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https://www.readbyqxmd.com/read/27912873/pomolic-acid-suppresses-hif1%C3%AE-vegf-mediated-angiogenesis-by-targeting-p38-mapk-and-mtor-signaling-cascades
#1
Ji-Hyun Park, Jaewoo Yoon, Byoungduck Park
BACKGROUND: Pomolic acid (PA), an active triterpenoid from Euscaphis japonica, inhibits the proliferation of a variety of cancer cells, but the molecular mechanisms of the anti-angiogenic potential of PA have not been fully elucidated in breast cancer cells. HYPOTHESIS/PURPOSE: We investigated the molecular mechanisms underlying the anti-angiogenic effect of PA in epidermal growth factor (EGF)-responsive human breast cancer cells, MCF-7 and MDA-MB-231, and human umbilical vascular endothelial cells (HUVEC)...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27911877/icariside-ii-activates-egfr-akt-nrf2-signaling-and-protects-osteoblasts-from-dexamethasone
#2
Weidong Liu, Li Mao, Feng Ji, Fengli Chen, Shouguo Wang, Yue Xie
The potential effect of icariside II on dexamethasone-induced osteoblast cell damages was evaluated here. In MC3T3-E1 osteoblastic cells and the primary murine osteoblasts, co-treatment with icariside II dramatically attenuated dexamethasone- induced cell death and apoptosis. Icariside II activated Akt signaling, which is required for its actions in osteoblasts. Akt inhibitors (LY294002, perifosine and MK-2206) almost abolished icariside II-induced osteoblast cytoprotection against dexamethasone. Further studies showed that icariside II activated Nrf2 signaling, downstream of Akt, to inhibit dexamethasone-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary osteoblasts...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910913/loss-of-egfr-asap1-signaling-in-metastatic-and-unresectable-hepatoblastoma
#3
Sarangarajan Ranganathan, Mylarappa Ningappa, Chethan Ashokkumar, Brandon W Higgs, Jun Min, Qing Sun, Lori Schmitt, Shankar Subramaniam, Hakon Hakonarson, Rakesh Sindhi
Hepatoblastoma (HBL), the most common childhood liver cancer is cured with surgical resection after chemotherapy or with liver transplantation if local invasion and multifocality preclude resection. However, variable survival rates of 60-80% and debilitating chemotherapy sequelae argue for more informed treatment selection, which is not possible by grading the Wnt-β-catenin over activity present in most HBL tumors. A hypothesis-generating whole transcriptome analysis shows that HBL tumors removed at transplantation are enriched most for cancer signaling pathways which depend predominantly on epidermal growth factor (EGF) signaling, and to a lesser extent, on aberrant Wnt-β-catenin signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909244/cd4-down-regulation-by-hiv-1-nef-reveals-distinct-roles-for-%C3%AE-1-and-%C3%AE-2-subunits-of-ap-1-complex-in-protein-trafficking
#4
Lucas A Tavares, Eulália M L da Silva, Mara E da Silva-Januário, Yunan C Januário, Julianne V de Cavalho, Érika S Czernisz, Gonzalo A Mardones, Luis L P daSilva
The HIV accessory protein Nef is a major determinant of viral pathogenesis that facilitates viral particle release, prevents viral antigen presentation and increases infectivity of new virus particles. These functions of Nef involve its ability to remove specific host proteins from the surface of infected cells, including the CD4 receptor. Nef binds to the adaptor protein 2 (AP-2) and CD4 in clathrin-coated pits, forcing CD4 internalization and subsequent target to lysosomes. Herein, we report that this lysosomal targeting requires a variant of the AP-1 comprising the isoform 2 of γ-adaptin...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27905560/increased-emr2-expression-on-neutrophils-correlates-with-disease-severity-and-predicts-overall-mortality-in-cirrhotic-patients
#5
Chien-Hao Huang, Wen-Juei Jeng, Yu-Pin Ho, Wei- Teng, Yi-Chung Hsieh, Wei-Ting Chen, Yi-Cheng Chen, Hsi-Hsien Lin, I-Shyan Sheen, Chun-Yen Lin
Patients with liver cirrhosis are susceptible to infections with high short-term mortalities. One CD97-related EGF-TM7 molecule, EMR2 (EGF-like molecule containing mucin-like hormone receptor 2), had been shown to regulate human neutrophil function, potentiate systemic inflammation. Nevertheless, EMR2 could also suppress neutrophil survival. Studying the role of EMR2 on neutrophil would be intriguing. 48 healthy volunteers and 100 cirrhotic patients were enrolled. Neutrophils were isolated from peripheral blood and cell surface markers were measured by flow cytometry...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904688/molecular-mechanism-of-prostate-cancer-cell-apoptosis-induced-by-busulfan-via-adjustment-of-androgen-receptor-phosphatization
#6
Jun Liu, Guojun Jiang, Aiping Yang, Guohui Yang, Wenjuan Yang, Yi Fang
OBJECTIVE: To probe killing effect of busulfan to prostate cancer cell without androgen and the influence of androgen receptor phosphatization and analyze its molecular mechanism. METHODS: prostate cancer cell line 22RV1, LAPC4 and LNCaP treated with busulfan under androgen-free condition underwent CCK-8 examination to probe killing ability of the medicine. Flow cytometry was used to check the influence of busulfan on apoptosis rate of prostate cancer cell line LAPC4...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27902765/loss-of-cathepsin-b-and-l-leads-to-lysosomal-dysfunction-npc-like-cholesterol-sequestration-and-accumulation-of-the-key-alzheimer-s-proteins
#7
Stjepko Cermak, Marko Kosicek, Aleksandra Mladenovic-Djordjevic, Kosara Smiljanic, Selma Kanazir, Silva Hecimovic
Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment of lysosomal function plays an important role in neuronal degeneration and in the pathogenesis of numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss of the major lysosomal proteases, the cysteine cathepsins B and L (CtsB/L), affects lysosomal function, cholesterol metabolism and degradation of the key Alzheimer's disease (AD) proteins...
2016: PloS One
https://www.readbyqxmd.com/read/27902699/modeling-cellular-noise-underlying-heterogeneous-cell-responses-in-the-epidermal-growth-factor-signaling-pathway
#8
Kazunari Iwamoto, Yuki Shindo, Koichi Takahashi
Cellular heterogeneity, which plays an essential role in biological phenomena, such as drug resistance and migration, is considered to arise from intrinsic (i.e., reaction kinetics) and extrinsic (i.e., protein variability) noise in the cell. However, the mechanistic effects of these types of noise to determine the heterogeneity of signal responses have not been elucidated. Here, we report that the output of epidermal growth factor (EGF) signaling activity is modulated by cellular noise, particularly by extrinsic noise of particular signaling components in the pathway...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27902484/depletion-of-mitochondrial-reactive-oxygen-species-downregulates-epithelial-to-mesenchymal-transition-in-cervical-cancer-cells
#9
Galina Shagieva, Lidiya Domnina, Olga Makarevich, Boris Chernyak, Vladimir Skulachev, Vera Dugina
In the course of cancer progression, epithelial cells often acquire morphological and functional characteristics of mesenchymal cells, a process known as epithelial-to-mesenchymal transition (EMT). EMT provides epithelial cells with migratory, invasive, and stem cell capabilities. Reactive oxygen species produced by mitochondria (mtROS) could be of special importance for pro-tumorigenic signaling and EMT.In our study, we used mitochondria-targeted antioxidant SkQ1 to lower the mtROS level and analyze their role in the regulation of the actin cytoskeleton, adhesion junctions, and signaling pathways critical for tumorigenesis of cervical carcinomas...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902463/novel-multi-targeted-erbb-family-inhibitor-afatinib-blocks-egf-induced-signaling-and-induces-apoptosis-in-neuroblastoma
#10
Xinfang Mao, Zhenghu Chen, Yanling Zhao, Yang Yu, Shan Guan, Sarah E Woodfield, Sanjeev A Vasudevan, Ling Tao, Jonathan C Pang, Jiaxiong Lu, Huiyuan Zhang, Fuchun Zhang, Jianhua Yang
Neuroblastoma is the most common extracranial solid tumor in children. The ErbB family of proteins is a group of receptor tyrosine kinases that promote the progression of various malignant cancers including neuroblastoma. Thus, targeting them with small molecule inhibitors is a promising strategy for neuroblastoma therapy. In this study, we investigated the anti-tumor effect of afatinib, an irreversible inhibitor of members of the ErbB family, on neuroblastoma. We found that afatinib suppressed the proliferation and colony formation ability of neuroblastoma cell lines in a dose-dependent manner...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901111/optogenetic-clustering-of-cnk1-reveals-mechanistic-insights-in-raf-and-akt-signalling-controlling-cell-fate-decisions
#11
Adrian Fischer, Bettina Warscheid, Wilfried Weber, Gerald Radziwill
Scaffold proteins such as the multidomain protein CNK1 orchestrate the signalling network by integrating and controlling the underlying pathways. Using an optogenetic approach to stimulate CNK1 uncoupled from upstream effectors, we identified selective clusters of CNK1 that either stimulate RAF-MEK-ERK or AKT signalling depending on the light intensity applied. OptoCNK1 implemented in MCF7 cells induces differentiation at low light intensity stimulating ERK activity whereas stimulation of AKT signalling by higher light intensity promotes cell proliferation...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900155/normal-platelet-function-in-platelet-concentrates-requires-non-platelet-cells-a-comparative-in-vitro-evaluation-of-leucocyte-rich-type-1a-and-leucocyte-poor-type-3b-platelet-concentrates
#12
William R Parrish, Breana Roides, Julia Hwang, Michael Mafilios, Brooks Story, Samir Bhattacharyya
BACKGROUND: Therapeutic success of platelet-rich plasma (PRP) may vary based on the composition and preparation method. The objective of this study was to evaluate the cellular components of platelet concentrates produced by a leucocyte-rich (LR-PRP) and a leucocyte-poor PRP systems (LP-PRP). METHODS: Parameters evaluated included platelet recovery, platelet concentration, red blood cell (RBC) and white blood cell (WBC) composition, platelet growth factor release and stimulation of human tendon cell proliferation in vitro...
2016: BMJ Open Sport & Exercise Medicine
https://www.readbyqxmd.com/read/27899655/visualization-of-self-delivering-hydrophobically-modified-sirna-cellular-internalization
#13
Socheata Ly, Deanna M Navaroli, Marie-Cécile Didiot, James Cardia, Lakshmipathi Pandarinathan, Julia F Alterman, Kevin Fogarty, Clive Standley, Lawrence M Lifshitz, Karl D Bellve, Matthieu Prot, Dimas Echeverria, Silvia Corvera, Anastasia Khvorova
siRNAs are a new class of therapeutic modalities with promising clinical efficacy that requires modification or formulation for delivery to the tissue and cell of interest. Conjugation of siRNAs to lipophilic groups supports efficient cellular uptake by a mechanism that is not well characterized. Here we study the mechanism of internalization of asymmetric, chemically stabilized, cholesterol-modified siRNAs (sd-rxRNAs(®)) that efficiently enter cells and tissues without the need for formulation. We demonstrate that uptake is rapid with significant membrane association within minutes of exposure followed by the formation of vesicular structures and internalization...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27898753/-oncogen-dependent-regulation-of-the-migration-and-proliferation-of-human-tumor-cells
#14
Tamás M Garay
The high mortality of solid tumors can be attributed to their invasive and metastatic potential that is based on their migration and proliferation. Importantly, growth factor receptor (GF) signaling pathways regulating proliferation and migration are often affected by oncogenic mutations and are important targets for antitumor therapy. We found positive correlation between migration and proliferation in melanoma and lung cancer cells using videomicroscopy, not supporting the "go or grow" hypothesis. Furthermore, the invasion into collagen I matrices from brain tumor spheroids was not impaired upon the inhibition of proliferation...
November 29, 2016: Magyar Onkologia
https://www.readbyqxmd.com/read/27897268/germline-polymorphisms-as-biomarkers-of-tumor-response-in-colorectal-cancer-patients-treated-with-anti-egfr-monoclonal-antibodies-a-systematic-review-and-meta-analysis
#15
E K Morgen, H-J Lenz, D J Jonker, D Tu, G Milano, F Graziano, J Zalcberg, C S Karapetis, A Dobrovic, C J O'Callaghan, G Liu
Studies of germline polymorphisms as predictors of tumor response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody agents in metastatic colorectal cancer have reported inconsistent results. We performed a systematic review of studies from 1990 to September 2015, followed by random-effects meta-analyses for polymorphisms examined in at least three studies. Of 87 studies, 40 passed the criteria for systematic review and 23 for meta-analysis. The polymorphisms suitable for meta-analysis were CCND1 (rs17852153), COX2 (rs20417), EGF (rs4444903), EGFR (rs712829, rs11543848, 3'UTR CA repeat), FCGR2A (rs1801274), FCGR3A (rs396991), IL8 (rs4073), KRAS (rs61764370) and VEGFA (rs3025039)...
November 29, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27896869/identifying-the-location-of-epidermal-growth-factor-responsive-element-involved-in-the-regulation-of-type-iib-sodium-phosphate-cotransporter-expression-in-porcine-intestinal-epithelial-cells
#16
T Xing, X Tan, Q Yu, T Yang, R Fang
Phosphate is an important mineral nutrient for both human and animals in growth and physiological functions; thus, much effort in the past has been made to clarify the mechanisms governing its absorption. Previous studies have found that epidermal growth factor (EGF) inhibits phosphate absorption in human intestinal cells via modulating the interaction of transcriptional factor c-myb with sodium-phosphate cotransporter (NaPi-IIb) gene promoter. This finding provoked our interest in determining the effect of EGF on NaPi-IIb gene expression in intestinal cells of pigs and the location of EGF-responsive element in the gene promoter...
November 29, 2016: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/27894083/suppression-of-nestin-reveals-a-critical-role-for-p38-egfr-pathway-in-neural-progenitor-cell-proliferation
#17
Wentao Hu, Hong Lu, Shang Wang, Wenhan Yin, Xujie Liu, Lin Dong, Richard Chiu, Li Shen, Wen-Jing Lu, Feng Lan
The expression of intermediate filament Nestin is necessary for the neural progenitor cells (NPCs) to maintain stemness, but the underlying cellular and molecular mechanism remains unclear. In this study, we demonstrated that Nestin is required for the self-renew of NPCs through activating MAPK and EGFR pathways. Knockdown of Nestin by shRNA inhibited cell cycle progression and proliferation in mouse NPCs. Moreover, suppression of Nestin reduced expression of the epidermal growth factor receptor (EGFR) in NPCs and inhibited the mitogenic effects of EGF on these cells...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893713/phosphorylation-of-nfat3-by-cdk3-induces-cell-transformation-and-promotes-tumor-growth-in-skin-cancer
#18
T Xiao, J J Zhu, S Huang, C Peng, S He, J Du, R Hong, X Chen, A M Bode, W Jiang, Z Dong, D Zheng
The nuclear factor of activated T cells (NFAT) family proteins are transcription factors that regulate the expression of pro-inflammatory cytokines and other genes during the immune response. Although the NFAT proteins have been extensively investigated in the immune system, their role in cancer progression remains controversial. Here, we report that NFAT3 is highly expressed in various skin cancer cell lines and tumor tissues. Knockdown of endogenous NFAT3 expression by short hairpin RNA (shRNA) significantly inhibited tumor cell proliferation, colony formation and anchorage-independent cell growth...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27890841/development-of-a-scoring-system-for-the-prediction-of-early-graft-failure-after-peripheral-arterial-bypass-surgery
#19
Andreas M Lazaris, Sotiria Mastoraki, Evangelos Kontopantelis, Konstantinos Seretis, Maria Karouki, Konstantinos Moulakakis, Miltiadis Matsagkas, Spyros N Vasdekis
OBJECTIVES: An occluded lower limb arterial bypass is associated with poor prognosis for the limb. Currently, no risk assessment method to estimate the risk of early graft failure exists. Aim of this study was to investigate the effect of various potential factors on early graft failure of infrainguinal bypass surgery and to develop a risk-scoring model to predict it. DESIGN AND METHODS: A prospective observational clinical study was performed. One hundred infrainguinal bypass procedures (60 autologous and 40 synthetic grafts), throughout a 3-year period were included...
November 24, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27888810/m2-macrophages-induce-ovarian-cancer-cell-proliferation-via-a-heparin-binding-epidermal-growth-factor-matrix-metalloproteinase-9-intercellular-feedback-loop
#20
Molly J Carroll, Arvinder Kapur, Mildred Felder, Manish S Patankar, Pamela K Kreeger
In ovarian cancer, a high ratio of anti-inflammatory M2 to pro-inflammatory M1 macrophages correlates with poor patient prognosis. The mechanisms driving poor tumor outcome as a result of the presence of M2 macrophages in the tumor microenvironment remain unclear and are challenging to study with current techniques. Therefore, in this study we utilized a micro-culture device previously developed by our lab to model concentrated paracrine signaling in order to address our hypothesis that interactions between M2 macrophages and ovarian cancer cells induce tumor cell proliferation...
November 19, 2016: Oncotarget
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