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Human IgG1 antibodies suppress angiogenesis in a target-independent manner

Signal Transduction and Targeted Therapy 2016年第1期1卷 158-171页

作者： 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 Department of Ophthalmology and Visual Sciences University of KentuckyLexingtonKYUSA Department of Ophthalmology and Visual Science Nagoya City University Graduate School of Medical SciencesNagoyaJapan Department of Ophthalmology Nagoya University Graduate School of MedicineNagoyaJapan Angiogenesis Lab Institute of Genetics and Biophysics—CNRNaplesItaly Bio-Ker MultiMedica GroupNaplesItaly Department of Advanced Biomedical Sciences University of Naples‘Federico II’NaplesItaly CEINGE—Biotecnologie Avanzate s.c.a.r.l.NaplesItaly Istituto di Biostrutture e Bioimmagini CNRNaplesItaly Department of Ophthalmology and Visual Sciences Moran Eye CenterUniversity of Utah School of MedicineSalt Lake CityUTUSA Department of Ophthalmology Veterans Affairs Salt Lake City Healthcare SystemSalt Lake CityUTUSA Immunotherapy Laboratory Laboratory for Translational ImmunologyUniversity Medical Center UtrechtUtrechtThe Netherlands School of Pathology and Laboratory Medicine University of Western AustraliaCrawleyWAAustralia Division of Immunology Department of PathologyUniversity of CambridgeCambridgeUK Department of Immunology Unit of Antibodies in Therapy and PathologyInstitut PasteurParisFrance Institut National de la Santéet de la Recherche Médicale(INSERM)U1222 ParisFrance Department of Human Genetics Leiden University Medical CenterLeidenThe Netherlands Department of Biomedical Engineering University of KentuckyLexingtonKYUSA Department of Microbiology Immunologyand Molecular GeneticsUniversity of KentuckyLexingtonKYUSA IRCCS MultiMedica MilanoItaly Department of Physiology University of KentuckyLexingtonKYUSA.

Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s *** most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human *** bevacizumab does not recognize mouse Vegfa,it inhibits angiogenesis in *** 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 *** 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 *** 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 ***,bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA ***,mice deficient in FcγRI exhibited increased developmental and pathological *** findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.

关键词： CD64 angiogenesis antibodies

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Quantitative Assessment of Chronic Skin Reactions Including Erythema and Pigmentation after Breast Conserving Therapy

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Advances in Breast Cancer Research 2016年第3期5卷 121-128页

作者： miho Kawashima Miwako nozaki Kazuhiro Komazaki Ryuko Yamamuro Kazuo Ishizuna Makoto Kojima Department of Radiology Dokkyo Medical University Koshigaya Hospital Saitama Japan Breast Center Dokkyo Medical University Koshigaya Hospital Saitama Japan

Purpose: To evaluate long-term skin reactions following breast-conserving therapy by using the melanin-erythema index meter. Patients and Methods: 164 patients were followed for at least three years after breast-conserving therapy. For both the erythema and the melanin indices, the ratio of the irradiated-side index to the non-irradiated-side index was calculated. The time course of index ratios alternation was examined. Influences from additional therapies and patients’ age were also evaluated. Result: Both erythema and melanin index ratios of the breast skin were recovered to pre-radiation level three years after radiotherapy. However, both index ratios of the area administrated with 10-Gy boost irradiation were still high even after five years after radiotherapy. Endocrine therapy, chemotherapy and age had no significant influence on skin color reactions three years after radiotherapy. Conclusion: Quantitative assessment using the melanin-erythema index meter demonstrated that chronic skin reactions following breast conserving therapy had recovered to pre-radiation level for three years after irradiation except for the 10-Gy boost irradiated area.

关键词： Breast Cancer Erythema Index Melanin Index Breast-Conserving Therapy

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