Development of molecular- targeting therapy and prediction of mode of recurrence by analysis of molecular mechanism of invasion and metastasis of hepatocellular carcinoma

肝细胞癌侵袭转移分子机制分析分子靶向治疗发展及复发模式预测

• 批准号: 16390375
• 负责人: ARII Shigeki
• 金额: $ 9.15万
• 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390375/
• 关键词: hepatocellular carcinoma; invasion and metastasis; DNA binding protein; angiopoietin-2; hexisokinas-II; COX-2; VEGF; Skp-2; 浸潤・転移; dbpA; YB-1; Angiopioietin; Cox-2; 慢性肝障害; dbpa; 解糖系; 低酸素状態; 血管新生; 高癌化状態

1) Based on the previous studies, we focused on DNA binding protein A (dbpA) to investigate the candidate gene for occurrence and development of HCC. By the analyses of immunostaining of 82 resected specimen of HCC we clarified that dbpA was closely related to the portal invasion, venous invasion, differentiation grade of cancer cell and serum level of α fetoprotein, and further showed that transformation of T to G in the promoter region may be associated with poor prognosis. These findings suggested that dbpA might be not only a biomarker for invasion of HCC, but also a candidate gene of molecular-targeting therapy.2) Based on the previous studies showing that angiopoietin-2 is an important angiogenic factor in HCC, we studied the mechanism on the induction of this molecule. Consequently, we found that PGE2 and COX-2 is strong inducers for angiopoietin-2, and that COX-2 inhibitor suppressed the tumor growth in vivo through inhibiting the tumor angiogenesis. We also suggested that angiopoietin-2 and its receptor Tie-2 may be candidate molecules for targeting therapy.3) We found that not only VEGF but also anaerobic glycolysis- related enzyme of hexisokinase-II was enhanced under the hypoxic environment in HCC, suggesting the limitation of antiangiogenic therapy.

1）基于先前的研究，我们专注于DNA结合蛋白A（DBPA），研究了候选基因的发生和发展HCC的E分析。发明，静脉发明，癌症的分化等级和α胎蛋白的血清水平以及促进剂区域的进一步发展可能与预后不良有关。分子靶向疗法的基因。2）基于HCC中的IOGENIC因子，我们研究了工业分子的机制。 -2和IS受体TIE-2可能是用于靶向治疗的候选分子。3）我们发现，HECISOKINASE-II的VEGF和与糖酵解相关的酶也增强了HCC中HCC中的低氧RONMENT，这表明了抗血管增生疗法的局限性。

项目成果

Current status and perspective of antiangiognic therapy for cancer : hepatocellular carcinoma.

癌症抗血管生成治疗的现状和前景：肝细胞癌。

• 发表时间: 2006
• 期刊: Int J Clin Oncol. 11
• 作者: Tanaka S;Arii S.
• 通讯作者: Arii S.

Induction of angiopoietin-2 gene expression by Cox-2.A novelrol for Cox-2 inhibitors during hepatocarcinogenesis.

Cox-2 诱导血管生成素 2 基因表达。肝癌发生过程中用于 Cox-2 抑制剂的novrol。

• 发表时间: 2006
• 期刊: Journal of Hepatology 44
• 作者: Tanaka S;Arii S;Wand J
• 通讯作者: Wand J

肝細胞癌の血管新生 : HIF-1を機軸とした新たな視点 肝細胞癌 : 発癌・血管新生と血流イメージング(監修 松井修)

肝细胞癌的血管生成：以HIF-1为中心的新视角肝细胞癌：癌发生、血管生成和血流成像（指导老师：Osamu Matsui）

• 发表时间: 2004
• 作者: 有井滋樹;寺本研一;安田誠一;森章
• 通讯作者: 森章

Predictive factors affecting early recurrence after hepatectomy for hepatocellular carcinoma in 5-year survivors.

影响肝细胞癌肝切除术后 5 年幸存者早期复发的预测因素。

• 发表时间: 2005
• 期刊: Hepatogastroenterology 52
• 作者: Kaido T;Arii S;Oe H;Mori A;Imamura M
• 通讯作者: Imamura M

腫瘍血管新生と遺伝子治療 遺伝子治療フロンテア(編集 外科遺伝子治療研究会)

肿瘤血管生成与基因治疗基因治疗前沿（外科基因治疗研究组编）

• 发表时间: 2004
• 作者: 森章;有井滋樹;今村正之
• 通讯作者: 今村正之