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https://www.readbyqxmd.com/read/29058103/effects-of-transgenic-expression-of-brevibacterium-linens-methionine-gamma-lyase-mgl-on-accumulation-of-tylenchulus-semipenetrans-and-key-aminoacid-contents-in-carrizo-citrange
#1
Elenor Castillo, Federico Martinelli, Florence Zakharov-Negre, Susan E Ebeler, Tom R Buzo, Michael V McKenry, Abhaya M Dandekar
Carrizo transgenic plants overexpressing methionine-gamma-lyase produced dimethyl sulfide. The transgenic plants displayed more resistance to nematode attacks (Tylenculus semipenetrans) and may represent an innovative strategy for nematode control. Tylenchulus semipenetrans is a nematode pest of many citrus varieties that causes extensive damage to commercial crops worldwide. Carrizo citrange vr. (Citrus sinensis L. Usb × Poncirus trifoliate L. Raf) plants overexpressing Brevibacterium linens methionine-gamma-lyase (BlMGL) produced the sulfur volatile compound dimethyl sulfide (DMS)...
October 20, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/29056104/a-maternal-high-fat-high-sucrose-diet-alters-insulin-sensitivity-and-expression-of-insulin-signalling-and-lipid-metabolism-genes-and-proteins-in-male-rat-offspring-effect-of-folic-acid-supplementation
#2
Candace E Cuthbert, Jerome E Foster, D Dan Ramdath
A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured...
October 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/29055842/clinical-and-molecular-characterisation-of-hereditary-and-sporadic-metastatic-colorectal-cancers-harbouring-microsatellite-instability-dna-mismatch-repair-deficiency
#3
R Cohen, O Buhard, P Cervera, E Hain, S Dumont, A Bardier, J-B Bachet, J-M Gornet, D Lopez-Trabada, S Dumont, R Kaci, P Bertheau, F Renaud, F Bibeau, Y Parc, D Vernerey, A Duval, M Svrcek, Thierry André
BACKGROUND: Patients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs. PATIENTS AND METHODS: MSI/dMMR mCRC patients were retrospectively identified in six French hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1 methylation...
October 19, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29054855/h-ras-deletion-protects-against-angiotensin-ii-induced-arterial-hypertension-and-cardiac-remodeling-through-protein-kinase-g-i%C3%AE-pathway-activation
#4
Paloma Martín-Sánchez, Alicia Luengo, Mercedes Griera, María Jesús Orea, Marina López-Olañeta, Antonio Chiloeches, Enrique Lara-Pezzi, Sergio de Frutos, Manuel Rodríguez-Puyol, Laura Calleros, Diego Rodríguez-Puyol
Ras proteins regulate cell survival, growth, differentiation, blood pressure, and fibrosis in some organs. We have demonstrated that H-ras gene deletion produces mice hypotension via a soluble guanylate cyclase-protein kinase G (PKG)-dependent mechanism. In this study, we analyzed the consequences of H-ras deletion on cardiac remodeling induced by continuous angiotensin II (AngII) infusion and the molecular mechanisms implied. Left ventricular posterior wall thickness and mass and cardiomyocyte cross-sectional area were similar between AngII-treated H-Ras knockout (H-ras(-/-) ) and control wild-type (H-ras(+/+) ) mice, as were extracellular matrix protein expression...
October 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29054680/phosphorylation-of-protein-phosphatase-2a-facilitated-an-early-stage-of-chemical-carcinogenesis
#5
Yuji Ishii, Ken Kuroda, Kohei Matsushita, Yuh Yokoo, Shinji Takasu, Aki Kijima, Takehiko Nohmi, Kumiko Ogawa, Takashi Umemura
Protein phosphatase 2A (PP2A) is a serine-threonine phosphatase that regulates cell signaling pathways. Its inactivation is correlated with tumor malignancy, possibly due to the effects on cell differentiation and malignant cell transformation. Therefore, it has been noted that PP2A could be a promising target for cancer therapy. In our previous study of the hepatocarcinogen estragole (ES), cell proliferation may be required to convert ES-specific DNA adducts to mutations. To explore the trigger for cell proliferation, gpt delta rats were administered ES by gavage at doses of 3, 30 and 300mg/kg/day for 4weeks...
October 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29051820/vqmapkkk38-is-essential-for-stilbene-accumulation-in-grapevine
#6
Yuntong Jiao, Dan Wang, Lan Wang, Changyue Jiang, Yuejin Wang
Vitis species, including grapevine, produce a class of secondary metabolites called stilbenes that are important for plant disease resistance and can have positive effects on human health. Mitogen-activated protein kinase (MAPK) signaling cascades not only play key roles in plant defense responses but also contribute to stilbene biosynthesis in grapevine. MAPKKKs function at the upper level of the MAPK network and initiate signaling through this pathway. In this study, a Raf-like MAPKKK gene, VqMAPKKK38, was identified and functionally characterized from the Chinese wild grapevine V...
2017: Horticulture Research
https://www.readbyqxmd.com/read/29050202/phosphodiesterase-10a-is-overexpressed-in-lung-tumor-cells-and-inhibitors-selectively-suppress-growth-by-blocking-%C3%AE-catenin-and-mapk-signaling
#7
Bing Zhu, Ashley Lindsey, Nan Li, Kevin Lee, Veronica Ramirez-Alcantara, Joshua C Canzoneri, Alexandra Fajardo, Luciana Madeira da Silva, Meagan Thomas, John T Piazza, Larry Yet, Brian T Eberhardt, Evrim Gurpinar, Dennis Otali, William Grizzle, Jacob Valiyaveettil, Xi Chen, Adam B Keeton, Gary A Piazza
Phosphodiesterase 10A (PDE10) is a cyclic nucleotide (e.g. cGMP) degrading enzyme highly expressed in the brain striatum where it plays an important role in dopaminergic neurotransmission, but has limited expression and no known physiological function outside the central nervous system. Here we report that PDE10 mRNA and protein levels are strongly elevated in human non-small cell lung cancer cells and lung tumors compared with normal human airway epithelial cells and lung tissue, respectively. Genetic silencing of PDE10 or inhibition by small molecules such as PQ10 was found to selectively inhibit the growth and colony formation of lung tumor cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048639/phenotype-characterization-of-human-melanoma-cells-resistant-to-dabrafenib
#8
Fabiola Gilda Cordaro, Anna Lisa De Presbiteris, Rosa Camerlingo, Nicola Mozzillo, Giuseppe Pirozzi, Ernesta Cavalcanti, Antonella Manca, Giuseppe Palmieri, Antonio Cossu, Gennaro Ciliberto, Paolo A Ascierto, Salvatore Travali, Eduardo J Patriarca, Emilia Caputo
In the present study, the phenotype of melanoma cells resistant to dabrafenib (a B-RAF inhibitor) was investigated, to shed more light on melanoma resistance to B-RAF inhibition. Melanoma cells resistant to dabrafenib were generated using 3 different cell lines, A375, 397 and 624.38, all carrying B-RAFV600E, and they were characterized by cytofluorometric analysis, Ion Torrent technology, immunofluorescence and biochemistry. All dabrafenib-resistant cells showed, in addition to a re-activation of MAPK signaling, morphological changes compared to their sensitive counterparts, accompanied by an increase in CD90 (mesenchymal marker) expression and a decrease in E-cadherin (epithelial marker) expression, suggesting an epithelial-to-mesenchymal-like phenotypic transition...
September 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048617/mek-inhibitor-pd98059-promotes-breast-cancer-cell-migration-by-inducing-%C3%AE-catenin-nuclear-accumulation
#9
Ying Zhao, Chao-Chao Ge, Jun Wang, Xiao-Xiao Wu, Xiao-Min Li, Wei Li, Sha-Sha Wang, Tong Liu, Jiu-Zhou Hou, Hua Sun, Dong Fang, Song-Qiang Xie
Abnormal activation of the RAF/MEK/ERK signaling pathway has been observed in breast cancer. Thus, a number of MEK inhibitors have been designed as one treatment option for breast cancer. Although some studies have found that these MEK inhibitors inhibit the growth of a variety of human cancer cells, some trials have shown that the use of MEK inhibitors as a treatment for breast cancer does not adequately improve survival for unknown reasons. In the present study, MEK inhibitor PD98059 was used to evaluate its anticancer effects on human breast cancer MCF-7 and MDA-MB-231 cells and to explore the possible mechanism of action...
September 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048592/the-yeast-2-%C3%AE-m-plasmid-raf-protein-contributes-to-plasmid-inheritance-by-stabilizing-the-rep1-and-rep2-partitioning-proteins
#10
Mary E McQuaid, Jordan B Pinder, Niroshaathevi Arumuggam, Jessica S C Lacoste, Joyce S K Chew, Melanie J Dobson
The yeast 2-μm plasmid is a remarkable genetic parasite, managing efficient maintenance at high-copy number with minimal impact on the host. Equal partitioning of the plasmid upon host cell division requires plasmid proteins Rep1 and Rep2 and the plasmid STB locus. The Rep proteins and the plasmid-encoded Raf protein also regulate plasmid gene transcription. In this study, protein interaction assays, sequence analyses and mutational approaches were used to identify domains and residues in Rep2 and Raf required for association with Rep1 and Rep2 and to delineate the Rep2 DNA-binding domain...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29046298/identification-of-dual-mechanisms-mediating-5-hydroxytryptamine-receptor-1f-induced-mitochondrial-biogenesis
#11
Whitney S Gibbs, Sara M Garrett, Craig C Beeson, Rick G Schnellmann
Our laboratory recently made the novel observation that 5-hydroxytryptamine 1F (5-HT1F) receptor activation induces mitochondrial biogenesis (MB), the production of new, functional mitochondria, in vitro and vivo. We sought to determine the mechanism linking the 5-HT1F receptor to MB in renal proximal tubule cells. Using LY344864, a selective 5-HT1F receptor agonist, we determined that the 5-HT1F receptor is coupled to Gαi/o and induces MB through Gβγ dependent activation of Akt, endothelial nitric oxide (eNOS), cyclic guanosine-monophosphate (cGMP), protein kinase G (PKG) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)...
October 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29045529/impact-of-genetic-variations-in-the-mapk-signaling-pathway-on-outcome-in-metastatic-colorectal-cancer-patients-treated-with-first-line-folfiri-and-bevacizumab-data-from-fire-3-and-tribe-trials
#12
M D Berger, S Stintzing, V Heinemann, D Yang, S Cao, Y Sunakawa, Y Ning, S Matsusaka, S Okazaki, Y Miyamoto, M Suenaga, M Schirripa, S Soni, W Zhang, A Falcone, F Loupakis, H-J Lenz
Background: The MAPK-interacting kinase 1 (MKNK1) is localized downstream of the RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway. Through phosphorylation MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a key player in translational control, whose expression is often upregulated in metastatic colorectal cancer patients (mCRC). Preclinical data suggest that MKNK1 increases angiogenesis by upregulating angiogenic factors. We therefore hypothesize that variations in the MKNK1 gene predict outcome in mCRC patients treated with first-line FOLFIRI and bevacizumab (bev)...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045061/suppression-of-mapk-signaling-in-braf-activated-pten-deficient-melanoma-by-blocking-%C3%AE-catenin-signaling-in-cancer-associated-fibroblasts
#13
Linli Zhou, Kun Yang, Spencer Dunaway, Zalfa Abdel-Malek, Thomas Andl, Ana Luisa Kadekaro, Yuhang Zhang
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with formation of a dynamic and optimized niche for tumor cells to grow and evade cell death induced by therapeutic agents. We recently reported that ablation of β-catenin expression in stromal fibroblasts and CAFs disrupted their biological activities in in vitro studies and in an in vivo B16F10 mouse melanoma model. Here, we show that the development of a BRAF-activated PTEN-deficient mouse melanoma was significantly suppressed in vivo after blocking β-catenin signaling in CAFs...
October 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29045039/design-of-potent-b-raf-v600e-inhibitors-by-mcss-strategy
#14
Ze-Feng Wang, Peng-Fei Wang, Jun-Ting Ma, Ying-Zi Chai, Hui-Min Hu, Wen-Long Gao, Zhong-Chang Wang, Bao-Zhong Wang, Hai-Liang Zhu
B-Raf kinase is a vital intermedium in the mitogen-activated protein kinase (MAPK) signaling pathway, which transforms extracellular signals into cellular mechanisms. Mutations in this kinase, for instance, the most common V600E mutation, can lead to the ERK signaling pathologically activated and hence cause severe diseases like somatic tumors. So far, the development of B-Raf inhibitors has made remarkable progress. However, the resistance and relapse of approved Raf drugs have been widely reported, and the optimization for old drugs and the discovery for new inhibitors still remain a significant task...
October 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29044159/global-identification-classification-and-expression-analysis-of-mapkkk-genes-functional-characterization-of-mdraf5-reveals-evolution-and-drought-responsive-profile-in-apple
#15
Meihong Sun, Yang Xu, Jinguang Huang, Zesheng Jiang, Huairui Shu, Huasen Wang, Shizhong Zhang
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are pivotal components of Mitogen-activated protein kinase (MAPK) cascades, which play a significant role in many biological processes. Although genome-wide analysis of MAPKKKs has been conducted in many species, extant results in apple are scarce. In this study, a total of 72 putative MdMAPKKKs in Raf-like group, 11 in ZIK-like group and 37 in MEEK were identified in apple firstly. Predicted MdMAPKKKs were located in 17 chromosomes with diverse densities, and there was a high-level of conservation in and among the evolutionary groups...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042709/derivation-and-basic-characterization-of-colorectal-carcinoma-primary-cell-lines
#16
Lukas Krbal, Jiri Soukup, Stanislav John, Veronika Hanusova
BACKGROUND: Colorectal carcinoma is one of the most common malignancies in western countries. Among different approaches to its research, primary cancer cell lines can play an important role. AIM: The main purposes of this study were: 1) to establish an effective and reproducible method of colorectal cancer cell isolation and cultivation from primary tumours and lymph node metastases and 2) to elucidate the biological features of the tumours favouring successful cell cultivation...
October 17, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/29042256/antiseptic-effects-of-dabrafenib-on-tgfbip-induced-septic-responses
#17
In-Chul Lee, Jong-Sup Bae
Transforming growth factor-β-induced protein (TGFBIp), an extracellular protein, is expressed on several cell types in response to TGF-β stimulation. Human umbilical vein endothelial cell (HUVEC)-derived TGFBIp functions as a mediator of sepsis. Screening of bioactive compound libraries is an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases (drug repositioning). Dabrafenib (DAB), a B-Raf inhibitor, was initially used for treating metastatic melanoma...
October 14, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29040282/colorectal-carcinoma-tumour-budding-and-podia-formation-in-the-xenograft-microenvironment
#18
Friedrich Prall, Claudia Maletzki, Maja Hühns, Mathias Krohn, Michael Linnebacher
Tumour budding and podia formation are well-appreciated in surgical pathology as an aggressive invasion phenotype of colorectal carcinoma cells that is attained in the microenvironment of the invasive margin. In this study, we addressed how tumour budding and podia formation feature in xenografts. Primary colorectal carcinomas (N = 44) of various molecular types (sporadic standard type, high-degree microsatellite-unstable, CpG island methylator phenotype) were transplanted subcutaneously into T and B cell-deficient NSG mice, making possible immunohistochemistry with routine surgical pathology antibodies...
2017: PloS One
https://www.readbyqxmd.com/read/29038312/dynamic-stroma-reorganization-drives-blood-vessel-dysmorphia-during-glioma-growth
#19
Thomas Mathivet, Claire Bouleti, Matthias Van Woensel, Fabio Stanchi, Tina Verschuere, Li-Kun Phng, Joost Dejaegher, Marly Balcer, Ken Matsumoto, Petya B Georgieva, Jochen Belmans, Raf Sciot, Christian Stockmann, Massimiliano Mazzone, Steven De Vleeschouwer, Holger Gerhardt
Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages...
October 16, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29037218/clinicopathologic-features-and-treatment-efficacy-of-chinese-patients-with-braf-mutated-metastatic-colorectal-cancer-a-retrospective-observational-study
#20
Xicheng Wang, Qing Wei, Jing Gao, Jian Li, Jie Li, Jifang Gong, Yanyan Li, Lin Shen
BACKGROUND: The prognostic role of the V600E mutation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in metastatic colorectal cancer (mCRC) is well established, but the therapeutic regimen targeting this disease is lacking. This study aimed to analyze the clinicopathologic features of and treatment efficacy of commonly used regimens on BRAF-mutated mCRCs. METHODS: We collected and reviewed the medical records of mCRC patients treated at Peking University Cancer Hospital & Institute (Beijing, China) between July 2011 and July 2016...
October 16, 2017: Chinese Journal of Cancer
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