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Suppressive Effect of the Angiogenesis Inhibitor TNP‐470 on the Development of Carcinogen‐induced Hepatic Nodules in Rats

Tumor metastasis can be prevented by inhibiting angiogenesis. In the present study, we have demonstrated that the angiogenesis inhibitor TNP‐470 also suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was performed by the feeding of 2‐acetylaminofluorene to hepatectomized ra...

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Autores principales: Ikebe, Takashi, Yamamoto, Takatsugu, Kubo, Shoji, Hirohashi, Kazuhiro, Kinoshita, Hiroaki, Kaneda, Kenji, Sakurai, Masami
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921767/
https://www.ncbi.nlm.nih.gov/pubmed/9548441
http://dx.doi.org/10.1111/j.1349-7006.1998.tb00542.x
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author Ikebe, Takashi
Yamamoto, Takatsugu
Kubo, Shoji
Hirohashi, Kazuhiro
Kinoshita, Hiroaki
Kaneda, Kenji
Sakurai, Masami
author_facet Ikebe, Takashi
Yamamoto, Takatsugu
Kubo, Shoji
Hirohashi, Kazuhiro
Kinoshita, Hiroaki
Kaneda, Kenji
Sakurai, Masami
author_sort Ikebe, Takashi
collection PubMed
description Tumor metastasis can be prevented by inhibiting angiogenesis. In the present study, we have demonstrated that the angiogenesis inhibitor TNP‐470 also suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was performed by the feeding of 2‐acetylaminofluorene to hepatectomized rats during 8–14 weeks of age. Predominantly arterial‐to‐portal circulation and sinusoidal capillarization were determined by the staining of nodules with arterially infused ink and immunostaining for factor VIII‐related antigen, respectively. Intraperitoneal administration of 30 mg/kg b.w. of TNP‐470 twice a week significantly reduced the number of hepatic nodules. Among the nodules, hyperplastic nodules stained with ink, atypical hyperplastic nodules and hepatocellular carcinoma, all of which possess structurally altered sinusoidal endothelial cells or capillary‐type endothelial cells, were dramatically decreased in number. Suppression was observed equally in nodules of all sizes. TNP‐470 was more effective when administered during 8–20 weeks than during 14–26 weeks. In contrast, ink‐non‐stained hyperplastic nodules, which have normal sinusoidal endothelial cells, were not affected at all. The present results indicate that TNP‐470 suppresses the development of primary hepatic nodules whose microvessels are capillaries or transitional forms from sinusoids to capillaries.
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spelling pubmed-59217672018-05-11 Suppressive Effect of the Angiogenesis Inhibitor TNP‐470 on the Development of Carcinogen‐induced Hepatic Nodules in Rats Ikebe, Takashi Yamamoto, Takatsugu Kubo, Shoji Hirohashi, Kazuhiro Kinoshita, Hiroaki Kaneda, Kenji Sakurai, Masami Jpn J Cancer Res Article Tumor metastasis can be prevented by inhibiting angiogenesis. In the present study, we have demonstrated that the angiogenesis inhibitor TNP‐470 also suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was performed by the feeding of 2‐acetylaminofluorene to hepatectomized rats during 8–14 weeks of age. Predominantly arterial‐to‐portal circulation and sinusoidal capillarization were determined by the staining of nodules with arterially infused ink and immunostaining for factor VIII‐related antigen, respectively. Intraperitoneal administration of 30 mg/kg b.w. of TNP‐470 twice a week significantly reduced the number of hepatic nodules. Among the nodules, hyperplastic nodules stained with ink, atypical hyperplastic nodules and hepatocellular carcinoma, all of which possess structurally altered sinusoidal endothelial cells or capillary‐type endothelial cells, were dramatically decreased in number. Suppression was observed equally in nodules of all sizes. TNP‐470 was more effective when administered during 8–20 weeks than during 14–26 weeks. In contrast, ink‐non‐stained hyperplastic nodules, which have normal sinusoidal endothelial cells, were not affected at all. The present results indicate that TNP‐470 suppresses the development of primary hepatic nodules whose microvessels are capillaries or transitional forms from sinusoids to capillaries. Blackwell Publishing Ltd 1998-02 /pmc/articles/PMC5921767/ /pubmed/9548441 http://dx.doi.org/10.1111/j.1349-7006.1998.tb00542.x Text en
spellingShingle Article
Ikebe, Takashi
Yamamoto, Takatsugu
Kubo, Shoji
Hirohashi, Kazuhiro
Kinoshita, Hiroaki
Kaneda, Kenji
Sakurai, Masami
Suppressive Effect of the Angiogenesis Inhibitor TNP‐470 on the Development of Carcinogen‐induced Hepatic Nodules in Rats
title Suppressive Effect of the Angiogenesis Inhibitor TNP‐470 on the Development of Carcinogen‐induced Hepatic Nodules in Rats
title_full Suppressive Effect of the Angiogenesis Inhibitor TNP‐470 on the Development of Carcinogen‐induced Hepatic Nodules in Rats
title_fullStr Suppressive Effect of the Angiogenesis Inhibitor TNP‐470 on the Development of Carcinogen‐induced Hepatic Nodules in Rats
title_full_unstemmed Suppressive Effect of the Angiogenesis Inhibitor TNP‐470 on the Development of Carcinogen‐induced Hepatic Nodules in Rats
title_short Suppressive Effect of the Angiogenesis Inhibitor TNP‐470 on the Development of Carcinogen‐induced Hepatic Nodules in Rats
title_sort suppressive effect of the angiogenesis inhibitor tnp‐470 on the development of carcinogen‐induced hepatic nodules in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921767/
https://www.ncbi.nlm.nih.gov/pubmed/9548441
http://dx.doi.org/10.1111/j.1349-7006.1998.tb00542.x
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