Lewis X antigen mediates adhesion of human breast carcinoma cells to activated endothelium. Possible involvement of the endothelial scavenger receptor C-Type lectin

Lewis x (Lex, CD15), also known as SSEA-1 (stage specific embryonic antigen-1), is a trisaccharide with the structure Galβ(1–4)Fucα(1–3)GlcNAc, which is expressed on glycoconjugates in human polymorphonuclear granulocytes and various tumors such as colon and breast carcinoma. We have investigated the role of Lex in the adhesion of MCF-7 human breast cancer cells and PMN to human umbilical endothelial cells (HUVEC) and the effects of two different anti-Lex mAbs (FC-2.15 and MCS-1) on this adhesion. We also analyzed the cytolysis of Lex+-cells induced by anti-Lex mAbs and complement when cells were adhered to the endothelium, and the effect of these antibodies on HUVEC. The results indicate that MCF-7 cells can bind to HUVEC, and that MCS-1 but not FC-2.15 mAb inhibit this interaction. Both mAbs can efficiently lyse MCF-7 cells bound to HUVEC in the presence of complement without damaging endothelial cells. We also found a Lex-dependent PMN interaction with HUVEC. Although both anti-Lex mAbs lysed PMN in suspension and adhered to HUVEC, PMN aggregation was only induced by mAb FC-2.15. Blotting studies revealed that the endothelial scavenger receptor C-type lectin (SRCL), which binds Lex-trisaccharide, interacts with specific glycoproteins of Mr␣∼␣28 kD and 10 kD from MCF-7 cells. The interaction between Lex+-cancer cells and vascular endothelium is a potential target for cancer treatment.Fil: Elola, Maria Teresa. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capurro, Mariana Isabel. University of Toronto; CanadáFil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; ArgentinaFil: Coombs, Peter J.. Imperial College London; Reino UnidoFil: Taylor, Maureen E.. Imperial College London; Reino UnidoFil: Drickamer, Kurt. Imperial College London; Reino UnidoFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; Argentin

The glycan-binding protein galectin-1 controls survival of epithelial cells along the crypt-villus axis of small intestine

Intestinal epithelial cells serve as mechanical barriers and active components of the mucosal immune system. These cells migrate from the crypt to the tip of the villus, where different stimuli can differentially affect their survival. Here we investigated, using in vitro and in vivo strategies, the role of galectin-1 (Gal-1), an evolutionarily conserved glycan-binding protein, in modulating the survival of human and mouse enterocytes. Both Gal-1 and its specific glyco-receptors were broadly expressed in small bowel enterocytes. Exogenous Gal-1 reduced the viability of enterocytes through apoptotic mechanisms involving activation of both caspase and mitochondrial pathways. Consistent with these findings, apoptotic cells were mainly detected at the tip of the villi, following administration of Gal-1. Moreover, Gal-1-deficient (Lgals1−/−) mice showed longer villi compared with their wild-type counterparts in vivo. In an experimental model of starvation, fasted wild-type mice displayed reduced villi and lower intestinal weight compared with Lgals1−/− mutant mice, an effect reflected by changes in the frequency of enterocyte apoptosis. Of note, human small bowel enterocytes were also prone to this pro-apoptotic effect. Thus, Gal-1 is broadly expressed in mucosal tissue and influences the viability of human and mouse enterocytes, an effect which might influence the migration of these cells from the crypt, the integrity of the villus and the epithelial barrier function

Intensive enteral nutrition is ineffective for individuals with severe alcoholic hepatitis treated with corticosteroids.

peer reviewedBACKGROUND & AIMS: Severe alcoholic hepatitis (AH) is a lifethreatening disease for which adequate oral nutritional support is recommended. We performed a randomized controlled trial to determine whether the combination of corticosteroid and intensive enteral nutrition therapy is more effective than corticosteroid therapy alone in patients with severe AH. METHODS: We enrolled 136 heavy consumers of alcohol (age, 18–75 y) with recent onset of jaundice and biopsy-proven severe AH in our study, performed at 18 hospitals in Belgium and 2 in France, from February 2010 through February 2013. Subjects were assigned randomly (1:1) to groups that received either intensive enteral nutrition plus methylprednisolone or conventional nutrition plus methylprednisolone (controls). In the intensive enteral nutrition group, enteral nutrition was given via feeding tube for 14 days. The primary end point was patient survival for 6 months. RESULTS: In an intention-to-treat analysis, we found no significant difference between groups in 6-month cumulative mortality: 44.4% of patients died in the intensive enteral nutrition group (95% confidence interval [CI], 32.2%–55.9%) and 52.1% of controls died (95% CI, 39.4%– 63.4%) (P ¼ .406). The enteral feeding tube was withdrawn prematurely from 48.5% of patients, and serious adverse events considered to be related to enteral nutrition occurred in 5 patients. Regardless of group, a greater proportion of patients with a daily calorie intake less than 21.5 kcal/kg/day died (65.8%; 95% CI, 48.8–78.4) than patients with a higher intake of calories (33.1%; 95% CI, 23.1%–43.4%) (P < .001). CONCLUSIONS: In a randomized trial of patients with severe AH treated with corticosteroids, we found that intensive enteral nutrition was difficult to implement and did not increase survival. However, low daily energy intake was associated with greater mortality, so adequate nutritional intake should be a main goal for treatment

Intragastric balloon for weight loss: results in 100 individuals followed for at least 2.5 years.

BACKGROUND AND STUDY AIMS: To determine long-term outcome after treatment with an intragastric balloon for 6 months, with no structured weight maintenance program offered after balloon removal. PATIENTS AND METHODS: 100 consecutive overweight/obese individuals (mean body mass index [BMI] 35.0 +/- 5.6 kg/m (2)) were prospectively followed after endoscopic implantation of a saline-filled intragastric balloon; 97 completed final follow-up at a mean of 4.8 +/- 1.6 years. Successful intragastric balloon therapy was defined as weight loss at 6 months of > or = 10 % of weight at baseline, that remained > or = 10 % until 2.5 years, without bariatric surgery. All analyses followed intention-to-treat principles. RESULTS: At 6 months, mean weight loss was 12.6 +/- 8.3 kg, 63 individuals had > or = 10 % baseline weight loss; no severe morbidity was detected. During the first and second years following intragastric balloon removal, mean body mass increased by 4.2 +/- 6.8 and 2.3 +/- 6.0 kg, respectively ( P or = 10 % baseline weight loss, 35 had undergone bariatric surgery (60 % had preoperative mass higher than baseline), and 3 were lost to follow-up; the 34 remaining had lost 1.5 +/- 5.8 kg compared with baseline. During follow-up, 13 had a second intragastric balloon implanted and 13 took sibutramine for short periods. CONCLUSION: Intragastric balloon therapy was relatively innocuous and associated with successful weight loss and maintenance at 2.5 years in a quarter of participants. It represents a valid option for weight loss.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Intragastrischer ballon zur gewichtsreduktion: Ergebnisse bei 100patienten nach 2,5 Jahren

Background and study aims: To determine long-term outcome after treatment with an intra-gastric balloon for 6months, with no structured weight maintenance program offered after balloon removal. Patients and methods: 100 consecutive overweight/obese individuals (mean body mass index [BMI] 35.0±5.6kg/ m2) were prospectively fol-lowed after endoscopic implantation of a saline filled intragastric balloon; 97 completed final -follow-up at a mean of 4.8±1.6years. Success-ful intragastric balloon therapy was defined as weight loss at 6 months of ≥ 10% of weight at -baseline, that remained ≥ 10% until 2.5years, with-out bariatric surgery. All analyses followed intention-to-treat principles. Results: At 6months, mean weight loss was 12.6±8.3kg, 63 individuals had ≥ 10% baseline weight loss; no severe morbidity was detected. During the first and second years following intragastric balloon removal, mean body mass in-creased by 4.2±6.8 and 2.3±6.0kg, respectively (P<0.001 for both year-on-year comparisons). At 2.5years, intragastric balloon therapy had been successful in 24 participants. At final follow-up (4.8±1.6years), 28 had ≥ 10% baseline weight loss, 35had undergone bariatric surgery (60% had preoperative mass higher than baseline), and 3were lost to follow-up; the 34remaining had lost 1.5±5.8kg compared with baseline. During follow-up, 13 had a second intragastric balloon implanted and 13 took sibutramine for short -periods. Conclusion: Intragastric balloon therapy was relatively innocuous and associated with successful weight loss and maintenance at 2.5years in a quarter of participants. It represents a valid op-tion for weight loss. © Georg Thieme Verlag KG Stuttgart - New York.SCOPUS: ar.jinfo:eu-repo/semantics/publishe