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    BACKGROUND:Although the presence of numerous cell signaling receptors in osteosarcoma is known, their simultaneous characterization has not been performed to date. The current study sought to characterize and quantify the expression of cell surface receptors across a variety of osteosarcoma cell lines.METHODS:Standard (n = 4) and patient-derived (n = 10) osteosarcoma cell lines were cultured and labeled with antibodies to epidermal growth factor receptor, human epidermal growth factor receptor (HER)-2, HER-3, HER-4, insulin-like growth factor 1 receptor (IGF-1R), IGF-2R, insulin receptor (IR), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, c-Met, fibroblast growth factor receptor (FGFR)-2, FGFR-3, and platelet-derived growth factor receptor (PDGFR)-?. Cell surface examination was performed using flow cytometry, and the geometric fluorescent mean for each receptor was calculated and compared against a positive control.RESULTS:Significant overexpression of IGF-2R was shown in all cell lines, with an average geometric mean above the upper expression quartile. A variable expression pattern was seen for c-Met, PDGFR-?, IR, IGFR-1, HER-2, and VEGFR-3 with expression values for the remaining receptors mainly in the lower quartile. An apparent association between the expression of IGF-1R and HER-2 and between the expression of PDGFR-? and IR was demonstrated.CONCLUSION:IGF-2R was consistently overexpressed on the cell surface across all tested osteosarcoma cell lines. Substantial, although variable, expression of c-Met, HER-2, IGF-1R, VEGFR-3, IR, and PDGFR-? was demonstrated as well, suggesting that these receptors may contribute to osteosarcoma aggressiveness and biological heterogeneity and may serve as potential targets within a subset of tumors. Associated receptor expression may provide new insight into common regulatory factors or pathways. Targeting either common factors or targeting multiple specific receptors may have therapeutic relevance. Cancer 2011;. © 2011 American Cancer Society.dx.doi.org


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    BACKGROUND:The detection of a small number of circulating tumor cells (CTCs) is important, especially in the early stages of cancer. Small numbers of CTCs are hard to detect, because very few approaches are sensitive enough to differentiate these from the pool of other cells. Improving the affinity of a selective, surface-functionalized molecule is important given the scarcity of CTCs in vivo. There are several proteins and aptamers that provide such high affinity; however, using surface nanotexturing increases this affinity even further.METHODS:The authors report an approach to improve the affinity of tumor cell capture by using novel aptamers against cell membrane overexpressed epidermal growth factor receptors (EGFRs) on a nanotextured polydimethylsiloxane (PDMS) substrate. Surface-immobilized aptamers were used to specifically capture tumor cells from physiologic samples.RESULTS:The nanotexturing of PDMS increased surface roughness at the nanoscale. This increased the effective surface area and resulted in a significantly higher degree of surface functionalization. The phenomenon resulted in increased density of immobilized EGFR-specific RNA aptamer molecules and provided significantly higher efficiency to capture cancer cells from a mixture. The data indicated that CTCs could be captured and enriched, leading to higher yield yet higher background.CONCLUSIONS:A comparison between glass slides, plain PDMS, and nanotextured PDMS functionalized with aptamers demonstrated that a 2-fold approach of using aptamers on nanotextured PDMS can be important for cancer cytology devices, and especially for the idea of a “lab-on-chip,” toward higher yield in capture efficiency. Cancer 2011;. © 2011 American Cancer Society.dx.doi.org


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    Immunogenic cell death is characterized by the early surface exposure of chaperones including calreticulin and HSPs, which affect dendritic cell (DC) maturation and the uptake and presentation of tumor antigens. It has also been shown that it is characterized by the late release of high mobility group box 1 (HMGB1), which acts through Toll-like receptor 4 (TLR4) and augments the presentation of antigens from dying tumor cells to DCs. Most of the data on immunogenic tumor cell death were obtained using mouse models. In this study, we investigated the capacity of clinically used chemotherapeutics to induce immunogenic cell death in human tumor cell lines and primary tumor cells. We found that only anthracyclines induced a rapid translocation of calreticulin, HSP70, and HSP90 to the cell surface and the release of HMGB1 12 hours after the treatment. The interaction of immature DCs with immunogenic tumor cells led to an increased tumor cell uptake and induces moderate phenotypic maturation of DCs. Killed tumor cell–loaded DCs efficiently stimulated tumor-specific IFN-?–producing T cells. DCs pulsed with killed immunogenic tumor cells also induced significantly lower numbers of regulatory T cells than those pulsed with nonimmunogenic tumor cells. These data indicate that human prostate cancer, ovarian cancer, and acute lymphoblastic leukemia cells share the key features of immunogenic cell death with mice tumor cells. These data also identify anthracyclines as anticancer drugs capable of inducing immunogenic cell death in sensitive human tumor cells. Cancer Res; 71(14); 4821–33. ©2011 AACR. cancerres.aacrjournals.org


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    science: Water striders don't stride - they row across the surface of the water. http://t.co/bL3Bufm  ...Read On

    During malignant progression cancer cells tend to lose cell surface expression of MHC and other immune antigens, making them invisible to cytotoxic T cells and therefore inaccessible to tumor antigen-directed immunotherapy. Moreover, cancer cell variants that have lost antigen expression frequently contribute to deadly tumor relapses that occur following treatments that had been initially effective. In an effort to destroy antigen-loss cancer cells in tumors, we created a strategy that combines a chimeric antigen receptor (CAR)-redirected T-cell attack with an engineered local release of the cytokine interleukin 12 (IL-12), which recruits and reinforces macrophage function. Cytotoxic T cells were engineered to release inducible IL-12 upon CAR engagement in the tumor lesion, resulting in destruction of antigen-loss cancer cells that would normally escape. Importantly, elimination of the antigen-loss cancer cells was accompanied by an accumulation of activated macrophages that was critical to the antitumor response, because removing the macrophages abolished the response and restoring them reengaged it. Neutralizing TNF-? also abrogated the elimination of antigen-loss cancer cells, implying this proinflammatory factor in the process. Taken together, our results show how IL-12 supplementation by CAR T cells can target otherwise inaccessible tumor lesions, in a manner associated with reduced systemic toxicity, by recruiting and activating innate immune cells for a proinflammatory response. Cancer Res; 71(17); 5697–706. ©2011 AACR.
    cancerres.aacrjournals.org   ...Read On


    		   
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