Oncolytic virus therapy for biliary and pancreas cancer using a replication-competent herpes simplex virus mutant and proapoptotic reagent
使用具有复制能力的单纯疱疹病毒突变体和促凋亡试剂进行胆管癌和胰腺癌的溶瘤病毒治疗
基本信息
- 批准号:13671310
- 负责人:
- 金额:$ 2.24万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 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:
- 关键词:
项目摘要
1) Antitumor efficacy of oncolytic virus therapy for gallbladder cancerGallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbaladder carcinoma cell lines (4 human and 1 hamster) showed nearly total cell killing within 72 hours of G207 infection at a MOI of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 x 107 pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (3 times with 4-day intervals) were significantly more effications than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one … More tumor alone with G207 caused regression or growth reduction of noninoculated tumors as well as inoculated tumors. In athymic mice, however, the antitumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T cell-mediated immune responses to both local and systemic antitumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.2) Combination effect of oncolytic virus and proapoptotic factor for pancreas cancerA proapoptotic reagent, Tetrocarcin A, did not enhance the oncolytic effect of G207 for pancreas cancer cells in vitro. Combination of irradiation and chemotherapeutic reagents did not increase the oncolytic viral activity. These results suggest that pancreas cancer has a resistance to the proapoptotic reagent or the cytopathic effect of oncolytic virus does not depend on the apoptosis.3) Therapeutic efficacy of oncolytic virus for peritoneal disseminationWe also elucidated the therapeutic efficacy of oncolytic virus on peritoneal dissemination of gallbladder, colonic and gastric cancer, G207 prolonged the survival of animals bearing a microscopic peritoneal dissemination as compared with the controls, and some of the animals were cured. On the other hand, the animals harboring macroscopic dissemination were not cured although their survivals were also elongated than the control group.These data above have been summarized and published in Molechular Therapy 3(4), 2001 and Surgical Therapy 87 (3), 2002. Less
1)溶瘤病毒治疗胆囊癌的抗肿瘤疗效胆囊癌是一种一旦发生转移就很难治愈的疾病。在这篇文章中,我们探索了G207,一个溶瘤的,复制能力强的1型单纯疱疹病毒突变体,作为一种新的胆囊癌治疗手段的潜力。人胆囊癌细胞株(4只人和1只仓鼠)在MOI为0.25~2.5的条件下,感染G207后72小时内几乎全部被杀伤。对G207细胞病变活性的敏感性与LacZ表达显示的感染效率相关。免疫活性仓鼠皮下接种G207(1×107pfu)可明显抑制肿瘤生长,延长生存期。重复接种(每隔4天接种3次)的效果明显高于单次接种。金黄地鼠双侧KIGB-5皮下接种一种…单独使用G207的肿瘤数量较多,导致未接种肿瘤和接种肿瘤的消退或生长减少。然而,在裸鼠中,G207的抗肿瘤作用在接种的肿瘤中大大降低,在远处的肿瘤中完全消失,这表明T细胞介导的免疫反应对G207的局部和全身抗肿瘤作用都有很大贡献。上述结果表明,G207可能成为治疗胆囊癌的一种新策略。2)溶瘤病毒和促凋亡因子对胰腺癌促凋亡试剂Tetrocarcin A的联合作用不能增强G207对胰腺癌细胞的体外溶瘤作用。联合应用放化疗药物不能提高溶瘤病毒的活性。3)溶瘤病毒对腹膜播散的治疗效果我们还阐明了溶瘤病毒对胆囊癌、结肠癌和胃癌腹膜播散的治疗效果,与对照组相比,G207延长了腹膜播散的动物的存活时间,部分动物被治愈。另一方面,尽管存活时间也比对照组延长,但肉眼可见播散的动物并未治愈。上述数据已被总结并发表在2001年《分子治疗》第3期和2002年《外科治疗》第87期(3)上。较少
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nakano K, Todo T, Chijiiwa K, Tanaka M: "Therapeutic efficacy of G207, a conditionally-replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters"Molecular Therapy. 3(4). 431-437 (2001)
Nakano K、Todo T、Chijiiwa K、Tanaka M:“G207(一种条件复制型单纯疱疹病毒 1 型突变体)对免疫活性仓鼠胆囊癌的治疗效果”分子疗法。
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NAKANO Kenji其他文献
NAKANO Kenji的其他文献
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{{ truncateString('NAKANO Kenji', 18)}}的其他基金
Detection of cancer stem cells and minimal invasion by DNP-MRI and hyperspectral enodoscopy redox imaging
DNP-MRI 和高光谱内窥镜氧化还原成像检测癌症干细胞和微侵袭
- 批准号:
26670016 - 财政年份:2014
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Development of YB-1-silencing miRNA/ decoy gene therapy against intractable solid tumor to regulate malignant microcircumstances
开发针对难治性实体瘤的 YB-1 沉默 miRNA/诱饵基因疗法以调节恶性微环境
- 批准号:
24390322 - 财政年份:2012
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Non-invasive assessment for therapeutic response to gene therapy using redox imaging and MALDI-TOF mass-spectrometry
使用氧化还原成像和 MALDI-TOF 质谱法对基因治疗的治疗反应进行非侵入性评估
- 批准号:
22659111 - 财政年份:2010
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Regulation for multidrug resistant cancer and cancer stem cells by ABC transporter-targeted virus
ABC转运蛋白靶向病毒对多重耐药癌症和癌症干细胞的调节
- 批准号:
18590315 - 财政年份:2006
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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