Development of molecular target therapy using new angiogenin inhibitor against cancer induced bone diseases

使用新型血管生成素抑制剂针对癌症引起的骨疾病开发分子靶向疗法

• 批准号: 23390463
• 负责人: SASAKI AKIRA
• 金额: $ 8.24万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390463/
• 关键词: angiogenin; neomycine; 口腔扁平上皮癌; 骨浸潤; 癌誘発骨破壊; 血管新生因子; 破骨細胞; 血管新生阻害薬; angionenin; 骨破壊モデル; ノックアウトマウス; 骨破壊; 癌; 骨吸収

Osteoclast-mediated bone resorption plays an important role in bone invasion or bone destruction of the cancer. We have been establishing the treatment of the cancer induced-bone diseases which assumed angiogenesis factor, angiogenin (ANG) as a molecular target.In the present study, we examined a therapeutic utility of ANG inhibitor and investigated the role of ANG using ANG-1 knockout mouse (ANG-KO). Trabecular bone formation of the early period of growth was suppressed in ANG-KO compare to the wild type mice (WT), and the in vitro osteoclasts formation using cells of ANG-KO was inhibited, but there were few differences in vivo model. The ANG inhibitor was able to confirm a utility for a mouse cancer bone destruction model. Newly developed medicine, Terrein, which inhibit the production of ANG, had not only the inhibition of angiogenesis, but also the antitumor activity. Therefore, a utility of ANG inhibitors against the cancer induced bone diseases was suggested.

破骨细胞介导的骨吸收在肿瘤的骨侵袭或骨破坏中起重要作用。我们已经建立了以血管生成因子血管生成素（angiogenin， ANG）为分子靶点的癌症性骨病的治疗方法。在本研究中，我们检测了ANG抑制剂的治疗效用，并使用ANG-1敲除小鼠（ANG- ko）研究了ANG的作用。与野生型小鼠（WT）相比，ANG-KO能抑制生长早期骨小梁的形成，并能抑制ANG-KO细胞体外破骨细胞的形成，但在体内模型中差异不大。ANG抑制剂能够证实对小鼠癌症骨破坏模型的效用。新开发的药物Terrein抑制ANG的产生，不仅具有抑制血管生成的作用，而且具有抗肿瘤活性。因此，ANG抑制剂对癌症引起的骨病有一定的应用价值。

项目成果

Neamineの口腔癌に対する抗腫瘍効果の検討

Neamine 对口腔癌的抗肿瘤作用研究

• 发表时间: 2013
• 作者: Uchida D;Kuribayashi N;Kinouchi M;Ohe G;Tamatani T;Nagai H;Miyamoto Y;岸本晃治6名
• 通讯作者: 岸本晃治6名

Neamine inhibits oral cancer progression by suppressing angiogenin-mediated angiogenesis and cancer cell proliferation.

• 发表时间: 2014-05
• 期刊: Anticancer research
• 影响因子: 2
• 作者: K. Kishimoto;S. Yoshida;S. Ibaragi;Norie Yoshioka;G. Hu;A. Sasaki

Angiogeninの発現亢進は口腔癌の増殖と進展に関与する

血管生成素表达增加参与口腔癌的生长和进展

• 发表时间: 2011
• 作者: Hayashido Y;Hamana T;Ishida Y;Shintani T;Koizumi K;Okamoto T.;岸本晃治
• 通讯作者: 岸本晃治

Neamine inhibits progression of oral cancer by suppressing angiogenin-stimulated angiogenesis and cancer cell proliferation

Neamine 通过抑制血管生成素刺激的血管生成和癌细胞增殖来抑制口腔癌的进展

• 发表时间: 2012
• 作者: Murase R;Sumida T;Ishikawa A;Murase R;McAllister SD;Hamakawa H;Desprez PY.;岸本晃治6名
• 通讯作者: 岸本晃治6名

血管新生因子angiogeninを標的とした口腔扁平上皮癌の癌骨破壊制御に関する研究

靶向血管生成因子血管生成素控制口腔鳞癌癌骨破坏的研究

• 发表时间: 2012
• 期刊: 岡山歯学会雑誌
• 作者: 山田瑛子;木内 英;吉本順子;高木律男;加藤真吾;青木香澄
• 通讯作者: 青木香澄