Purpose: A 3 adenosine receptor (A 3 AR) activation was shown to inhibit the growth of various tumor cells via the down-regulation of nuclear factor B and cyclin D1. To additionally elucidate whether A 3 AR is a specific target, a survey of its expression in tumor versus adjacent normal cells was conducted.Experimental Design: A 3 AR mRNA expression in various tumor tissues was tested in paraffin-embedded slides using reverse transcription-PCR analysis. A comparison with A 3 AR expression in the relevant adjacent normal tissue or regional lymph node metastasis was performed. In addition, A 3 AR protein expression was studied in fresh tumors and was correlated with that of the adjacent normal tissue.Results: Reverse transcription-PCR analysis of colon and breast carcinoma tissues showed higher A 3 AR expression in the tumor versus adjacent non-neoplastic tissue or normal tissue. Additional analysis revealed that the lymph node metastasis expressed even more A 3 AR mRNA than the primary tumor tissue. Protein analysis of A 3 AR expression in fresh tumors derived from colon (n ‫؍‬ 40) or breast (n ‫؍‬ 17) revealed that 61% and 78% had higher A 3 AR expression in the tumor versus normal adjacent tissue, respectively. The high A 3 AR expression level in the tumor tissues was associated with elevated nuclear factor B and cyclin D1 levels. High A 3 AR mRNA expression was also demonstrated in other solid tumor types.Conclusions: Primary and metastatic tumor tissues highly express A 3 AR indicating that high receptor expression is a characteristic of solid tumors. These findings and our previous data suggest A 3 AR as a potential target for tumor growth inhibition.

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Objective. Studies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A 3 adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model.Methods. OA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 g/kg given twice daily) was initiated. The A 3 adenosine receptor antagonist MRS1220 (100 g/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O-fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses.Results. CF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF-B signaling pathway, resulting in down-regulation of tumor necrosis factor ␣. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes.Conclusion. CF101 deregulated the NF-B signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA.Osteoarthritis (OA) is the most common chronic joint disease. Articular cartilage is a major component of the joint, and its mechanical properties depend on the integrity of the extracellular matrix, which is composed mainly of proteoglycans and collagens. Degeneration of joint cartilage is the central feature in OA, but the disease is associated with concomitant changes in synovium and subchondral bone metabolism, causing inflammation of the synovial membrane in the involved joints (1).The cause of OA is multifactorial and includes both systemic and local biomechanical factors (2). Systemic factors that have been associated with OA include age, sex, race-and gene-based susceptibility, bone density, estrogen levels, and nutritional factors. OA results from the failure of chondrocytes that lie within the joint to synthesize a good-quality matrix and to maintain a balance between synthesis and degradation of the extracellular matrix. Synovial inflammation and local concentration of proinflammatory mediators seem to Supported by Can-Fite BioPharma.