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二氯二茂钛衍生物Ti IV (C5H5)(2) NCS(2)对荷艾氏瘤小鼠造血反应的影响

The effect of a Titanocene Dichloride derivative, Ti IV (C5H5)(2) NCS(2), on the haematopoietic response of Ehrlich tumour-bearing mice.

作者信息

Valadares Marize C, Queiroz Mary L S

机构信息

Departamento de Farmacologia/Hemocentro, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), P.O. Box 6111, CEP 13083-970, SP, Campinas, Brazil.

出版信息

Eur J Pharmacol. 2002 Mar 29;439(1-3):35-42. doi: 10.1016/s0014-2999(02)01411-5.

Abstract

The effects of the [Ti IV (C(5)H(5))(2) NCS(2)] metallocene (BCDT), a Titanocene Dichloride derivative, on the growth and differentiation of granulocyte-macrophage progenitor cells [colony-forming unit-granulocyte-macrophage (CFU-GM)] and bone marrow cellularity in normal and Ehrlich ascites tumour-bearing mice were studied. As expected for the Ehrlich ascites tumour-model, concomitant myelosuppression, increased number of spleen CFU-GM and changes in bone marrow cellularity were observed. The treatment of Ehrlich ascites tumour-bearing mice with BCDT (10-30 mg/kg/day) produced a dose-dependent increase in myelopoiesis, a reduction in splenic colonies and a restoration in the total and differential marrow cell counts. We also observed an increase in CFU-GM number when bone marrow cells obtained from normal mice were incubated in vitro with serum from normal mice treated with BCDT. In addition, BCDT prolonged, in a dose-dependent manner, the survival of mice inoculated with Ehrlich ascites tumour. Although it has been previously reported that substitutions in the two halides of the titanocene do not interfere with antitumoural effect, our results with BCDT demonstrated a reduction in antitumour efficacy when compared to previous results with the original titanocene produced in our laboratory.

摘要

研究了二氯二茂钛衍生物[Ti IV (C(5)H(5))(2) NCS(2)]金属茂(BCDT)对正常小鼠和艾氏腹水瘤荷瘤小鼠中粒细胞-巨噬细胞祖细胞[集落形成单位-粒细胞-巨噬细胞(CFU-GM)]生长和分化以及骨髓细胞数量的影响。正如艾氏腹水瘤模型所预期的那样,观察到了伴随的骨髓抑制、脾脏CFU-GM数量增加以及骨髓细胞数量的变化。用BCDT(10 - 30毫克/千克/天)治疗艾氏腹水瘤荷瘤小鼠可使骨髓生成呈剂量依赖性增加、脾集落减少以及骨髓细胞总数和分类计数恢复。当将从正常小鼠获得的骨髓细胞与用BCDT治疗的正常小鼠的血清在体外孵育时,我们还观察到CFU-GM数量增加。此外,BCDT以剂量依赖性方式延长了接种艾氏腹水瘤小鼠的存活时间。尽管先前已有报道称二茂钛两个卤化物中的取代不会干扰抗肿瘤作用,但我们用BCDT得到的结果表明,与我们实验室之前用原始二茂钛得到的结果相比,其抗肿瘤功效有所降低。

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