ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Ihre E-Mail wurde erfolgreich gesendet. Bitte prüfen Sie Ihren Maileingang.

Leider ist ein Fehler beim E-Mail-Versand aufgetreten. Bitte versuchen Sie es erneut.

Vorgang fortführen?

Exportieren
  • 11
    facet.materialart.
    Unbekannt
    EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2012-12-15
    Beschreibung: Epigenetic regulators represent a promising new class of therapeutic targets for cancer. Enhancer of zeste homolog 2 (EZH2), a subunit of Polycomb repressive complex 2 (PRC2), silences gene expression via its histone methyltransferase activity. We found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer is independent of its role as a transcriptional repressor. Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor. This functional switch is dependent on phosphorylation of EZH2 and requires an intact methyltransferase domain. Hence, targeting the non-PRC2 function of EZH2 may have therapeutic efficacy for treating metastatic, hormone-refractory prostate cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625962/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625962/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Kexin -- Wu, Zhenhua Jeremy -- Groner, Anna C -- He, Housheng Hansen -- Cai, Changmeng -- Lis, Rosina T -- Wu, Xiaoqiu -- Stack, Edward C -- Loda, Massimo -- Liu, Tao -- Xu, Han -- Cato, Laura -- Thornton, James E -- Gregory, Richard I -- Morrissey, Colm -- Vessella, Robert L -- Montironi, Rodolfo -- Magi-Galluzzi, Cristina -- Kantoff, Philip W -- Balk, Steven P -- Liu, X Shirley -- Brown, Myles -- CA090381/CA/NCI NIH HHS/ -- CA097186/CA/NCI NIH HHS/ -- CA111803/CA/NCI NIH HHS/ -- CA131945/CA/NCI NIH HHS/ -- CA166507/CA/NCI NIH HHS/ -- CA85859/CA/NCI NIH HHS/ -- CA89021/CA/NCI NIH HHS/ -- CA90381/CA/NCI NIH HHS/ -- GM99409/GM/NIGMS NIH HHS/ -- K99 CA166507/CA/NCI NIH HHS/ -- P50 CA090381/CA/NCI NIH HHS/ -- R01 GM099409/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Dec 14;338(6113):1465-9. doi: 10.1126/science.1227604.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23239736" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Castration ; Cell Line, Tumor ; Cohort Studies ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Male ; Methyltransferases/chemistry/genetics/metabolism ; Mice ; Mice, Inbred ICR ; Mice, SCID ; Oncogene Proteins/genetics/*metabolism ; Polycomb Repressive Complex 2/genetics/*metabolism ; Prostatic Neoplasms/genetics/*metabolism/mortality ; Protein Structure, Tertiary ; Receptors, Androgen/metabolism ; Xenograft Model Antitumor Assays
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
  • 12
    facet.materialart.
    Unbekannt
    Genome-wide comparison of medieval and modern Mycobacterium leprae (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2013-06-15
    Beschreibung: Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. The ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schuenemann, Verena J -- Singh, Pushpendra -- Mendum, Thomas A -- Krause-Kyora, Ben -- Jager, Gunter -- Bos, Kirsten I -- Herbig, Alexander -- Economou, Christos -- Benjak, Andrej -- Busso, Philippe -- Nebel, Almut -- Boldsen, Jesper L -- Kjellstrom, Anna -- Wu, Huihai -- Stewart, Graham R -- Taylor, G Michael -- Bauer, Peter -- Lee, Oona Y-C -- Wu, Houdini H T -- Minnikin, David E -- Besra, Gurdyal S -- Tucker, Katie -- Roffey, Simon -- Sow, Samba O -- Cole, Stewart T -- Nieselt, Kay -- Krause, Johannes -- New York, N.Y. -- Science. 2013 Jul 12;341(6142):179-83. doi: 10.1126/science.1238286. Epub 2013 Jun 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Archaeological Sciences, University of Tubingen, 72070 Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23765279" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bone and Bones/microbiology ; DNA, Bacterial/chemistry/genetics/isolation & purification ; Denmark ; Endemic Diseases/history ; *Evolution, Molecular ; Genome, Bacterial/*genetics ; Great Britain ; History, Medieval ; Humans ; Leprosy/epidemiology/history/*microbiology ; Mycobacterium leprae/*classification/*genetics/isolation & purification ; Mycolic Acids/chemistry ; Phylogeny ; Sweden ; Tooth/microbiology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
  • 13
    facet.materialart.
    Unbekannt
    Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2013-08-10
    Beschreibung: Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-beta induction by the virus, suggesting that the reverse-transcribed HIV DNA triggers the innate immune response. Knockout or knockdown of cGAS in mouse or human cell lines blocked cytokine induction by HIV, murine leukemia virus, and simian immunodeficiency virus. These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860819/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860819/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Daxing -- Wu, Jiaxi -- Wu, You-Tong -- Du, Fenghe -- Aroh, Chukwuemika -- Yan, Nan -- Sun, Lijun -- Chen, Zhijian J -- R01 AI093967/AI/NIAID NIH HHS/ -- R01 AI098569/AI/NIAID NIH HHS/ -- R01-AI093967/AI/NIAID NIH HHS/ -- R01-AI098569/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 23;341(6148):903-6. doi: 10.1126/science.1240933. Epub 2013 Aug 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23929945" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cell Line ; Gene Knockdown Techniques ; HEK293 Cells ; HIV/drug effects/enzymology/*immunology ; HIV Infections/enzymology/*immunology/virology ; HIV Reverse Transcriptase/antagonists & inhibitors ; Humans ; *Immunity, Innate ; Interferon-beta/biosynthesis ; Membrane Proteins/metabolism ; Mice ; Nucleotidyltransferases/genetics/*metabolism ; Retroviridae/immunology ; Retroviridae Infections/enzymology/immunology/virology ; Reverse Transcriptase Inhibitors/pharmacology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
  • 14
    facet.materialart.
    Unbekannt
    Crystal structure of inhibitor of kappaB kinase beta (2011)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2011-03-23
    Beschreibung: Inhibitor of kappaB (IkappaB) kinase (IKK) phosphorylates IkappaB proteins, leading to their degradation and the liberation of nuclear factor kappaB for gene transcription. Here we report the crystal structure of IKKbeta in complex with an inhibitor, at a resolution of 3.6 A. The structure reveals a trimodular architecture comprising the kinase domain, a ubiquitin-like domain (ULD) and an elongated, alpha-helical scaffold/dimerization domain (SDD). Unexpectedly, the predicted leucine zipper and helix-loop-helix motifs do not form these structures but are part of the SDD. The ULD and SDD mediate a critical interaction with IkappaBalpha that restricts substrate specificity, and the ULD is also required for catalytic activity. The SDD mediates IKKbeta dimerization, but dimerization per se is not important for maintaining IKKbeta activity and instead is required for IKKbeta activation. Other IKK family members, IKKalpha, TBK1 and IKK-i, may have a similar trimodular architecture and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081413/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081413/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Guozhou -- Lo, Yu-Chih -- Li, Qiubai -- Napolitano, Gennaro -- Wu, Xuefeng -- Jiang, Xuliang -- Dreano, Michel -- Karin, Michael -- Wu, Hao -- R01 AI050872/AI/NIAID NIH HHS/ -- R01 AI050872-10/AI/NIAID NIH HHS/ -- R01 AI079260/AI/NIAID NIH HHS/ -- England -- Nature. 2011 Apr 21;472(7343):325-30. doi: 10.1038/nature09853. Epub 2011 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Weill Cornell Medical College, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21423167" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Motifs ; Animals ; Biocatalysis ; Crystallography, X-Ray ; Enzyme Activation ; Humans ; I-kappa B Kinase/*antagonists & inhibitors/*chemistry/metabolism ; Models, Molecular ; Protein Binding ; Protein Multimerization ; Protein Structure, Tertiary ; Substrate Specificity ; Ubiquitin/chemistry ; Xenopus laevis
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
  • 15
    facet.materialart.
    Unbekannt
    Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-10-30
    Beschreibung: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530898/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530898/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biankin, Andrew V -- Waddell, Nicola -- Kassahn, Karin S -- Gingras, Marie-Claude -- Muthuswamy, Lakshmi B -- Johns, Amber L -- Miller, David K -- Wilson, Peter J -- Patch, Ann-Marie -- Wu, Jianmin -- Chang, David K -- Cowley, Mark J -- Gardiner, Brooke B -- Song, Sarah -- Harliwong, Ivon -- Idrisoglu, Senel -- Nourse, Craig -- Nourbakhsh, Ehsan -- Manning, Suzanne -- Wani, Shivangi -- Gongora, Milena -- Pajic, Marina -- Scarlett, Christopher J -- Gill, Anthony J -- Pinho, Andreia V -- Rooman, Ilse -- Anderson, Matthew -- Holmes, Oliver -- Leonard, Conrad -- Taylor, Darrin -- Wood, Scott -- Xu, Qinying -- Nones, Katia -- Fink, J Lynn -- Christ, Angelika -- Bruxner, Tim -- Cloonan, Nicole -- Kolle, Gabriel -- Newell, Felicity -- Pinese, Mark -- Mead, R Scott -- Humphris, Jeremy L -- Kaplan, Warren -- Jones, Marc D -- Colvin, Emily K -- Nagrial, Adnan M -- Humphrey, Emily S -- Chou, Angela -- Chin, Venessa T -- Chantrill, Lorraine A -- Mawson, Amanda -- Samra, Jaswinder S -- Kench, James G -- Lovell, Jessica A -- Daly, Roger J -- Merrett, Neil D -- Toon, Christopher -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Australian Pancreatic Cancer Genome Initiative -- Kakkar, Nipun -- Zhao, Fengmei -- Wu, Yuan Qing -- Wang, Min -- Muzny, Donna M -- Fisher, William E -- Brunicardi, F Charles -- Hodges, Sally E -- Reid, Jeffrey G -- Drummond, Jennifer -- Chang, Kyle -- Han, Yi -- Lewis, Lora R -- Dinh, Huyen -- Buhay, Christian J -- Beck, Timothy -- Timms, Lee -- Sam, Michelle -- Begley, Kimberly -- Brown, Andrew -- Pai, Deepa -- Panchal, Ami -- Buchner, Nicholas -- De Borja, Richard -- Denroche, Robert E -- Yung, Christina K -- Serra, Stefano -- Onetto, Nicole -- Mukhopadhyay, Debabrata -- Tsao, Ming-Sound -- Shaw, Patricia A -- Petersen, Gloria M -- Gallinger, Steven -- Hruban, Ralph H -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Schulick, Richard D -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Capelli, Paola -- Corbo, Vincenzo -- Scardoni, Maria -- Tortora, Giampaolo -- Tempero, Margaret A -- Mann, Karen M -- Jenkins, Nancy A -- Perez-Mancera, Pedro A -- Adams, David J -- Largaespada, David A -- Wessels, Lodewyk F A -- Rust, Alistair G -- Stein, Lincoln D -- Tuveson, David A -- Copeland, Neal G -- Musgrove, Elizabeth A -- Scarpa, Aldo -- Eshleman, James R -- Hudson, Thomas J -- Sutherland, Robert L -- Wheeler, David A -- Pearson, John V -- McPherson, John D -- Gibbs, Richard A -- Grimmond, Sean M -- 13031/Cancer Research UK/United Kingdom -- 2P50CA101955/CA/NCI NIH HHS/ -- P01CA134292/CA/NCI NIH HHS/ -- P50 CA101955/CA/NCI NIH HHS/ -- P50 CA102701/CA/NCI NIH HHS/ -- P50CA062924/CA/NCI NIH HHS/ -- R01 CA097075/CA/NCI NIH HHS/ -- R01 CA97075/CA/NCI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2012 Nov 15;491(7424):399-405. doi: 10.1038/nature11547. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103869" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Axons/*metabolism ; Carcinoma, Pancreatic Ductal/*genetics/*pathology ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Genome/*genetics ; Humans ; Kaplan-Meier Estimate ; Mice ; Mutation ; Pancreatic Neoplasms/*genetics/*pathology ; Proteins/genetics ; Signal Transduction
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
  • 16
    facet.materialart.
    Unbekannt
    A metagenome-wide association study of gut microbiota in type 2 diabetes (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-10-02
    Beschreibung: Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qin, Junjie -- Li, Yingrui -- Cai, Zhiming -- Li, Shenghui -- Zhu, Jianfeng -- Zhang, Fan -- Liang, Suisha -- Zhang, Wenwei -- Guan, Yuanlin -- Shen, Dongqian -- Peng, Yangqing -- Zhang, Dongya -- Jie, Zhuye -- Wu, Wenxian -- Qin, Youwen -- Xue, Wenbin -- Li, Junhua -- Han, Lingchuan -- Lu, Donghui -- Wu, Peixian -- Dai, Yali -- Sun, Xiaojuan -- Li, Zesong -- Tang, Aifa -- Zhong, Shilong -- Li, Xiaoping -- Chen, Weineng -- Xu, Ran -- Wang, Mingbang -- Feng, Qiang -- Gong, Meihua -- Yu, Jing -- Zhang, Yanyan -- Zhang, Ming -- Hansen, Torben -- Sanchez, Gaston -- Raes, Jeroen -- Falony, Gwen -- Okuda, Shujiro -- Almeida, Mathieu -- LeChatelier, Emmanuelle -- Renault, Pierre -- Pons, Nicolas -- Batto, Jean-Michel -- Zhang, Zhaoxi -- Chen, Hua -- Yang, Ruifu -- Zheng, Weimou -- Li, Songgang -- Yang, Huanming -- Wang, Jian -- Ehrlich, S Dusko -- Nielsen, Rasmus -- Pedersen, Oluf -- Kristiansen, Karsten -- Wang, Jun -- England -- Nature. 2012 Oct 4;490(7418):55-60. doi: 10.1038/nature11450. Epub 2012 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BGI-Shenzhen, Shenzhen 518083, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023125" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Asian Continental Ancestry Group ; Butyrates/metabolism ; China/ethnology ; Cohort Studies ; Diabetes Mellitus, Type ; 2/classification/complications/*microbiology/physiopathology ; Feces/microbiology ; Genetic Linkage/genetics ; Genetic Markers ; Genome-Wide Association Study/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Intestines/*microbiology ; Metabolic Networks and Pathways/genetics ; Metagenome/*genetics ; Metagenomics/*methods ; Opportunistic Infections/complications/microbiology ; Reference Standards ; Sulfates/metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
  • 17
    facet.materialart.
    Unbekannt
    Identification of genomic alterations in oesophageal squamous cell cancer (2014)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2014-03-29
    Beschreibung: Oesophageal cancer is one of the most aggressive cancers and is the sixth leading cause of cancer death worldwide. Approximately 70% of global oesophageal cancer cases occur in China, with oesophageal squamous cell carcinoma (ESCC) being the histopathological form in the vast majority of cases (〉90%). Currently, there are limited clinical approaches for the early diagnosis and treatment of ESCC, resulting in a 10% five-year survival rate for patients. However, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we describe a comprehensive genomic analysis of 158 ESCC cases, as part of the International Cancer Genome Consortium research project. We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases, plus an additional 70 ESCC cases not used in the whole-genome and whole-exome sequencing, were subjected to array comparative genomic hybridization analysis. We identified eight significantly mutated genes, of which six are well known tumour-associated genes (TP53, RB1, CDKN2A, PIK3CA, NOTCH1, NFE2L2), and two have not previously been described in ESCC (ADAM29 and FAM135B). Notably, FAM135B is identified as a novel cancer-implicated gene as assayed for its ability to promote malignancy of ESCC cells. Additionally, MIR548K, a microRNA encoded in the amplified 11q13.3-13.4 region, is characterized as a novel oncogene, and functional assays demonstrate that MIR548K enhances malignant phenotypes of ESCC cells. Moreover, we have found that several important histone regulator genes (MLL2 (also called KMT2D), ASH1L, MLL3 (KMT2C), SETD1B, CREBBP and EP300) are frequently altered in ESCC. Pathway assessment reveals that somatic aberrations are mainly involved in the Wnt, cell cycle and Notch pathways. Genomic analyses suggest that ESCC and head and neck squamous cell carcinoma share some common pathogenic mechanisms, and ESCC development is associated with alcohol drinking. This study has explored novel biological markers and tumorigenic pathways that would greatly improve therapeutic strategies for ESCC.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Yongmei -- Li, Lin -- Ou, Yunwei -- Gao, Zhibo -- Li, Enmin -- Li, Xiangchun -- Zhang, Weimin -- Wang, Jiaqian -- Xu, Liyan -- Zhou, Yong -- Ma, Xiaojuan -- Liu, Lingyan -- Zhao, Zitong -- Huang, Xuanlin -- Fan, Jing -- Dong, Lijia -- Chen, Gang -- Ma, Liying -- Yang, Jie -- Chen, Longyun -- He, Minghui -- Li, Miao -- Zhuang, Xuehan -- Huang, Kai -- Qiu, Kunlong -- Yin, Guangliang -- Guo, Guangwu -- Feng, Qiang -- Chen, Peishan -- Wu, Zhiyong -- Wu, Jianyi -- Ma, Ling -- Zhao, Jinyang -- Luo, Longhai -- Fu, Ming -- Xu, Bainan -- Chen, Bo -- Li, Yingrui -- Tong, Tong -- Wang, Mingrong -- Liu, Zhihua -- Lin, Dongxin -- Zhang, Xiuqing -- Yang, Huanming -- Wang, Jun -- Zhan, Qimin -- England -- Nature. 2014 May 1;509(7498):91-5. doi: 10.1038/nature13176. Epub 2014 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China [2]. ; 1] BGI-Shenzhen, Shenzhen 518083, Guangdong 518083, China [2]. ; 1] State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China [2] Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China [3]. ; 1] Department of Biochemistry and Molecular Biology, The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China [2]. ; State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. ; BGI-Shenzhen, Shenzhen 518083, Guangdong 518083, China. ; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China. ; Department of Tumor Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou 515041, Guangdong, China. ; Department of Biochemistry and Molecular Biology, The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China. ; Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670651" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Alcohol Drinking/adverse effects ; Biomarkers, Tumor/genetics ; Carcinoma, Squamous Cell/*genetics/pathology ; Cell Cycle/genetics ; Chromosomes, Human, Pair 11/genetics ; Comparative Genomic Hybridization ; DNA Copy Number Variations/genetics ; Esophageal Neoplasms/*genetics/pathology ; Exome/genetics ; Female ; Genome, Human/*genetics ; Genomics ; Histones/metabolism ; Humans ; Male ; MicroRNAs/genetics ; Mutation/*genetics ; Oncogenes/genetics ; Phenotype ; Receptors, Notch/genetics ; Risk Factors ; Wnt Signaling Pathway/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
  • 18
    facet.materialart.
    Unbekannt
    Therapeutic antibody targeting of individual Notch receptors (2010)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2010-04-16
    Beschreibung: The four receptors of the Notch family are widely expressed transmembrane proteins that function as key conduits through which mammalian cells communicate to regulate cell fate and growth. Ligand binding triggers a conformational change in the receptor negative regulatory region (NRR) that enables ADAM protease cleavage at a juxtamembrane site that otherwise lies buried within the quiescent NRR. Subsequent intramembrane proteolysis catalysed by the gamma-secretase complex liberates the intracellular domain (ICD) to initiate the downstream Notch transcriptional program. Aberrant signalling through each receptor has been linked to numerous diseases, particularly cancer, making the Notch pathway a compelling target for new drugs. Although gamma-secretase inhibitors (GSIs) have progressed into the clinic, GSIs fail to distinguish individual Notch receptors, inhibit other signalling pathways and cause intestinal toxicity, attributed to dual inhibition of Notch1 and 2 (ref. 11). To elucidate the discrete functions of Notch1 and Notch2 and develop clinically relevant inhibitors that reduce intestinal toxicity, we used phage display technology to generate highly specialized antibodies that specifically antagonize each receptor paralogue and yet cross-react with the human and mouse sequences, enabling the discrimination of Notch1 versus Notch2 function in human patients and rodent models. Our co-crystal structure shows that the inhibitory mechanism relies on stabilizing NRR quiescence. Selective blocking of Notch1 inhibits tumour growth in pre-clinical models through two mechanisms: inhibition of cancer cell growth and deregulation of angiogenesis. Whereas inhibition of Notch1 plus Notch2 causes severe intestinal toxicity, inhibition of either receptor alone reduces or avoids this effect, demonstrating a clear advantage over pan-Notch inhibitors. Our studies emphasize the value of paralogue-specific antagonists in dissecting the contributions of distinct Notch receptors to differentiation and disease and reveal the therapeutic promise in targeting Notch1 and Notch2 independently.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Yan -- Cain-Hom, Carol -- Choy, Lisa -- Hagenbeek, Thijs J -- de Leon, Gladys P -- Chen, Yongmei -- Finkle, David -- Venook, Rayna -- Wu, Xiumin -- Ridgway, John -- Schahin-Reed, Dorreyah -- Dow, Graham J -- Shelton, Amy -- Stawicki, Scott -- Watts, Ryan J -- Zhang, Jeff -- Choy, Robert -- Howard, Peter -- Kadyk, Lisa -- Yan, Minhong -- Zha, Jiping -- Callahan, Christopher A -- Hymowitz, Sarah G -- Siebel, Christian W -- England -- Nature. 2010 Apr 15;464(7291):1052-7. doi: 10.1038/nature08878.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Antibody Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393564" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Angiogenesis Inhibitors/immunology/pharmacology/therapeutic use ; Animals ; Antibodies/adverse effects/immunology/*pharmacology/*therapeutic use ; Antibody Specificity/immunology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Goblet Cells/drug effects/pathology ; Humans ; Mice ; Mice, Inbred BALB C ; NIH 3T3 Cells ; Neoplasms/blood supply/*drug therapy/*metabolism/pathology ; Neovascularization, Pathologic/drug therapy ; Peptide Library ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug ; therapy/metabolism/pathology ; Receptor, Notch1/antagonists & inhibitors/immunology ; Receptor, Notch2/antagonists & inhibitors/immunology ; Receptors, Notch/*antagonists & inhibitors/genetics/immunology/metabolism ; Signal Transduction/drug effects
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
  • 19
    facet.materialart.
    Unbekannt
    SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression (2011)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2011-02-04
    Beschreibung: Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression. Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFbeta/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753179/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753179/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Zhihu -- Wu, Chang-Jiun -- Chu, Gerald C -- Xiao, Yonghong -- Ho, Dennis -- Zhang, Jingfang -- Perry, Samuel R -- Labrot, Emma S -- Wu, Xiaoqiu -- Lis, Rosina -- Hoshida, Yujin -- Hiller, David -- Hu, Baoli -- Jiang, Shan -- Zheng, Hongwu -- Stegh, Alexander H -- Scott, Kenneth L -- Signoretti, Sabina -- Bardeesy, Nabeel -- Wang, Y Alan -- Hill, David E -- Golub, Todd R -- Stampfer, Meir J -- Wong, Wing H -- Loda, Massimo -- Mucci, Lorelei -- Chin, Lynda -- DePinho, Ronald A -- P50 CA090381/CA/NCI NIH HHS/ -- P50 CA090381-08/CA/NCI NIH HHS/ -- P50 CA90381/CA/NCI NIH HHS/ -- R01 5R01CA136578/CA/NCI NIH HHS/ -- R01 CA131945/CA/NCI NIH HHS/ -- R01CA131945/CA/NCI NIH HHS/ -- R01CA141298/CA/NCI NIH HHS/ -- U01-CA84313/CA/NCI NIH HHS/ -- England -- Nature. 2011 Feb 10;470(7333):269-73. doi: 10.1038/nature09677. Epub 2011 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21289624" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Bone Morphogenetic Proteins/metabolism ; Cell Proliferation ; Cyclin D1/genetics/metabolism ; *Disease Progression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor/physiology ; Humans ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Mice ; Mice, Transgenic ; Models, Biological ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis/genetics/*pathology ; Osteopontin/genetics/metabolism ; PTEN Phosphohydrolase/deficiency/genetics ; Penetrance ; Prognosis ; Prostate/metabolism ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/diagnosis/genetics/*pathology ; Smad4 Protein/deficiency/genetics/*metabolism ; Transforming Growth Factor beta
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
  • 20
    facet.materialart.
    Unbekannt
    Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-03-23
    Beschreibung: In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578422/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cui, Yujie -- Wang, Wei -- Dong, Ningzheng -- Lou, Jinglei -- Srinivasan, Dinesh Kumar -- Cheng, Weiwei -- Huang, Xiaoyi -- Liu, Meng -- Fang, Chaodong -- Peng, Jianhao -- Chen, Shenghan -- Wu, Shannon -- Liu, Zhenzhen -- Dong, Liang -- Zhou, Yiqing -- Wu, Qingyu -- HD064634/HD/NICHD NIH HHS/ -- HL089298/HL/NHLBI NIH HHS/ -- R01 HD064634/HD/NICHD NIH HHS/ -- R01 HL089298/HL/NHLBI NIH HHS/ -- England -- Nature. 2012 Mar 21;484(7393):246-50. doi: 10.1038/nature10897.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Cardiology, Nephrology and Hypertension, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22437503" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Atrial Natriuretic Factor/deficiency/genetics/metabolism ; Blood Pressure/genetics ; Case-Control Studies ; Cells, Cultured ; Disease Models, Animal ; Female ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Ischemia/metabolism/pathology ; Kidney/blood supply/pathology ; Kidney Diseases/genetics/pathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Mutation ; Pre-Eclampsia/genetics/metabolism/pathology/physiopathology ; Pregnancy ; Serine Endopeptidases/chemistry/genetics/*metabolism ; Trophoblasts/*cytology/metabolism ; Uterine Artery/*growth & development ; Uterus/*blood supply/*metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    AKTUELLE ARTIKEL
Schließen ⊗
Diese Webseite nutzt Cookies und das Analyse-Tool Matomo. Weitere Informationen finden Sie hier...