ANTIANGIOGENETIC THERAPY WITH PLATELET FACTOR-4 TO LIVER CANCER.

使用血小板因子 4 治疗肝癌的抗血管生成疗法。

• 批准号: 11671259
• 负责人: KOYAMA Yoshihisa
• 金额: $ 1.6万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671259/
• 关键词: Liver cancer; Antiangiogenetic therapy; Platelet factor-4; HUVEC; HepG cell; Adenovirus vector; 遺伝子治療

[Objective] Platelet Factor 4 (PF4) has been shown to inhibit neovascularization by suppressing the growth of vascular endothelial cells, and thus significantly suppressing tumor growth. In the present study, an adenovirus vector encoding PF4 release was directly injected into experimental liver tumors to determine whether tumor growth could be suppressed.[Materials and Methods] An adenovirus vector encoding PF4 release was made, and we determined whether the vector could suppress growth of vascular endothelial cells in vitro using human umbilical vein endothelial cells (HUVEC). Next, the ability of the adenovirus vector encoding PF4 release to inhibit neovascularization of cultured human hepatoma cells (HepG) and HUVEC in vivo was compared to that of a control vector.[Results] PF4 was found to suppress the growth of experimental liver tumors, while physiological saline (control) did not affect suppression significantly. Adenovirus vector encoding PF4 release did not significantly suppress growth of human umbilical vein endothelial cells (HUVEC) in vitro. Further, the ability of the adenovirus vector encoding PF4 release to inhibit the neovascularization of cultured human hepatoma cells (HepG) and HUVEC in vivo was compared to that of a control vector, but no significant suppression was confirmed. Failure to detect significant differences in the present study was attributable to the stability and reproducibility of the adenovirus vector.

[目的] 血小板因子4（PF4）已被证明可以通过抑制血管内皮细胞的生长来抑制新生血管形成，从而显着抑制肿瘤生长。本研究将编码PF4释放的腺病毒载体直接注射到实验性肝肿瘤中，以确定是否能够抑制肿瘤生长。[材料与方法]制备编码PF4释放的腺病毒载体，并利用人脐静脉内皮细胞（HUVEC）体外测定该载体是否能够抑制血管内皮细胞的生长。接下来，将编码PF4释放的腺病毒载体在体内抑制培养的人肝癌细胞（HepG）和HUVEC新生血管的能力与对照载体进行比较。 [结果]发现PF4可以抑制实验性肝肿瘤的生长，而生理盐水（对照）没有显着影响抑制。编码PF4释放的腺病毒载体在体外没有显着抑制人脐静脉内皮细胞(HUVEC)的生长。此外，将编码PF4释放的腺病毒载体在体内抑制培养的人肝癌细胞(HepG)和HUVEC的新生血管形成的能力与对照载体进行比较，但未证实有显着的抑制。本研究未能检测到显着差异是由于腺病毒载体的稳定性和重现性。

项目成果

Yashima R. et al.: "Heterogeneity of the signal transduction pathways for VEGF-induced MAPKs activation in human vascular endothelial cells"Journal of Cellular Physiology. 188(2). 201-210 (2001)

Yashima R.等人：“人血管内皮细胞中VEGF诱导的MAPK激活的信号转导途径的异质性”细胞生理学杂志。

Yashima R. Abe M. Tanaka K. Ueno H. Shitara K. Takenoshita S. Sato Y.: "Heterogeneity of the signal transduction pathways for VEGF-induced MAPKs activation in human vascular endothelial cells."Journal of Cellular Physiology. 188(2). 201-210 (2001)

Yashima R. Abe M. Tanaka K. Ueno H. Shitara K. Takenoshita S. Sato Y.：“人血管内皮细胞中 VEGF 诱导的 MAPK 激活的信号转导途径的异质性。”细胞生理学杂志。

Yuichi H, et al.: "Usefulness of the tactile sensor for estimating the degree of liver fibrosis and the DNA synthesis activity of remnant liver cells after partial hepatectomy"Fukushima Journal of Medical Science. 48(2). 93-101 (2002)

Yuichi H 等人：“触觉传感器对于估计部分肝切除术后残余肝细胞的肝纤维化程度和 DNA 合成活性的有用性”《福岛医学科学杂志》。

Yuichi H, Toshiyuki O, Naoki S, Hiroshi S, Yoshihisa K, Norio I, Seiichi T and Sadao Omata: "Usefulness of the tactile sensor for estimating the degree of liver fibrosis and the DNA synthesis activity of remnant liver cells after partial hepatectomy"Fukus

Yuichi H、Toshiyuki O、Naoki S、Hiroshi S、Yoshihisa K、Norio I、Seiichi T 和 Sadao Omata：“触觉传感器对于估计肝纤维化程度和部分肝切除术后残余肝细胞 DNA 合成活性的有用性”