並列タイトル等Effect of Histidine on Sorafenib-induced Vascular Damage : Analysis using Novel Medaka Fish Model
分子標的薬ソラフェニブによる血管障害とヒスチジンによる軽減効果の検討 : トランスジェニックメダカモデルを用いた解析
一般注記Background Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model. Methods The fli::GFP transgenic medaka fish model has a fluorescently visible systemic vasculature. We fed the fish with SFN with and without histidine to compare blood flow and vascular structure among the differently fed models. The vascular cross-sectional area of each fish was measured to determine vascular diameter changes. Results Our results demonstrated that SFN-fed medaka developed a narrower vascular diameter. In addition, this narrowing was counteracted by addition of histidine to the medaka diet. We observed no positive effect of histidine on regeneration of cut vessels or on cell growth of endothelial cells and HCC cell lines. Conclusion We proved the efficacy of the medaka model to assess vascular changes after administration of specific chemicals. And our results suggest that SFN causes vascular damage by narrowing peripheral vessel diameter, and that histidine effectively counteracts these changes to maintain blood flow.
学位の種類: 博士（医学）. 報告番号: 甲第4393号. 学位記番号: 新大院博（医）甲第792号. 学位授与年月日: 平成30年3月23日
Biochem Biophys Res Commun. 2018, 496(2), 556-561. Article first published online: 10 January 2018.
新大院博（医）甲第792号
開始ページ : 1
終了ページ : 22
DOIinfo:doi/10.1016/j.bbrc.2018.01.057
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