Evolution of ovarian carcinoma cells through peritoneal dissemination ; genome-wide analysis and clinical application.

卵巢癌细胞通过腹膜播散的进化；

• 批准号: 21390452
• 负责人: KONISHI Ikuo
• 金额: $ 11.32万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390452/
• 关键词: 婦人科腫瘍学; 卵巣癌; 播種性転移; 腫瘍免疫; TGF-beta経路; エピジェネティクス; TGFβ; マイクロアレイ; メチル化; 低分子化合物

1) Treatment of 39 ovarian cancer cell lines and 17 primary culture samples with the inhibitor of DNA methylation, followed by expression microarray, identified genes targeted by DNA methylation in ovarian cancer. This analysis revealed TGF-beta signaling pathway is regulated by genome-wide DNA methylation. 2) We found TGF-beta pathway activity is upregulated in the omental metastases of ovarian cancer. Then we demonstrated the inhibitor of TGF-beta signaling pathway is effective against disseminated metastasis of ovarian cancer using a mouse model. 3) We found expression of PDL-1 in ovarian cancer cells suppresses activity of CD8 positive T lymphocytes, causes immune escape, and facilitates peritoneal dissemination of ovarian cancer.

1）用DNA甲基化的抑制剂对39个卵巢癌细胞系和17种原代培养样品的处理，然后是表达微阵列，在卵巢癌中鉴定出由DNA甲基化靶向的基因。该分析表明，TGF-β信号通路受基因组DNA甲基化调节。 2）我们发现TGF-β途径活性在卵巢癌的肿瘤转移中被上调。然后，我们证明了TGF-β信号传导途径的抑制剂有效地使用小鼠模型来防止卵巢癌的传播转移。 3）我们发现PDL-1在卵巢癌细胞中的表达抑制了CD8阳性T淋巴细胞的活性，导致免疫逃逸，并促进卵巢癌的腹膜传播。

项目成果

Clinical value of FDG-PET for preoperative evaluation of endometrial cancer

• DOI: 10.1007/s12149-011-0474-2
• 发表时间: 2011-05-01
• 期刊: ANNALS OF NUCLEAR MEDICINE
• 影响因子: 2.6
• 作者: Suga, Tsuyoshi;Nakamoto, Yuji;Togashi, Kaori
• 通讯作者: Togashi, Kaori

The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors

• DOI: 10.1016/j.clim.2011.08.013
• 发表时间: 2011-12-01
• 期刊: CLINICAL IMMUNOLOGY
• 影响因子: 8.6
• 作者: Hamanishi, Junzo;Mandai, Masaki;Konishi, Ikuo
• 通讯作者: Konishi, Ikuo

Suppression of Metastatic Murine Ovarian Cancer Cells by Transduced Embryonic Progenitor Cells

• DOI: 10.1007/s12672-010-0046-2
• 发表时间: 2010-11
• 期刊: Hormones and Cancer
• 影响因子: 3
• 作者: M. Mandai;J. Hamanishi;K. Abiko;N. Matsumura;T. Baba;Y. Yoshioka;I. Konishi

Minimal deviation mucinous adenocarcinoma ('adenoma malignum') of the uterine corpus

• DOI: 10.1111/j.1440-1827.2009.02473.x
• 发表时间: 2010-01-01
• 期刊: PATHOLOGY INTERNATIONAL
• 影响因子: 2.2
• 作者: Abiko, Kaoru;Baba, Tsukasa;Konishi, Ikuo
• 通讯作者: Konishi, Ikuo

Successful recovery from delayed amniotic fluid embolism with prolonged cardiac resuscitation

通过长时间的心脏复苏成功从延迟性羊水栓塞中恢复

• DOI: 10.1111/j.1447-0756.2010.01470.x
• 发表时间: 2011
• 期刊: J Obstet Gynaecol Res
• 作者: Hosono K;Matsumura N;Matsuda N;Fujiwara H;Sato Y;Konishi I.
• 通讯作者: Konishi I.