caa a22 4500 475791231 CHVBK 20180406123711.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s004230050248 doi (NATIONALLICENCE)springer-10.1007/s004230050248 Helicobactor pylori infection and carcinogenesis of the stomach [Elektronische Daten] [H. Kuniyasu, W. Yasui, H. Yokozaki, E. Tahara] Abstract : Introduction: Human stomach carcinogenesis occurs after a multi-step process of genetic and epigenetic alterations in oncogenes, tumor-suppressor genes, cell-adhesion molecules, telomere and telomerase activity as well as genetic instability at several microsatellite loci. Results and discussion: These sequential alterations found in gastric cancer differ between the two histological types, indicating that different genetic pathways exist for well-differentiated or intestinal-type and poorly differentiated or diffuse-type gastric cancers, even though both types of gastric cancer may arise from epithelial ”stem cells”, which express human telomerase reverse transcriptase (hTERT) protein and telomerase activity. Infection with Helicobacter pylori, which evidently causes the release of reactive oxygen species (ROMs) and reactive nitrogen species (NO), may be a strong trigger for ”stem cell” hyperplasia in intestinal metaplasia, followed by telomere reduction and increased telomerase activity as well as hTERT overexpression. They may precede DNA replication error, DNA hypermethylation, CD44 abnormal transcript, and p53 mutations, all of which occur in at least 30% of intestinal metaplasias as early events of multi-step pathogenesis of well-differentiated type gastric cancer. Here, we propose a new concept for gastric preneoplasic lesion, ”metaplastic dysplasia”, based on our molecular observations. Springer-Verlag Berlin Heidelberg, 2000 Key words Gastric cancer nationallicence Intestinal metaplasia nationallicence Helicobacter pylori nationallicence hTERT nationallicence Telomere nationallicence Kuniyasu H. First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan e-mail: kuni@mcai.med.hiroshima-u.ac.jp Tel.: +81-82-2575145 Fax: +81-82-2575149, JP aut Yasui W. First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan e-mail: kuni@mcai.med.hiroshima-u.ac.jp Tel.: +81-82-2575145 Fax: +81-82-2575149, JP aut Yokozaki H. First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan e-mail: kuni@mcai.med.hiroshima-u.ac.jp Tel.: +81-82-2575145 Fax: +81-82-2575149, JP aut Tahara E. First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan e-mail: kuni@mcai.med.hiroshima-u.ac.jp Tel.: +81-82-2575145 Fax: +81-82-2575149, JP aut https://doi.org/10.1007/s004230050248 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004230050248 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kuniyasu H. First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan e-mail: kuni@mcai.med.hiroshima-u.ac.jp Tel.: +81-82-2575145 Fax: +81-82-2575149, JP aut NATIONALLICENCE 700 1- Yasui W. First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan e-mail: kuni@mcai.med.hiroshima-u.ac.jp Tel.: +81-82-2575145 Fax: +81-82-2575149, JP aut NATIONALLICENCE 700 1- Yokozaki H. First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan e-mail: kuni@mcai.med.hiroshima-u.ac.jp Tel.: +81-82-2575145 Fax: +81-82-2575149, JP aut NATIONALLICENCE 700 1- Tahara E. First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan e-mail: kuni@mcai.med.hiroshima-u.ac.jp Tel.: +81-82-2575145 Fax: +81-82-2575149, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer