{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:16:43Z","timestamp":1763036203782},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":4828,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Surgical Oncology"],"published-print":{"date-parts":[[1993,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The effects of cholecystokinin (CCK) and a CCK antagonist, loxiglumide (CR\u20101505), on four freshly separated and six xenografted human pancreatic cancers, were investigated. The level of DNA synthesis in only one of five tested pancreatic cancers was enhanced by CCK at concentrations of 0.01\u201310 nM, while in the other four cancers DNA synthesis was not affected. The levels of DNA, RNA, and protein synthesis (by <jats:sup>3<\/jats:sup>H\u2010thymidine, <jats:sup>3<\/jats:sup>H\u2010uridine, and <jats:sup>3<\/jats:sup>H\u2010leucine incorporation tests, respectively) in all the tested cancers were dose\u2010dependently inhibited by loxiglumide at concentrations of 20\u20132000 \u03bcM, and the IC<jats:sub>50<\/jats:sub> of loxiglumide for DNA synthesis in pancreatic cancers was 156 \u00b1 80 \u03bcM (means \u00b1 SD). The in vivo effect of loxiglumide was assessed using a xenografted line (PC\u2010HN) transplanted in nude mice. The in vivo 50% lethal dose of loxiglumide for nude mice was about 500 mg\/kg. Death was caused by respiratory failure due to severe congestion of the lung after the administration of a large dose of loxiglumide. The growth of a PC\u2010HN transplanted in the nude mice was significantly inhibited by subcutaneous loxiglumide at 250 mg\/kg, twice a day for 28 days, which did not cause death. It is suggested that loxiglumide inhibits the in vivo and in vitro growth of human pancreatic cancer, perhaps independently of its action as a CCK antagonist, and this study also suggests that loxiglumide may be a new type of therapeutic agent to be used for the treatment of human pancreatic cancer. \u00a9 1993 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jso.2930530113","type":"journal-article","created":{"date-parts":[[2007,2,20]],"date-time":"2007-02-20T13:02:21Z","timestamp":1171976541000},"page":"47-53","source":"Crossref","is-referenced-by-count":9,"title":["Inhibitory effects of a cholecystokinin antagonist, loxiglumide (CR\u20101505), on the growth of freshly separated and xenografted human pancreatic cancer"],"prefix":"10.1002","volume":"53","author":[{"given":"Hideki","family":"Morimoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Nio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michihiko","family":"Tsubono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen\u2010Chiu","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Kawabata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshikazu","family":"Masai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuo","family":"Baba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadao","family":"Manabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youhei","family":"Hosokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayoshi","family":"Tobe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,20]]},"reference":[{"key":"e_1_2_1_2_2","volume-title":"A Report on the Patients Registered With Pancreatic Cancer","author":"Japanese Study Group","year":"1982"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01656020"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.250.11.1433"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01655810"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)72307-0"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.1.248"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-175-41797"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.4.1112"},{"key":"e_1_2_1_10_2","first-page":"1293","article-title":"Bombesin inhibits growth of a xenografted human adenocarcinoma","volume":"92","author":"Alexander RW","year":"1987","journal-title":"Gastroenterology"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1982.242.3.C250"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(19)33077-X"},{"key":"e_1_2_1_13_2","first-page":"73","article-title":"The trophic influence of cholecystokinin on the rat pancreas","volume":"238","author":"Barrowman JA","year":"1973","journal-title":"J Physiol"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107418"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(76)80024-8"},{"key":"e_1_2_1_16_2","first-page":"1150","article-title":"CCK stimulates growth of human pancreatic cancer","volume":"31","author":"Smith JP","year":"1986","journal-title":"Dig Dis Sci"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9610(89)90582-5"},{"key":"e_1_2_1_18_2","first-page":"3651","article-title":"Attivita antisecretiva di alcuni nuovi composti privi di attivita anticolenergica","volume":"58","author":"Rovati AL","year":"1967","journal-title":"Minerva Med"},{"key":"e_1_2_1_19_2","first-page":"1048","article-title":"New glutaramic acid derivatives with potent competitive and specific cholecystokinin\u2010antagonistic activity","volume":"35","author":"Makovec F","year":"1985","journal-title":"Arzneimforsch Drug Res"},{"key":"e_1_2_1_20_2","unstructured":"SentnikarI:Experimental characterization of a new pharmacological class: the CCK receptor antagonists. 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