Role of gastrin in gastric cancerogenesis in Helicobacter pylori infected humans.

摘要: Numerous epidemiological studies demonstrated the association between Helicobacter pylori (H. pylori) infection and gastric cancer but mechanism of involvement H. in cancerogenesis remains virtually unknown. This study was designed to determine seropositivity cytotoxin associated gene A (CagA), serum gastrin lumen levels under basal conditions following stimulation with histamine patients controls. 100 aging from 21 60 years 300 gender- age-adjusted controls hospitalized non-ulcer dyspepsia (NUD) entered this study. 13C-Urea Breath Test (UBT), immunoglobulin (IgG) antibodies CagA were used assess IL-1beta, IL-8 TNFalpha measured by enzyme-linked immunosorbent assay (ELISA) evaluate degree inflammation . Gastrin-17 mRNA receptors (CCK(B)) expression mucosal samples taken biopsy macroscopically intact fundic antral mucosa as well tumor determined using RT-PCR. The overall at age 21-60 about 92%, compared, respectively, 68%, summary odds ratio (OR) for infected 5.0 58.5% compared 32.4% controls, giving OR positive 8.0. prevalence pylori- CagA-seropositivity significantly higher cancers than irrespective histology (intestinal, diffuse or mixed type). Median IL-1beta reached values (9.31 30.8 pg/ml) (0.21 3.12, respectively). In contrast, median (as total group) several folds (62.6 pM) (19.3 pM). Also luminal concentration many (310 (20 shows first time that are capable releasing large amounts into increase hormone level recently reported stimulate growth pylori. There no any correlation plasma suggesting that: 1) originates different source hormone, most probably cells, 2) cells expressing it mainly juice 3) equipped gastrin-specific receptor so they exhibit self-growth promoting activity autocrine fashion. notion is supported direct detection (CCK(B)-receptors) RT-PCR tissue. To our knowledge showing an important role self-stimulant Basal maximally stimulated acid outputs lower despite enhanced release, particularly might reflect inflammatory changes (increased proinflammtory interleukins - IL-8), known release. We conclude patients, those CagA-seropositivity, greatly increased risk development cancer, pylori-infected produce more (ABSTRACT TRUNCATED)