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- W2274848754 abstract "13164 Background: The A 3 adenosine receptor (A 3 AR) belongs to the family of the Gi-protein associated receptors and is highly expressed in various solid tumor tissues. The high receptor expression is reflected also in the peripheral blood mononuclear cells (PBMNC) of the cancer patients. Synthetic agonists to A 3 AR such as IB-MECA and Cl-IB-MECA (CF101 and CF102, respectively) suppress the development of melanoma, colon and prostate carcinoma in vitro and in vivo. The molecular mechanism involves de-regulation of the Wnt and the NF-kB signal transduction pathways. In this study we looked at A 3 AR expression in tumor and PBMNC of hepatocellular carcinoma (HCC) patients. In addition, receptor status model and the effect of CF102 on tumor development were examined in an HCC rat. Methods: A 3 AR mRNA expression level was examined in paraffin embedded slides derived from human HCC samples. A 3 AR protein expression was evaluated in human PBMNC by Western blot (WB) analysis. Rat HCC was established by inoculating N1S1 cells to the liver. Oral treatment with CF102, administered BID, was initiated 24h after tumor inoculation. A 3 AR and key growth regulatory proteins expression level in tumor lesions and PBMNC was tested by WB analysis. Results: A 3 AR was found to be highly expressed in the human HCC tumor tissue and the PBMNC compared to normal adjacent and PBMNC from healthy subjects, respectively. Similar data were found in tumor and PBMNC derived from N1S1 hepatoma bearing rats. In tumor lesions from CF102 treated animals, down-regulation of PKB/Akt, IKK, NF-κB and TNF-α, members of the NF-kB pathway was noted. In addition de-regulation of the Wnt pathway was observed by up-regulation of GSK-3β and down-regulation of β-catenin, Lef/Tcf and c-Myc, resulting in tumor growth inhibition. Conclusion: CF102, a small orally bioavailable molecule, binds to the A 3 AR which is highly expressed on tumor cells and via the de-regulation of the NF-kB and Wnt pathway induces inhibition of HCC growth. No significant financial relationships to disclose." @default.
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- W2274848754 date "2006-06-20" @default.
- W2274848754 modified "2023-09-26" @default.
- W2274848754 title "A3 adenosine receptor is highly expressed in hepatocellular carcinoma: A new therapeutic target" @default.
- W2274848754 doi "https://doi.org/10.1200/jco.2006.24.18_suppl.13164" @default.
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