Facultative intracellular bacteria have also been assessed for tumor therapy

Facultative intracellular Sertindole bacteria such as Salmonella have also been assessed for tumor therapy and their intratumoral accumulation was studied using different technologies, albeit beyond cellular resolution. In most syngenic experimental models the therapeutic effect was moderate, whereas in xenograft models a more pronounced effect was described. It was speculated that induction of an inflammatory response was mediating the anti-tumor effect. In contrast to extracellular bacteria, intracellular bacteria can deliver DNA into eukaryotic cells. Therefore, intracellular bacteria could be employed to deliver toxins or prodrug converting enzymes directly into tumor cells. Yet, no quantitative information on the distribution of intracellular bacteria in different stromal versus tumor cells is available even though such data are key to the design of effective therapeutic regimens. Tumors consist of a complex mixture of transformed cells and stroma cells. In many tumors, tumor-associated macrophages represent a major component of the leukocytic infiltrate. High macrophage numbers have been reported in breast, ovarian, prostate, Metamizole sodium hydrate pancreatic and cervical cancers and are associated with poor prognosis. Some authors have characterized TAMs as macrophages expressing protumoral functions, including promotion of tumor angiogenesis, metastasis, matrix remodelling and suppression of adaptive immunity. Similar results have recently been obtained for tumor associated neutrophils. Removal of macrophages or neutrophils reduced the rate of tumor progression in murine tumor models. Evidence suggests that TAMs are tumor-educated macrophages that appear to have defective production of reactive oxygen and nitrogen intermediates and are impaired in phagocytic activity. For normal macrophages it is known that they are a primary target of virulent Shigella flexneri. Shigella flexneri infection triggers caspase-1 activation leading to apotosis and processing of IL-1 and IL-18. To analyse the distribution of shigellae after i.v. application in tumor models with high numbers of macrophages, we quantified the numbers of bacteria in the extracellular space or within tumor cells, distinguishing between the macrophages and non-macrophages.

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