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沙门氏菌细菌单一疗法可减轻TRAMP小鼠模型中的原发性前列腺肿瘤负担。

Salmonella Bacterial Monotherapy Reduces Autochthonous Prostate Tumor Burden in the TRAMP Mouse Model.

作者信息

Kazmierczak Robert A, Gentry Bettina, Mumm Tyler, Schatten Heide, Eisenstark Abraham

机构信息

Cancer Research Center, Columbia, Missouri, United States of America.

Division of Biological Sciences, University of Missouri, Columbia, Missouri, United States of America.

出版信息

PLoS One. 2016 Aug 9;11(8):e0160926. doi: 10.1371/journal.pone.0160926. eCollection 2016.

Abstract

Attenuated Salmonella typhimurium injected in the circulatory system of mammals selectively targets tumors. Using weekly intraperitoneal injections of attenuated Salmonella strain CRC2631, we tested for regression and/or inhibition of tumor development in the TRAMP prostate tumor mouse model, which utilizes SV40 early region expression for autochthonous formation of prostate tumors that progress into metastatic, poorly differentiated prostatic carcinomas in an immunocompetent murine model. Thirteen weekly intraperitoneal administrations of 105-107 CFU CRC2631 into 10 week old mice were well tolerated by the TRAMP model. Sacrifice and histological analysis of TRAMP prostates at 22 weeks indicated that Salmonella monotherapy at administrated levels decrease visible tumor size (>29%) but did not significantly inhibit previously described SV40 expression-driven TRAMP tumor progression to undifferentiated carcinomas when histologically examined. In conclusion, this work demonstrates baseline results for CRC2631 Salmonella monotherapy using the immunocompetent TRAMP prostate tumor model in preparation for study of combination therapies that resolve autochthonously generated TRAMP prostate tumors, further reduce tumor size, or inhibit prostate tumor progression.

摘要

注射到哺乳动物循环系统中的减毒鼠伤寒沙门氏菌会选择性地靶向肿瘤。我们使用每周腹腔注射减毒沙门氏菌菌株CRC2631,在TRAMP前列腺肿瘤小鼠模型中测试肿瘤的消退和/或肿瘤发展的抑制情况,该模型利用SV40早期区域表达来在免疫活性小鼠模型中自发生成前列腺肿瘤,并进展为转移性、低分化前列腺癌。将105-107 CFU的CRC2631每周腹腔注射13次到10周龄小鼠体内,TRAMP模型对其耐受性良好。在22周时对TRAMP前列腺进行处死和组织学分析表明,在组织学检查时,所给药水平的沙门氏菌单一疗法可减小可见肿瘤大小(>29%),但并未显著抑制先前描述的由SV40表达驱动的TRAMP肿瘤进展为未分化癌。总之,这项工作展示了在免疫活性TRAMP前列腺肿瘤模型中使用CRC2631沙门氏菌单一疗法的基线结果,为研究解决自发生成的TRAMP前列腺肿瘤、进一步减小肿瘤大小或抑制前列腺肿瘤进展的联合疗法做准备。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c14/4978392/437fb26fb3da/pone.0160926.g001.jpg

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