Ben-Barak et al. identified four phenotypic classes of S. enterica under defined standard culture conditions

eptors required for infection. Previously, we and others have analyzed the modulation of adenovirus primary receptor Chlorphenoxamine chemical information expression on the cell surface by various substances including a number of chemotherapeutics and anti-inflammatory reagents. We found no effect on Oncolytic Adenoviruses receptor level, as assessed by flow cytometry analysis, after dexamethasone treatment, while others detected a slight reduction in the level of both primary receptor and 17640949 avb integrins. The effect of dexamethasone on the serotype 3 receptor had not been studied, nor had the cell lines used here been studied before with regard to the other relevant adenovirus receptors. We therefore analyzed the effect of the substances on gene delivery and found that in some cases luciferase expression was increased. Thus, the reduced replication seen here was probably not due to receptor downregulation. Another mechanistic possibility might involve induction of Cox-2 by virus replication per se. With regard to herpes, cytomegalovirus, and other DNA viruses, it has been demonstrated that virus infection induces Cox-2. Further, the finding that inhibition of Cox-2 reduces replication of these viruses suggests that Cox-2 induction is beneficial for virus propagation. These viruses may utilize the anabolic effects of Cox-2 for optimization of their replication efficacy. Preliminary data suggests that the same may also be true for adenovirus, which might help explain why the oncolytic effect of wildtype adenovirus was attenuated by dexamethasone. Although oncolysis is likely to correlate with replication of the virus, we investigated this separately. As expected, virus replication was reduced with dexamethasone treatment in vitro. This seems to support 22803826 the theoretical assumption that oncolysis is tightly linked with virus replication. As human adenoviruses do not replicate productively in murine normal tissues, human xenografts in mice were utilized for replication attenuation in vivo studies. In these models, if replication and/or cell killing efficacy is reduced in vivo with dexamethasone, tumors in mice treated with virus and dexamethasone would be larger than virus only treated. In both models studied, dexamethasone did not significantly reduce the antitumor efficacy of the analyzed oncolytic adenoviruses, despite a trend in that direction. Finally, we analyzed the amount of infectious particles in subcutaneous tumors with and without dexamethasone treatment. Despite a trend prominent at early time points, no significant differences were seen, which may be due to variation typical of in vivo experiments. The most likely reason for the discrepancy between the observed in vitro and in vivo effect of dexamethasone on the oncolytic potential of the viruses may relate to the higher complexity of in vivo models. These complexities were well demonstrated in a recent study where an increase in VEGF levels in Cox-2 positive and Cox-2 negative pancreatic cancer cells was seen after treatment with high concentrations of Cox-2 inhibitors, suggesting that the relationship between Cox-2 protein inhibition and VEGF or Cox-2 promoter expression may not always be tightly linked. Contrary to expectations, both Cox-2 positive and negative in vitro models displayed increased levels of VEGF following Cox-2 inhibition. However, in the Cox-2 positive tumor in vivo model, non-malignant cells expressed a markedly decreased level of murine VEGF leading to reduced total VEGF and tumor angiogenesis a

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