ABSTRACT
BACKGROUND: Delivery of a pharmacologically effective drug dosage to a target tissue is critical. Barrett's epithelia are a unique challenge for drug delivery of orally administered zinc due to rapid transit down the esophageal lumen, incomplete absorptive differentiation of these epithelia, and the use of proton-pump inhibitor drugs abrogating intestinal uptake of supplemental zinc. METHODS: Barrett's esophagus patients were administered oral zinc gluconate (26 mg zinc twice daily) for 14 days prior to biopsy procurement. Barrett's biopsies were analyzed for total zinc content by atomic absorption spectroscopy and by western immunoblot for cellular proteins known to be regulated by zinc. RESULTS: Cellular levels of both the Znt-1 transport protein and the alpha isoform of PKC were over 50% lower in the zinc treatment group. CONCLUSION: Oral zinc administration can result in effective delivery of zinc to Barrett's epithelia with resulting effects on intracellular signal transduction.
Subject(s)
Barrett Esophagus/drug therapy , Dietary Supplements , Drug Delivery Systems , Esophagus/drug effects , Gluconates/administration & dosage , Administration, Oral , Adult , Aged , Barrett Esophagus/metabolism , Barrett Esophagus/pathology , Biopsy , Blotting, Western , Cation Transport Proteins/drug effects , Cation Transport Proteins/metabolism , Esophagus/metabolism , Esophagus/pathology , Female , Gluconates/pharmacokinetics , Humans , Male , Metaplasia , Middle Aged , Protein Kinase C-alpha/metabolism , Signal Transduction/drug effects , Spectrophotometry, Atomic , Time Factors , Treatment OutcomeSubject(s)
Colitis, Ischemic/genetics , Mutation , Prothrombin/genetics , Adult , Colitis, Ischemic/pathology , DNA Mutational Analysis , Female , Humans , Recurrence , RiskABSTRACT
Colorectal cancer (CRC) is one of the most common cancers in the western world. Early screening and detection could be highly preventative and therefore reduce mortality. Tight junctions (TJ) are well known for their function in controlling paracellular traffic of ions and molecules. It has become increasingly evident that TJs play a crucial role in maintaining cell-cell integrity, and the loss of cell junctional sealing could involve itself in the processes of carcinoma and cancer metastasis. If correlations between altered TJ proteins and CRC presence or invasiveness could be established, they may serve as important markers and guidelines for prophylactic and prognostic purposes, along with other screening methods. This review will present recent data from clinical and animal studies showing how altered TJ protein expression is a feature of certain CRCs. The up-regulation of claudin-1 in many CRCs is especially noteworthy. The focus of this article is simply on the association - however imperfect - between CRC and the major TJ transmembrane barrier proteins, namely claudins and occludin. Any causal relationship between TJ protein change and neoplasia remains conclusively unproven at present.
