No abstract

The aim of this study was to evaluate the role of epithelial signal transducer and activator of transcription 3 (STAT3) in mouse incisor amelogenesis. Since Stat3 is expressed in the epithelial component of developing and adult mouse teeth, we generated and analyzed Krt14^Cre/+;Stat3^fl/fl mutant mice in which Stat3 was inactivated in epithelia including ameloblast progenitors and ameloblasts, the cells responsible for enamel formation. Histological analysis showed little enamel matrix in mutant incisors compared to controls. Delayed incisor enamel mineralization was demonstrated using micro-computed X-ray tomography analysis and was supported by an increase in the pre-expression distance of enamel-enriched proteins such as amelogenin, ameloblastin, and kallikrein-4. Lastly, scanning electron microscopy analysis showed little enamel mineralization in mutant incisors underneath the mesial root of the 1st molar; however, the micro-architecture of enamel mineralization was similar in the erupted portion of control and mutant incisors. Taken together, our findings demonstrate for the first time that the absence of epithelial Stat3 in mice leads to delayed incisor amelogenesis.

No abstract

Salmonella can colonize and survive in both hypoxic and oxygenated regions of solid tumors. Avirulent Salmonella mutants have been investigated as anticancer agents in human clinical trials. The strains used, derived from Salmonella enterica subspecies I (sspI) strains, proved to be highly toxic. Salmonella non-subspecies I (nsspI) strains are known as commensals of cold-blooded species and rarely cause disease in humans. Therefore, nsspI strains could present a safer alternative for the treatment of human cancer. Here, we explore the potential of nsspI strains for use as an anticancer therapy. Strains representing the five nsspI subspecies were tested for virulence and tumor targeting in mice, and for their ability to invade and kill human breast, prostate, and colorectal cancer cell lines. We identified nsspI strains that were successful at tumor targeting and capable of invading and killing a variety of cancer cell lines in vitro while being incapable of causing disease in mice. The nsspI strains were engineered to express two key therapeutic enzymes: cytosine deaminase and uracil phosphoribosyltransferase. After invading cancer cells in culture, intracellular bacteria from all five nsspI classes caused significant cytotoxicity in the presence of 5-FC. We conclude that nsspI strains could serve as potential improved anticancer vectors, to be used in combination with a therapeutic gene, for the treatment of primary or metastatic tumors. Due to their safety profile, nsspI strains present an excellent alternative to conventional Salmonella sspI strains for the treatment of human cancer. Citation Format: Vy Khan Ly, Edward Viloria, Priyanka Saxena, Bossakara Sokhom, Michael McClelland, Nabil Arrach. Salmonella commensal subspecies: a new model for the treatment of human cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3299. doi:10.1158/1538-7445.AM2013-3299 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.