title: TNP-470 inhibits growth and the production of vascular endothelial growth factor of uterine carcinosarcoma cells in vitro.
abstract: BACKGROUND
  Carcinosarcoma is the most aggressive neoplasm among the known uterine malignancies. Most patients who are affected with this biphasic neoplasm hardly show any response to common anti-cancer drugs or radiotherapy and thus they tend to show an extremely poor prognosis. This is the first study to examine the inhibitory and anti-angiogenic effects of angiogenesis inhibitor TNP-470, a synthetic analogue of fumagillin, for human uterine carcinosarcoma in vitro.
  
  
  METHODS
  The direct growth-inhibitory effect of TNP-470 was examined by an MTT assay in vitro. The levels of vascular endothelial growth factor (VEGF) in the culture supernate of TNP-470 treated FU-MMT-1 cells were also analyzed by an enzyme-linked immunosorbent assay (ELISA). The VEGF expression of TNP-470 treated FU-MMT-1 cells was also immunohistochemically examined using an anti-VEGF antibody.
  
  
  RESULTS
  TNP-470 inhibited the growth of FU-MMT-1 cells in vitro. The level of VEGF in the culture supernatant of TNP-470 treated FU-MMT-1 cells was significantly lower than that of the control (TNP-470 untreated FU-MMT-1 cells) in vivo. The expression of VEGF in TNP-470 treated FU-MMT-1 cells immunocytochemically decreased in comparison to that of the control TNP-470 untreated FU-MMT-1 cells).
  
  
  CONCLUSIONS
  Our in vitro findings suggest that this angiogenesis inhibitor, TNP-470, might be a novel therapeutic agent for uterine carcinosarcoma. However, further in vivo experimental studies using TNP-470 for this tumor will be necessary before any definitive conclusions can be made.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Japan. mm036123@msat.fukuoka-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Emoto
authors.forename: M
authors.initials: M
authors.lastname: Ishiguro
authors.forename: H
authors.initials: H
authors.lastname: Iwasaki
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: T
authors.initials: T
authors.lastname: Kawarabayashi
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002296:Carcinosarcoma / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D003510:Cyclohexanes; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D003510:Cyclohexanes; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077609:O-(Chloroacetylcarbamoyl)fumagillol