Development of cancer specific viral vector for carcinoma by inducing the plural genes

通过诱导复数基因开发癌症特异性病毒载体

• 批准号: 13470230
• 负责人: KONDO Satoshi
• 金额: $ 8.96万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470230/
• 关键词: cancer gene therapy; specific promotor; adenoviralvector; RCAS1; Caveolin-1; SCCA; IRRES; 癌; SCCA2; hTERT; 遺伝子治療

We studied the cancer specific antigens expressed in the several organ tumors. In pancreatic cancer, 90% were positive for RCAS1 gene. Moreover, overexpression of RCAS1 gene was correlated with the prognosis of patients with pancreatic cancer, extrahepatic bile duct carcinoma and esophageal cancer. Caveolin-1 expression was also correlated with with the prognosis of patients with pancreatic cancer.We made a replication-deficient recombinant KLAKLAK2 or Bax adenovirus driven by the RCAS1promoter (Ad RCAS1-KLAKLAK2, Ad RCAS1-Bax) or the SCCA promoter (Ad SCCA-KLAKLAK2). We demonstrated that the expression of KLAKLAK2 and growth inhibition were all specific to the cancer cell lines that were SCCA positive, whereas no growth retardation was observed in human normal cell lines after Ad SCCA-KLAKLAK2 infection.

我们研究了几种器官肿瘤中表达的癌症特异性抗原。在胰腺癌中，RCAS1基因阳性90％。此外，RCAS1基因的过表达与胰腺癌，肝外胆管癌和食管癌的预后相关。小窝蛋白-1的表达也与胰腺癌患者的预后相关。我们制造了由RCAS1-promoter驱动的（AD RCAS1-KLAKLAK2，AD RCAS1-BAX），AD RCAS1-BAX）或SCCA促销促进剂（AD RCAS1-KLAKLAK2）或BAX腺病毒（AD RCAS1-KLAKLAK2）或BAX腺病毒。我们证明了Klaklak2和生长抑制作用的表达都是SCCA阳性的癌细胞系的特异性，而在AD SCCA-Klaklak2感染后，在人正常细胞系中未观察到生长迟缓。

项目成果

Hiraoka K: "High expression of tumor-associated antigen RCAS1 in pancreatic ductal adenocarcinoma is an unfavorable prognostic marker"Int J Cancer. 99. 418-423 (2002)

Hiraoka K：“胰腺导管腺癌中肿瘤相关抗原 RCAS1 的高表达是一个不利的预后标志物”Int J Cancer。

Tetsuro Takebayashi: "NF-kB-dependent induction of cyclinD1 by retinoblastoma protein (pRB) family proteins and tumor-derived pRB mutants"The Journal of Biological Chemistry. 278・17. 14897-14905 (2003)

Tetsuro Takebayashi：“视网膜母细胞瘤蛋白 (pRB) 家族蛋白和肿瘤衍生的 pRB 突变体对细胞周期蛋白 D1 的 NF-kB 依赖性诱导”《生物化学杂志》278・17 (2003)。

Masato Suzuoki: "RCAS1 expression as a prognositc factor after curative surgery for extrahepatic bile duct carcinoma"Annals of Surgical Oncology. 9. 388-392 (2002)

Masato Suzuoki：“RCAS1 表达作为肝外胆管癌根治性手术后的预后因素”《肿瘤外科年鉴》。

Nakakubo Y.: "The prognostic significance of RCAS1 expression in squamous cell carcinoma of the oesophagus"Cancer Lett. 177(1). 101-105 (2002)

Nakakubo Y.：“食管鳞状细胞癌中 RCAS1 表达的预后意义”Cancer Lett。

Masato Suzuoki: "Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma"British Journal of Cancer. 87. 1140-1144 (2002)

Masato Suzuoki：“caveolin-1 表达对胰腺导管腺癌预后的影响”英国癌症杂志。