Clarify of the mechanism of anti-angiogenesis by PEDF and clinical application of PEDF gene therapy

PEDF抗血管生成机制的阐明及PEDF基因治疗的临床应用

• 批准号: 18591496
• 负责人: HIRANO Satoshi
• 金额: $ 2.45万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591496/
• 关键词: Anti-angiogenesis; PEDF; gene therapy; cancer; 膵癌; 血管新生阻害; 受容体; 食道癌

Pigment epithelium-derived factor (PEDF), which has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, is also expressed in the pancreas. Previously, we have screened the expression of PEDF by immunohistochemical analysis and demonstrated that PEDF expression is associated with increased risk of hepatic metastasis and short survival. In this study, we investigated both in vitro and in vivo growth characteristics of human pancreatic adenocarcinoma cell lines that were stably transfected to overexpress human PEDF. We discovered that cells secreted PEDF protein in the media, and this exhibited strong inhibitory effects on proliferation and migration of human umbilical vein endothelial cells. The size of PEDF-overexpressing pancreatic adenocarcinoma cells was significantly smaller than that of control cells in subcutaneous tumor models. Moreover, the growth of PEDF-overexpressing pancreatic adenocarcinoma cells was significantly suppressed in comparison with control cells in peritoneal metastasis models. In gene transfer models, intratumoral injection of a lentivirus. vector encoding PEDF (LV-PEDF) caused significant inhibition of tumor growth. The antitumor effect observed after treatment with LV-PEDF was associated with decreased microvessel density in tumors. The data presented here show that lentivirus-mediated gene transfer of PEDF could significantly reduce tumoral neoangiogenesis and tumor growth in animal models with human pancreatic adenocarcinoma. In conclusion, our data suggest that PEDF may exert a biological effect on tumor angiogenesis, and PEDF gene therapy may provide a new approach for treatment of pancreatic adenocarcinom

色素上皮衍生因子(PEDF)最近被证明是哺乳动物眼睛中最有效的血管生成抑制因子，它也在胰腺中表达。此前，我们已经通过免疫组织化学分析筛选了PEDF的表达，并证明PEDF的表达与肝转移风险增加和短生存期相关。在这项研究中，我们研究了稳定表达人PEDF的人胰腺癌细胞株的体外和体内生长特性。我们发现细胞在培养液中分泌PEDF蛋白，这对人脐静脉内皮细胞的增殖和迁移具有很强的抑制作用。在皮下肿瘤模型中，高表达PEDF的胰腺癌细胞的体积明显小于对照细胞。此外，在腹膜转移模型中，高表达PEDF的胰腺癌细胞的生长明显受到抑制。在基因转移模型中，瘤内注射慢病毒。编码PEDF的载体(LV-PEDF)对肿瘤生长有明显的抑制作用。LV-PEDF治疗后观察到的抗肿瘤作用与肿瘤微血管密度降低有关。这些数据表明，慢病毒介导的PEDF基因转移可以显著减少人胰腺癌动物模型中肿瘤新生血管的生成和肿瘤的生长。综上所述，我们的数据提示PEDF可能在肿瘤血管生成中发挥生物学作用，PEDF基因治疗可能为胰腺癌的治疗提供一种新的途径。

项目成果

術前リンパ節転移予測因子からみた肺癌に対する積極的縮小手術の適応の検討

从术前淋巴结转移预测因素探讨肺癌积极减容手术的指征

• 发表时间: 2007
• 作者: Uchinami;H.;Uchinami H;Matsumura Y;打波 宇;樋田泰浩;阿部ゆき;石川慶大;Abe Y;吉岡達也;Hida Y;Ishikawa K;Yoshioka T;樋田泰浩;Hida Y;樋田泰浩
• 通讯作者: 樋田泰浩

Gene therapy of esophageal squamous cell carcinoma with Angiogenesis inhibitor thrombospondin Pigment epithelium-Derived factor (PEDF).

使用血管生成抑制剂血小板反应蛋白色素上皮衍生因子（PEDF）对食管鳞状细胞癌进行基因治疗。

• 发表时间: 2006
• 作者: Uchinami;H.;Uchinami H;Matsumura Y;打波 宇;樋田泰浩;阿部ゆき;石川慶大;Abe Y;吉岡達也;Hida Y;Ishikawa K;Yoshioka T;樋田泰浩;Hida Y;樋田泰浩;石川慶大;Hida Y;Ishikawa K;樋田泰浩;石川慶大;Hida Y;Ishikawa K;樋田泰浩;Hida Y;長谷龍之介;角谷昌俊;Kadoya T
• 通讯作者: Kadoya T

Subcarinal Node Is the Significant Node That Affects Survival in Resected Small Cell Lung Cancer

隆突下淋巴结是影响小细胞肺癌切除术后生存的重要淋巴结

• 发表时间: 2006
• 期刊: Surg Today 36
• 作者: Miyamoto M;Morikawa T etc
• 通讯作者: Morikawa T etc

血管新生阻害因子PEDFによる遺伝子治療

使用血管生成抑制剂 PEDF 进行基因治疗

• 发表时间: 2007
• 作者: De minicis S;Seki E;Uchinami H;他;宮本正樹
• 通讯作者: 宮本正樹

Suppression of metastasis with tumor cells and vascular endothelium For Natural VEGF antagonist SEMA3F

天然 VEGF 拮抗剂 SEMA3F 抑制肿瘤细胞和血管内皮的转移

• 发表时间: 2007
• 作者: Uchinami;H.;Uchinami H;Matsumura Y;打波 宇;樋田泰浩;阿部ゆき;石川慶大;Abe Y;吉岡達也;Hida Y;Ishikawa K;Yoshioka T;樋田泰浩;Hida Y;樋田泰浩;石川慶大;Hida Y;Ishikawa K;樋田泰浩;石川慶大;Hida Y
• 通讯作者: Hida Y