Clinical trial: ulcerative colitis maintenance treatment with 5-ASA: a 1-year, randomized multicentre study comparing MMX with Asacol.

BACKGROUND: 5-ASA-MMX (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis. AIM: To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study. METHODS: In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for >or=1 month prior to the trial, with >or=1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months' treatment. RESULTS: In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated. CONCLUSIONS: Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis.

Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal growth factor receptor by 5-aminosalicylic acid in colon cancer cells.

Recent studies have suggested that 5-aminosalicylic acid (5-ASA) inhibits colorectal cancer (CRC) development. However, the mechanism underlying the antineoplastic effect of 5-ASA remains unknown. We here examined the effect of 5-ASA on epidermal growth factor receptor (EGFR) activation, a pathway that triggers mitogenic signals in CRC cells. We show that 5-ASA inhibits EGFR activation, through a mechanism that does not rely on CRC cell death induction. 5-ASA enhances the activity, but not expression, of phosphorylated (p)-EGFR-targeting phosphatases (PTPs), and treatment of cells with PTP inhibitors abrogates the 5-ASA-mediated EGFR dephosphorylation. Both SH-PTP1 and SH-PTP2 interact with EGFR upon 5-ASA treatment. However, knockdown of SH-PTP2 but not SH-PTP1 by small interference RNAs prevents the 5-ASA-induced EGFR dephosphorylation. Finally, we show that 5-ASA attenuates p-EGFR in ex vivo organ cultures of CRC explants. Data indicate that 5-ASA disrupts EGFR signalling by enhancing SH-PTP2 activity, and suggest a mechanism by which 5-ASA interferes with CRC growth.

[Ca 19-9 in the diagnosis of pancreatic carcinoma]. / Il CA-19-9 nella diagnosi di carcinoma pancreatico.

This study was undertaken in order to ascertain the role of CA 19-9 in pancreatic cancer diagnosis. Therefore CA 19-9 was determined in the sera of 83 control subjects, 108 patients with pancreatic cancer, 112 with chronic pancreatitis and 126 with extrapancreatic diseases. Sensitivity, specificity and accuracy in detecting pancreatic cancer were: 75%, 86% and 61% respectively. The receiver-operating characteristic curves showed that CA 19-9 is able to well discriminate pancreatic cancer from controls; satisfactorily it differentiated pancreatic malignancy from chronic pancreatitis and other benign extrapancreatic diseases. Extrapancreatic neoplasms were not accurately separated. No difference was detected in CA 19-9 levels between pancreatic cancer patients with or without hepatic metastases. We can conclude that CA 19-9 is a test for pancreatic malignancy with a satisfactory sensitivity and specificity in respect of other pancreatic and extrapancreatic benign pathologies; the presence of hepatic metastases is only one of the factors which may increase its serum levels.

C reactive protein in pancreatic cancer and chronic pancreatitis.

Serum C reactive protein was determined in 30 control subjects, 32 patients with pancreatic cancer, 28 with chronic pancreatitis and 23 with extra-pancreatic diseases of the upper gastrointestinal tract. The aim was to ascertain possible alterations of this index in chronic pancreatic disease and to speculate on some influencing factors. Higher C reactive protein levels were found in pancreatic cancer as compared to controls. Pancreatic cancer patients with systemic metastases had higher levels of this index compared to those with non-metastatic disease. Raised concentrations of C reactive protein were detected in 7/28 subjects with chronic pancreatitis. In this group these higher levels were found in patients in a relapsing phase of the disease; no association was observed with pancreatic pseudocysts. Among all subjects a correlation was found, between C reactive protein and age; patients with abnormal fasting blood glucose levels or increased white blood cell count had higher levels of this protein as compared to the remaining patients. We may conclude that C reactive protein increases in pancreatic cancer, specially in relation to tumour extent; in chronic pancreatitis it reflects the inflammatory status of the gland. While acting in the context of the acute phase response, this test may provide an adjunct in evaluating patients with a chronic pancreatic disease.