Chronic inflammation is frequently associated with malignant growth and is thought to promote and enhance tumor progression, although the mechanisms which regulate this relationship remain elusive. We reported previously that interleukin (IL)-1B promoted tumor progression by enhancing the accumulation of myeloid-derived suppressor cells (MDSC), and hypothesized that inflammation leads to cancer through the production of MDSC which inhibit tumor immunity. If inflammation-induced MDSC promote tumor progression by blocking antitumor immunity, then a reduction in inflammation should reduce MDSC levels and delay tumor progression, whereas an increase in inflammation should increase MDSC levels and hasten tumor progression. We have tested this hypothesis using the 4T1 mammary carcinoma and IL-1 receptor (IL-1R)-deficient mice which have a reduced potential for inflammation, and IL-1R antagonist-deficient mice, which have an increased potential for inflammation. Consistent with our hypothesis, IL-1R-deficient mice have a delayed accumulation of MDSC and reduced primary and metastatic tumor progression. Accumulation of MDSC and tumor progression are partially restored by IL-6, indicating that IL-6 is a downstream mediator of the IL-1B-induced expansion of MDSC. In contrast, excessive inflammation in IL-1R antagonistdeficient mice promotes the accumulation of MDSC and produces MDSC with enhanced suppressive activity. These results show that immune suppression by MDSC and tumor growth are regulated by the inflammatory milieu and support the hypothesis that the induction of suppressor cells which downregulate tumor immunity is one of the mechanisms linking inflammation and cancer.

This study prepared a composite scaffold composed of curcumin and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymer using coelectrospinning technology. Incorporation of curcumin into the polymeric matrix had an obvious effect on the morphology and dimension of PCEC/curcumin fibers. The results of in vitro anti-oxidant tests and of the cytotoxicity assay demonstrated that the curcumin-loaded PCEC fibrous mats had significant anti-oxidant efficacy and low cytotoxicity. Curcumin could be sustainably released from the fibrous scaffolds. More importantly, in vivo efficacy in enhancing wound repair was also investigated based on a full-thickness dermal defect model for Wistar rats. The results indicated that the PCEC/curcumin fibrous mats had a significant advantage in promoting wound healing. At 21 days post-operation, the dermal defect was basically recovered to its normal condition. A percentage of wound closure reached up to 93.3 ± 5.6% compared with 76.9 ± 4.9% of the untreated control (p < 0.05). Therefore, the as-prepared PCEC/curcumin composite mats are a promising candidate for use as wound dressing.

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Tumor endothelial cells have long been regarded as genomically stable and therefore less likely to develop resistance to antiangiogenic therapies. However, recent findings have challenged this notion. We have shown that DNA can be transferred between cells through phagocytosis of apoptotic bodies by adjacent viable cells. Propagation of the ingested DNA is prevented by the activation of the p53-p21 pathway. In this study, we examined whether concomitant transfer of tumor DNA with genes that inactivate the p53 pathway could overcome the barrier to tumor DNA propagation. Our results demonstrate that fibroblasts and endothelial cells are capable of acquiring and replicating tumor DNA when the apoptotic tumor cells contain the SV40 large T antigen. Analysis of the tumor stroma of xenotransplanted tumors in severe combined immunodeficient mice revealed that a sub-population of the endothelial cells contained tumor DNA. These cells maintained the ability to form functional vessels in an in vivo assay and concurrently express tumor-encoded and endothelial-specific genes. Malignant and non-malignant cells are dependent on a functional blood circulation for the supply of oxygen and nutrients.1 Evidence from transgenic mouse models demonstrate that tumors initially lack the ability to induce blood vessel formation but subsequently acquire the capacity to recruit vessels from the adjoining stroma.2 This 'angiogenic switch' coincides with increase in tumor mass and invasiveness. Tumor cells secrete a plethora of angiogenic factors that induce sprouting angiogenesis (i.e. the formation of new capillaries from pre-existing capillaries) and the differentiation of hematopoietic stem cells into endothelial cells, which then contribute to tumor vessel formation. 3A potential advantage in targeting the endothelial cells of the tumor vasculature is that these cells are regarded as diploid and genetically stable. However, recent data have challenged this notion. Uveal melanomas have been reported to form their own circulatory network by the formation of vascular channels lined by tumor cells. 4 These vasculogenic channels apparently link directly to normal vessels without evidence of angiogenesis. Streubel et al.5 analyzed the cellular origin of the microvascular endothelial cells of B-cell lymphomas in patients. Chromosomal translocations specific for the tumor cells were detected in the tumor endothelium, suggesting a close relationship between the two cell types. Furthermore, analyses of human tumors transplanted in severe combined immunodeficient (SCID) mice demonstrate that the endothelial cells of solid human tumors grown in mice are genetically unstable and exhibit aneuploidy with multiple chromosomes and centrosomes. 6 Cumulatively, these studies potentially imply that tumor endothelial cells exhibit genetic instability albeit the mechanisms by which genetic alterations are induced are presently unclear.Our previous studies and those of others have demonstrated that viral and chromosomal DNA can be efficiently transferred be...