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Levels of heavy metals in a multifloral Saudi honey
In: Environmental science and pollution research: ESPR, Band 26, Heft 4, S. 3946-3953
ISSN: 1614-7499
Validation of RegCM-CHEM4 model by comparison with surface measurements in the Greater Cairo (Egypt) megacity
In: Environmental science and pollution research: ESPR, Band 26, Heft 23, S. 23524-23541
ISSN: 1614-7499
Photolysis degradation of polyaromatic hydrocarbons (PAHs) on surface sandy soil
In: Environmental science and pollution research: ESPR, Band 22, Heft 13, S. 9603-9616
ISSN: 1614-7499
Advillin acts upstream of phospholipase C ?1 in steroid-resistant nephrotic syndrome
PubMed ID: 29058690 ; Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted colocalization with F-actin, thereby leading to impaired actin binding and severing. Additionally, AVIL colocalized and interacted with the phospholipase enzyme PLCE1 and with the ARP2/3 actin-modulating complex. Knockdown of AVIL in human podocytes reduced actin stress fibers at the cell periphery, prevented recruitment of PLCE1 to the ARP3-rich lamellipodia, blocked EGF-induced generation of diacylglycerol (DAG) by PLCE1, and attenuated the podocyte migration rate (PMR). These effects were reversed by overexpression of WT AVIL but not by overexpression of any of the 3 patient-derived AVIL mutants. The PMR was increased by overexpression of WT Avil or PLCE1, or by EGF stimulation; however, this increased PMR was ameliorated by inhibition of the ARP2/3 complex, indicating that ARP-dependent lamellipodia formation occurs downstream of AVIL and PLCE1 function. Together, these results delineate a comprehensive pathogenic axis of SRNS that integrates loss of AVIL function with alterations in the action of PLCE1, an established SRNS protein. ; VE 196/1-1, HE 7456/1-1, Jo 1324/1-1 U.S. Public Health Service: DK-56338 National Institutes of Health: DK076683 National Institute of Diabetes and Digestive and Kidney Diseases: DK-98120 National Research Foundation of Korea, NRF: 2015R1D1A1A01056685 Department of Science and Technology, Government of Kerala NAS LPDS-2015-07 Fudan University ; We are grateful to the families and study participants for their contributions. We thank the Yale Center for Mendelian Genomics (U54HG006504) for WES analysis. FH is a William E. Harmon Professor of Pediatrics. This research was supported by the NIH (DK076683, to FH); the Young Scholars Program of Children's Hospital of Fudan University (to JR); Basic Science Research Program through the National Research Foundation of Korea 2015R1D1A1A01056685 (to HYG); DFG fellowships (VE 196/1-1, to ATvdV; Jo 1324/1-1, to TJS; and HE 7456/1-1, to TH); the German National Academy of Sciences Leopoldina (LPDS-2015-07, to EW); the Egyptian Group for Orphan Renal Diseases (EGORD) (to NAS); the Department of Science and Technology, Government of India (DST-SERB, to MAJ); the National Institute of Diabetes and Digestive and Kidney Diseases (DK-98120, to SK); and the Public Health Service (DK-56338, to SK). --
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Tissue invasion and metastasis: molecular, biological and clinical perspectives
Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks. ; W.G. Jiang . S.K. Thompson . et al.
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
Janice E. Drew was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division Copyright © 2015 The Authors. Published by Elsevier Ltd. All rights reserved. ; Peer reviewed ; Publisher PDF
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd. ; Funding Agencies|Terry Fox Foundation Grant [TF-13-20]; UAEU Program for Advanced Research (UPAR) [31S118]; NIH [AR47901, R21CA188818, R15 CA137499-01, F32CA177139, P20RR016477, P20GM103434, R01CA170378, U54CA149145, U54CA143907, R01-HL107652, R01CA166348, R01GM071725, R01 CA109335-04A1, 109511R01CA151304CA168997 A11106131R03CA1711326 1P01AT003961RO1 CA100816P01AG034906 R01AG020642P01AG034906-01A1R01HL108006]; NIH NRSA Grant [F31CA154080]; NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer [AI076535]; Sky Foundation Inc. Michigan; University of Glasgow; Beatson Oncology Centre Fund; Spanish Ministry of Economy and Competitivity, ISCIII [PI12/00137, RTICC: RD12/0036/0028]; FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion [CTS-6844, CTS-1848]; Consejeria de Salud of the Junta de Andalucia [PI-0135-2010, PI-0306-2012]; ISCIII [PIE13/0004]; FEDER funds; United Soybean Board; NIH NCCAM Grant [K01AT007324]; NIH NCI Grant [R33 CA161873-02]; Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Ovarian and Prostate Cancer Research Trust, UK; West Virginia Higher Education Policy Commission/Division of Science Research; National Institutes of Health; Italian Association for Cancer Research (AIRC) [IG10636, 15403]; GRACE Charity, UK; Breast Cancer Campaign, UK; Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Connecticut State University; Swedish Research Council; Swedish Research Society; University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; CPRIT; Cancer Prevention and Research Institute of Texas; NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA); Gilead and Shire Pharmaceuticals; NIH/NCI [1R01CA20009, 5R01CAl27258-05, R21CA184788, NIH P30 CA22453, NCI RO1 28704]; Scottish Governments Rural and Environment Science and Analytical Services Division; National Research Foundation; United Arab Emirates University; Terry Fox Foundation; Novartis Pharmaceutical; Aveo Pharmaceutical; Roche; Bristol Myers Squibb; Bayer Pharmaceutical; Pfizer; Kyowa Kirin; NIH/NIAID Grant [A1076535]; Auckland Cancer Society; Cancer Society of New Zealand; NIH Public Service Grant from the National Cancer Institute [CA164095]; Medical Research Council CCU-Program Grant on cancer metabolism; EU Marie Curie Reintegration Grant [MC-CIG-303514]; Greek National funds through the Operational Program Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program THALES [MIS 379346]; COST Action CM1201 `Biomimetic Radical Chemistry; Duke University Molecular Cancer Biology T32 Training Grant; National Sciences Engineering and Research Council Undergraduate Student Research Award in Canada; Charles University in Prague projects [UNCE 204015, PRVOUK P31/2012]; Czech Science Foundation projects [15-03834Y, P301/12/1686]; Czech Health Research Council AZV project [15-32432A]; Internal Grant Agency of the Ministry of Health of the Czech Republic project [NT13663-3/2012]; National Institute of Aging [P30AG028716-01]; NIH/NCI training grants to Duke University [T32-CA059365-19, 5T32-CA059365]; Ministry of Education, Culture, Sports, Science and Technology, Japan [24590493]; Ministry of Health and Welfare [CCMP101-RD-031, CCMP102-RD-112]; Tzu-Chi University of Taiwan [61040055-10]; Svenska Sallskapet for Medicinsk Forskning; Cancer Research Wales; Albert Hung Foundation; Fong Family Foundation; Welsh Government A4B scheme; NIH NCI; University of Glasgow, Beatson Oncology Centre Fund, CRUK [C301/A14762]; NIH Intramural Research Program; National Science Foundation; American Cancer Society; National Cancer Center [NCC-1310430-2]; National Research Foundation [NRF-2005-0093837]; Sol Goldman Pancreatic Cancer Research Fund Grant [80028595]; Lustgarten Fund Grant [90049125, NIHR21CA169757]; Alma Toorock Memorial for Cancer Research; National Research Foundation of Korea (NRF); Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea [2011-0017639, 2011-0030001]; Ministry of Education of Taiwan [TMUTOP103005-4]; International Life Sciences Institute; United States Public Health Services Grants [NIH R01CA156776]; VA-BLR&D Merit Review Grant [5101-BX001517-02]; V Foundation; Pancreatic Cancer Action Network; Damon Runyon Cancer Research Foundation; Childrens Cancer Institute Australia; University Roma Tre; Italian Association for Cancer Research (AIRC-Grant) [IG15221]; Carlos III Health Institute; Feder funds [AM: CP10/00539, PI13/02277]; Basque Foundation for Science (IKERBASQUE); Marie Curie CIG Grant [2012/712404]; Canadian Institutes of Health Research; Avon Foundation for Women [OBC-134038]; Canadian Institutes of Health [MSH-136647, MOP 64308]; Bayer Healthcare System G4T (Grants4Targets); NIH NIDDK; NIH NIAAA; Shire Pharmaceuticals; Harvard-MIT Health Sciences and Technology Research Assistantship Award; Italian Ministry of University; University of Italy; Auckland Cancer Society Research Centre (ACSRC); German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF) [16SV5536K]; European Commission [FP7 259679 "IDEAL"]; Cinque per Mille dellIRPEF-Finanziamento della Ricerca Sanitaria; European Union Seventh Framework Programme (FP7) [278570]; AIRC [10216, 13837]; European Communitys Seventh Framework Program FP7 [311876]; Canadian Institute for Health Research [MOP114962, MOP125857]; Fonds de Recherche Quebec Sante [22624]; Terry Fox Research Institute [1030]; FEDER; MICINN [SAF2012-32810]; Junta de Castilla y Leon [BIO/SA06/13]; ARIMMORA project [FP7-ENV-2011]; European Union; NIH NIDDK [K01DK077137, R03DK089130]; NIH NCI grants [R01CA131294, R21 CA155686]; Avon Foundation; Breast Cancer Research Foundation Grant [90047965]; National Institute of Health, NINDS Grant [K08NS083732]; AACR-National Brain Tumor Society Career Development Award for Translational Brain Tumor Research [13-20-23-SIEG]; Department of Science and Technology, New Delhi, India [SR/FT/LS-063/2008]; Yorkshire Cancer Research; Wellcome Trust, UK; Italian Ministry of Economy and Finance Project CAMPUS-QUARC, within program FESR Campania Region; National Cancer Institute [5P01CA073992]; IDEA Award from the Department of Defense [W81XWH-12-1-0515]; Huntsman Cancer Foundation; University of Miami Clinical and Translational Science Institute (CTSI) Pilot Research Grant [CTSI-2013-P03]; SEEDS You Choose Awards; DoD [W81XVVH-11-1-0272, W81XWH-13-1-0182]; Kimmel Translational Science Award [SKF-13-021]; ACS Scholar award [122688-RSG-12-196-01-TBG]; National Cancer Institute, Pancreatic Cancer Action Network, Pew Charitable Trusts; American Diabetes Association; Elsa U. Pardee Foundation; Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin [2012RFLX5011]; United States National Institutes of Health [ES019458]; California Breast Cancer Research Program [17UB-8708]; National Institutes of Health through the RCMI-Center for Environmental Health [G1200MD007581]; NIH/National Heart, Lung, and Blood Institute Training Grant [T32HL098062]; European FP7-TuMIC [HEALTH-F2-2008-201662]; Italian Association for Cancer research (AIRC) Grant IG [11963]; Regione Campania L.R:N.5; European National Funds [PON01-02388/1 2007-2013]
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