Oncolytic vaccinia virus as an adjuvant treatment to enhancement of chemosensitivity in human pancreatic cancer cells through overexpression of Gemcitabine transporter proteins

溶瘤牛痘病毒作为辅助治疗通过吉西他滨转运蛋白的过度表达增强人胰腺癌细胞的化疗敏感性

• 批准号: 24790315
• 负责人: HASHIMOTO Yasushi
• 金额: $ 2.83万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790315/
• 关键词: 膵癌; 抗癌剤耐性; ワクシニアウイルス; ｈENT; ワクチン; 化学療法; 腫瘍溶解性組換えワクシニアウイルス; Gemcitabine

This experimental study aimed to examine the potential of modified vaccinia virus in enhancement of chemosensitivity in human pancreatic cancer cells through overexpression of Gemcitabine transporter proteins to investigate the relevant underlying mechanisms. hENT expression affected tumor cell chemosensitivity to gemcitabine and tumor cell invasive capacity in different pancreatic cancer cell lines. The cytotoxic effects was significantly increased compared with the control non-cancer cell line. In mouse models, virus vaccine induced tumor regression, prolonging median and long-term survival. Higher efficacy of the virus vaccine in the pancreatic cancer suggests the use of the virus as an adjuvant treatment to complete surgical resection. These promising results justify further studies of vaccinia virus in humans as a novel treatment for pancreatic cancer.

本实验旨在研究修饰的牛痘病毒通过过表达吉西他滨转运蛋白增强人胰腺癌细胞化疗敏感性的潜力，并探讨相关的潜在机制。hENT表达影响不同胰腺癌细胞系中肿瘤细胞对吉西他滨的化疗敏感性和肿瘤细胞侵袭能力。与对照非癌细胞系相比，细胞毒性效应显著增加。在小鼠模型中，病毒疫苗诱导肿瘤消退，延长中位和长期生存期。病毒疫苗在胰腺癌中的更高功效表明使用病毒作为辅助治疗以完成手术切除。这些有希望的结果证明了进一步研究牛痘病毒在人类作为一种新的治疗胰腺癌。

项目成果

Impact of margin clearance on survival after pancreaticoduodenectomy for pancreatico ductal adenocarcinoma; What is a "true" negative margin?

切缘清除对胰十二指肠腺癌胰十二指肠切除术后生存的影响；

• 发表时间: 2013
• 作者: 1. Hashimoto Y;Murakami Y;Uemura K;Sudo T;Kondo N;Sueda T
• 通讯作者: Sueda T

Pancreaticogastrostomy after distal pancreatectomy: a clue to preventing postoperative pancreatic fistula

远端胰腺切除术后胰胃造口术：预防术后胰瘘的线索

• 发表时间: 2014
• 作者: Hashimoto Y;Murakami Y;Uemura K;Sudo T;Kondo N;Sueda T
• 通讯作者: Sueda T

Pancreaticogastrostomy after distal pancreatectomy: a clue to preventing postoperative pancreatic fistula.

远端胰腺切除术后胰胃造口术：预防术后胰瘘的线索。

• 发表时间: 2014
• 作者: Yasushi Hashimoto;Yoshiaki Murakami;Kenichiro Uemura;Takeshi Sudo;Naru Kondo;Taijiro Sueda
• 通讯作者: Taijiro Sueda

Impact of margin clearance on survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: What is a “true” negative margin?

切缘清除对胰腺导管腺癌胰十二指肠切除术后生存的影响：什么是“真正的”阴性切缘？

• 发表时间: 2013
• 作者: Yasushi Hashimoto;Yoshiaki Murakami;Kenichiro Uemura;Takeshi Sudo;Naru Kondo;Taijiro Sueda
• 通讯作者: Taijiro Sueda

Combined analysis of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression is a powerful predictor of survival in patients with pancreatic carcinoma treated with adjuvant gem

肿瘤内人平衡核苷转运蛋白 1 (hENT1) 和核糖核苷酸还原酶调节亚基 M1 (RRM1) 表达的联合分析是接受 gem 辅助治疗的胰腺癌患者生存的有力预测因子

• 发表时间: 2013
• 期刊: Surgery
• 影响因子: 3.8
• 作者: Nakagawa N;Murakami Y;Uemura K;Sudo T;Hashimoto Y;Kondo N;Sueda T.
• 通讯作者: Sueda T.