ABSTRACT
Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) represent a novel class of compounds that hold promise as agents for the control of colon cancer. They are derivatives of conventional NSAIDs that have been modified by adding to them, via a spacer molecule, a nitric oxide releasing moiety. The expectation is that the combined effects of NO and the NSAID moiety will exceed those of each structural component alone. Extensive work has demonstrated their potency and efficacy in preclinical models of colon cancer. The mechanism of action of NO-NSAIDs involves the modulation of several critical cellular signaling pathways, whereas the induction of a state of oxidative stress, at least by NO-aspirin, appears to be a major proximal event. Clinical trials are needed to assess the role of NO-NSAIDs in the control of colon cancer.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anticarcinogenic Agents/therapeutic use , Colonic Neoplasms/prevention & control , Nitric Oxide Donors/therapeutic use , Nitric Oxide/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anticarcinogenic Agents/chemistry , Colonic Neoplasms/drug therapy , Humans , Nitric Oxide Donors/chemistryABSTRACT
OBJECTIVES: This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. METHODS: The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. RESULTS: Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. CONCLUSIONS: These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.
