Establishment of severe combined immune deficient mice introduced with human MDR1 geneinducted by murine endothelin promoter

鼠内皮素启动子诱导导入人MDR1基因的严重联合免疫缺陷小鼠的建立

• 批准号: 07457588
• 负责人: TAMAOKI Norikazu
• 金额: $ 1.28万
• 依托单位: Tokai 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 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457588/
• 关键词: brain tumor; multidrug resistance; MDR1 gene; blood brain barrier; molecular pathology; reversal of MDR; transgenic mouse; expreimental therapy; MDR; P糖蛋白質; 膜能動輸送; 化学療法

Human glioma usually shows intrinsic multidrug resistance due to the blood brain barrier (BBB), in which membrane-associated P-glycoprotein (PGp) encoded by human multidrug resistance gene MDR1 plays certain roles. We established severe combined immune deficient (SCID) mice harboring murine endothelin driven human MDR1 gene. Then, we are studying drug sensitivity to vincristine (VCR), doxorubicin (DOX) and nimustine (ACNU) in subcutaneously xenotransplanted human glioma. We examined the levels of MDR1 gene expression in the xenografts by reverse transcriptase-polymerase chain reaction, and the localization of PGp by immunohistochemistry. The localization of PGp was limited to the stromal vessels in the xenografts by immunohistochemistry. The in vivo chemosensitivity test, now going, will provide us some insights for PGp expressed on the stromal vessels as a major contributing factor to multidrug resistance in human glioma.

人脑胶质瘤通常因血脑屏障（BBB）而表现出内在的多药耐药，其中人多药耐药基因MDR 1编码的膜相关P-糖蛋白（PGp）发挥着一定的作用。我们建立了携带鼠内皮素驱动的人MDR 1基因的严重联合免疫缺陷（SCID）小鼠。然后，我们正在研究皮下异种移植的人胶质瘤对长春新碱（VCR）、阿霉素（DOX）和尼莫司汀（ACNU）的药物敏感性。我们通过逆转录-聚合酶链反应检测了移植瘤中MDR 1基因的表达水平，并通过免疫组化检测了PGp的定位。通过免疫组织化学，PGp的定位仅限于异种移植物中的间质血管。体内化疗敏感性试验，现在去，将为我们提供一些见解PGp表达的基质血管作为一个主要的因素，在人类胶质瘤多药耐药。

项目成果

Yoshiyuki Abe, Yoshiro Oshika, Yasuyuki Ohnishi, Ryuji Suto, Tetsuji Tokunaga, Hitoshi Yamazaki, Hiroshi Kijima, Nobuyoshi Hiraoka, Yoshito Ueyama, Norikazu Tamaoki, Masato Nakamura: "A xenograft line of human teratocarcinoma established by serial transpl

Yoshiyuki Abe、Yoshiro Oshika、Yasuyuki Ohnishi、Ryuji Suto、Tetsuji Tokunaga、Hitoshi Yamazaki、Hiroshi Kijima、Nobuyoshi Hiraoka、Yoshito Ueyama、Norikazu Tamaoki、Masato Nakamura：“通过连续移植建立的人类畸胎癌异种移植系

Eiichiro Ota, Yoshiyuki Abe, Norikazu Tamaoki, et al.: ""Expression of the multidrug resistance-associated protein (MRP) gene in non-small cell lung cancer"" British Journal of Cancer. 72. 550-554 (1995)

Eiichiro Ota、Yoshiyuki Abe、Norikazu Tamaoki 等人：“非小细胞肺癌中多药耐药相关蛋白 (MRP) 基因的表达”《英国癌症杂志》。

Yukihito Takamiya, Yoshiyuki Abe, Atsushi Tsugu, Yoshiro Oshika, Yasuyuki Ohnishi, Osamu Sato, Hitoshi Yamazaki, Hiroshi Kijima, Norikazu Tamaoki, Masato Nakamura: "Murine glycoprotein on stromal vessels mediates multidrug resistance in intracerebral huma

Yukihito Takamiya、Yoshiyuki Abe、Atsushi Tsugu、Yoshiro Oshika、Yasuyuki Ohnishi、Osamu Sato、Hitoshi Yamazaki、Hiroshi Kijima、Norikazu Tamaoki、Masato Nakamura：“基质血管上的小鼠糖蛋白介导脑内人体内的多药耐药性

Ryuji Suto, Yoshiyuki Abe, Yoon Hwan Lee, Yoshito Ueyama, Hitoshi Yamazaki, Hiroshi Kijima, Nobuyoshi Hiraoka, Hiroaki Fukuda, Norikazu Tamaoki, Masato Nakamura: "A case of malignant schwannoma with overexpression of multidrug resistance gene (MDR1) after

Ryuji Suto、Yoshiyuki Abe、Yoon Hwan Lee、Yoshito Ueyama、Hitoshi Yamazaki、Hiroshi Kijima、Nobuyoshi Hiraoka、Hiroaki Fukuda、Norikazu Tamaoki、Masato Nakamura：“恶性神经鞘瘤伴多药耐药基因 (MDR1) 过度表达

Yoshiyuki Abe,Yasyuki Ohnishi Norikazu Tamaoki et al: "“A xenograft line of human teratocarcinoma established by serial transplantation in severe combined immunodeficient (SCID) mice"" APMIS. 105(in press). (1997)

Yoshiyuki Abe、Yasyuki Ohnishi Norikazu Tamaoki 等人：“通过在严重联合免疫缺陷 (SCID) 小鼠中连续移植建立的人类畸胎癌异种移植系”APMIS. 105（印刷中）。（1997 年）