CDH17 over-expression. Here we aimed at obtaining a better understanding of the CDH17-related HCC biology and to obtain further indications for the design of targeted therapies in CDH17 over-expressing HCC patients. RESULTS: We found that SPINK1 acts as a downstream effector of the CDH17/β-catenin axis in HCC...
June 19, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28630043/the-small-gtpases-k-ras-n-ras-and-h-ras-have-distinct-biochemical-properties-determined-by-allosteric-effects
#9
Christian W Johnson, Derion Reid, Jillian A Parker, Shores Salter, Ryan Knihtila, Petr Kuzmic, Carla Mattos
H-, K-, and N-Ras are small GTPases that are important in the control of cell proliferation, differentiation and survival, and their mutants occur frequently in human cancers. The G-domain, which catalyzes GTP hydrolysis and mediates downstream signaling, is 95% conserved between the Ras isoforms. Due to their very high sequence identity, biochemical studies done on H-Ras have been considered representative of all three Ras proteins. We show here that this is not a valid assumption. Using enzyme kinetic assays under identical conditions, we observed clear differences between the three isoforms in intrinsic catalysis of GTP by Ras in the absence and presence of the Ras-binding domain (RBD) of the C-Raf Kinase protein (Raf-RBD)...
June 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28627723/vitamin-d-enhances-omega-3-polyunsaturated-fatty-acids-induced-apoptosis-in-breast-cancer-cells
#10
Jing Yang, Shenglong Zhu, Guangxiao Lin, Ci Song, Zhao He
Breast cancer is a leading type of cancer in women and generally classified into three subtypes of ER(+) /PR(+) , HER2(+) and triple negative. Both omega-3 polyunsaturated fatty acids and vitamin D3 play positive role in the reduction of breast cancer incidence. However, whether combination of omega-3 polyunsaturated fatty acids and vitamin D3 has stronger protective effect on breast carcinogenesis still remains unknown. In this study, we show that the combination of ω-3 free fatty acids (ω-3 FFAs) and 1α, 25-dihydroxy-vitamin D3 (VD3 ) dramatically enhances cell apoptosis among three subtypes of breast cancer cell lines...
June 19, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28627617/sorafenib-controls-the-epithelial%C3%A2-mesenchymal-transition-of-ovarian-cancer-cells-via-egf-and-the-cd44%C3%A2-ha-signaling-pathway-in-a-cell-type%C3%A2-dependent-manner
#11
Ga Bin Park, Hyun-Suk Ko, Daejin Kim
Cluster of differentiation (CD) 44 and epidermal growth factor (EGF) are closely involved in cellular migration and have been used as stem cell markers. Although the hyaluronan (HA)‑binding CD44 is responsible for enhanced cellular motility, the mechanism underlying its actions in various cell types and clinical conditions have yet to be elucidated. In the present study, the multikinase inhibitor sorafenib was used to investigate the diverse effects of EGF stimulation on epithelial‑mesenchymal transition (EMT) in ovarian cancer cells using immunoblotting and reverse transcription‑polymerase chain reaction...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624057/surveillance-strategies-in-the-follow-up-of-melanoma-patients-too-much-or-not-enough
#12
James Kurtz, Georgia M Beasley, Doreen Agnese, Kari Kendra, Thomas E Olencki, Alicia Terando, J Harrison Howard
BACKGROUND: After appropriate initial therapy for patients with stage II-III melanoma, there is no consensus regarding surveillance. Thus, follow-up is highly variable among institutions and individual providers. The National Comprehensive Cancer Network recommends routine clinical examination and consideration of imaging for stage IIB-IIIC every 3-12 mo with no distinction between stages. Detection of recurrence is important as novel systemic therapies and surgical resection of recurrence may provide survival benefits...
June 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28623940/clonorchis-sinensis-lysophospholipase-a-upregulates-il-25-expression-in-macrophages-as-a-potential-pathway-to-liver-fibrosis
#13
Lina Zhou, Mengchen Shi, Lu Zhao, Zhipeng Lin, Zeli Tang, Hengchang Sun, Tingjin Chen, Zhiyue Lv, Jin Xu, Yan Huang, Xinbing Yu
BACKGROUND: Liver fibrosis is an excessive wound-healing reaction that requires the participation of inflammatory cells and hepatic stellate cells (HSCs). The pathogenesis of liver fibrosis caused by viruses and alcohol has been well characterized, but the molecular mechanisms underlying liver fibrosis induced by the liver fluke Clonorchis sinensis are poorly understood. Lysophospholipase A (LysoPLA), which deacylates lysophospholipids, plays a critical role in mediating the virulence and pathogenesis of parasites and fungi; however, the roles of C...
June 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28622036/molecular-targeted-drugs-and-treatment-of-colorectal-cancer-recent-progress-and-future-perspectives
#14
Fang Geng, Zheng Wang, Hang Yin, Junxian Yu, Bangwei Cao
Nowadays, colorectal cancer is the fourth most common type of tumor all over the world. When diagnosed, ∼50%-60% of tumors have metastasized, thus resulting in a grim prognosis. Chemotherapy is regarded as standard treatment for patients with colorectal cancer, however, limitations of chemotherapy cannot be ignored, such as low selectivity, insufficient concentrations in tumor tissues, and systemic toxicity. Recently, six targeted drugs have been approved by the U.S. Food and Drug Administration (FDA) for treatment of metastatic colorectal cancer (mCRC), including bevacizumab, aflibercept, regorafenib, cetuximab, and panitumumab...
June 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28621952/gastrointestinal-and-systemic-disposition-of-diclofenac-under-fasted-and-fed-state-conditions-supporting-the-evaluation-of-in-vitro-predictive-tools
#15
Jens Van Den Abeele, Ronald Schilderink, FElix Schneider, Raf Mols, Mans Minekus, Werner Weitschies, Joachim Brouwers, Jan Tack, Patrick Augustijns
This study aimed to gain further insight into the gastrointestinal disposition of the weakly acidic BCS Class II drug diclofenac and the implications for systemic drug exposure in humans under fasted and fed state conditions. For this purpose, gastrointestinal and blood samples were collected from healthy volunteers after oral intake of a commercially available tablet of the potassium salt of diclofenac (i.e. Cataflam®) in different prandial states. Subsequently, these in vivo data served as a reference for the evaluation of in vitro tools with different levels of complexity, i...
June 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28620782/role-of-key-genetic-mutations-on-increasing-migration-of-brain-cancer-cells-through-confinement
#16
Loan Bui, Sayem H Bhuiyan, Alissa Hendrick, Cheng-Jen Chuong, Young-Tae Kim
Uncontrolled invasive cancer cell migration is among the major challenges for the treatment and management of brain cancer. Although the genetic profiles of brain cancer cells have been well characterized, the relationship between the genetic mutations and the cells' mobility has not been clearly understood. In this study, using microfluidic devices that provide a wide range of physical confinements from 20 × 5 μm(2) to 3 × 5 μm(2) in cross sections, we studied the effect of physical confinement on the migratory capacity of cell lines with different types of mutations...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28619817/canoe-and-scribble-loss-synergizes-causing-tumor-like-overgrowth-via-ras-activation-in-neural-stem-cells-and-epithelia
#17
Noemí Rives-Quinto, Maribel Franco, Ana de Torres-Jurado, Ana Carmena
Over the past decade an intriguing connection between asymmetric cell division, stem cells and tumorigenesis has emerged. Neuroblasts, the neural stem cells of the Drosophila central nervous system, divide asymmetrically and constitute an excellent paradigm for further investigating that connection. Here we show that the simultaneous loss of the asymmetric cell division regulators Canoe (Afadin in mammals) and Scribble in neuroblast clones leads to tumor-like overgrowth through both a severe disruption of the asymmetric cell division process and a canoe loss-mediated Ras-PI3K-Akt activation...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28615322/in-vivo-manipulation-of-the-extracellular-matrix-induces-vascular-regression-in-a-basal-chordate
#18
Delany Rodriguez, Brian P Braden, Scott W Boyer, Daryl A Taketa, Leah Setar, Chris Calhoun, Alessandro Di Maio, Adam Langenbacher, Megan T Valentine, Anthony W De Tomaso
We investigated the physical role of the extracellular matrix in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent extracorporeal vascular network encompassing areas >100 cm(2) We found that the collagen crosslinking enzyme lysyl oxidase is expressed in all vascular cells, and that in vivo inhibition using ß-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 hours. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose-dependent...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28611205/mouse-pdx-trial-suggests-synergy-of-concurrent-inhibition-of-raf-and-egfr-in-colorectal-cancer-with-braf-or-kras-mutations
#19
Yung-Mae M Yao, Gregory P Donoho, Philip Iversen, Youyan Zhang, Robert D Van Horn, Amelie Forest, Ruslan Novosiadly, Yue Webster, Ebert J Philip, Steven M Bray, Jason C Ting, Amit Aggarwal, James R Henry, Ramon V Tiu, Gregory D Plowman, Sheng-Bin Peng
Purpose: It is to evaluate the anti-tumor efficacy of cetuximab in combination with LSN3074753, an analogue of LY3009120 and pan-RAF inhibitor in 79 colorectal cancer (CRC) patient derived xenograft (PDX) models.<br />Experimental Design: 79 well characterized CRC PDX models were employed to conduct a single mouse per treatment group (n=1) trial.<br />Results: Consistent with clinical results, cetuximab was efficacious in wild type KRAS and BRAF PDX models, with an overall response rate (ORR) of 6...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28609009/triage-of-the-indeterminate-thyroid-aspirate-what-are-the-options-for-the-practicing-cytopathologist
#20
Ayse M Onenerk, Marc P Pusztaszeri, Sule Canberk, William C Faquin
Fine-needle aspiration (FNA) plays a key role in the early evaluation of patients with thyroid nodules; however, from 15% to 30% of FNA specimens are cytologically indeterminate. Molecular testing has proven useful when applied to indeterminate thyroid FNAs, and its use has been endorsed in the American Thyroid Association guidelines. In addition to the noncommercial ("in-house") application of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), rat sarcoma (RAS), rearranged in transformation/papillary thyroid carcinoma (RET/PTC), and peroxisome proliferator-activated receptor γ/paired box gene 8 (PPARγ/PAX8) testing, there are currently 3 commercially available molecular panels that vary in their relative reported performances, strengths, and limitations...
June 2017: Cancer
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