However, while PTXGs have been shown to mimic the original tumor response to treatment quite accurately, they are still exposed to selection forces related to differences between human and mouse microenvironments. Thus it is important to assess the degree to which PTXGs diverge from the primary patient tumors at the genomic and protein level prior to embarking on extensive drug studies. We have previously described PTXG model development. The next logical step is the overarching goal of the present study: to assess the utility and limitations of using PTXG models for drug testing. Specifically, to what degree are E/GEJ tumors representative of patient tumors, in the context of pharmacologic evaluation? Our own experiments across multiple cancer types have identified common PTXG issues such as: lack of engraftment of many tumors; unexpected mouse deaths, leading to the need to alter and run experiments across different passages; technical reasons, such as the need to expand xenografts into large cohorts and to freeze down earlier passages to ensure accessibility for future Torin 1 1222998-36-8 studies, resulting in having to use later passages for drug experiments; and an occasional inability to identify specific PTXG models with the same molecular characteristics observed in a patient. These technical issues raise four important BMS-354825 model-related questions, which can be stated as testable hypotheses: PTXG models are representative of the underlying population of gastro-esophageal cancers, and if not wholly representative, we are able to describe what biases are present and how they could affect conclusions; PTXG models are useful generally, even at later passages, as their gene/protein expression patterns remain stable; this hypothesis measures the degree of confounding by selection pressures during passaging; PTXGs can recapitulate the broad spectrum of molecular characteristics representative of their underlying primary cancers; this addresses the concerns of not finding the inter-tumor heterogeneity necessary to develop personalized medicine approaches to therapy; and PTXGs respond to pharmacologic therapy stably across multiple passages. Thus, we evaluated the potential of E/GEJ PTXGs to replicate what is found clinically in human E/GEJ tumors, and the conditions in which these PTXGs are appropriate to use as pre-clinical drug testing models. Despite these findings, the genetic basis for S. mutans VicRK-modulated stress tolerance is not well-understood and the signal that stimulate VicK activation remain unknown. Therefore, an improved understanding of how VicRK modulates these various stress responses through gene expression could provide insight into how bacterial TCSs might be manipulated, thereby fostering the development of therapeutics against bacterial infections. In the present study, we report that S. mutans VicK can transphosphorylate not only its cognate RR, VicR, but also the orphan RR, GcrR; the latter is only demonstrable in vitro in the presence of manganese.