Central to fibrogenesis and the scarring of organs is the activation of fibroblasts into matrix-secreting myofibroblasts. We demonstrate that Galectin-3 expression is up-regulated in established human fibrotic liver disease and is temporally and spatially related to the induction and resolution of experimental hepatic fibrosis. Disruption of theGalectin-3gene blocks myofibroblast activation and procollagen (I) expressionin vitroandin vivo, markedly attenuating liver fibrosis. Addition of exogenous recombinant Galectin-3in vitroreversed this abnormality. The reduction in hepatic fibrosis observed in theGalectin-3^−/−mouse occurred despite equivalent liver injury and inflammation, and similar tissue expression of TGF-β. TGF-β failed to transactivateGalectin-3^−/−hepatic stellate cells, in contrast with WT hepatic stellate cells; however, TGF-β-stimulated Smad-2 and -3 activation was equivalent. These data suggest that Galectin-3 is required for TGF-β mediated myofibroblast activation and matrix production. Finally,in vivosiRNA knockdown of Galectin-3 inhibited myofibroblast activation after hepatic injury and may therefore provide an alternative therapeutic approach to the prevention and treatment of liver fibrosis.

Three point mutations (A2143G, A2142G, and A2142C) have been involved in Helicobacter pylori clarithromycin resistance. To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. Post hoc subgroup study from a multicenter, randomized trial. Two hospitals in central and southern Italy between January and December 2001. 156 patients with H. pylori infection. Real-time polymerase chain reaction for assessing clarithromycin resistance; histology, rapid urease test, and ¹³C-urea breath test at entry and after 4 to 6 weeks. 7-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 1 g of amoxicillin) in 75 patients or a 10-day sequential regimen (20 mg of rabeprazole plus 1 g of amoxicillin for 5 days and 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of tinidazole for the remaining 5 days) in 81 patients. All drugs were given twice daily. Helicobacter pylori infection was eradicated in 11 of 23 patients (48%) with the A2143G mutation and in 14 of 15 patients (93%) with either A2142G or A2142C strains (difference, 45 percentage points [95% CI, 15 to 65 percentage points]; P = 0.004). The sequential regimen achieved a higher cure rate than triple therapy in A2143G mutate strains (difference, 49 percentage points [CI, 8 to 72 percentage points]; P = 0.024). The post hoc substudy design may require further confirmation. Other limitations are the accessibility to the tool and the cost of investigations (€70 per patient). The A2143G mutation seemed to be associated with a very low eradication rate. The sequential regimen achieved a higher cure rate than standard therapy even in patients with these strains.

Data from literature suggest the possible use of probiotics as chemopreventive agents against colon cancer, but few investigations are available on their effects on gastric cancer proliferation. In our previous study, a specific Lactobacillus, strain L. paracasei IMPC2.1, was demonstrated to colonize the human gut and positively affect fecal bacteria and biochemical parameters. The aims of the present study were to investigate the effects of L. paracasei IMPC2.1, comparing them with those of Lactobacillus rhamnosus GG (L.GG), either as viable or heat-killed cells, on cell proliferation and apoptosis in a gastric cancer (HGC-27) and a colorectal cancer cell line (DLD-1). Both the gastric and colon cancer cells were sensitive to the growth inhibition and apoptosis induction by both viable or heat-killed cells from L. paracasei IMPC2.1 and L.GG. These findings suggest the possibility for a food supplement, based on dead probiotics, including L. paracasei IMPC2.1 cells, which could represent an effective component of a functional food strategy for cancer growth inhibition, with potential for cancer prevention.