Telomerase activity correlates with growth of transplantable osteosarcomas in rats treated with cis-diammine dichloroplatinum or the angiogenesis inhibitor AGM-1470

Telomerase activity correlates with growth of transplantable osteosarcomas in rats treated with cis-diammine dichloroplatinum or the angiogenesis inhibitor AGM-1470
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DOI:
10.1111/j.1349-7006.1998.tb00499.x
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发表时间:
1998-10-01
期刊:
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子:
--
通讯作者:
Konishi, Y
Konishi, Y
中科院分区:
其他
文献类型:
--
作者:
Kido, A;Tsujiuchi, T;Konishi, Y

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为了确定端粒酶活性在化疗大鼠肿瘤生长中的作用,比较了抗肿瘤药物顺二胺二氯铂(CDDP)和血管生成抑制剂O-(氯乙酰氨基甲酰)烟酰胺醇(AGM-1470)处理的大鼠可移植骨肉瘤的体积。8周龄雄性F344大鼠将肉眼可见的肺转移结节移植到皮下,第14天静脉注射顺铂开始治疗。剂量分别为0.625、1.5、1.2、2.5 mg/kg体重(B.W.)AGM-1470按0、2.5、5、10 mg/kg体重灌胃。2周以上通过渗透泵,也植入皮下背部,但远离移植瘤。第28天处死动物,用端粒重复序列扩增法(TRAP)测定移植瘤大小和端粒酶活性。端粒酶活性与治疗前后肿瘤大小比值呈高度正相关(r=0.96,P
To determine the role of telomerase activity in the growth of tumors in rats undergoing chemotherapy a comparison of the volumes of telomerase-positive transplantable osteosarcomas was made in rats treated with the antineoplastic agent cis-diammine dichloroplatinum (CDDP) or the angiogenesis inhibitor O-(chloroacetylcarbamoyl)fumagillol (AGM-1470). Male F344 rats, 8 weeks old, received transplants of macroscopic lung metastatic nodules into the subcutaneous hack space and treatment was started on day 14 thereafter CDDP was injected i.v. at doses of 0, 0.625, 1.25 and 2.5 mg/kg body weight (b.w.) and AGM-1470 was administered at total doses of 0, 2.5, 5 and 10 mg/kg b.w. over 2 weeks by osmotic pumps, also implanted into the subcutaneous back space, but remote from the transplanted tumors. On day 28, ail animals were killed for measurement of transplanted tumor size and determination of telomerase activities by telomeric repeat amplification protocol (TRAP) assay. The results showed telomerase activity to be highly correlated with the treated/non-treated (T/C) tumor size ratio (r = 0.96, P