Treatment of pancreatic and biliary cancer using adenovirus whose proliferation isstimulated by radiation

使用放射刺激增殖的腺病毒治疗胰腺癌和胆管癌

• 批准号: 13670492
• 负责人: KAWABE Takao
• 金额: $ 2.24万
• 依托单位: The University of Tokyo
• 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: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670492/
• 关键词: pancreato-biliary; cancer; adenovirus; gene therapy; radiation; in vitro; アデノウィルス; 遺伝子治; アデノウイルス

A) Preparation of promoters activated by radiationEarly growth response-1 (egr-1) is known as a promoter activated by radiation. We attempted to make more sensitive mutants for radiation. However, such mutant gene was not obtained.B) Preparation of adenovirus whose proliferation is stimulated by radiationAs mentioned above, we failed to make more effective promoter. Then, we employed mild egr-1 promoter in the present study. We constructed adenovirus as E1A was regulated by egr-1. Theoretically, radiation activates egr-1 and it activats E1A gene to lead virus proliferation. However, constructed virus did not proliferate by radiation. It was considered because egr-1 did not activate satisfactory E1A gene.C) Preparation of suicide-gene integrated adenovirusTo avoid uncontrollable proliferation, we integrated suicide-gene system using thymidine kinase from herpes simplex and ganciclovir into the above mention virus. Ganciclovir caused death of the cell infected with this virus.

A）放射线活化的启动子的制备作为放射线活化的启动子，已知有早期生长反应-1（Early growth response-1，简写为ERK-1）。我们试图制造对辐射更敏感的突变体。B）辐射刺激增殖的腺病毒的制备如上所述，我们未能制备更有效的启动子。然后，我们在本研究中使用温和的启动子。我们构建了E1 A受E1 B-1调控的腺病毒。从理论上讲，辐射激活了E1 A基因，激活了E1 A基因，导致病毒增殖。然而，构建的病毒没有通过辐射增殖。C）自杀基因整合腺病毒的制备为避免病毒增殖失控，我们将单纯疱疹病毒胸苷激酶和更昔洛韦的自杀基因系统整合到上述病毒中。更昔洛韦导致感染该病毒的细胞死亡。

项目成果

Tada M (Kawabe T, et al.): "Quantity of mutant K-ras gene in pancreatic secretions for diagnosis of pancreatic carcinoma with different assays : analysis of 100 patients"Clin Chim Acta. 324・1-2. 105-111 (2002)

Tada M（Kawabe T等人）：“通过不同测定法诊断胰腺癌的胰腺分泌物中突变K-ras基因的数量：100名患者的分析”Clin Chim Acta 324・1-2。 2002）

Yamaji Y(Kawabe T, et al.): "Inverse background of Helicobacter pylori antibody and pepsinogen in reflux oesophagitis compared with gastric cancer : analysis of 5732 Japanese subjects"Gut 2001 Sep ; 49(3):335-40. 49・3. 335-340 (2001)

Yamaji Y（Kawabe T等人）：“反流性食管炎中幽门螺杆菌抗体和胃蛋白酶原与胃癌的相反背景：对5732名日本受试者的分析”Gut 2001年9月（3）：335-40。 .335-340 (2001)

Isayama H, Kawabe T.: "Polyurethane-covered metal stent fou manadement of distal malignant biliary obstruction."Gastrointest Endosc. 55・3. 366-367 (2002)

Isayama H，Kawabe T.：“远端恶性胆道梗阻的聚氨酯覆盖金属支架。”55・3（2002）。

Tada M, Tateishi K, Kawabe T, Sasahira N, Isayama H, Komatsu Y, Shiratori Y, Omata M.: "Quantitative of mutant K-ras gene in pancreatic secretions for diagnosis of pancreatic carcinoma with different assays of 100 patients."Clin Chim Acta. 324・1-2. 105-11

Tada M、Tateishi K、Kawabe T、Sasahira N、Isayama H、Komatsu Y、Shiratori Y、Omata M.：“通过对 100 名患者进行不同的测定，对胰腺分泌物中突变 K-ras 基因进行定量，用于诊断胰腺癌。”临床化学学报 324・1-2。

Tada M, Kawabe T.: "Quantitative analysis of K-ras gene mutation in pancreatic tissue obtained by endoscopic ultrasonography-guided fine needle aspiration : clinical utility for diagnosis of pancreatic tumor."Am J Gastroenterol. 97・9. 2263-2270 (2002)

Tada M，Kawabe T.：“通过内镜超声引导细针抽吸获得的胰腺组织中 K-ras 基因突变的定量分析：诊断胰腺肿瘤的临床实用性。”Am J Gastroenterol 97・9。 2002）