Molecular targeting agents that suppress invasion and metastasis of cancer cells

抑制癌细胞侵袭和转移的分子靶向剂

• 批准号: 17016058
• 负责人: AKIYAMA Shinichi
• 金额: $ 28.03万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17016058/
• 关键词: thymidine phosphorylase; 2-deoxy-D-ribose; IL-8; ROS; NFκB; TSP-1; 5-FU; Thymidine phosphorylase (TP); NADPHオキシダーゼTegafur; GBL; 血管新生阻害効果; TP; NF-κB; IKKα; β; IkB; HIF-1; BNIP3; 5-Fu; マイクロDNA; 線維芽細胞; thymdine phosphorylase; drug resis

Thymidine phosphorylase is an enzyme that has an angiogenic activity. 2-Deoxy-D-ribose, one of the degradation products of thymidine produced by TP also has an angiogenic activity. As well as the inhibitor of TP, 2-deoxy-L-ribose, an stereoisomer of 2-deoxy-D-ribose, suppressed the growth, invasion and metastasis of the TP-expressing tumors. ROS was produced by TP and 2-deoxy-D-ribose, and the ROS activated NFκB. The activated NFκB enhanced the expression of IL-8 and MMPs that are involved in angiogenesis.

胸苷磷酸化酶是一种具有血管生成活性的酶。 2-脱氧-D-核糖是TP产生的胸苷降解产物之一，也具有血管生成活性。除了 TP 抑制剂之外，2-脱氧-L-核糖（2-脱氧-D-核糖的立体异构体）也能抑制表达 TP 的肿瘤的生长、侵袭和转移。 TP和2-脱氧-D-核糖产生ROS，ROS激活NFκB。激活的 NFκB 增强了参与血管生成的 IL-8 和 MMP 的表达。

项目成果

腫瘍微小血管に対する5-FUとその活性化酵素の作用

5-FU及其激活酶对肿瘤微血管的影响

• 发表时间: 2008
• 作者: Iwata;T.;Sumimoto;H.;Mizuguchi;H.;Kawakami;Y.;秋山伸一
• 通讯作者: 秋山伸一

Anti-angiogeneic effect of 5-fluorouracil-based drugs against human colon cancer xenoerafts

5-氟尿嘧啶类药物对人结肠癌异种移植物的抗血管生成作用

• 期刊: Cancer Letters (In press)
• 作者: 阿部英輔;溝脇尚志;則久佳毅;成田雄一郎;松尾幸憲;楢林正流;永田 靖;平岡眞寛;Ooyama A
• 通讯作者: Ooyama A

Thymidine phosphorylase inhibits the expression of proapoptotic protein BNIP3

• DOI: 10.1016/j.bbrc.2008.03.067
• 发表时间: 2008-05-30
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Ikeda, Ryuji;Tajitsu, Yusuke;Yamadaa, Katsushi
• 通讯作者: Yamadaa, Katsushi

Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in KM12C cells

KM12C 细胞中 5-FU 下调 c-Myc 并诱导血管生成抑制剂血小板反应蛋白-1

• 发表时间: 2008
• 期刊: Cancer Lett. 270
• 作者: He;L.;Kim;et al.;Hong-Ye Zhao
• 通讯作者: Hong-Ye Zhao

ヒト大腸癌における5-FUによる血管新生阻害因子TSP-1の誘導

5-FU 在人结直肠癌中诱导血管生成抑制剂 TSP-1

• 发表时间: 2008
• 作者: Sasada T;Komatsu N;Suekane S;Yamada A.;Masanori N;Itoh K.;趙紅業
• 通讯作者: 趙紅業