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  • 1
    Abstract: Pediatric high-grade gliomas (pedHGG) belong to the most aggressive cancers in children with a poor prognosis due to a lack of efficient therapeutic strategies. The beta-catenin/Wnt-signaling pathway was shown to hold promising potential as a treatment target in adult high-grade gliomas by abrogating tumor cell invasion and the acquisition of stem cell-like characteristics. Since pedHGG differ from their adult counterparts in genetically and biologically we aimed to investigate the effects of beta-catenin/Wnt-signaling pathway-inhibition by the beta-catenin/CBP antagonist ICG-001 in pedHGG cell lines. In contrast to adult HGG, pedHGG cells displayed minimal detectable canonical Wnt-signaling activity. Nevertheless, low doses of ICG-001 inhibited cell migration/invasion, tumorsphere- and colony formation, proliferation in vitro as well as tumor growth in vivo/ovo, suggesting that ICG-001 affects pedHGG tumor cell characteristics independent of beta-catenin/Wnt-signaling. RNA-sequencing analyses support a Wnt/beta-catenin-independent effect of ICG-001 on target gene transcription, revealing strong effects on genes involved in cellular metabolic/biosynthetic processes and cell cycle progression. Among these, high mRNA expression of cell cycle regulator JDP2 was found to confer a better prognosis for pedHGG patients. In conclusion, ICG-001 might offer an effective treatment option for pedHGG patients functioning to regulate cell phenotype and gene expression programs in absence of Wnt/beta-catenin signaling-activity.
    Type of Publication: Journal article published
    PubMed ID: 28460484
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  • 2
    ISSN: 0022-4731
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0166-6851
    Keywords: Filariasis ; Glutathione S-transferase ; L3 ; Litomosoides sigmodontis ; Molecular cloning ; Onchocerca volvulus ; [abr] GST; glutathione S-transferase ; [abr] L3; third larval stage ; [abr] UWGCG; University of Wisconsin Genetics Computer Group
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2013-03-15
    Description: Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964345/" 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/PMC3964345/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsai, Isheng J -- Zarowiecki, Magdalena -- Holroyd, Nancy -- Garciarrubio, Alejandro -- Sanchez-Flores, Alejandro -- Brooks, Karen L -- Tracey, Alan -- Bobes, Raul J -- Fragoso, Gladis -- Sciutto, Edda -- Aslett, Martin -- Beasley, Helen -- Bennett, Hayley M -- Cai, Jianping -- Camicia, Federico -- Clark, Richard -- Cucher, Marcela -- De Silva, Nishadi -- Day, Tim A -- Deplazes, Peter -- Estrada, Karel -- Fernandez, Cecilia -- Holland, Peter W H -- Hou, Junling -- Hu, Songnian -- Huckvale, Thomas -- Hung, Stacy S -- Kamenetzky, Laura -- Keane, Jacqueline A -- Kiss, Ferenc -- Koziol, Uriel -- Lambert, Olivia -- Liu, Kan -- Luo, Xuenong -- Luo, Yingfeng -- Macchiaroli, Natalia -- Nichol, Sarah -- Paps, Jordi -- Parkinson, John -- Pouchkina-Stantcheva, Natasha -- Riddiford, Nick -- Rosenzvit, Mara -- Salinas, Gustavo -- Wasmuth, James D -- Zamanian, Mostafa -- Zheng, Yadong -- Taenia solium Genome Consortium -- Cai, Xuepeng -- Soberon, Xavier -- Olson, Peter D -- Laclette, Juan P -- Brehm, Klaus -- Berriman, Matthew -- 085775/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- BBG0038151/Biotechnology and Biological Sciences Research Council/United Kingdom -- MOP#84556/Canadian Institutes of Health Research/Canada -- TW008588/TW/FIC NIH HHS/ -- England -- Nature. 2013 Apr 4;496(7443):57-63. doi: 10.1038/nature12031. Epub 2013 Mar 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Parasite Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23485966" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; Animals ; Biological Evolution ; Cestoda/drug effects/*genetics/physiology ; Cestode Infections/drug therapy/metabolism ; Conserved Sequence/genetics ; Echinococcus granulosus/genetics ; Echinococcus multilocularis/drug effects/genetics/metabolism ; Genes, Helminth/genetics ; Genes, Homeobox/genetics ; Genome, Helminth/*genetics ; HSP70 Heat-Shock Proteins/genetics ; Humans ; Hymenolepis/genetics ; Metabolic Networks and Pathways/genetics ; Molecular Targeted Therapy ; Parasites/drug effects/*genetics/physiology ; Proteome/genetics ; Stem Cells/cytology/metabolism ; Taenia solium/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2014-09-02
    Description: Several features common to a Western lifestyle, including obesity and low levels of physical activity, are known risk factors for gastrointestinal cancers. There is substantial evidence suggesting that diet markedly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking dysbiosis to cancer development. However, the mechanisms by which high-fat diet (HFD)-mediated changes in the microbial community affect the severity of tumorigenesis in the gut remain to be determined. Here we demonstrate that an HFD promotes tumour progression in the small intestine of genetically susceptible, K-ras(G12Dint), mice independently of obesity. HFD consumption, in conjunction with K-ras mutation, mediated a shift in the composition of the gut microbiota, and this shift was associated with a decrease in Paneth-cell-mediated antimicrobial host defence that compromised dendritic cell recruitment and MHC class II molecule presentation in the gut-associated lymphoid tissues. When butyrate was administered to HFD-fed K-ras(G12Dint) mice, dendritic cell recruitment in the gut-associated lymphoid tissues was normalized, and tumour progression was attenuated. Importantly, deficiency in MYD88, a signalling adaptor for pattern recognition receptors and Toll-like receptors, blocked tumour progression. The transfer of faecal samples from HFD-fed mice with intestinal tumours to healthy adult K-ras(G12Dint) mice was sufficient to transmit disease in the absence of an HFD. Furthermore, treatment with antibiotics completely blocked HFD-induced tumour progression, suggesting that distinct shifts in the microbiota have a pivotal role in aggravating disease. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting a microbiota that favours carcinogenesis, and they suggest that tumorigenesis is transmissible among genetically predisposed individuals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233209/" 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/PMC4233209/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schulz, Manon D -- Atay, Cigdem -- Heringer, Jessica -- Romrig, Franziska K -- Schwitalla, Sarah -- Aydin, Begum -- Ziegler, Paul K -- Varga, Julia -- Reindl, Wolfgang -- Pommerenke, Claudia -- Salinas-Riester, Gabriela -- Bock, Andreas -- Alpert, Carl -- Blaut, Michael -- Polson, Sara C -- Brandl, Lydia -- Kirchner, Thomas -- Greten, Florian R -- Polson, Shawn W -- Arkan, Melek C -- 8 P20 GM103446-12/GM/NIGMS NIH HHS/ -- P20 GM103446/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Oct 23;514(7523):508-12. doi: 10.1038/nature13398. Epub 2014 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute of Molecular Immunology, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany [2]. ; Institute of Molecular Immunology, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany. ; Department of Molecular Biology and Genetics, Bogazici University, 34342 Bebek, Istanbul, Turkey. ; 1] Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt am Main, Germany [2] German Cancer Consortium (DKTK), 69120 Heidelberg, Germany [3] German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ; Department of Internal Medicine II, Universitatsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany. ; Microarray and Deep-Sequencing Core Facility, University Medical Center Gottingen, 37077 Gottingen, Germany. ; Institute for Mathematical Statistics, Technical University Munich, 81675 Munich, Germany. ; 1] Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany [2]. ; Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany. ; Center for Bioinformatics and Computational Biology, Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19711, USA. ; Institute of Pathology, Ludwig Maximilians University, 80337 Munich, Germany. ; 1] German Cancer Consortium (DKTK), 69120 Heidelberg, Germany [2] German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [3] Institute of Pathology, Ludwig Maximilians University, 80337 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25174708" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Butyrates/pharmacology ; Carcinogenesis/*drug effects ; Diet, High-Fat/*adverse effects ; Dietary Fats/*adverse effects ; Disease Progression ; Dysbiosis/*chemically induced/*microbiology ; Intestinal Mucosa/immunology ; Intestinal Neoplasms/chemically induced/*microbiology ; Intestines/drug effects/microbiology ; Mice ; *Obesity/chemically induced/microbiology ; Prebiotics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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