Annexin A1 (ANXA1), a mediator of the anti-inflammatory action of glucocorticoids, is important in cancer development and progression, whereas NF-κB regulates multiple cellular phenomena, some of them associated with inflammation and cancer. We showed that glucocorticoids and chemopreventive modified nonsteroidal anti-inflammatory drugs, such as nitric oxide-donating aspirin (NO-ASA) and phospho-aspirin, induced ANXA1 in cultured human colon and pancreatic cancer cells. ANXA1 associated with NF-κB and suppressed its transcriptional activity by preventing NF-κB binding to DNA. The induction of ANXA1 by glucocorticoids was proportional to their anti-inflammatory potency, as was the suppression of NF-κB activity, which was accompanied by enhanced apoptosis and inhibition of cell growth mediated by changes in NF-κB-dependent cell signaling. The proposed novel mechanism was operational in the intestinal mucosa of mice treated with dexamethasone or NO-ASA. ANXA1-based oligopeptides displayed the same effects as ANXA1 on NF-κB. One such tripeptide (Gln-Ala-Trp) administered to nude mice inhibited the growth of SW480 human colon cancer xenografts by 58% compared with control (P < 0.01). Our findings reveal that ANXA1 is an inducible endogenous inhibitor of NF-κB in human cancer cells and mice, provide a novel molecular mechanism for the action of anti-inflammatory agents, and suggest the possibility of mechanism-driven drug development.

Background & Aims-Non-steroidal anti-inflammatory drugs (NSAIDs) are effective cancer chemopreventive agents. However, chronic administration of NSAIDs is associated with significant side effects, mainly gastrointestinal. Given these limitations, we synthesized phospho-sulindac (P-S; OXT-328), a novel sulindac derivative.

BackgroundThis study aimed to investigate the relationships among overactive bladder (OAB) symptom severity, bother, help-seeking behavior, and quality of life (QOL) in patients with type 2 diabetes.MethodsA total of 127 diabetic patients, aged at least 18 years, with overactive bladder from a hospital in Shandong Province, China, were recruited for this study. Symptom severity, bother, and quality of life were assessed using the Overactive Bladder Symptom Score (OABSS), Patient Perception of Bladder Condition (PPBC), and Overactive Bladder Questionnaire Short Form (OAB-q SF), respectively. Help-seeking behavior was assessed by asking patients whether they consulted health care professionals or received treatment for their bladder problems. A two-step path analysis was performed to analyze the data.ResultsOAB symptom severity was directly associated with lower levels of QOL, and the strength of this association was no longer significant when taking bother and help-seeking behavior into account. Bother increased with OAB symptom severity, and patients with bothersome OAB tended to have lower levels of QOL. Moreover, bother increased help-seeking behavior; however, patients who sought help tended to have lower levels of QOL.ConclusionsOur findings highlight the role of bother and help-seeking behavior in the relationship between OAB symptom severity and QOL. To improve a patient’s QOL, health care providers should focus not only on symptom bother but also on dysfunctional help-seeking patterns.

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