H. pylori infection, atrophic gastritis, cytokines, gastrin, COX-2, PPAR gamma and impaired apoptosis in gastric carcinogenesis.
BACKGROUND
Helicobacter pylori (Hp) infection represents a crucial factor in pathogenesis of gastric cancer (GC). Factors emanating from bacterium as well as from environmental contributions such as salt diet and inadequate supply of antioxidants, affect the risk for GC development.


RESULTS
Atrophic gastritis is considered to be a precursor lesion of intestinal type GC that is accompanied by hypergastrinemia with subsequent induction of cyclooxygenase-2 (COX-2), whose products are responsible for slowing apoptosis and for angiogenesis in GC tumor. The involvement of proinflammatory cytokines (especially IL-1 and IL-8) and reactive oxygen species (ROS) due to NF kappa B activation, increased cell proliferation combined with inhibition of apoptosis as well as upregulation of peroxisome proliferation activated receptor gamma (PPAR gamma) and inducible nitric oxide synthase (iNOS) appear to be major molecular biology alterations in pathogenesis of GC.


CONCLUSIONS
These results suggest the therapeutic usefulness of inhibitors of gastrin expression and release such as powerful somatostatin analogs (Sandostatin) or blockers of COX-2 (coxibs) in the control of GC development and progression as chemopreventive agents. Comparative genomic and proteomic is the key in identifying biomarkers in host and bacterium for the prediction of gastric cancer in Hp-infected patients.
Konturek
Peter C
PC
1st Department of Medicine, University of Erlangen-Nuremberg, Erlangen, Germany. mpkontur@cyf-edu.kr.pl
Kania
Joanna
J
Konturek
Jan W
JW
Nikiforuk
Agnieszka
A
Konturek
Stanisław J
SJ
Hahn
Eckhart G
EG
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism*; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005757:Gastritis, Atrophic / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*
D001426:Bacterial Proteins; D016207:Cytokines; D005755:Gastrins; D007527:Isoenzymes; D008565:Membrane Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases