Developing of polymeric micelle for molecular targeting to cancer stem cells in ovarian cancer patients.

开发用于分子靶向卵巢癌患者癌症干细胞的聚合物胶束。

• 批准号: 22659303
• 负责人: OHMICHI Masahide
• 金额: $ 2.11万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659303/
• 关键词: CD24, 婦人科悪性腫瘍; 上皮間葉形質転換; EMT, 高分子ミセル; 抗癌剤耐性; CD24; 婦人科悪性腫瘍; EMT; 高分子ミセル; 癌幹細胞; 卵巣癌; GPR30; ミセル; 白金製剤耐性卵巣癌; EGFR

The epithelial-mesenchymal-transition (EMT) is an important step in the invasion and metastasis of cancer cells. EMT is an important step in the invasion and metastasis of cancer. G protein-coupled receptor 30 (GPR30) is a 7-transmembrane estrogen receptor that functions alongside traditional estrogen receptors to regulate the cellular responses to estrogen. Current study suggested that the expression of both GPR30 and EGFR is associated with a poor outcome in ovarian cancer, and GPR30 increases the phosphorylation of Akt via the EGFR in ovarian cancer cells. The regulation of GPR30 might be a potentially useful new therapeutic target in ovarian cancer. Furthermore, Recently CD24 has been considered as a prognostic maker in various cancers. So we analyzed the prognostic impact of the CD24 expression in ovarian cancer by immunostaining. The CD24 expression was significantly associated with FIGO stage, lymph node metastasis and peritoneal metastasis. The in vitro examination showedthat high expression level of CD24 is significantly associated with EMT positivity. In addition, the CD24 overexpression increased invasiveness, and knockdown of CD24 suppressed cell invasion. In conclusion CD24 expression in ovarian cancer may be related to tumor invasion and migration. Based on the results, the anti-cancer agent incorporated polymeric micelles, which have anti-GPR30 or anti-CD24 antibodies in their outer layer, are in development

上皮-间充质-转化(EMT)是癌细胞侵袭转移的重要环节。EMT是肿瘤侵袭转移的重要环节。G蛋白偶联受体30(GPR30)是一种7-跨膜的雌激素受体，与传统的雌激素受体一起调节细胞对雌激素的反应。目前的研究表明，GPR30和EGFR的表达与卵巢癌的不良预后有关，GPR30通过EGFR促进Akt的磷酸化。GPR30的调控可能成为卵巢癌治疗的新靶点。此外，最近CD24被认为是多种癌症的预后标志物。因此，我们通过免疫组织化学方法分析CD24在卵巢癌中的表达对预后的影响。CD24的表达与FIGO分期、淋巴结转移、腹膜转移密切相关。体外检测显示CD24高表达与EMT阳性显著相关。此外，CD24的过表达增加了细胞的侵袭力，而CD24的敲除则抑制了细胞的侵袭。结论：CD24在卵巢癌中的表达可能与肿瘤的侵袭和转移有关。根据研究结果，含有聚合物胶束的抗癌剂正在开发中，这种胶束的外层含有抗GPR30或抗CD24抗体。

项目成果

白金製剤耐性卵巣癌におけるAktをターゲットとした分子標的薬としてのGemcitabineの機能解析

吉西他滨作为 Akt 分子靶向药物在铂耐药卵巢癌中的功能分析

• 发表时间: 2012
• 作者: Nakashima A;Shima T;Inada K;Ito M;Saito S;川口浩史
• 通讯作者: 川口浩史

卵巣癌の播種転移はEMT現象を反映する

卵巢癌播散转移反映EMT现象

• 发表时间: 2012
• 作者: Osawa Y;Suzuki D;et al.;Kiyoko Kato;高井雅聡
• 通讯作者: 高井雅聡

Prognostic impact of EMT (epithelial-mesenchymal-transition)-related protein expression in endometrial cancer.

• DOI: 10.4161/cbt.22625
• 发表时间: 2013-01
• 期刊: Cancer biology & therapy
• 影响因子: 3.6
• 作者: Tanaka Y;Terai Y;Kawaguchi H;Fujiwara S;Yoo S;Tsunetoh S;Takai M;Kanemura M;Tanabe A;Ohmichi M
• 通讯作者: Ohmichi M

卵巣癌治療の新たな展開

卵巢癌治疗新进展

• 发表时间: 2011
• 作者: Hasegawa T.;Yonezawa R.;Shima T.;Tatematsu M.;Nakashima A.;Hidaka T.;Saito S.;大道正英
• 通讯作者: 大道正英

ランチョンセミナー「難治性卵巣癌の新たな治療戦略～分子生物学的アプローチ～」

午餐研讨会“难治性卵巢癌的新治疗策略~分子生物学方法~”

• 发表时间: 2011
• 作者: Yamamoto H;Yamada T;et al.;大道正英
• 通讯作者: 大道正英