Development of chemokine-expressing retrovirus vector system in malignant gliomas

恶性胶质瘤表达趋化因子的逆转录病毒载体系统的开发

• 批准号: 07557359
• 负责人: YAMASHITA Junkoh
• 金额: $ 1.41万
• 依托单位: KANAZAWA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557359/
• 关键词: chemokine; MIP-1alpha; MCAF; retrovirus vector; adenovirus vector; glioma; MIP-1alpha; retrovirusvector; specificity; chimera; env; EGF

The C-C chemokines including such molecules as MIP-1alpha (macrophage inflammatory protein-1 alpha) and MCAF (monocyte chemotactic and activity factor) exhibit chemoattractant potential for monocytes and T lymphocytes. We have developed retrovirus and adenovirus vector system which allow expression of the C-C chemokines to evaluate the effect of localized secretion of the chemokines on host anti-tumor response in rat given subcutaneous innoculation of 9L gliosarcoma cells followed by virus injection in vivio. The production of MIP-1alpha by infected adenovirus did not influence the growth rate in vitro, but suppressed tumor growth when the virus is injected into 9L flank tumor of F344 rats. Histological examination of the site of injection of 9L injected with MIP-1alpha expressing adenovirus vector showed predominantly T cell infiltration. These results indicated that chemokines have potent anti-tumor activities when released at the tumor site. Our studies highlight the potential usefulness of localized chemokine secretion in inducing potent antitumor host responses.

C-C趋化因子包括mip -1 α（巨噬细胞炎症蛋白-1 α）和MCAF（单核细胞趋化和活性因子）等分子，对单核细胞和T淋巴细胞具有趋化潜能。我们开发了逆转录病毒和腺病毒载体系统，可以表达C-C趋化因子，以评估皮下接种9L胶质瘤细胞并在体内注射病毒后，局部分泌趋化因子对宿主抗肿瘤反应的影响。感染腺病毒的mip -1 α在体外不影响肿瘤的生长速度，但在F344大鼠9L侧腹肿瘤中注射该病毒可抑制肿瘤的生长。表达MIP-1alpha腺病毒载体的9L注射部位组织学检查显示以T细胞浸润为主。这些结果表明趋化因子在肿瘤部位释放时具有强大的抗肿瘤活性。我们的研究强调了局部趋化因子分泌在诱导强效抗肿瘤宿主反应中的潜在作用。

项目成果

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Fueki T、Sugiura S、Yamaguchi K，：“与 iteron 相邻的开放链促进 pSC101 的复制起始蛋白 (Rep) 在体外与 iterons 的单位序列结合” Biochemica et Biophysical Acta。

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Tetsumori Yamashima、Sumihiro Yamashita 等：“胶质瘤最新内科系统 72：脊髓肿瘤、创伤、畸形和脊髓异常 II”13-25（1996 年）

Hassan M,Hlgashi S,.Yamashita J: "Risk in using siphon-reducing devices in adult patients with normalpressure hydrocephalus : bench test investigations with Delta valves" J Neurosurg. 84. 634-641 (1996)

Hassan M，Hlgashi S，.Yamashita J：“在正常压力脑积水的成年患者中使用虹吸减少装置的风险：使用 Delta 阀进行台架测试研究”J Neurosurg。

Okada T,Imae S,Igarashi S,Koyama T,Yamashita J: "Occult intrasacral meningocele associated with spina bifida : A case report" Surg Neurol. 46. 147-149 (1996)

Okada T、Imae S、Igarashi S、Koyama T、Yamashita J：“与脊柱裂相关的隐匿性骶骨内脑膜膨出：病例报告”Surg Neurol。

Yamashita J,Yamashima T,: "Transient brain ischemia provokes Ca2+,PIP2 and calpain responses prior to delayed neuronal death in monkeys" Eur J Neurosci. 8. 1932-1944

Yamashita J，Yamashima T，：“在猴子的延迟性神经元死亡之前，短暂的脑缺血会引发 Ca2、PIP2 和钙蛋白酶反应”Eur J Neurosci。