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.
Highlights
Combatting advanced and metastatic tumors is still one of the most difficult cancer treatment challenges and new therapeutic approaches are necessary to target this heterogeneous disease in which different cancer cells may require different treatments
In order to investigate the ability of CRC2631 to serve as a chemotherapeutic carrying vector, we have explored its effect as a monotherapy in the TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mouse, an autochthonous prostate cancer model triggered by testosterone driven SV40 large and small T-antigen expression [45]
Weekly intraperitoneal Salmonella injections are well tolerated in the TRAMP mouse model
Summary
Combatting advanced and metastatic tumors is still one of the most difficult cancer treatment challenges and new therapeutic approaches are necessary to target this heterogeneous disease in which different cancer cells may require different treatments. Salmonella Cancer Therapy in the TRAMP Mouse Prostate Tumor Model. Kazmierczak and Abraham Eisenstark are employed by the Cancer Research Center and have appointments at the University of Missouri (Columbia, MO). This did not alter the authors' adherence to PLOS ONE policies on sharing data and materials
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