DPC4/Smad4 Expression Adenovirus Vector for Pancreas Cancer Therapy

用于胰腺癌治疗的 DPC4/Smad4 表达腺病毒载体

• 批准号: 12671202
• 负责人: KOBAYASHI Susumu
• 金额: $ 1.73万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671202/
• 关键词: DPC4; Smad4; Cancer-Related Gene; Pancreas Cancer; Adenovirus Vector; Gene Therapy; Gene Expression; コスミッド

The prognoses of pancreas cancer patients have been miserable even after radical surgery, and the adjuvant therapy is necessary to improve the surgical results. DPC4/Smad4 is a major gene, which acts as a signal messenger of TGF-β. DPC4/Smad4 gene deletion is frequently identified in human pancreas cancer. The impaired gene function of DPC4/Smad4 leads to loss of TGF-β function, which controls the cancer-cell proliferation. In this study, we tried to construct adenovirus DPC4/Smad4 expression vector and investigate the effect 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 intended to construct the adenovirus DPC4/Smad4 expression vector by inserting DPC4/Smad4 cDNA to a cassette cosmid containing a nearly full-length adenovirus type 5 genome with E1 and E3 deletions. However, we could not succeed the construction of the vector.Along with this experiments, we investigated p21WAF1/CIP1gene expression in human cancer and Ki-ras mutation in stool samples to establish new mass screening method for colorectal cancer.

胰腺癌根治术后患者的生活质量一直很差，为提高手术效果，辅助治疗是必要的。DPC 4/Smad 4是TGF-β的主效基因，是TGF-β的信号信使。DPC 4/Smad 4基因缺失在胰腺癌中是常见的。DPC 4/Smad 4基因功能受损导致控制癌细胞增殖的TGF-β功能丧失。本研究尝试构建腺病毒DPC 4/Smad 4表达载体，并研究其对胰腺癌细胞增殖的影响，以探讨该载体是否有可能成为胰腺癌辅助手术治疗的一种有前景的模式。我们打算通过将DPC 4/Smad 4 cDNA插入到含有几乎完整的具有E1和E3缺失的5型腺病毒基因组长度。本实验沿着的是p21 WAF 1/CIP 1基因在人大肠癌组织中的表达和粪便标本中Ki-ras基因突变的检测，以期建立一种新的大肠癌筛查方法。

项目成果

Kobayashi, S., Matsushita, K., Saigo, K., Urashima, T., Asano, T., Hayashi, H. and Ochiai, T.: "p21^<WAF1/CIP1> messenger RNA expression in hepatitis B, C virus infected human hepatocellular carcinoma tissues"Cancer. 91(11). 2096-2103 (2001)

Kobayashi, S.、Matsushita, K.、Saigo, K.、Urashima, T.、Asano, T.、Hayashi, H. 和 Ochiai, T.：“乙型肝炎中的 p21^<WAF1/CIP1> 信使 RNA 表达，

Ito, Y., Kobayashi, S., et al.: "Frequent detection of K-ras mutation in stool samples of colorectal carcinoma patients after improved DNA extraction"International Journal of Oncology. 20. 1263-1268 (2002)

Ito, Y.、Kobayashi, S. 等人：“改进 DNA 提取后结直肠癌患者粪便样本中 K-ras 突变的频繁检测”国际肿瘤学杂志。

S.Kobayashi, et al.: "p21 WAF1/CIP1 messenger RNA expression in hepatitis B, C virus infected human hepatocellular carcinoma tissues"Cancer. (In Press). (2001)

S.Kobayashi等人：“乙型肝炎、丙型肝炎病毒感染的人肝细胞癌组织中p21 WAF1/CIP1信使RNA的表达”癌症。

Kobayashi, S., et al.: "p21^<WAFJ/CIP1> messenger RNA expression in hepatitis B, C virus infected human hepatocellular carcinoma tissues"Cancer. 91. 2096-2103 (2001)

Kobayashi, S.等人：“乙型肝炎、丙型肝炎病毒感染的人肝细胞癌组织中p21^<WAFJ/CIP1>信使RNA的表达”癌症。

S. Kobayashi, et al.: "Prophylactic Excision of Gallbladder and Bile Duct for the Patients with Pancreaticobiliary Maljunction"Archives of Surgery. 136. 759-763 (2001)

S. Kobayashi 等人：“胰胆管连接不良患者的胆囊和胆管预防性切除术”外科档案。