Targeting soluble CD146 with a neutralizing antibody inhibits vascularization, growth and survival of CD146-positive tumors.

CD146 (MUC-18, MCAM) expression on cancer cells correlates with cancer progression and a bad prognosis in several tumors, including melanoma and pancreatic tumors. Deciphering the mechanism mediating the CD146 role in cancer is essential for generating new therapeutic strategies. We found that CD146 expression in cancer cells is associated with a secretion of soluble CD146 (sCD146) that constitutes an active player in tumor development. Indeed, sCD146 induces the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. These last effects are mediated in part through the induction and phosphorylation of c-myc in cancer cells. In mice models xenografted with human CD146-positive melanoma or pancreatic cancer cells, administration of a novel monoclonal antibody specifically targeting sCD146, but not its membrane form, successfully suppresses tumor vascularization and growth. Our findings demonstrate that sCD146 secreted by CD146-positive tumors mediates important pro-angiogenic and pro-tumoral effects. Targeting sCD146 with a novel neutralizing antibody could thus constitute an innovative therapeutic strategy for the treatment of CD146-positive tumors.

Effects of triflusal on arteriosclerosis progression assessed with high-resolution arterial ultrasound.

In order to evaluate the effect of triflusal (2-acetyloxy-4-trifluoromethyl benzoic acid), an orally active antiplatelet agent, on arteriosclerosis progression, a pilot, parallel, double-dummy, double-blind clinical trial vs acetylsalicylic acid (ASA) was carried out in patients with subclinical atherosclerotic lesions. The trial consisted of a 2-week run-in placebo phase, followed by a 12-month oral treatment with triflusal (600 mg/day) or ASA (300 mg/day). The primary variable was identified in the ultrasonic biopsy (UB) score; the secondary variables were the UB class changes of each arterial site, the rate of progression (ROP), the intima-media thickness (IMT), and the symptoms of arteriosclerosis. Data were evaluated by use of analysis of variance and Chi-square test. Forty-three patients (31 men, 12 women, mean age 62.8 +/- 8.4 SD) were randomized to triflusal (15 men, 6 women, mean age 64.3 +/- 6.7) or to ASA (16 men, 6 women, mean age 61.3 +/- 9.6). The analysis of variance on the UB score showed no difference between treatments: the patients' UB scores remained unchanged with no progression, thus indicating that no patient worsened during treatment. When all arterial sites under evaluation are considered, 86% of the sites in the triflusal group and 85% in the ASA group remained unchanged. No relevant change was recorded in vital signs and routine laboratory tests. Gastric disturbances were reported by two and three patients treated with triflusal and ASA, respectively. In conclusion, triflusal appears as effective as ASA in slowing arteriosclerosis progression.

[Azithromycin versus amoxicillin in triple therapy for the treatment of Helicobacter pylori infection]. / Azitromicina versus amoxicillina in tripla terapia nel trattamento eradicante Helicobacter pylori.

BACKGROUND: To establish if azithromycin, in association with omeprazole and metronidazole, is effective to eradicate Helicobacter pylori, compared to amoxicillin in triple therapy. METHODS: Two hundred consecutive patients with duodenal ulcer and Helicobacter pylori infection were enrolled in the study: group a) 100 patients (69 males, 31 females; mean age 47.61 years; range 23-75); group b) 100 patients (70 males, 30 females; mean age 45.56 years; range 22-72). Group a) omeprazole 20 mg od, azithromycin 500 mg od the first three and the last three days of association with metronidazole, this one 250 mg qid, for ten days; group b) omeprazole 20 mg od, amoxicillin 1 g bid, metronidazole 250 mg qid for ten days. Omeprazole was continued for other four weeks in each treatment with the same dosage. RESULTS: In group a ulcer healing was observed in 89 patients (89 %), while in group b in 93 patients (93%) (p=n.s.). Helicobacter pylori infection was eradicated in group a in 70 patients (70 %), while in group b in 78 patients (78 %) (p=n.s.). Side effects in 11 patients (5.5 %), in particular: group a 5 (5 %), group b 6 (6 %) (p=n.s.). CONCLUSIONS: Azithromycin could be proposed for treatment of Helicobacter pylori eradication.

[Endoscopy of the upper digestive tract in anti-HIV positive subjects]. / L'endoscopia del tratto digestivo superiore in soggetti anti-HIV positivi.

BACKGROUND: The aim of our study was to evaluate any correlation between symptoms of the upper digestive tract, endoscopic findings and the clinical stage of disease. METHODS: Thirty-four anti-HIV positive patients were enrolled and subdivided, according to CDC classification, as follows: 28 CDC II/III (asymptomatics) and 6 CDC IV (AIDS). The past medical history of all patients was investigated and oesophagogastroduodenoscopy (OGDS) was carried out. RESULTS: All anti-HIV positive patients complained of gastrointestinal symptoms (100%), while endoscopic lesions were observed in 11/34 (32.3%). CONCLUSIONS: The data did not show any correlation between symptoms and endoscopic alterations; we showed more frequent endoscopic alteration in CDC IV patients, even if being treated, compared with CDC II/III.

Ex vivo evaluation of pidotimod activity on cell-mediated immunity.

The activity of pidotimod ((R)-3-[(S)-(5-oxo2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) on immunological parameters was evaluated in a double-blind trial, involving two Research Centres. 16 patients with a primary or metastatic neoplasm, 16 elderly patients under immunodeficiency conditions and 11 healthy volunteers were enrolled in the present study. The patients, randomized within each centre, were assigned to one of the following treatments lasting 15 days: one vial i.m. of pidotimod 50 mg, 100 mg, 200 mg twice a day, respectively; one vial i.m. of physiological saline twice a day. The lymphocyte PHA-stimulation test evidenced a significant variability due to the different treatment groups (p = 0.004). The analysis of the stimulation index (SI), computed from the mean c.p.m. before and after PHA-stimulation, showed a significant difference, dose-independent, between saline and active treatment (p = 0.002). The SI analysis, on the basis of the data of the allogenic stimulation test (mixed lymphocyte culture), confirmed the difference between saline and active treatment (p = 0.05) with a significant linear component in the time-effect curve (p = 0.001) but not in the dose-effect curve. A 12% increase in CD 3 lymphocytes compartment was observed with pidotimod 400 mg/day. The drug was well tolerated by all the patients included in the study.

Pidotimod in the treatment of patients affected by bacterial exacerbations of chronic bronchitis.

A multicentre double-blind placebo-controlled study was conducted in order to assess the effects of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a new synthetic biological response modifier, on the clinical picture of bacterial exacerbations of chronic bronchitis. Seven centres of respiratory diseases participated in the trial. A total of 137 patients, 103 males and 34 females (mean age: 65.0 years) were admitted to the study. The trial was subdivided into 3 phases. During the first 8-day phase (D0-D8), 68 patients received 800 mg pidotimod orally (one sachet) twice daily and an antibiotic treatment (amoxycillin plus clavulanic acid: 1 g twice daily), while 69 patients received placebo (one sachet) and antibiotic according to the same dosage schedule. In the second 7-day phase (D8-D15), while the double-blind therapy proceeded, the antibiotic treatment was stopped. The third phase (D15-D45) consisted of a 30-day follow-up period. Five clinical observations, at D0, D4, D8, D15 and D45, were scheduled. The Skin test, to evaluate immunocompetence, was carried out at D0, D15 and D45. The faster improvement of symptomatology (dyspnoea, cough, sputum, hyperpyrexia) in the patients in the pidotimod group compared with the placebo group was reflected in recovery time: mean 8.9 days in the pidotimod group versus 10.7 days in the placebo group (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)