Chrono-biological genetherapy for bile duct cancer

胆管癌的时间生物学基因治疗

• 批准号: 14571172
• 负责人: KATAYOSE Yu
• 金额: $ 2.5万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571172/
• 关键词: per2; adenovirus; cholangiocarcinoma; p27; 時計遺伝子; 細胞周期; 生体リズム

The susceptibility of the cancer cell to anti-neoplasm medicine is prescribed by the multiplication state of a cancer cell, and the cell cycle, it is uniting the cell cycle of a cancer cell, and the timing of medicine medication, and cancer medical treatment with few side effects is expected. Research of a clock gene is progressing recently, molecular biology-examination of each clock gene is progressing, per1, per2, cry1 and cry2, BMAL-1, etc. attract attention as main clock genes, and it is said that per2 is closely related with carcinogenesis.Existence of the clock gene in various cancer cells was checked centering on the PAS domain and CKI domain of per2 considered to be first the most important as a result in this research period. The cell lines examined bile duct cancer cells, TFK-1, the HuCCT1, liver cancer cell, HepG2, Hep3B, HT-17,Li-7,HuH-7,PLC/PR/5, breast cancer cells, MCF-7, and MDA-MB-231, and checked existence of per2 by RT-PCR and the sequence.On the other hand, preparing the adenoviral vector for genetherapy, Adenovirus expressing CDK inhibitor p27 was used for check efficiency of transduction for cholangiocarcinoma. CDK inhibitor p27 is closely related with clock gene as a control of cell cycle. The cell cycle stopped and induced apotosis to cholangiocarcinoma,TFK-1, using. Adp27. This result can expect the effect of the gene therapy by the clock gene.

癌细胞对抗肿瘤药物的敏感性由癌细胞的增殖状态和细胞周期决定，通过将癌细胞的细胞周期与药物治疗的时机结合起来，期待副作用少的癌症治疗。最近对时钟基因的研究正在取得进展，对各时钟基因的分子生物学研究正在取得进展，per1、per2、cry1和cry2、BMAL-1等作为主要时钟基因而受到关注，据说per2与癌发生密切相关。以本研究结果认为最重要的per2的PAS结构域和CKI结构域为中心检查了各种癌细胞中时钟基因的存在。 时期。细胞系检测胆管癌细胞TFK-1、HuCCT1、肝癌细胞HepG2、Hep3B、HT-17、Li-7、HuH-7、PLC/PR/5、乳腺癌细胞MCF-7和MDA-MB-231，并通过RT-PCR和序列检查per2的存在。 另一方面，制备用于基因治疗的腺病毒载体， 表达CDK抑制剂p27的腺病毒用于检查胆管癌的转导效率。 CDK抑制剂p27与控制细胞周期的时钟基因密切相关。使用胆管癌TFK-1，细胞周期停止并诱导细胞凋亡。 Adp27。这一结果可以预期时钟基因的基因治疗效果。

项目成果

Sasaki T, Katayose Y, et al.: "Adenovirus Expressing Mutant p27^<kip1> Enhanced Apoptosis Against Cholangiocarcinoma than Adenivirus-p27^<kip1> wild type."Hepatogastroenterology. 51. 68-75 (2004)

Sasaki T、Katayose Y 等人：“表达突变体 p27^<kip1> 的腺病毒比腺病毒-p27^<kip1> 野生型增强了针对胆管癌的细胞凋亡。”肝胃肠病学。

Yoshida H, Katayose Y, et al.: "A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity"Cancer Immunol Immunother. 52. 97-105 (2003)

Yoshida H、Katayose Y 等人：“表达人 4-1BB 配体的新型腺病毒可增强抗肿瘤免疫力”Cancer Immunol Nutritionother。

Yamamoto K, Katayose Y, et al.: "Adenovirus expressing p27KIP1 induces apoptosis against cholangiocarcinoma cells by triggering Fas ligand on the cell surface."Hepatogastroenterology. 50. 1847-1853 (2003)

Yamamoto K、Katayose Y 等人：“表达 p27KIP1 的腺病毒通过触发细胞表面的 Fas 配体诱导胆管癌细胞凋亡。”肝胃肠病学。

Sasaki T, Katayose Y, et al.: "Adenovirus Expressing Mutant p27^<kip1> Enhanced Apoptosis Against Cholangiocarcinoma than Adenivirus-p27^<kip1> wild type Heoatogastroenterology"Hepatogastroenterology. 55. 68-75 (2004)

Sasaki T、Katayose Y 等人：“表达突变体 p27^<kip1> 的腺病毒比腺病毒-p27^<kip1> 野生型肝脏胃肠病学增强了针对胆管癌的细胞凋亡”肝胃肠病学。

Yamamoto K, Katayose Y, Suzuki M, Unno M, Sasaki T, Mizuma M, Shiraso S, Ohtuka H, Cowan KH, Seth P, Matsuno S.: "Adenovirus expressing p27KIP1 induces apoptosis against cholangiocarcinoma cells by triggering Fas ligand on the cell surface"Hepatogastroent

Yamamoto K、Katayose Y、Suzuki M、Unno M、Sasaki T、Mizuma M、Shiraso S、Ohtuka H、Cowan KH、Seth P、Matsuno S.：“表达 p27KIP1 的腺病毒通过触发细胞上的 Fas 配体诱导胆管癌细胞凋亡