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通过六周抗c-myc硫代磷酸酯DNA治疗预防伯基特淋巴瘤小鼠模型中的肿瘤形成。

Prevention of tumor formation in a mouse model of Burkitt's lymphoma by 6 weeks of treatment with anti-c-myc DNA phosphorothioate.

作者信息

Huang Y, Snyder R, Kligshteyn M, Wickstrom E

机构信息

Department of Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA.

出版信息

Mol Med. 1995 Sep;1(6):647-58.

Abstract

BACKGROUND

Transgenic mice bearing a murine immunoglobulin enhancer/c-myc fusion transgene (Emu-myc) provide a useful model for Burkitt's lymphoma.

MATERIALS AND METHODS

Groups of 12 Emu-myc mice were treated prophylactically for 6 weeks after weaning with anti-c-myc DNA phosphorothioate (20 mg/kg/day), scrambled control DNA, or saline, delivered by micro-osmotic pumps.

RESULTS

Half of the mice treated with saline or scrambled control DNA displayed palpable tumors by 8-9 weeks after birth, and 95% of them did so by 16 weeks, but 75% of the mice treated with antisense DNA were still free of tumors at the age of 26 weeks. Antisense therapy ablated MYC antigen in the spleens of tumor-bearing mice. Plasma physiological parameters indicated no acute toxicity.

CONCLUSIONS

Long-term tumor resistance after anti-c-myc DNA therapy implies induction of a host response. Prophylactic anti-c-myc DNA therapy might prevent lymphoma in asymptomatic individuals displaying c-myc translocations.

摘要

背景

携带鼠免疫球蛋白增强子/c-myc融合转基因(Emu-myc)的转基因小鼠为伯基特淋巴瘤提供了一个有用的模型。

材料与方法

将12只Emu-myc小鼠分为几组,断奶后用微渗透泵给予抗c-myc硫代磷酸酯DNA(20毫克/千克/天)、随机对照DNA或生理盐水进行预防性治疗6周。

结果

用生理盐水或随机对照DNA治疗的小鼠中有一半在出生后8至9周出现可触及的肿瘤,其中95%在16周时出现,而用反义DNA治疗的小鼠中有75%在26周龄时仍无肿瘤。反义疗法消除了荷瘤小鼠脾脏中的MYC抗原。血浆生理参数表明无急性毒性。

结论

抗c-myc DNA治疗后的长期肿瘤抗性意味着诱导了宿主反应。预防性抗c-myc DNA治疗可能预防显示c-myc易位的无症状个体发生淋巴瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/2229988/1c9fb0a20a14/molmed00048-0068-c.jpg

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