EVALUATION OF CYCLOSPORINE-TREATED MICE AS HOSTS FOR GROWING AND TESTING THE CHEMOSENSITIVITY OF 1ST-TRANSPLANT-GENERATION HUMAN-TUMOR XENOGRAFTS IMPLANTED UNDER THE KIDNEY CAPSULE

EVALUATION OF CYCLOSPORINE-TREATED MICE AS HOSTS FOR GROWING AND TESTING THE CHEMOSENSITIVITY OF 1ST-TRANSPLANT-GENERATION HUMAN-TUMOR XENOGRAFTS IMPLANTED UNDER THE KIDNEY CAPSULE
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DOI:
10.1093/jnci/75.5.925
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发表时间:
1985-01-01
影响因子:
10.3
通讯作者:
MCKNEALLY, MF
MCKNEALLY, MF
中科院分区:
医学1区
文献类型:
--
作者:
BENNETT, JA;PILON, VA;MCKNEALLY, MF

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新鲜切除的人类肿瘤作为异种移植物生长在常规小鼠的肾囊下,每天用环孢素 A(CsA;60 mg/kg/天,皮下注射)进行免疫抑制。 CsA 治疗小鼠的肿瘤持久性和生长与裸鼠的肿瘤持续性和生长相当。较低剂量或较不积极的 CsA 方案会导致异种移植排斥。 CsA(60 毫克/公斤/天,皮下注射)治疗小鼠有毒性,但不致死。它导致水消耗量减少 20%,体重减轻 10%,胸腺、肾脏和肝脏重量显着减轻。 CsA 治疗的小鼠可以耐受治疗剂量的癌症化疗药物,但 10% 的致死剂量对 100% 的小鼠来说是致命的。这些结果表明,CsA 治疗的小鼠将是裸鼠的经济替代品,用于生长人类肿瘤异种移植物和测试其化疗敏感性,但需要注意的是,在 CsA 治疗的小鼠中,较低剂量时将达到癌症化疗药物的剂量限制毒性。
Freshly resected human tumors were grown as xenografts under the kidney capsules of conventional mice immunosuppressed by daily treatment with cyclosporine A (CsA; 60 mg/kg/day, s.c.). Tumor persistence and growth in CsA-treated mice were comparable to those found in nude mice. Lower doses or less aggressive schedules of CsA resulted in xenograft rejection. CsA (60 mg/kg/day, s.c.) treatment of mice was toxic but not lethal. It resulted in a 20% decrease in water consumption, a 10% loss in body weight, and significant reductions in thymus, kidney, and liver weights. Therapeutic doses of cancer chemotherapeutic agents were tolerated by CsA-treated mice, but 10% lethal doses were lethal in 100% of the mice. These results indicate that CsA-treated mice would be an economic alternative to nude mice for growing human tumor xenografts and for testing their chemosensitivity, with the caveat that the dose-limiting toxicity of cancer chemotherapeutic agents will be reached at lower doses in CsA-treated mice.