title: Inhibition of surgical trauma-enhanced peritoneal dissemination of tumor cells by human catalase derivatives in mice.
abstract: Surgical trauma, which is inevitably associated with the surgical removal of cancer, has been reported to accelerate tumor metastasis. The close association of reactive oxygen species with the trauma and tumor metastasis supports the possibility of using antioxidants for the inhibition of metastasis. To inhibit surgical trauma-enhanced peritoneal dissemination, human catalase (hCAT) derivatives, i.e., hCAT-nona-arginine peptide (hCAT-R9) and hCAT-albumin-binding peptide (hCAT-ABP), were designed to increase the retention time of the antioxidant enzyme in the abdominal cavity after intraperitoneal administration. Both (125)I-labeled derivatives showed significantly prolonged retention in the cavity compared to (125)I-hCAT. Cauterization of the cecum of mice with a hot iron, an experimental model of surgical trauma, induced abdominal adhesions. In addition, cauterization followed by colon26 tumor cell inoculation increased lipid peroxidation in the cecum and mRNA expression of molecules associated with tissue repair/adhesion and inflammation in the peritoneum. hCAT derivatives significantly suppressed the increased mRNA expression. The cauterization also increased the number of tumor cells in the abdominal organs, and the number was significantly reduced by hCAT-R9 or hCAT-ABP. These results indicate that hCAT-R9 and hCAT-ABP, both of which have a long retention time in the peritoneal cavity, can be effective at inhibiting surgery-induced peritoneal metastasis.
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Nishizaki
authors.forename: Makiya
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yata
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Masahide
authors.initials: M
authors.lastname: Oku
authors.forename: Hiroya
authors.initials: H
authors.lastname: Yurimoto
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Sakai
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takakura
mesh_terms: D000007:Abdominal Injuries / Q000209:etiology* / Q000517:prevention & control; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D002425:Cautery / Q000009:adverse effects*; D002432:Cecum / Q000293:injuries* / Q000601:surgery; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics; D010529:Peritoneal Cavity / Q000293:injuries* / Q000473:pathology / Q000601:surgery; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011183:Postoperative Complications; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D010446:Peptide Fragments; D002374:Catalase