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Michael Detmar - One of the best experts on this subject based on the ideXlab platform.
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thrombospondin 2 overexpression in the skin of transgenic mice reduces the susceptibility to chemically induced multistep skin carcinogenesis
Journal of Dermatological Science, 2014Co-Authors: Rainer Kunstfeld, Thomas Hawighorst, Youngkwon Hong, Lynh Nguyen, Michael Streit, Lawrence F Brown, Michael DetmarAbstract:Background We have previously reported stromal upregulation of the endogenous Angiogenesis Inhibitor thrombospondin-2 (TSP-2) during multistep carcinogenesis, and we found accelerated and enhanced skin Angiogenesis and carcinogenesis in TSP-2 deficient mice.
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targeted overexpression of the Angiogenesis Inhibitor thrombospondin 1 in the epidermis of transgenic mice prevents ultraviolet b induced Angiogenesis and cutaneous photo damage
Journal of Investigative Dermatology, 2002Co-Authors: Kiichiro Yano, Hajimu Oura, Michael DetmarAbstract:Chronic ultraviolet-B irradiation of the skin results in epidermal hyperplasia, degradation of extracellular matrix molecules, and formation of wrinkles. To characterize the biologic role of the vascular system in the mediation of ultraviolet-B-induced skin damage, we performed quantitative analyses of cutaneous blood vessels of mice after 10 wk of ultraviolet-B irradiation. Skin vascularization was greatly increased after chronic ultraviolet-B exposure with a significant increase of both the number and the size of dermal blood vessels, associated with upregulation of vascular endothelial growth factor expression in the hyperplastic epidermis. To directly study whether inhibition of Angiogenesis may diminish ultraviolet-B-induced cutaneous damage, wild-type and transgenic mice with skin-specific overexpression of the endogenous Angiogenesis Inhibitor thrombospondin-1 were subjected to the same ultraviolet-B irradiation regimen. Ultraviolet-B-irradiated thrombospondin-1 transgenic mice showed a significantly reduced skin vascularization, decreased endothelial cell proliferation, and increased endothelial cell apoptosis rates, compared with wild-type mice. Moreover, dermal photo-damage and wrinkle formation were greatly reduced in thrombospondin-1 transgenic mice. These results reveal an important role of the cutaneous vascular system in mediating ultraviolet-B-induced skin damage and suggest inhibition of Angiogenesis as a potential new approach for the prevention of chronic cutaneous photo-damage.
Shinobu Sakamoto - One of the best experts on this subject based on the ideXlab platform.
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Effects of Angiogenesis Inhibitor TNP-470 on the development of uterine adenomyosis in mice.
Fertility and sterility, 2003Co-Authors: Ying-fang Zhou, Takao Mori, Hideki Kudo, Rei Asakai, Shuji Sassa, Shinobu SakamotoAbstract:To investigate the effects of Angiogenesis Inhibitor TNP-470 on uterine microvessels in mice. Pituitary grafting frequently induced uterine adenomyosis. In vivo experimental study. Department of Biological Sciences, University of Tokyo and Medical Research Institute, Tokyo Medical and Dental University. SHN mice, which are known to develop uterine adenomyosis spontaneously, and also very soon after pituitary grafting. Immunohistochemical study on uterine blood vessels using an antibody to von Willebrand factor in pituitary gland-implanted mice with or without TNP-470. Reduced incidence of uterine adenomyosis. Twelve of 15 mice developed uterine adenomyosis with dilated blood vessels, but none of the TNP-470-treated mice with shrunken microvessels. The number of bromodeoxyuridine immunoreactive cells and activities of thymidylate synthase and thymidine kinase in uterine tissues were markedly reduced in TNP-470-treated mice. TNP-470, a potent Inhibitor of the development of vascular endothelium, reduced the development of endometrial blood vessels resulting in a lowered incidence of uterine adenomyosis induced by pituitary grafting in mice, and reduced the increase in S-phase cells and enzyme activity for pyrimidine nucleotide synthesis.
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Effects of Angiogenesis Inhibitor TNP-470 on the development of uterine adenomyosis in mice.
Fertility and Sterility, 2003Co-Authors: Ying-fang Zhou, Takao Mori, Hideki Kudo, Rei Asakai, Shuji Sassa, Shinobu SakamotoAbstract:Abstract Objective To investigate the effects of Angiogenesis Inhibitor TNP-470 on uterine microvessels in mice. Pituitary grafting frequently induced uterine adenomyosis. Design In vivo experimental study. Setting Department of Biological Sciences, University of Tokyo and Medical Research Institute, Tokyo Medical and Dental University. Animal(s) SHN mice, which are known to develop uterine adenomyosis spontaneously, and also very soon after pituitary grafting. Intervention(s) Immunohistochemical study on uterine blood vessels using an antibody to von Willebrand factor in pituitary gland-implanted mice with or without TNP-470. Main outcome measure(s) Reduced incidence of uterine adenomyosis. Result(s) Twelve of 15 mice developed uterine adenomyosis with dilated blood vessels, but none of the TNP-470-treated mice with shrunken microvessels. The number of bromodeoxyuridine immunoreactive cells and activities of thymidylate synthase and thymidine kinase in uterine tissues were markedly reduced in TNP-470-treated mice. Conclusion(s) TNP-470, a potent Inhibitor of the development of vascular endothelium, reduced the development of endometrial blood vessels resulting in a lowered incidence of uterine adenomyosis induced by pituitary grafting in mice, and reduced the increase in S-phase cells and enzyme activity for pyrimidine nucleotide synthesis.
Ying-fang Zhou - One of the best experts on this subject based on the ideXlab platform.
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Effects of Angiogenesis Inhibitor TNP-470 on the development of uterine adenomyosis in mice.
Fertility and sterility, 2003Co-Authors: Ying-fang Zhou, Takao Mori, Hideki Kudo, Rei Asakai, Shuji Sassa, Shinobu SakamotoAbstract:To investigate the effects of Angiogenesis Inhibitor TNP-470 on uterine microvessels in mice. Pituitary grafting frequently induced uterine adenomyosis. In vivo experimental study. Department of Biological Sciences, University of Tokyo and Medical Research Institute, Tokyo Medical and Dental University. SHN mice, which are known to develop uterine adenomyosis spontaneously, and also very soon after pituitary grafting. Immunohistochemical study on uterine blood vessels using an antibody to von Willebrand factor in pituitary gland-implanted mice with or without TNP-470. Reduced incidence of uterine adenomyosis. Twelve of 15 mice developed uterine adenomyosis with dilated blood vessels, but none of the TNP-470-treated mice with shrunken microvessels. The number of bromodeoxyuridine immunoreactive cells and activities of thymidylate synthase and thymidine kinase in uterine tissues were markedly reduced in TNP-470-treated mice. TNP-470, a potent Inhibitor of the development of vascular endothelium, reduced the development of endometrial blood vessels resulting in a lowered incidence of uterine adenomyosis induced by pituitary grafting in mice, and reduced the increase in S-phase cells and enzyme activity for pyrimidine nucleotide synthesis.
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Effects of Angiogenesis Inhibitor TNP-470 on the development of uterine adenomyosis in mice.
Fertility and Sterility, 2003Co-Authors: Ying-fang Zhou, Takao Mori, Hideki Kudo, Rei Asakai, Shuji Sassa, Shinobu SakamotoAbstract:Abstract Objective To investigate the effects of Angiogenesis Inhibitor TNP-470 on uterine microvessels in mice. Pituitary grafting frequently induced uterine adenomyosis. Design In vivo experimental study. Setting Department of Biological Sciences, University of Tokyo and Medical Research Institute, Tokyo Medical and Dental University. Animal(s) SHN mice, which are known to develop uterine adenomyosis spontaneously, and also very soon after pituitary grafting. Intervention(s) Immunohistochemical study on uterine blood vessels using an antibody to von Willebrand factor in pituitary gland-implanted mice with or without TNP-470. Main outcome measure(s) Reduced incidence of uterine adenomyosis. Result(s) Twelve of 15 mice developed uterine adenomyosis with dilated blood vessels, but none of the TNP-470-treated mice with shrunken microvessels. The number of bromodeoxyuridine immunoreactive cells and activities of thymidylate synthase and thymidine kinase in uterine tissues were markedly reduced in TNP-470-treated mice. Conclusion(s) TNP-470, a potent Inhibitor of the development of vascular endothelium, reduced the development of endometrial blood vessels resulting in a lowered incidence of uterine adenomyosis induced by pituitary grafting in mice, and reduced the increase in S-phase cells and enzyme activity for pyrimidine nucleotide synthesis.
Hiroyuki Osada - One of the best experts on this subject based on the ideXlab platform.
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Asymmetric total synthesis of (-)-azaspirene, a novel Angiogenesis Inhibitor.
Journal of the American Chemical Society, 2002Co-Authors: Yujiro Hayashi, Hideaki Kakeya, Yukihiro Asami, Mitsuru Shoji, Junichiro Yamaguchi, Kenji Sato, Shinpei Yamaguchi, Takasuke Mukaiyama, Ken Sakai, Hiroyuki OsadaAbstract:The asymmetric total synthesis of (−)-azaspirene, an Angiogenesis Inhibitor, has been accomplished, establishing its absolute stereochemistry. The key steps are a MgBr2·OEt2-mediated, diastereoselective Mukaiyama aldol reaction, a NaH-promoted, intramolecular cyclization of an alkynylamide, and the aldol reaction of a ketone containing functionalized γ-lactam moiety without protection of tert-alcohol and amide functionalities.
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Azaspirene: a novel Angiogenesis Inhibitor containing a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione skeleton produced by the fungus Neosartorya sp.
Organic letters, 2002Co-Authors: Yukihiro Asami, Hideaki Kakeya, Rie Onose, Arika Yoshida, Hiroshi Matsuzaki, Hiroyuki OsadaAbstract:[structure: see text] Azaspirene isolated from the fungus Neosartorya sp. is a novel Angiogenesis Inhibitor with a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione skeleton. Azaspirene inhibits the endothelial migration induced by vascular endothelial growth factor (ED100 = 27.1 microM).
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azaspirene a novel Angiogenesis Inhibitor containing a 1 oxa 7 azaspiro 4 4 non 2 ene 4 6 dione skeleton produced by the fungus neosartorya sp
Organic Letters, 2002Co-Authors: Yukihiro Asami, Hideaki Kakeya, Rie Onose, Arika Yoshida, Hiroshi Matsuzaki, Hiroyuki OsadaAbstract:Azaspirene isolated from the fungus Neosartorya sp. is a novel Angiogenesis Inhibitor with a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione skeleton. Azaspirene inhibits the endothelial migration induced by vascular endothelial growth factor (ED100 = 27.1 μM).
Lini Pandite - One of the best experts on this subject based on the ideXlab platform.
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association of germ line genetic markers in il8 hif1a vegfa and vegfr2 with treatment response to pazopanib in renal cell carcinoma
Journal of Clinical Oncology, 2010Co-Authors: H A Ball, Cora N Sternberg, N Bing, Dilip Rajagopalan, Colin F Spraggs, Vincent Mooser, R G Amado, Lon R Cardon, Lini PanditeAbstract:4520 Background: Pazopanib (Votrient, P), an oral Angiogenesis Inhibitor targeting VEGFR-1, -2, and -3, PDGFR-α and -β, and c-Kit, is approved in the US for the treatment of advanced renal cell car...
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pazopanib a multikinase Angiogenesis Inhibitor in patients with relapsed or refractory advanced soft tissue sarcoma a phase ii study from the european organisation for research and treatment of cancer soft tissue and bone sarcoma group eortc study 62
Journal of Clinical Oncology, 2009Co-Authors: Stefan Sleijfer, M Scurr, Isabelle Raycoquard, Zsuzsa Papai, Axel Le Cesne, Patrick Schoffski, Francoise Collin, Lini Pandite, Sandrine Marreaud, Annick De BrauwerAbstract:Purpose Given the importance of Angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral Angiogenesis Inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS. Patients and Methods Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR12 weeks). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; α = β = .1) for each stratum. Results One hundred forty-two patients were enrolled. The adipocytic STS s...
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pazopanib a multikinase Angiogenesis Inhibitor in patients with relapsed or refractory advanced soft tissue sarcoma a phase ii study from the european organisation for research and treatment of cancer soft tissue and bone sarcoma group eortc study 62
Journal of Clinical Oncology, 2009Co-Authors: Stefan Sleijfer, Isabelle Raycoquard, Zsuzsa Papai, Axel Le Cesne, Patrick Schoffski, Francoise Collin, Lini Pandite, Sandrine Marreaud, Michelle Scurr, Annick De BrauwerAbstract:PURPOSE Given the importance of Angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral Angiogenesis Inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS. PATIENTS AND METHODS Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR(12 weeks)). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; alpha = beta = .1) for each stratum. Results One hundred forty-two patients were enrolled. The adipocytic STS stratum was closed after the first stage, given insufficient activity (PFR(12 weeks), five [26%] of19). PFR(12 weeks) was 18 (44%) of 41 patients in the leiomyosarcoma cohort, 18 (49%) of 37 in the synovial sarcomas, and 16 (39%) of 41 in the other STS types. Compared with historical controls who were treated with second-line chemotherapy, progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached. The most frequent drug-related toxicities were hypertension, fatigue, hypopigmentation, and nausea. Other toxicities included liver enzyme elevations, myelosuppression, and proteinuria, all of which were mostly grades 1 to 2. The most frequent grades 3 to 4 toxicities were hyperbilirubinemia (6.3%), hypertension (7.7%), and fatigue (7.7%). CONCLUSION Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas, synovial sarcomas, and other STS types.