Molecular mechanisms of epigenetic alterations in gastrointestinal cancer and application to diagnosis and therapy

胃肠癌表观遗传改变的分子机制及其在诊断和治疗中的应用

• 批准号: 17109008
• 负责人: IMAI Kohzoh
• 金额: $ 70.89万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 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/grant/KAKENHI-PROJECT-17109008/
• 关键词: DNAメチル化; エピジェネティクス; ヒストン修飾; 個別化医療; 遺伝子診断; 分子標的治療; メチル化; 消化器癌; 遺伝子発現; 腫瘍マーカー; 分子標的

Molecular mechanisms how this epigenetic alterations contribute to development of tumors remains to be determined. DNA methylation also leads to silencing of genes involved in cell signaling, which in turn leads to dysregulation of the oncogenic signaling such as Ras, WNT, and microRNA. We found that epigenetic inactivation of IGFBP7 plays a critical role in escaping senescence in CIMP positive colorectal cancers. We also found that epigenetic information can be used to detect cancer cells from colorectal mucosal solution.

这种表观遗传改变如何促进肿瘤发展的分子机制仍有待确定。 DNA 甲基化还会导致参与细胞信号传导的基因沉默，进而导致 Ras、WNT 和 microRNA 等致癌信号传导失调。我们发现 IGFBP7 的表观遗传失活在 CIMP 阳性结直肠癌逃避衰老中发挥着关键作用。我们还发现表观遗传信息可用于检测结直肠粘膜溶液中的癌细胞。

项目成果

High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability

胃肿瘤中 EPHB2 突变率较高，但微卫星不稳定性子宫内膜肿瘤中则不然

• DOI: 10.1038/sj.onc.1209780
• 发表时间: 2007-01-11
• 期刊: Oncogene
• 影响因子: 8
• 作者: V. Davalos;Higinio Dopeso;S. Velho;Ana M. Ferreira;L. Cirnes;Nicolás Díaz;C. Bilbao;C. Bilbao;Raquel Ramírez;G. Rodríguez;O. Falcón;L. Leon;R. Niessen;G. Keller;G. Dallenbach‐Hellweg;E. Espı́n;M. Armengol;A. Plaja;M. Perucho;K. Imai;Hiroyuki Yamamoto;J. Gebert;J. Díaz;R. Hofstra;S. Woerner;R. Seruca;S. Schwartz;D. Arango
• 通讯作者: D. Arango

Homocysteine, Cysteine, and Glutathione in Human Colonic Mucosa: Elevated Levels of Homocysteine in Patients with Inflammatory Bowel Disease

人类结肠粘膜中的同型半胱氨酸、半胱氨酸和谷胱甘肽：炎症性肠病患者同型半胱氨酸水平升高

• DOI: 10.1023/a:1026338812708
• 发表时间: 2003-10-01
• 期刊: Digestive Diseases and Sciences
• 影响因子: 3.1
• 作者: I. Morgenstern;M. Raijmakers;W. Peters;H. Hoensch;Wilhelm Kirch
• 通讯作者: Wilhelm Kirch

Insulin-like growth factor-I receptor blockade reduces the invasiveness of gastrointestinal cancers via blocking production of matrilysin.

胰岛素样生长因子-I 受体阻断剂通过阻断基质溶解素的产生来减少胃肠道癌症的侵袭性。

• DOI: 10.1093/carcin/bgp134
• 发表时间: 2009-08-01
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: Y. Adachi;Rong;Hiroyuki Yamamoto;Yongfen Min;Wenhua Piao;Yu Wang;A. Imsumran;Hua Li;Y. Arimura;Choon‐Taek Lee;K. Imai;D. Carbone;Y. Shinomura
• 通讯作者: Y. Shinomura

Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics.

致癌作用和微卫星不稳定性：遗传学和表观遗传学之间的相互关系。

• DOI: 10.1093/carcin/bgm228
• 发表时间: 2008-04-01
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: K. Imai;Hiroyuki Yamamoto
• 通讯作者: Hiroyuki Yamamoto

Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells.

与抗 EGFR 单克隆抗体 ICR62 和 IGF-IR 酪氨酸激酶抑制剂 NVP-AEW541 共同靶向结直肠癌细胞中的 EGFR 和 IGF-IR。

• DOI: 10.3892/ijo_00000100
• 发表时间: 2024-09-13
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: M. P. Cunningham;H. Thomas;Christopher Marks;Margaret Green;Z. Fan;H. Modjtahedi
• 通讯作者: H. Modjtahedi