Comparative study of concentrations of antitumor agents in serum and tumor in nude mouse and human

裸鼠与人血清及肿瘤中抗肿瘤药物浓度的比较研究

• 批准号: 62570579
• 负责人: KUBOTA Tetsuro
• 金额: $ 1.54万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570579/
• 关键词: Concentration of antitumor agents; Human tumor xenografts; Surgical specimen; Nude mouse; Comparative pharmacology; ヌードマウス

The pharmacokinetic comparison between nude mouse and human beings is important to use the human tumor xenografts - nude mouse system as a screening panel of newly developed antiunor agents. Mitomycin C (MMC), adriamycin (ADM), 5-fluorouracil (5-FU), cisplatin (DDP), DWA2114R (DWA) and carboplatin (CBDCA) were administered to nude mice bearing human tumor xenografts in maximum tolerated doses and to patinets with cancer in conventionally available doses in clinics. The concentrations of antitumor agents in serum and tumor were detected by bioassay for MMC and 5-FU, high performance liquid chromatography for ADM and atom absorption method for DDP, DWA and CBDCA.The maximum serum concentration (Cmax in ug/ml) and concentration in tumor (T in ug/g) in nude mouse and human were as follows; mmc ADM 5-FU DDP DWA CBDCA Cmax in mouse 1.09 1.44 44.7 4.8 30.3 61.2 Cmax in human 0.84 0.42 85.4 2.2 24.0 6.5 T/Cmax% (mouse) 1.3 209.1 10.4 40.6 31.0 27.9 T/Cmax% (human) 0.9 354.6 3.1 42.9 30.7 10.4 T/Cmax ratio of each agent in mouse and human was similar to each other with a statistical significance at r = 0.996 (p 0.001).

裸鼠与人的药代动力学比较，对于将人肿瘤移植瘤-裸鼠系统作为新型抗肿瘤药物的筛选平台具有重要意义。以最大耐受剂量的丝裂霉素C（MMC）、阿霉素（ADM）、5-氟尿嘧啶（5-FU）、顺铂（DDP）、DWA 2114 R（DWA）和卡铂（CBDCA）对荷人肿瘤裸鼠进行给药，并以临床常用剂量对患者进行给药。MMC、5-FU采用生物活性测定法，ADM采用高效液相色谱法，DDP、DWA、CBDCA采用原子吸收法，测定血清及肿瘤组织中抗癌药物浓度，（Cmax，ug/ml）和肿瘤中的浓度在裸鼠和人中的T（以μ g/g计）如下：mmc ADM 5-FU DDP DWA CBDCA小鼠Cmax 1.09 1.44 44.7 4.8 30.3 61.2人Cmax 0.84 0.42 85.4 2.2 24.0 6.5 T/Cmax%（小鼠）1.3 209.1 10.4 40.6 31.0 27.9 T/Cmax%（人体）0.9 354.6 3.1 42.9 30.7 10.4小鼠和人体中每种药物的T/Cmax比值相似，具有统计学显著性，r = 0.996（p 0.001）。

项目成果

久保田哲朗ほか: "^<125>Iモノクロ-ナル抗体NCC-ST-433を用いたヒト肺小細胞癌の免疫画像診断ー基礎的検討" 癌と化学癌法. 16. 393-398 (1989)

Tetsuro Kubota等人：“使用125 I单克隆抗体NCC-ST-433进行人类小细胞肺癌的免疫成像诊断-基础研究”癌症和化学癌症方法16. 393-398(1989)。

Kubota,T.,et al.: "Antitumor activity of KW2149 against human tumor xenografts serially transplanted into nude mice" Japanese Journal of Clinical Oncology. 19. 216-221 (1989)

Kubota,T.,et al.：“KW2149 对连续移植到裸鼠体内的人类肿瘤异种移植物的抗肿瘤活性”《日本临床肿瘤学杂志》。

Yamada, Y., Kubota, T., et al.: "Human tumor clonogenic assay with reference to the clinical effect of chemotherapy" Surg. Res. Comm., 4 41-51, 1988.

Yamada, Y., Kubota, T., et al.：“人类肿瘤克隆形成分析参考化疗的临床效果”Surg。

Kubota, T., et al.: "Antitumor activity of KW2149 against human tumor xenografts serially transplanted into nude mice" Jpn. J. Clin. Oncol., 19, 216-221, 1989.

Kubota, T., et al.：“KW2149 对连续移植到裸鼠体内的人肿瘤异种移植物的抗肿瘤活性”Jpn。

Kubota,T.;et al.: "The clinical usefulness of human xenografts in nude mice.In,Predicition of response to cancer therapy" Alan,R.Liss, 213-225 (1988)

Kubota,T.；等人：“人类异种移植物在裸鼠中的临床用途。癌症治疗反应的预测”Alan,R.Liss, 213-225 (1988)