{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:50:23Z","timestamp":1791021023200,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,4,15]],"date-time":"2008-04-15T00:00:00Z","timestamp":1208217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    TNF\u2010\u03b1 inducing protein (Tip\u03b1) is secreted from\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    (\n                    <jats:italic>H. pylori<\/jats:italic>\n                    ): it is a potent inducer of\n                    <jats:italic>TNF\u2010<\/jats:italic>\n                    \u03b1 and\n                    <jats:italic>chemokine<\/jats:italic>\n                    genes, mediated through NF\u2010\u03baB activation, and it also induces tumor\u2010promoting activity in Bhas 42 cells. To investigate the carcinogenic mechanisms of\n                    <jats:italic>H. pylori<\/jats:italic>\n                    with Tip\u03b1, we first examined how Tip\u03b1 acts on gastric epithelial cells. We found that fluorescent\u2010Tip\u03b1 specifically bound to, and then entered, the cells in a dose\u2010 and temperature\u2010dependent manner, whereas deletion mutant of Tip\u03b1 (del\u2010Tip\u03b1), an inactive form, neither bound to nor entered the cells, suggesting the presence of a specific binding molecule. Mutagenesis analysis of Tip\u03b1 revealed that a dimer formation of Tip\u03b1 with a disulfide bond is required for both specific binding and induction of\n                    <jats:italic>TNF\u2010<\/jats:italic>\n                    \u03b1 gene expression. A confocal laser scanning microscope revealed some Tip\u03b1 in the nuclei, but del\u2010Tip\u03b1 was not present, which indicated that an active form of Tip\u03b1 can penetrate the nucleus and may be involved in the induction of\n                    <jats:italic>TNF\u2010<\/jats:italic>\n                    \u03b1 gene expression. Examination of Tip\u03b1 production and secretion in 28 clinical isolates revealed that\n                    <jats:italic>H. pylori<\/jats:italic>\n                    obtained from gastric cancer patients secreted Tip\u03b1 in significantly higher amounts than did\n                    <jats:italic>H. pylori<\/jats:italic>\n                    from patients with chronic gastritis, suggesting that Tip\u03b1 is an essential factor in\n                    <jats:italic>H. pylori<\/jats:italic>\n                    inflammation and cancer microenvironment in the human stomach. Tip\u03b1 is thus a new carcinogenic factor of\n                    <jats:italic>H. pylori<\/jats:italic>\n                    that can enter the nucleus through a specific binding molecule, and its mechanism of action is completely different from that of CagA. \u00a9 2008 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ijc.23484","type":"journal-article","created":{"date-parts":[[2008,4,15]],"date-time":"2008-04-15T18:13:21Z","timestamp":1208283201000},"page":"117-122","source":"Crossref","is-referenced-by-count":70,"title":["TNF\u2010\u03b1\u2010inducing protein, a carcinogenic factor secreted from\n                    <i>H. pylori<\/i>\n                    , enters gastric cancer cells"],"prefix":"10.1002","volume":"123","author":[{"given":"Masami","family":"Suganuma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensei","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshie","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruo","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazue","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kuzuhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Nishizono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirota","family":"Fujiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,4,24]]},"reference":[{"key":"e_1_2_6_2_2","series-title":"IARC monographs on the evaluation of carcinogenic risks to humans","first-page":"1","volume-title":"Schistosomes, liver flukes and Helicobacter pylori","author":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans","year":"1994"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc703"},{"key":"e_1_2_6_4_2","first-page":"4516","article-title":"Essential role of tumor necrosis factor \u03b1 (TNF\u2010\u03b1) in tumor promotion as revealed by TNF\u2010\u03b1\u2010deficient mice","volume":"59","author":"Suganuma M","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_6_5_2","first-page":"131","article-title":"Discrete roles of cytokines. TNF\u2010\u03b1, IL\u20101, IL\u20106 in tumor promotion and cell transformation","volume":"20","author":"Suganuma M","year":"2002","journal-title":"Int J Oncol"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/10552"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-004-0652-x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2006.39.1.001"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-006-0169-6"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/41483"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/16495"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.1.286-293.1999"},{"key":"e_1_2_6_13_2","first-page":"6356","article-title":"Helicobacter pylori membrane protein 1: a new carcinogenic factor of Helicobacter pylori","volume":"61","author":"Suganuma M","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.2133"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.08.058"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1998.tb03292.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.11.6846-6852.2001"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1079"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600183200"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.42.3.338"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1994.tb02656.x"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90263-2"},{"key":"e_1_2_6_23_2","unstructured":"InoueK SuganumaM ShiotaS MurakamiK FujiokaT NishizonoA.Effects of nasal vaccination with TNF\u2010\u03b1 inducing protein (Tip\u03b1) againstHelicobacter\u2010infected mice. 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