Order-made medicine for cancer in the viewpoint of angiogenesis

从血管生成的角度进行癌症定制治疗

• 批准号: 14370379
• 负责人: ARII Shigeki
• 金额: $ 9.34万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370379/
• 关键词: angiogenesis; order-made medicine; glycolysis; aerobic metabolism; anaerobic metabolism; vascular endothelial growth factor; hexokinase-II; hypoxia inducible factor-1; 転移性肝癌; 解糖系; ヘキソキナーゼ; VEGF(vascular endothelial growth factor); 遺伝子治療

It has been thought that solid tumors require tumor angiogenesis in their growth. However, we sometimes encounter the tumors that grow rapidly despite their poor vascularity. This clinical observation suggest.s the existence of tumors that require little neoangiogenesis for their growth. In this research project, we analyzed the expressions of hexokinase, a key enzyme in glycolysis, and VEGE in hepatocellular carcinoma and rnetastatic liver cancer in relation to tumor vascularity, and the participation of hypoxia-inducible factor-1(HIF-1) was studied. Consequently, we obtained some informative evidence. In HCC, main energy source of the growth was derived from angiogenesis, whereas in metastatic tumors glycolysis induced by HIF-1 is the predominant energy source. In addition, it was suggested that cancer cells obtain energy for growth by switching the metabolic profile to glycolysis through HIP-i in hypoxic condition. Although many kinds of antiangiogenic therapies have been reported to be effective, it is assumed that some tumors might resist these therapies by acquiring energy for growth through increased glycolysis induced by HIF-1.

据认为，实体瘤在其生长中需要肿瘤血管生成。然而，我们有时会遇到肿瘤生长迅速，尽管他们的血管分布不良。这项临床观察表明，存在几乎不需要新血管生成即可生长的肿瘤。本研究分析了糖酵解关键酶己糖激酶和VEGE在肝细胞癌和转移性肝癌中的表达及其与肿瘤血管生成的关系，并探讨了缺氧诱导因子-1（hypoxia-inducible factor-1，HIF-1）的参与。因此，我们获得了一些翔实的证据。在HCC中，生长的主要能量来源于血管生成，而在转移性肿瘤中，由HIF-1诱导的糖酵解是主要的能量来源。此外，表明癌细胞通过在缺氧条件下经由HIP-1将代谢谱转换为糖酵解来获得生长能量。尽管许多种类的抗血管生成疗法已被报道是有效的，但据推测，一些肿瘤可能通过HIF-1诱导的糖酵解增加来获得生长所需的能量而抵抗这些疗法。

项目成果

有井滋樹, 寺本研一: "浸潤転移・血管新生の分子生物学的解析と臨床意義"肝胆膵. 45(4). 555-560 (2002)

Shigeki Arii、Kenichi Teramoto：“侵袭性转移和血管生成的分子生物学分析和临床意义”肝胆胰 45(4) (2002)。

有井滋樹, 安田誠一, 森 章, 寺本研一: "肝細胞癌の血管新生の分子機構.肝細胞癌の血行動態はどこまで分かったか"メヂカルトリビューン(監修神代正道、岡崎正敏、板井悠二). 6-13 (2001)

Shigeki Arii、Seiichi Yasuda、Akira Mori、Kenichi Teramoto：“肝细胞癌血管生成的分子机制。我们对肝细胞癌的血流动力学了解多少？”（由 Masamichi Kamishiro、Masatoshi Okazaki、Yuji Itai 监督）6。 -13 (2001)

有井滋樹: "血管新生と肝細胞癌"Hepatica(Excerpta Medica). 21(3). 31-32 (2002)

Shigeki Arii：“血管生成和肝细胞癌”Hepatica（医学摘录）21（3）（2002）。

Arii S.: "Hexokinase II and VEGF expression in liver tumors : correlation with hypoxia-inducible factor 1 alpha and its significance."J Hepatol.. 40. 117-123 (2004)

Arii S.：“肝肿瘤中的己糖激酶 II 和 VEGF 表达：与缺氧诱导因子 1 α 的相关性及其意义。”J Hepatol.. 40. 117-123 (2004)

有井 滋樹: "肝細胞癌-発癌・血管新生と血流イメージング"(株)メディカルトリビューン(発表予定). (2004)

Shigeki Arii：“肝细胞癌 - 癌变、血管生成和血流成像”Medical Tribune, Inc.（即将出版）。