Background & Aims The efficacy of treatment of Helicobacter pylori infection has decreased steadily due to increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton-pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori. Methods We performed a large-scale, multi-hospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naïve (n=450) or treatment-experienced (n=168) patients with H pylori infection. Treatment-naïve patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days; group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected using the 13C–urea breath test. We evaluated factors associated with treatment outcomes. Results In the intention-to-treat treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval [CI], 91.9%–98.8%), 85.3% in B1 (95% CI, 79.6%–91.1%), and 80.7% in group C1 (95% CI, 74.3%–87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%–97.6%), 51.8% in group B2 (95% CI, 38.3%–65.3%), and 78.6% (95% CI, 67.5%–89.7%). The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence. Conclusions HDDT is superior to standard regimens as empiric first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov no: NCT01163435.

Folic acid can be covalently conjugated to chitosan molecules via its gamma-carboxyl moiety and thus retain a high affinity for colorectal cancer cells bearing folate receptor overexpression. Colorectal cancer is one of the leading causes of malignant death and often goes undetected with current colonoscopy practices. Improved methods of detecting dysplasia and tumors during colonoscopy will improve mortality. A folic acid conjugated chitosan nanoparticle as a suitable vehicle for carrying 5-aminolaevulinic acid (5-ALA) is developed to enhance the detection of colorectal cancer cells in vivo after a short-term uptake period. Chitosan can be successfully conjugated with folic acid to produce folic acid-chitosan conjugate, which is then loaded with 5-ALA to create nanoparticles (fCNA). The loading efficiency of 5-ALA in fCNA particles and the z-average diameter were in the range 35-40% and 100 nm, respectively. The zeta-potential for fCNA was 20 mV, enough to keep the nanoparticle stable without aggregation. The fCNA is then incubated with HT29 and Caco-2 colorectal cancer cell lines overexpressing folate receptor on the surface of the cell membrane to determine the rate of accumulation of protoporphyrin IX (PpIX). The results show that fCNA can be taken up more easily by HT29 and Caco-2 cell lines after short-term uptake period, most likely via receptor-mediated endocytosis, and the PpIX accumulates in cancer cells as a function of the folate receptor expression and the folic acid modification. Therefore, the folic acid-chitosan conjugate appears to be an ideal vector for colorectal-specific delivery of 5-ALA for fluorescent endoscopic detection.

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With a goal of enhancing endogenous antigen trafficking to the cellular MHC II compartment of antigen-presenting cells, we employ the use of genetic vaccines encoding the antigens as chimeras containing the lysosomal targeting sequences of the lysosome-associated membrane protein (LAMP). Our rationale is that the delivery of antigen to the cellular site of MHC II processing and binding of antigen epitopes could result in an enhanced immune response through greater antigen-specific activation of CD4 ϩ T-cells. LAMP molecules have steady-state localization in the outer membrane of lysosomes (15-17) with a trafficking pathway from the Golgi complex (18, 19) mediated by adaptor protein binding (20) to the carboxyl-terminal YXXØ (where the Ø symbol represents any hydropholic amino acid) recognition sequence of an 11-amino acid cytoplasmic tail (21-23). This LAMP trafficking pathway was found to coincide with that of MHC II in specialized multilaminar vesicular compartments of immature APCs, termed MIIC, sites associated with the formation of antigenic peptide-MHC II complexes (24 -28).

Reliable markers to distinguish human colon carcinoma from normal colonic epithelium are needed particularly for poorly differentiated tumors where no useful marker is currently available. To search for markers we constructed cDNA libraries from human colon carcinoma cell lines and screened for clones that hybridize to a greater degree with mRNAs of colon carcinomas than with their normal counterparts. Here we report one such cDNA clone that hybridizes with a 1.2-kilobase (kb) mRNA, the level of which is approximately equal to 9-fold greater in colon carcinoma than in adjacent normal colonic epithelium. Blot hybridization of total RNA from a variety of human colon carcinoma cell lines shows that the level of this 1.2-kb mRNA in poorly differentiated colon carcinomas is as high as or higher than that in well-differentiated carcinomas. Molecular cloning and complete sequencing of cDNA corresponding to the full-length open reading frame of this 1.2-kb mRNA unexpectedly show it to contain all the partial cDNA sequence encoding 135 amino acid residues previously reported for a human laminin receptor. The deduced amino acid sequence suggests that this putative laminin-binding protein from human colon carcinomas consists of 295 amino acid residues with interesting features. Containing only two cysteine residues, the protein does not have consensus sequences for asparagine-linked glycosylation, amphipathic alpha-helix, or the N-terminal leader signal sequences for entry into endoplasmic reticulum, although hydrophobic segments for potential membrane associations exist. There is an unusual C-terminal 70-amino acid segment, which is trypsin-resistant (no lysine or arginine) and highly negatively charged (13 aspartic plus glutamic residues). Within this segment are five repeats of (Asp/Glu)-Trp-(Ser/Thr); two of these are nearly tandem repeats of Thr-Glu-Asp-Trp-Ser-Ala-Xaa-Pro.