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| 1 | Intravenous immune globulin suppresses angiogenesis in mice and humans显示文摘Human intravenous immune globulin(IVIg),a purified IgG fraction composed of~60%IgG1 and obtained from the pooled plasma of thousands of donors,is clinically used for a wide range of diseases.The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG(IgG)Fc regions.Recently,we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI,a high-affinity receptor for IgG1.Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases,namely,neovascular age-related macular degeneration,corneal neovascularization,colorectal cancer,fibrosarcoma and peripheral arterial ischemic disease.Angioinhibition was mediated by the Fc region of IVIg,required FcγRI and had similar potency in transgenic mice expressing human FcγRs.Finally,IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities.These data place IVIg,an agent approved by the US Food and Drug Administration,as a novel angioinhibitory drug in doses that are currently administered in the clinical setting.In addition,they raise the possibility of an unintended effect of IVIg on blood vessels. | Reo Yasuma Valeria Cicatiello Takeshi Mizutani Laura Tudisco Younghee Kim Valeria Tarallo Sasha Bogdanovich Yoshio Hirano Nagaraj Kerur Shengjian Li Tetsuhiro Yasuma Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Balamurali K Ambati Sevim Barbasso Helmers Ingrid E Lundberg Ondrej Viklicky Jeanette HW Leusen J Sjef Verbeek Bradley D Gelfand Ana Bastos-Carvalho Sandro De Falco Jayakrishna Ambati | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 3 |
| 2 | Minimum 10years outcome of decompressive laminectomy for degenerativelumbar spinal stenosis显示文摘 | TETSUHIRO I AKIRA K JUNICHI N | 2000 | Spine2000，25，14： | 1 |
| 3 | Mininum 10-year outcome of decompressive laminectomy for degenetative lumbar spinal stenosis显示文摘 | Tetsuhiro I Akira K Junichi N | 2000 | Spine2000，25，4： | 1 |
| 4 | Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties显示文摘 | Tetsuhiro C Kaoru K Zheng YW | 2006 | Hepatology2006，44，： | 1 |
| 5 | Molecular dynamics simulation in SrTiO3显示文摘 | Tetsuhiro K Yoshiyuki I Mitsuru I | 1998 | Solid State Ionics1998，108，： | 1 |
| 6 | Cancer stem cells in hepato-cellular carcinoma: Recent progress and perspective显示文摘 | Tetsuhiro C Akihide K Osamu Y | 2009 | Cancer Letters2009，286，： | 1 |
| 7 | Minimum l O-Yearoutcome of decompressive laminectomy for degenerative lumbar spinal stenosis 显示文摘 | Tetsuhiro I Akira K | 2000 | Spine2000，25，14： | 1 |
| 8 | Minimum 10-Year outcome of decompressive laminectomy for degenerative lumbar spinal stenosis显示文摘 | Tetsuhiro I Akira K Junichi N | 2000 | Spine2000，25，14： | 1 |
| 9 | Minimum 10 years outcome of decompressive laminectomy for degenerative lumbar spinalstenosis显示文摘 | Tetsuhiro I Akira K Junichi N | 2000 | Spine2000，25，14： | 1 |
| 10 | Minimum 10 years out-come of decompressive laminectomy for degenerative lumbar spinal stenosis显示文摘 | Tetsuhiro I Akira K Junichi N | 2000 | Spine2000，25，14： | 1 |
| 11 | Evolution of animal multicellularity slimulated by dissolved organic carbon in early Ediacaran ocean: DOXAM hypothesis 显示文摘 | Akihiro K Yoko K Tetsuhiro T | 2011 | Island Arc2011，20，： | 1 |
| 12 | Mininum 10-year outcome of decompressive laminectomy for degenetative lumbar spinal stenosis显示文摘 | Tetsuhiro I Akira K Junichi N | 2000 | Spine2000，25，4： | 1 |
| 13 | New species in Aspergillus section Fumigati from reclamation sites in Wyoming (U.S.A.) and revision of A. viridinutans complex显示文摘The Aspergillus viridinutans complex includes morphologically similar,soil-inhabiting species.Although its species boundaries have not been fully defined,many isolates from the complex have been isolated as opportunistic human and animal pathogens.In the present study,these species were dominant in spoil sites subjected to various types of reclamation management after coal mining.These species were characterised using two different PCR-fingerprinting methods,sequence data from the β-tubulin(benA)and calmodulin(caM)genes,macro-and micromorphology(optical and scanning electron microscopy),maximum growth temperatures and mating experiments.In addition,RNA polymerase II gene(RPB2),actin(act1)and ITS sequences were deposited for the ex-type isolates of newly described species.The mating experiment results,phylogenetic analyses and ascospore morphology suggested the presence of five species in the A.viridinutans complex.Aspergillus aureolus(syn.Neosartorya aureola)was the only homothallic species.Three species,A.felis,A.udagawae(syn.N.udagawae)and A.wyomingensis sp.nov.,were heterothallic and their morphologically distinguishable teleomorph was induced by systematic mating experiments.Aspergillus viridinutans s.str.seems to be a very rare species and was represented only by the ex-type isolate in which the MAT1-1 locus was amplified.Aspegillus viridinutans and A.aureolus were typified in accordance with the rules of the new botanical code.Other species outside the A.viridinutans complex isolated from the reclamation sites were A.fumigatiaffinis and A.lentulus as well as two new sister species,A.brevistipitatus sp.nov.and A.conversis sp.nov.which were closely related each to other and to N.papuensis.Both new species are phylogenetically distant from all anamorphic species and resemble A.brevipes,A.duricaulis and A.unilateralis in micromorphology and are distinguishable from each other by the slower growth of A.conversis on all tested media.Interestingly,no isolate from the reclamation sites represented A.fumigatus s.str.which is usually reported as the dominant species from the section Fumigati in soil. | Alena Nováková Vit Hubka Zuzana Dudová Tetsuhiro Matsuzawa Alena Kubátová Takashi Yaguchi Miroslav Kolařík | 2014 | Fungal Diversity2014，，1： | 0 |
| 14 | Human IgG1 antibodies suppress angiogenesis in a target-independent manner显示文摘Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s population.The most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human VEGFA.Although bevacizumab does not recognize mouse Vegfa,it inhibits angiogenesis in mice.Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI(CD64)and c-Cbl,impairing macrophage migration.Other approved humanized or human IgG1 antibodies without mouse targets(adalimumab,alemtuzumab,ofatumumab,omalizumab,palivizumab and tocilizumab),mouse IgG2a,and overexpression of human IgG1-Fc or mouse IgG2a-Fc,also inhibited angiogenesis in wild-type and FcγR humanized mice.This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown,Fc cleavage,IgG-Fc inhibition,disruption of Fc-FcγR interaction,or elimination of FcRγ-initated signaling.Furthermore,bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice.Finally,mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis.These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies. | Sasha Bogdanovich Younghee Kim Takeshi Mizutani Reo Yasuma Laura Tudisco Valeria Cicatiello Ana Bastos-Carvalho Nagaraj Kerur Yoshio Hirano Judit Z Baffi Valeria Tarallo Shengjian Li Tetsuhiro Yasuma Parthasarathy Arpitha Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Menotti Ruvo Annamaria Sandomenico Miho Nozaki Ryo Ijima Hiroki Kaneko Yuichiro Ogura Hiroko Terasaki Balamurali K Ambati Jeanette HW Leusen Wallace Y Langdon Michael R Clark Kathryn L Armour Pierre Bruhns J Sjef Verbeek Bradley D Gelfand Sandro De Falco Jayakrishna Ambati | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 0 |
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