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醋酸考地瑞林,一种具有临床前抗肿瘤活性的合成促肾上腺皮质激素释放因子,单独使用和联合贝伐珠单抗,用于治疗人脑肿瘤模型。

Corticorelin acetate, a synthetic corticotropin-releasing factor with preclinical antitumor activity, alone and with bevacizumab, against human brain tumor models.

机构信息

Celtic Pharmaceutical Development Services America, Inc., New York, NY 10022, USA.

出版信息

Anticancer Res. 2010 Dec;30(12):5037-42.

Abstract

BACKGROUND

Corticorelin acetate (CrA) is a synthetic form of corticotropin-releasing factor that is currently undergoing clinical trials in the treatment of peritumoral brain edema (PBE). This study preclinically investigated its potential as an antitumor agent against human brain tumor xenografts.

MATERIALS AND METHODS

The in vivo efficacy of CrA as a single agent and in combination with the antiangiogenic agent, bevacizumab, was examined in three different patient-derived human brain tumor xenografts implanted orthotopically (intracranially) or subcutaneously in athymic mice.

RESULTS

CrA significantly increased the lifespan of mice implanted orthotopically with two different pediatric brain tumor xenograft models. In one of these tumor models, the combination of CrA with bevacizumab produced a therapeutic outcome superior to that found using either of the two agents alone.

CONCLUSION

The application of CrA for the treatment of PBE likely involves its activity as an anti-angiogenic agent, which may be one possible mechanism to explain its observed preclinical antitumor activity against orthotopic human brain tumor models. Additional studies to investigate other possible mechanisms of action are underway.

摘要

背景

醋酸考地瑞林(CrA)是一种合成的促肾上腺皮质激素释放因子,目前正在临床试验中用于治疗肿瘤周围脑水肿(PBE)。本研究在临床前研究了其作为一种针对人脑肿瘤异种移植物的抗肿瘤药物的潜力。

材料和方法

CrA 作为单一药物以及与抗血管生成药物贝伐单抗联合使用的体内疗效,在三种不同的患者来源的人脑肿瘤异种移植物中进行了研究,这些异种移植物通过原位(颅内)或皮下植入无胸腺小鼠。

结果

CrA 显著延长了两种不同小儿脑肿瘤异种移植物模型原位植入小鼠的寿命。在其中一个肿瘤模型中,CrA 与贝伐单抗联合使用产生的治疗效果优于两种药物单独使用的效果。

结论

CrA 用于治疗 PBE 的应用可能涉及到其作为抗血管生成剂的活性,这可能是解释其对原位人脑肿瘤模型观察到的临床前抗肿瘤活性的一种可能机制。正在进行其他可能的作用机制的研究。

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