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甲基化抑制剂处理39个卵巢癌细胞系和17个原代培养样品，然后用表达微阵列鉴定卵巢癌中DNA甲基化靶向的基因。该分析揭示了TGF-β信号通路受全基因组DNA甲基化的调节。2)我们发现TGF-β通路活性在卵巢癌的网膜转移中上调。然后，我们使用小鼠模型证明了TGF-β信号通路抑制剂对卵巢癌的播散性转移有效。3)我们发现卵巢癌细胞中PDL-1的表达抑制了CD 8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转移。

项目成果

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

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

Disseminated intravascular coagulation as the presenting sign of gastric cancer during pregnancy

弥散性血管内凝血是妊娠期胃癌的表现

• DOI: 10.1111/j.1447-0756.2011.01561.x
• 发表时间: 2011
• 期刊: J Obstet Gynaecol Res
• 作者: Takai H;Kondoh E;Sato Y;Kakui K;Tatsumi K;Konishi I.
• 通讯作者: Konishi I.

Management of retained products of conception with marked vascularity

• DOI: 10.1111/j.1447-0756.2010.01363.x
• 发表时间: 2011-05-01
• 期刊: JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
• 影响因子: 1.6
• 作者: Kitahara, Tomoko;Sato, Yukiyasu;Konishi, Ikuo
• 通讯作者: Konishi, Ikuo

EphrinA1 stimulates cell attachment and inhibits cell aggregation through the EphA receptor pathway in human endometrial carcinoma-derived Ishikawa cells

• DOI: 10.1093/humrep/der034
• 发表时间: 2011-05-01
• 期刊: HUMAN REPRODUCTION
• 影响因子: 6.1
• 作者: Fujii, Haruko;Fujiwara, Hiroshi;Konishi, Ikuo
• 通讯作者: Konishi, Ikuo