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The effect on cancer cells of the glycodendrimers believed to decrease tumor growth, prolong survival time, and enhance immune response

ABSTRACT: The potential therapeutic relevance of synthetic glycodendrimers was shown on animal subjects bearing colorectal carcinoma and melanoma. The application of glycodendrimers led to decreased tumor growth and prolonged survival time of the animals, accompanied by an enhancement of immune response. Comparison of mass spectra and biochemical analyses have indicated that the uptake of glycodendrimers by target cells resulted in changes of surface glycosylation. Moreover our research shows changes in membrane constitution. Recently our lab found changes in proliferation potential and expression of GnT-III and GnT-V in cancer cells in contrast to the peripheral blood mononuclear cells from healthy donors. As there are a sizable amount of enzymes involved in glycan metabolism and signaling pathways, the glyco-chip would be a very effective tool to determine which genes are involved in metabolism of these glycodendrimers. Our lab would like to develop expression profiles of cancer cells treated by glycodendrimers and a corresponding untreated control. For chip analyses we have chosen cell lines derived from chronic myeloid leukemia (K562), multiple myeloma (U266) and colon carcinoma (HT-29). There are untreated control samples and post glycodendrimers treatment samples from each cell line. All samples were produced and developed in triplicate for a total of 18 samples. The RNA was labeled and hybridized onto the GLYCOv3 array. .

ORGANISM(S): Homo sapiens

SUBMITTER: Head Steven

PROVIDER: S-ECPF-GEOD-29936 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:BackgroundVascularized composite tissue allotransplantation (VCA) to replace limbs or faces damaged beyond repair is now possible. The resulting clear benefit to quality of life is a compelling reason to attempt this complex procedure. Unfortunately, the high doses of immunosuppressive drugs required to protect this type of allograft result in significant morbidity and mortality giving rise to ethical concerns about performing this surgery in patients with non-life-threatening conditions. Here we tested whether we could suppress anti-graft immune activity by using a safe β2 -adrenergic receptor (AR) agonist, terbutaline, to mimic the natural immune suppression generated by nervous system-induced signalling through AR.MethodsA heterotopic hind limb transplantation model was used with C57BL/6 (H-2b) as recipients and BALB/c (H-2d) mice as donors. To test the modulation of the immune response, graft survival was investigated after daily intraperitoneal injection of β2 -AR agonist with and without tacrolimus. Analyses of immune compositions and quantification of pro-inflammatory cytokines were performed to gauge functional immunomodulation. The contributions to allograft survival of β2 -AR signalling in donor and recipient tissue were investigated with β2 -AR-/- strains.ResultsTreatment with the β2 -AR agonist delayed VCA rejection, even with a subtherapeutic dose of tacrolimus. β2 -AR agonist decreased T-cell infiltration into the transplanted grafts and decreased memory T-cell populations in recipient's circulation. In addition, decreased levels of inflammatory cytokines (IFN-γ, IL-6, TNF-α, CXCL-1/10 and CCL3/4/5/7) were detected following β2 -AR agonist treatment, and there was a decreased expression of ICAM-1 and vascular cell adhesion molecule-1 in donor stromal cells.Conclusionsβ2 -AR agonist can be used safely to mimic the natural suppression of immune responses, which occurs during adrenergic stress-signalling and thereby can be used in combination regimens to reduce the dose needed of toxic immunosuppressive drugs such as tacrolimus. This strategy can be further evaluated for feasibility in the clinic.

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The effect on cancer cells of the glycodendrimers believed to decrease tumor growth, prolong survival time, and enhance immune response

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