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建立并鉴定人宫颈癌异种移植模型。

Creation and characterization of a xenograft model for human cervical cancer.

机构信息

Charité-Campus Benjamin Franklin, Dept. of Obstetrics and Gynecology, Hindenburgdamm 30, 12200 Berlin, Germany.

出版信息

Gynecol Oncol. 2010 Jul;118(1):76-80. doi: 10.1016/j.ygyno.2010.03.019. Epub 2010 May 2.

Abstract

OBJECTIVE

Most of primary human cancer tissues show effective engraftment and proliferation after transplantation onto Scid mice. However xenotransplantation of vital specimens of cervical carcinoma has not been successful in the past, also the generation of cell lines from primary cervical cancer has hardly ever been possible. The lack of appropriate xenograft models impedes the search for improved specific therapeutic agents.

METHODS

We explored the efficiency of different techniques for tumor transplantation and describe the first protocol to enable reliable and efficient engraftment of human cervical cancer in Scid beige mice. To demonstrate the value of this tumor model, we explored the therapeutic potency of a novel immunotoxin (SA2E). SA2E is a chimeric protein constructed by fusing the human epidermal growth factor and the plant protein toxin saporin.

RESULTS

About 70% of transplanted tumors exhibited potent proliferation, and multiple retransplantation was possible in 40%. Local treatment with the immunotoxin SA2E had a dose dependent therapeutic effect and achieved a tumor volume reduction of up to 60%.

CONCLUSIONS

Reliable engraftment and high reproducibility make this novel xenograft model an attractive test system to identify new therapeutic agents for cervical cancer.

摘要

目的

大多数原发性人类癌症组织在移植到 Scid 小鼠后显示出有效的植入和增殖。然而,过去宫颈癌的重要标本的异种移植一直没有成功,而且从原发性宫颈癌中产生细胞系也几乎不可能。缺乏合适的异种移植模型阻碍了寻找改进的特异性治疗剂的研究。

方法

我们探索了不同肿瘤移植技术的效率,并描述了第一个能够可靠有效地将人宫颈癌植入 Scid beige 小鼠的方案。为了证明这种肿瘤模型的价值,我们探索了新型免疫毒素(SA2E)的治疗潜力。SA2E 是一种嵌合蛋白,由融合了人表皮生长因子和植物蛋白毒素蓖麻毒素的构建而成。

结果

约 70%的移植肿瘤表现出强烈的增殖,40%的肿瘤可进行多次再移植。局部应用免疫毒素 SA2E 具有剂量依赖性的治疗效果,可使肿瘤体积减少高达 60%。

结论

可靠的植入和高重现性使这种新型异种移植模型成为一种有吸引力的测试系统,可用于鉴定宫颈癌的新治疗剂。

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