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Potent antitumor effect of 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine on peritoneal dissemination models of gastrointestinal cancers.

Abstract
We investigated the antitumor activity of the nucleoside analog 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine (4'-thio-FAC) in peritoneal dissemination models of gastrointestinal cancers. Oral administration of 4'-thio-FAC showed a marked effect on the development of ascites and on the survival of nude mice implanted with the highly metastatic MKN-45-P gastric cancer cells into the peritoneal cavity. The toxic effect was observed at a dose of 15 mg/kg, however, no toxicity was observed at a dose of 10 mg/kg with excellent antitumor activity. We established another highly metastatic cell line HCT-15-P by serial intraperitoneal passage of the colon cancer cell line HCT-15. In the HCT-15-P model, 4'-thio-FAC showed an inhibitory effect of peritoneal dissemination and an increase in the life span at a dose of 10 mg/kg. On the other hand, oral administration of 5-fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR) did not show an increase in the life span of mice at a dose of 10 mg/kg. In conclusion, 4'-thio-FAC is a promising therapeutic agent for use against peritoneal dissemination of gastrointestinal cancers.
AuthorsShinji Miura, Yoshio Endo, Yuichi Yoshimura, Mikari Endo, Yutaka Yonemura, Takuma Sasaki
JournalOncology reports (Oncol Rep) 2002 Nov-Dec Vol. 9 Issue 6 Pg. 1319-22 ISSN: 1021-335X [Print] Greece
PMID12375041 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 1-(2-deoxy-2-fluoro-4-thio-arabinofuranosyl)cytosine
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Floxuridine
  • Cytarabine
  • Fluorouracil
Topics
  • Adenocarcinoma (drug therapy, secondary)
  • Administration, Oral
  • Animals
  • Antimetabolites, Antineoplastic (pharmacology)
  • Antineoplastic Agents (therapeutic use)
  • Body Weight (drug effects)
  • Cell Division (drug effects)
  • Colonic Neoplasms (drug therapy, pathology)
  • Cytarabine (analogs & derivatives, therapeutic use)
  • Disease Models, Animal
  • Female
  • Floxuridine (pharmacology)
  • Fluorouracil (pharmacology)
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Peritoneal Neoplasms (drug therapy, secondary)
  • Stomach Neoplasms (drug therapy, pathology)
  • Survival Rate
  • Tumor Cells, Cultured

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