salicylates and Carcinogenesis

To investigate the relative risk of cancer development in rheumatoid arthritis (RA) patients in Greece after taking into consideration treatment modalities. The present analysis used data on the medical history of 26 331 participants in the Greek arm of the European Prospective Investigation into Cancer and Nutrition that were collected at enrollment and thereafter during active follow-up. A history of RA and of drug treatment for the disease, as reported at baseline examination, was linked to cases of cancer reported during follow-up. A total of 91 (9.9%) patients with RA developed a cancer compared with 1542 (6.1%) patients without RA. The overall hazard ratios of all cancers increased 25% [95% confidence interval (CI): 1-54] among participants with prevalent RA, and almost all the site-specific incident cancer sites considered had rate ratios above unity. In terms of the contribution of RA medication, the hazard ratios of patients treated with salicylates was close to unity (1.07, 95% CI: 0.69-1.65), whereas those who were not treated with salicylates had a 31% (95% CI: 3-67) increased risk for cancer incidence compared with those without RA at baseline. RA patients have excess cancer risk because of either underlying complex disease pathways or treatment agents targeting immune function. Administration of salicylates appears to reduce the risk of developing malignancies.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Carcinogenesis; Cyclooxygenase Inhibitors; Female; Follow-Up Studies; Greece; Humans; Incidence; Male; Middle Aged; Neoplasms; Prevalence; Proportional Hazards Models; Prospective Studies; Risk Factors; Salicylates; Young Adult

The ErbB receptors, Ras proteins and nucleolin are major contributors to malignant transformation. The pleiotropic protein nucleolin can bind to both Ras protein and ErbB receptors. Previously, we have demonstrated a crosstalk between Ras, nucleolin and the ErbB1 receptor. Activated Ras facilitates nucleolin interaction with ErbB1 and stabilizes ErbB1 levels. The three oncogenes synergistically facilitate anchorage independent growth and tumor growth in nude mice.. In the present study we used several cancer cell lines. The effect of Ras and nucleolin inhibition was determined using cell growth, cell death and cell motility assays. Protein expression was determined by immunohistochemistry. We found that inhibition of Ras and nucleolin reduces tumor cell growth, enhances cell death and inhibits anchorage independent growth. Our results reveal that the combined treatment affects Ras and nucleolin levels and localization. Our study also indicates that Salirasib (FTS, Ras inhibitor) reduces cell motility, which is not affected by the nucleolin inhibitor.. These results suggest that targeting both nucleolin and Ras may represent an additional avenue for inhibiting cancers driven by these oncogenes.

Topics: Animals; Aptamers, Nucleotide; Carcinogenesis; Cell Death; Cell Line, Tumor; Cell Movement; Cell Proliferation; ErbB Receptors; Farnesol; Humans; Immunoblotting; Immunohistochemistry; Mice; Mice, Nude; Microscopy, Fluorescence; Nucleolin; Oligodeoxyribonucleotides; Phosphoproteins; ras Proteins; RNA-Binding Proteins; Salicylates