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  • 1
    Publication Date: 2015-03-13
    Description: After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510871/" 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/PMC4510871/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mitchell, Duane A -- Batich, Kristen A -- Gunn, Michael D -- Huang, Min-Nung -- Sanchez-Perez, Luis -- Nair, Smita K -- Congdon, Kendra L -- Reap, Elizabeth A -- Archer, Gary E -- Desjardins, Annick -- Friedman, Allan H -- Friedman, Henry S -- Herndon, James E 2nd -- Coan, April -- McLendon, Roger E -- Reardon, David A -- Vredenburgh, James J -- Bigner, Darell D -- Sampson, John H -- 1UL2 RR024128-01/RR/NCRR NIH HHS/ -- P01 CA154291/CA/NCI NIH HHS/ -- P01-CA154291-01A1/CA/NCI NIH HHS/ -- P50 CA108786/CA/NCI NIH HHS/ -- P50 NS020023/NS/NINDS NIH HHS/ -- P50-CA108786/CA/NCI NIH HHS/ -- P50-NS20023/NS/NINDS NIH HHS/ -- R01 CA134844/CA/NCI NIH HHS/ -- R01 CA177476/CA/NCI NIH HHS/ -- R01 NS067037/NS/NINDS NIH HHS/ -- R01-CA134844/CA/NCI NIH HHS/ -- R01-CA177476-01/CA/NCI NIH HHS/ -- R01-NS067037/NS/NINDS NIH HHS/ -- T32 AI052077/AI/NIAID NIH HHS/ -- T32 GM007171/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Mar 19;519(7543):366-9. doi: 10.1038/nature14320. Epub 2015 Mar 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA [3] Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA [3] Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA [4] Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA [5] Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25762141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/immunology ; CD4-Positive T-Lymphocytes/drug effects/immunology ; Cancer Vaccines/administration & dosage/*immunology/therapeutic use ; Cell Movement/drug effects ; Chemokine CCL3/*immunology ; Dendritic Cells/cytology/*drug effects/immunology ; Female ; Glioblastoma/drug therapy/*immunology/pathology/*therapy ; Humans ; Immunotherapy/methods ; Lymph Nodes/cytology/drug effects/immunology ; Mice ; Mice, Inbred C57BL ; Phosphoproteins/chemistry/genetics/immunology ; Substrate Specificity ; Survival Rate ; Tetanus Toxoid/*administration & dosage/*pharmacology/therapeutic use ; Treatment Outcome ; Viral Matrix Proteins/chemistry/genetics/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-05-15
    Description: The tumour microenvironment may contribute to tumorigenesis owing to mechanical forces such as fibrotic stiffness or mechanical pressure caused by the expansion of hyper-proliferative cells. Here we explore the contribution of the mechanical pressure exerted by tumour growth onto non-tumorous adjacent epithelium. In the early stage of mouse colon tumour development in the Notch(+)Apc(+/1638N) mouse model, we observed mechanistic pressure stress in the non-tumorous epithelial cells caused by hyper-proliferative adjacent crypts overexpressing active Notch, which is associated with increased Ret and beta-catenin signalling. We thus developed a method that allows the delivery of a defined mechanical pressure in vivo, by subcutaneously inserting a magnet close to the mouse colon. The implanted magnet generated a magnetic force on ultra-magnetic liposomes, stabilized in the mesenchymal cells of the connective tissue surrounding colonic crypts after intravenous injection. The magnetically induced pressure quantitatively mimicked the endogenous early tumour growth stress in the order of 1,200 Pa, without affecting tissue stiffness, as monitored by ultrasound strain imaging and shear wave elastography. The exertion of pressure mimicking that of tumour growth led to rapid Ret activation and downstream phosphorylation of beta-catenin on Tyr654, imparing its interaction with the E-cadherin in adherens junctions, and which was followed by beta-catenin nuclear translocation after 15 days. As a consequence, increased expression of beta-catenin-target genes was observed at 1 month, together with crypt enlargement accompanying the formation of early tumorous aberrant crypt foci. Mechanical activation of the tumorigenic beta-catenin pathway suggests unexplored modes of tumour propagation based on mechanical signalling pathways in healthy epithelial cells surrounding the tumour, which may contribute to tumour heterogeneity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fernandez-Sanchez, Maria Elena -- Barbier, Sandrine -- Whitehead, Joanne -- Bealle, Gaelle -- Michel, Aude -- Latorre-Ossa, Heldmuth -- Rey, Colette -- Fouassier, Laura -- Claperon, Audrey -- Brulle, Laura -- Girard, Elodie -- Servant, Nicolas -- Rio-Frio, Thomas -- Marie, Helene -- Lesieur, Sylviane -- Housset, Chantal -- Gennisson, Jean-Luc -- Tanter, Mickael -- Menager, Christine -- Fre, Silvia -- Robine, Sylvie -- Farge, Emmanuel -- England -- Nature. 2015 Jul 2;523(7558):92-5. doi: 10.1038/nature14329. Epub 2015 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Curie, Centre de Recherche, PSL Research University, CNRS UMR 168, Physicochimie Curie Mechanics and Genetics of Embryonic and Tumour Development, INSERM, Fondation Pierre-Gilles de Gennes, F-75005 Paris, France. ; UPMC, Sorbonne Universites, Laboratoire PHENIX Physico-chimie des Electrolytes et Nanosystemes Interfaciaux, CNRS UMR 8234, F-75005 Paris, France. ; Langevin Institut, Waves and Images ESPCI ParisTech, PSL Research University, CNRS UMR7587, Inserm U979. F-75005 Paris, France. ; Sorbonne Universites, UPMC and INSERM, UMR-S 938, CDR Saint-Antoine, F-75012 Paris, France. ; CNRS UMR3666/INSERM U1143, Endocytic Trafficking and Therapeutic Delivery, Institut Curie, Centre de Recherche, F-75005 Paris, France. ; Bioinformatic platform, U900, Institut Curie, MINES ParisTech, F-75005 Paris, France. ; Next-generation sequencing platform, Institut Curie, F-75005 Paris, France. ; CNRS UMR 8612, Laboratoire Physico-Chimie des Systemes Polyphases, Institut Galien Paris-Sud, LabEx LERMIT, Faculte de Pharmacie, Universite Paris-Sud, 92 296 Chatenay-Malabry, France. ; CNRS UMR 3215/INSERM U934, Unite de Genetique et Biologie du Developpement, Notch Signaling in Stem Cells and Tumors, Institut Curie, Centre de Recherche, F-75005 Paris, France. ; CNRS UMR144, Compartimentation et dynamique cellulaires, Morphogenesis and Cell Signalling Institut Curie, Centre de Recherche, F-75005 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25970250" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Carcinogenesis/*pathology ; Colonic Neoplasms/*physiopathology ; Epithelial Cells/cytology/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Magnets ; Male ; Metal Nanoparticles ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; *Pressure ; Proto-Oncogene Proteins c-ret/metabolism ; Receptors, Notch/genetics/metabolism ; Signal Transduction ; *Tumor Microenvironment ; beta Catenin/*genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-09-19
    Description: The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fumagalli, Matteo -- Moltke, Ida -- Grarup, Niels -- Racimo, Fernando -- Bjerregaard, Peter -- Jorgensen, Marit E -- Korneliussen, Thorfinn S -- Gerbault, Pascale -- Skotte, Line -- Linneberg, Allan -- Christensen, Cramer -- Brandslund, Ivan -- Jorgensen, Torben -- Huerta-Sanchez, Emilia -- Schmidt, Erik B -- Pedersen, Oluf -- Hansen, Torben -- Albrechtsen, Anders -- Nielsen, Rasmus -- R01-HG003229/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1343-7. doi: 10.1126/science.aab2319.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK. Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. ; Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. ; National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen, Denmark. Greenland Center for Health Research, University of Greenland, Nuuk, Greenland. ; National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen, Denmark. Steno Diabetes Center, 2820 Gentofte, Denmark. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark. ; Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK. Department of Anthropology, University College London, London WC1H 0BW, UK. ; Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ; Department of Medicine, Lillebaelt Hospital, Vejle, Denmark. ; Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark. ; Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Faculty of Medicine, University of Aalborg, Aalborg, Denmark. ; School of Natural Sciences, University of California-Merced, Merced, CA 95343, USA. ; Faculty of Medicine, University of Aalborg, Aalborg, Denmark. Department of Cardiology, Aalborg University Hospital, 9100 Aalborg, Denmark. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu. ; Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. Department of Statistics, University of California-Berkeley, Berkeley, CA 94720, USA. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383953" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/*genetics ; Alleles ; Arctic Regions ; Body Height/genetics ; Body Weight/genetics ; Chromosomes, Human, Pair 11/genetics ; Climate ; *Diet, High-Fat ; Fatty Acids, Omega-3/*administration & dosage/analysis ; Female ; Genetic Loci ; Genome, Human/genetics ; Genome-Wide Association Study ; Greenland ; Humans ; Inuits/*genetics ; Linkage Disequilibrium ; Male ; Membrane Lipids/analysis/genetics ; Polymorphism, Single Nucleotide ; Selection, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2016-01-02
    Description: CRISPR/Cas9-mediated genome editing holds clinical potential for treating genetic diseases, such as Duchenne muscular dystrophy (DMD), which is caused by mutations in the dystrophin gene. To correct DMD by skipping mutant dystrophin exons in postnatal muscle tissue in vivo, we used adeno-associated virus-9 (AAV9) to deliver gene-editing components to postnatal mdx mice, a model of DMD. Different modes of AAV9 delivery were systematically tested, including intraperitoneal at postnatal day 1 (P1), intramuscular at P12, and retro-orbital at P18. Each of these methods restored dystrophin protein expression in cardiac and skeletal muscle to varying degrees, and expression increased from 3 to 12 weeks after injection. Postnatal gene editing also enhanced skeletal muscle function, as measured by grip strength tests 4 weeks after injection. This method provides a potential means of correcting mutations responsible for DMD and other monogenic disorders after birth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760628/" 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/PMC4760628/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, Chengzu -- Amoasii, Leonela -- Mireault, Alex A -- McAnally, John R -- Li, Hui -- Sanchez-Ortiz, Efrain -- Bhattacharyya, Samadrita -- Shelton, John M -- Bassel-Duby, Rhonda -- Olson, Eric N -- DK-099653/DK/NIDDK NIH HHS/ -- HL-077439/HL/NHLBI NIH HHS/ -- HL-093039/HL/NHLBI NIH HHS/ -- HL-111665/HL/NHLBI NIH HHS/ -- R01 DK099653/DK/NIDDK NIH HHS/ -- R01 HL077439/HL/NHLBI NIH HHS/ -- R01 HL093039/HL/NHLBI NIH HHS/ -- R01 HL111665/HL/NHLBI NIH HHS/ -- U01 HL100401/HL/NHLBI NIH HHS/ -- U01-HL-100401/HL/NHLBI NIH HHS/ -- U54 HD 087351/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):400-3. doi: 10.1126/science.aad5725. Epub 2015 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. eric.olson@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721683" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *CRISPR-Cas Systems ; Dependovirus ; Disease Models, Animal ; Dystrophin/*genetics ; Exons/genetics ; Female ; Forelimb/physiopathology ; Genetic Therapy/*methods ; Genome/genetics ; Hand Strength ; Male ; Mice ; Mice, Inbred mdx ; Muscle, Skeletal/metabolism ; Muscular Dystrophy, Duchenne/genetics/*therapy ; Myocardium/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2016-03-19
    Description: De Montjoye et al. (Reports, 30 January 2015, p. 536) claimed that most individuals can be reidentified from a deidentified transaction database and that anonymization mechanisms are not effective against reidentification. We demonstrate that anonymization can be performed by techniques well established in the literature.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanchez, David -- Martinez, Sergio -- Domingo-Ferrer, Josep -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1274. doi: 10.1126/science.aad9295.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉United Nations Educational, Scientific, and Cultural Organization (UNESCO) Chair in Data Privacy, Department of Computer Engineering and Mathematics, Universitat Rovira i Virgili (URV), Avenue Paisos Catalans, 26, E-43007, Tarragona, Catalonia. david.sanchez@urv.cat. ; United Nations Educational, Scientific, and Cultural Organization (UNESCO) Chair in Data Privacy, Department of Computer Engineering and Mathematics, Universitat Rovira i Virgili (URV), Avenue Paisos Catalans, 26, E-43007, Tarragona, Catalonia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989243" target="_blank"〉PubMed〈/a〉
    Keywords: *Commerce ; *Data Collection ; Female ; Humans ; *Information Dissemination ; Male ; *Privacy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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