Angiogenesis inhibitor, TNP-470, suppresses growth of peritoneal disseminating foci.
OBJECTIVE
Angiogenesis is critical not only for growth of primary tumors but also for cells established at distant organs. We investigated the effects of angiogenesis inhibitor, TNP-470, on the establishment and growth of intraperitoneally inoculated human gastric cancer cell line, MKN-45, and survival of nude mice with this tumor.


METHODS
Human gastric cancer cell line, MKN-45, were injected into the peritoneal cavity of an ICR nude mouse and a model of peritoneal dissemination was developed. TNP-470 was injected subcutaneously every other day from day 1 until sacrifice or death. The effects of TNP-470 on MKN-45 cells were also examined in vitro.


RESULTS
Although the number of disseminated foci was not significantly different, the maximum size was significantly smaller in a TNP-treated group than those of a control. Survival time was significantly longer in a TNP-treated group. TNP-470 demonstrated no growth inhibition of MKN45 cells in vitro.


CONCLUSIONS
Those results suggested that anti-angiogenic agent, TNP-470, might be effective in treating peritoneal dissemination of gastric cancer by inhibiting growth of the seeded tumor cells on the peritoneum.
Yoshikawa
T
T
Third Department of Surgery, Kanagawa Cancer Center, Yokohama, Japan.
Yanoma
S
S
Tsuburaya
A
A
Kobayashi
O
O
Sairenji
M
M
Motohashi
H
H
Noguchi
Y
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003510:Cyclohexanes; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D012717:Sesquiterpenes / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol