Conventional cancer chemotherapies are not fully efficacious and do not target tumors, leading to significant treatment-related morbidities. A number of genetically attenuated cancer-targeting bacteria are being developed to safely target tumors . Here we report the toxicological, tumor-targeting, and efficacy profiles of serovar Typhimurium CRC2631 in a syngeneic and autochthonous TRAMP model of aggressive prostate cancer.
View Article and Find Full Text PDFThe Lilleengen type (LT) collection of serovar Typhimurium strains has served the scientific community as a group of model organisms for basic genetic and biochemical pathway research. Here, we report the whole-genome shotgun sequences of serovar Typhimurium strains LT1, LT18, LT19, LT20, LT21, and LT22.
View Article and Find Full Text PDFAttenuated 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.
View Article and Find Full Text PDFRecently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such as Salmonella, Listeria, Escherichia, and Clostridium have proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents.
View Article and Find Full Text PDFSalmonella has been of interest in cancer research due to its intrinsic ability to selectively target and colonize within tumors, leading to tumor cell death. Current research indicates promising use of Salmonella in regular administrations to remove tumors in mouse models while minimizing toxic side effects. However, selection of mutants during such long-term tumor colonization is a safety concern, and understanding selection of certain phenotypes within a tumor is an important consideration in predicting the long-term success of bacterium-based cancer treatment strategies.
View Article and Find Full Text PDFBackground: One of the cardinal requirements for effective therapeutic management of tumors is the selective delivery of cancer drugs to the right site by ligand-decorated nanomedicines. Screening of 2 × 109 clone landscape phage library provides a reliable avenue for generating protein ligands specific for tumor cells. It was shown that selective phage proteins derived from landscape phage libraries against breast and prostate cancer cells are able to navigate drug or siRNA loaded liposomes to corresponding cancer cells with minimal toxicity to non-neoplastic cells.
View Article and Find Full Text PDFDespite significant progress in the development of new drugs and radiation, deaths due to cancer remain high. Many novel therapies are in clinical trials and offer better solutions, but more innovative approaches are needed to eradicate the various subpopulations that exist in solid tumors. Since 1997, the use of bacteria for cancer therapy has gained increased attention.
View Article and Find Full Text PDFIncreasingly, genetically modified Salmonella are being explored as a novel treatment for cancer because Salmonella preferentially replicate within tumors and destroy cancer cells without causing the septic shock that is typically associated with wild-type S. typhimurium infections. However, the mechanisms by which genetically modified Salmonella strains preferentially invade cancer cells have not yet been addressed in cellular detail.
View Article and Find Full Text PDFSite-specific recombination catalyzed by bacteriophage lambda integrase (Int) is essential for establishment and termination of the viral lysogenic life cycle. Int is the archetype of the tyrosine recombinase family whose members are responsible for DNA rearrangement in prokaryotes, eukaryotes and viruses. The mechanism regulating catalytic activity during recombination is incompletely understood.
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