title: Short-term effects of TNP-470 in combination with cisplatin in the rat model of bladder cancer.
abstract: OBJECTIVE
  To investigate the short-term effects of TNP-470 in combination with cisplatin in a rat model of bladder cancer.
  
  
  METHODS
  Following treatment of TNP-470 with or without cisplatin for 7 days, the states of angiogenesis, apoptosis and cell proliferation were evaluated in rat bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.
  
  
  RESULTS
  In comparison with untreated tumors, we noted a significantly decreased microvessel density (MVD) in the rat bladder cancer treated by TNP-470, and a significantly increased apoptotic index (AI) when treated by cisplatin. In TNP-470 plus cisplatin-treated tumors, both significantly decreased MVD and increased AI were observed in non-invasive and invasive rat bladder cancers in addition to a significantly decreased proliferation index (PI) in invasive cancer.
  
  
  CONCLUSIONS
  The combination therapy of TNP-470 with cisplatin may act through both the inhibition of angiogenesis and induction of apoptosis, and invasive tumor cells may be much more sensitive to this combined therapy in rat bladder cancer.
authors.affiliation: Department of Urology, Kagawa Medical University, 1750-1 Miki-cho Kita-gun, Kagawa 761-0793, Japan. zhang@kms.ac.jp
authors.forename: Xianghua
authors.initials: X
authors.lastname: Zhang
authors.forename: Motoki
authors.initials: M
authors.lastname: Yamashita
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uetsuki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kakehi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D003510:Cyclohexanes; D004273:DNA, Neoplasm / Q000032:analysis; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D008833:Microcirculation / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012717:Sesquiterpenes; D002945:Cisplatin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol