p16 Expression Adenovirus Vector for Esophageal and Pancreas Cancer Therapy.

用于食管癌和胰腺癌治疗的 p16 表达腺病毒载体。

• 批准号: 09671280
• 负责人: KOBAYASHI Susumu
• 金额: $ 2.24万
• 依托单位: Chiba University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671280/
• 关键词: P16; Sdenovirus Vector; Pancreas Cancer; Gene Transfer; Esophageal Cancer; アデノシルスベクター

The prognoses of pancreas cancer patients have been miserable even after radical surgery, and the adjuvant therapy is necessary to improve the surgical results. P16ィイD1INK4aィエD1 (p16) is tight-binding and inhibitory protein for CDK4 to induce G1 arrest of cell cycle. P16 gene deletion is frequently identified in human pancreas cancer. The impaired gene function of p16 might be a major factor of the uncontrolled proliferation and malignancy of pancreas cancer cells. In this study, we investigated the effect of adenovirus p16 expression vector for pancreas cancer cell proliferation to clarify whether or not the vector might be a promising mode to assist the surgical therapy for pancreas cancer.First, we constructed the adenovirus p16 expression vector (AdexCACSp16) by inserting p16 cDNA to a cassette cosmid containing a nearly full-length adenovirus type 5 genome with E1 and E3 deletions. Thereafter, we assessed the activity of AdexCACSp16 to induce p16 gene mRNA expression in pancreas cancer cell line, MIAPaCa-2 and to control the cell proliferation.AdexCACSp16 induced the high level of p16 gene mRNA expression in MIAPaCa-2 cells with 1 hour contact to the cells. The cells proliferation was significantly suppressed by AdexCACSp16 compared with the control adenovirus group.These data indicated that AdexCACSp16 has the potential to induce p16 gene expression and control pancreas cancer cell proliferation and that the adenovirus p16 expression vector AdexCACSp16 might be a possible method of gene therapy to improve the surgical therapeutic results for pancreas cancer.

胰腺癌患者根治性手术后预后较差，辅助治疗是提高手术效果的必要手段。P16是CDK4诱导细胞周期G1阻滞的紧密结合抑制蛋白。P16基因缺失在人类胰腺癌中经常被发现。p16基因功能受损可能是导致胰腺癌细胞增殖失控和恶性化的重要因素。在本研究中，我们研究了腺病毒p16表达载体对胰腺癌细胞增殖的影响，以阐明该载体是否可能成为辅助胰腺癌手术治疗的一种有前景的模式。首先，我们将p16 cDNA插入到含有E1和E3缺失的几乎全长的腺病毒5型基因组的卡带中，构建了腺病毒p16表达载体（AdexCACSp16）。随后，我们评估了AdexCACSp16在胰腺癌细胞系MIAPaCa-2中诱导p16基因mRNA表达和控制细胞增殖的活性。AdexCACSp16在与MIAPaCa-2细胞接触1小时后诱导p16基因mRNA高水平表达。与腺病毒对照组相比，AdexCACSp16显著抑制了细胞的增殖。这些数据表明，AdexCACSp16具有诱导p16基因表达和控制胰腺癌细胞增殖的潜力，p16腺病毒表达载体AdexCACSp16可能是一种改善胰腺癌手术治疗效果的基因治疗方法。

项目成果

小林 進 他: "大腸癌におけるp21^<WAF1/CIP1>遺伝子のmRNA発現" 日本外科学会雑誌. 99・7. 457-462 (1998)

Susumu Kobayashi等：“结直肠癌中p21^<WAF1/CIP1>基因的mRNA表达”日本外科学会杂志99·7（1998）。

Susumu Kobayashi et al.: "p16^<INK4a> Expression Adenovirus Vector to Supress Pancreas Cancer Cell Proliferation"Clinical Cancer Research. 5. 4182-4185 (1999)

Susumu Kobayashi 等人：“p16^<INK4a>表达腺病毒载体抑制胰腺癌细胞增殖”临床癌症研究。

Susumu Kobayashi, Hiroshi Shirasawa, Hiroshi Sashiyama, Hiroshi Kawahira, Kentaro Kaneko, Takehide Asano, and Takenori Ochiai.: "p16 (INK4a) expression adenovirus vector to suppress pancreas cancer cell proliferation"Clln. Cancer Res.. 5(12). 4182-5 (1999

Susumu Kobayashi、Hiroshi Shirasawa、Hiroshi Sashiyama、Hiroshi Kawahira、Kentaro Kaneko、Takehide Asano 和 Takenori Ochiai.：“p16 (INK4a) 表达腺病毒载体抑制胰腺癌细胞增殖”Clln。