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https://www.readbyqxmd.com/read/29236326/knockdown-of-ski-decreased-the-reactive-astrocytes-proliferation-in-vitro-induced-by-oxygen-glucose-deprivation-reoxygenation
#1
Xin Zhao, Kai-Sheng Zhou, Zhong-Hao Li, Wei Nan, Jing Wang, Ya-Yi Xia, Hai-Hong Zhang
Glia scar is a pathological marker in late phase of brain ischemia disease, which constitutes a major physical biochemical barrier to impede axonal regrowth. Astrocytes are known to be critically involved in the formation of glial scar. However, their response to ischemia and their role in neuroprotection after central nervous system (CNS) injury are not completely clear. Recently, we have demonstrated for the first time that Ski was up-regulated in reactive astrocytes after spinal cord injury in vivo and in vitro, which indicates Ski may be a new molecule that control astrocytes biologic properties after CNS injury...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29235861/kras-switch-mutants-d33e-and-a59g-crystallize-in-the-state-1-conformation
#2
Jia Lu, Asim Bera, Sudershan R Gondi, Kenneth Dale Westover
KRAS switch loop movements play a crucial role in regulating RAS signaling and alteration in these sensitive dynamics are a principal mechanism through which disease-associated RAS mutations lead to aberrant RAS activation. Prior studies suggest that despite high sequence similarity, the switches in KRAS are more dynamic than HRAS. We solved x-ray crystal structures of the rare tumorigenic KRAS mutants KRASD33E, in switch 1 (SW1), and KRASA59G, in switch 2 (SW2), bound to GDP and found these adopt nearly identical, open SW1 conformations as well as altered SW2 conformations...
December 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/29235562/targeting-the-raf-kinases-in-human-cancer-the-raf-dimer-dilemma
#3
David E Durrant, Deborah K Morrison
The Raf protein kinases are key intermediates in cellular signal transduction, functioning as direct effectors of the Ras GTPases and as the initiating kinases in the ERK cascade. In human cancer, Raf activity is frequently dysregulated due to mutations in the Raf family member B-Raf or to alterations in upstream Raf regulators, including Ras and receptor tyrosine kinases. First-generation Raf inhibitors, such as vemurafenib and dabrafenib, have yielded dramatic responses in malignant melanomas containing B-Raf mutations; however, their overall usefulness has been limited by both intrinsic and acquired drug resistance...
December 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29234285/a-microarray-study-of-carpet-shell-clam-ruditapes-decussatus-shows-common-and-organ-specific-growth-related-gene-expression-differences-in-gills-and-digestive-gland
#4
Carlos Saavedra, Massimo Milan, Ricardo B Leite, David Cordero, Tomaso Patarnello, M Leonor Cancela, Luca Bargelloni
Growth rate is one of the most important traits from the point of view of individual fitness and commercial production in mollusks, but its molecular and physiological basis is poorly known. We have studied differential gene expression related to differences in growth rate in adult individuals of the commercial marine clam Ruditapes decussatus. Gene expression in the gills and the digestive gland was analyzed in 5 fast-growing and five slow-growing animals by means of an oligonucleotide microarray containing 14,003 probes...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29232553/synthetic-lethality-of-combined-bcl-2-inhibition-and-p53-activation-in-aml-mechanisms-and-superior-antileukemic-efficacy
#5
Rongqing Pan, Vivian Ruvolo, Hong Mu, Joel D Leverson, Gwen Nichols, John C Reed, Marina Konopleva, Michael Andreeff
Evasion of apoptosis is a hallmark of cancer. Bcl-2 and p53 represent two important nodes in apoptosis signaling pathways. We find that concomitant p53 activation and Bcl-2 inhibition overcome apoptosis resistance and markedly prolong survival in three mouse models of resistant acute myeloid leukemia (AML). Mechanistically, p53 activation negatively regulates the Ras/Raf/MEK/ERK pathway and activates GSK3 to modulate Mcl-1 phosphorylation and promote its degradation, thus overcoming AML resistance to Bcl-2 inhibition...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29232407/temporal-changes-in-cardiac-oxidative-stress-inflammation-and-remodeling-induced-by-exercise-in-hypertension-role-for-local-angiotensin-ii-reduction
#6
Sebastião D Silva, Zaira P Jara, Roseli Peres, Larissa S Lima, Cristóforo Scavone, Augusto C Montezano, Rhian M Touyz, Dulce E Casarini, Lisete C Michelini
Exercise training reduces renin-angiotensin system (RAS) activation, decreases plasma and tissue oxidative stress and inflammation in hypertension. However, the temporal nature of these phenomena in response to exercise is unknown. We sought to determine in spontaneously hypertensive rats (SHR) and age-matched WKY controls the weekly effects of training on blood pressure (BP), plasma and left ventricle (LV) Ang II and Ang-(1-7) content (HPLC), LV oxidative stress (DHE staining), gene and protein expression (qPCR and WB) of pro-inflammatory cytokines, antioxidant enzymes and their consequence on hypertension-induced cardiac remodeling...
2017: PloS One
https://www.readbyqxmd.com/read/29232129/the-effect-of-structural-modifications-to-glyoxalbis-thiosemicarbazanoto-copper-ii-complexes-on-cellular-copper-uptake-copper-mediated-atp7a-trafficking-and-p-glycoprotein-mediated-efflux
#7
Karla M Acevedo, David J Hayne, Lachlan E McInnes, Asif Noor, Clare Duncan, Diane Moujalled, Irene Volitakis, Angela Rigopoulos, Kevin Jeffrey Barnham, Victor L Villemagne, Anthony R White, Paul S Donnelly
Bis(thiosemicarbazonato)copper(II) complexes are of interest as potential therapeutics for cancer and neurodegenerative diseases as well as imaging agents for positron emission tomography (PET). The cellular uptake of six bis(thiosemcarbazonato)copper(II)complexes derived from glyoxal, with different functional groups, Cu(gtsx) where x = different functional groups, was investigated in SKOV-3, HEK293 and HEK293 P-gp cell lines. Treatment of the cells with the copper complexes increased intracellular copper and increased levels of p-ERK due to activation of the Ras-Raf-MEK-ERK pathway...
December 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29229683/mesenchymal-stem-cells-promote-endothelial-progenitor-cell-migration-vascularization-and-bone-repair-in-tissue-engineered-constructs-via-activating-cxcr2-src-pkl-vav2-rac1
#8
Zhilin Li, Aijun Yang, Xiaolong Yin, Shiwu Dong, Fei Luo, Ce Dou, Xu Lan, Zhao Xie, Tianyong Hou, Jianzhong Xu, Junchao Xing
Tissue-engineered constructs (TECs) hold great promise for treating large bone defects. Incorporated mesenchymal stem cells (MSCs) can facilitate the vascularization of TECs. Nevertheless, the underlying mechanism remains ambiguous. Here we analyzed the roles of C-X-C chemokine receptor 2 (CXCR2) and its downstream signal pathways in MSC-induced endothelial progenitor cell (EPC) migration. Transwell assays and immunofluorescence staining were performed for cell migration analysis in vitro and in vivo, respectively...
December 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29229669/kras-the-critical-driver-and-therapeutic-target-for-pancreatic-cancer
#9
Andrew M Waters, Channing J Der
RAS genes (HRAS, KRAS, and NRAS) comprise the most frequently mutated oncogene family in human cancer. With the highest RAS mutation frequencies seen with the top three causes of cancer deaths in the United States (lung, colorectal, and pancreatic cancer), the development of anti-RAS therapies is a major priority for cancer research. Despite more than three decades of intense effort, no effective RAS inhibitors have yet to reach the cancer patient. With bitter lessons learned from past failures and with new ideas and strategies, there is renewed hope that undruggable RAS may finally be conquered...
December 11, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29229665/ras-and-the-plasma-membrane-a-complicated-relationship
#10
Yong Zhou, Priyanka Prakash, Alemayehu A Gorfe, John F Hancock
The primary site of Ras signal transduction is the plasma membrane (PM). On the PM, the ubiquitously expressed Ras isoforms, H-, N-, and K-Ras, spatially segregate to nonoverlapping nanometer-sized domains, called nanoclusters, with further lateral segregation into nonoverlapping guanosine triphosphate (GTP)-bound and guanosine diphosphate (GDP)-bound nanoclusters. Effector binding and activation is restricted to GTP nanoclusters, rendering the underlying assembly mechanism essential to Ras signaling. Ras nanoclusters have distinct lipid compositions as a result of lipid-sorting specificity encoded in each Ras carboxy-terminal membrane anchor...
December 11, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29229608/statin-induced-cancer-cell-death-can-be-mechanistically-uncoupled-from-prenylation-of-ras-family-proteins
#11
Rosemary Yu, Joseph Longo, Jenna E van Leeuwen, Peter J Mullen, Wail Ba-Alawi, Benjamin Haibe-Kains, Linda Z Penn
The statin family of drugs preferentially trigger tumor cell apoptosis by depleting mevalonate pathway metabolites farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), which are used for protein prenylation, including the oncoproteins of the RAS superfamily. However, accumulating data indicate that activation of the RAS superfamily are poor biomarkers of statin sensitivity, and the mechanism of statin-induced tumor-specific apoptosis remains unclear. Here we demonstrate that cancer cell death triggered by statins can be uncoupled from prenylation of the RAS superfamily of oncoproteins...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29229605/mir-204-5p-and-mir-211-5p-contribute-to-braf-inhibitor-resistance-in-melanoma
#12
Marta Díaz-Martínez, Lucía Benito-Jardón, Lola Alonso, Lisa Koetz-Ploch, Eva Hernando, Joaquin Teixido
Melanoma treatment with the BRAF V600E inhibitor vemurafenib (VMF) provides therapeutic benefits but the common emergence of drug resistance remains a challenge. We generated A375 melanoma cells resistant to VMF with the goal of investigating changes in miRNA expression patterns that might contribute to resistance. Increased expression of miR-204-5p and miR-211-5p occurring in VMF-resistant cells was determined to impact VMF response. Their expression was rapidly affected by VMF treatment through RNA stabilization...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29229547/role-of-angiotensin-system-modulation-on-progression-of-cognitive-impairment-and-brain-mri-changes-in-aged-hypertensive-animals-a-randomized-double-blind-pre-clinical-study
#13
Heba A Ahmed, Tauheed Ishrat, Bindu Pillai, Kristopher M Bunting, Ashni Patel, Almira Vazdarjanova, Jennifer L Waller, Ali S Arbab, Adviye Ergul, Susan C Fagan
Growing evidence suggests that renin angiotensin system (RAS) modulators support cognitive function in various animal models. However, little is known about their long-term effects on the brain structure in aged hypertensive animals with chronic cerebral hypoperfusion as well as which specific domains of cognition are most affected. Therefore, in the current study we examined the effects of Candesartan and Compound 21 (C21) (RAS modulators) on aspects of cognition known to diminish with advanced age and accelerate with hypertension and vascular disease...
December 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29229483/outcomes-of-fundoplication-in-oesophageal-atresia-associated-gastrooesophageal-reflux-disease
#14
Antti I Koivusalo, Risto J Rintala, Mikko P Pakarinen
AIM OF THE STUDY: Conservative management of gastrooesophageal reflux (GORD) in oesophageal atresia (OA) is sometimes inefficient, and fundoplication is required. We assessed the outcomes of fundoplication among OA patients from 1980 to 2016. METHODS: After ethical consent, hospital records of 290 patients, including 22 referred patients, were reviewed. Included were 262 patients with end-to-end repair. Excluded were patients who underwent oesophageal reconstruction (n=23) or no repair (n=5)...
November 12, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29229414/lipid-droplets-induced-by-secreted-phospholipase-a2and-unsaturated-fatty-acids-protect-breast-cancer-cells-from-nutrient-and-lipotoxic-stress
#15
Eva Jarc, Ana Kump, Petra Malavašič, Thomas O Eichmann, Robert Zimmermann, Toni Petan
Cancer cells driven by the Ras oncogene scavenge unsaturated fatty acids (FAs) from their environment to counter nutrient stress. The human group X secreted phospholipase A2(hGX sPLA2) releases FAs from membrane phospholipids, stimulates lipid droplet (LD) biogenesis in Ras-driven triple-negative breast cancer (TNBC) cells and enables their survival during starvation. Here we examined the role of LDs, induced by hGX sPLA2and unsaturated FAs, in protection of TNBC cells against nutrient stress. We found that hGX sPLA2releases a mixture of unsaturated FAs, including ω-3 and ω-6 polyunsaturated FAs (PUFAs), from TNBC cells...
December 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29228930/gene-expression-analysis-in-asthma-using-a-targeted-multiplex-array
#16
Christopher D Pascoe, Ma'en Obeidat, Bryna A Arsenault, Yunlong Nie, Stephanie Warner, Dorota Stefanowicz, Samuel J Wadsworth, Jeremy A Hirota, S Jasemine Yang, Delbert R Dorscheid, Chris Carlsten, Tillie L Hackett, Chun Y Seow, Peter D Paré
BACKGROUND: Gene expression changes in the structural cells of the airways are thought to play a role in the development of asthma and airway hyperresponsiveness. This includes changes to smooth muscle contractile machinery and epithelial barrier integrity genes. We used a targeted gene expression arrays to identify changes in the expression and co-expression of genes important in asthma pathology. METHODS: RNA was isolated from the airways of donor lungs from 12 patients with asthma (8 fatal) and 12 non-asthmatics controls and analyzed using a multiplexed, hypothesis-directed platform to detect differences in gene expression...
December 11, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29228829/vanadium-pentoxide-increased-pten-and-decreased-shp1-expression-in-nk-92mi-cells-affecting-pi3k-akt-mtor-and-ras-mapk-pathways
#17
Francisco Gallardo-Vera, Miguel Tapia-Rodriguez, Daniel Diaz, Teresa Fortoul van der Goes, Luis F Montaño, Erika P Rendón-Huerta
Vanadium is an air pollutant that imparts immunosuppressive effects on NK cell immune responses, in part, by dysregulating interleukin (IL)-2/IL-2R-mediated JAK signaling pathways and inducing apoptosis. The aim of the present study was to evaluate effects of vanadium pentoxide (V2O5) on other IL-2 receptor-mediated signaling pathways, i.e. PI3K-AKT-mTOR and Ras-MAPK. Here, IL-2-independent NK-92MI cells were exposed to different V2O5 doses for 24 h periods. Expression of PI3K, Akt, mTOR, ERK1/2, MEK1, PTEN, SHP1, BAD and phosphorylated forms, as well as caspases-3, -8, -9, BAX and BAK in/on the cells were then determined by flow cytometry...
December 2018: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29228687/interactions-between-rasa2-cadm1-hif1an-gene-polymorphisms-and-body-fatness-with-breast-cancer-a-population-based-case-control-study-in-china
#18
Zheng Zhu, Zhimei Teng, Fränzel J B van Duijnhoven, Meihua Dong, Yun Qian, Hao Yu, Jie Yang, Renqiang Han, Jian Su, Wencong Du, Xingyu Huang, Jinyi Zhou, Xiaojin Yu, Ellen Kampman, Ming Wu
Genome-wide association studies (GWAS) have indicated that gene polymorphisms in alleles of RAS p21 protein activator 2 (RASA2), cell adhesion molecule 1 (CADM1) and hypoxia inducible factor 1 alpha subunit inhibitor (HIF1AN) are associated with the risk of obesity. In this study, we explored the interactions between candidate SNPs of RASA2 (rs16851483), CADM1 (rs12286929) and HIF1AN (rs17094222) and body fatness for breast cancer risk. Unconditional logistic regression models were applied to measure the associations of related factors with breast cancer by odds ratios (ORs) and 95% confidence intervals (CIs)...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228684/atorvastatin-downregulates-co-inhibitory-receptor-expression-by-targeting-ras-activated-mtor-signalling
#19
Isobel Okoye, Afshin Namdar, Lai Xu, Nicole Crux, Shokrollah Elahi
Regulation of T cell function in the steady state is mediated by co-inhibitory receptors or immune checkpoints such as PD-1, CTLA-4, TIM-3 and LAG-3. Persistent antigen stimulation, during chronic viral infections and cancer, results in sustained expression of multiple co-inhibitory receptors and subsequently poor effector T cell function. Immune checkpoint blockade using monoclonal antibodies against PD-1, PDL-1 and CTLA-4 has been implemented as an immunotherapy strategy- resulting in restoration of T cell function and reduction of viral load or tumour growth...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228418/long-noncoding-rna-hoxd-as1-regulates-proliferation-of-cervical-cancer-cells-by-activating-ras-erk-signaling-pathway
#20
Y-C Hu, A-M Wang, J-K Lu, R Cen, L-L Liu
OBJECTIVE: To investigate the effects of HOXD cluster antisense RNA 1 (HOXD-AS1) in cervical cancer and its underlying mechanism. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of HOXD-AS1 in human cervical cancer tissues. x2-test was used for analyzing the association of HOXD-AS1 expression and clinical parameters. Cell viability, colony formation capacity, and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) in treated HeLa and CaSki cells were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, colony formation assay, and Western blot analysis, respectively...
November 2017: European Review for Medical and Pharmacological Sciences
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