Inhibition by an angiogenesis inhibitor, TNP-470, of the growth of a human hepatoblastoma heterotransplanted into nude mice.
OBJECTIVE
The effect of TNP-470, an angiogenesis inhibitor, on the growth of a hepatoblastoma transplanted into nude mice was examined.


METHODS
A hepatoblastoma obtained from a 3-year-old girl was serially transplanted into nude mice subcutaneously, and the transplant tumors of the seventh and eighth generations were used for experiments. Expression of various markers in the tumors was examined immunohistochemically. TNP-470 was injected subcutaneously every other day into tumor-bearing mice from 3 weeks after tumor transplantation. The proliferation of tumor cells and endothelial cells was estimated by means of the bromodeoxyuridine labeling index.


RESULTS
The original hepatoblastoma showed the histology of the epithelial type, consisting of both the fetal and embryonal subtypes and was positively stained with anti-alpha-fetoprotein (AFP), anti-cytokeratin-19 and polyclonal anticarcinoembryonic antigen antibodies, and an antihuman hepatocyte antibody (hepatocyte paraffin 1). The transplant tumors consisted of solid nests of tumor cells with numerous vascular lakes of various sizes, and showed positive staining with all antibodies that reacted positively with the original hepatoblastoma. Injections of TNP-470 at the doses of 15 mg and 30 mg/kg body weight suppressed the tumor growth and the increase in the serum level of AFP dose dependently. Injections of TNP-470 also suppressed the proliferation of tumor cells and endothelial cells in the tumors.


CONCLUSIONS
Hepatoblastomas maintained in nude mice retained the immunohistochemical characteristics of the original hepatoblastoma, and TNP-470 suppressed the growth of hepatoblastomas transplanted into nude mice. TNP-470 may be worth investigating further as to its usefulness as a therapy for hepatoblastomas.
Matsusaka
S
S
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
Nakasho
K
K
Terada
N
N
Sugihara
A
A
Tsujimura
T
T
Takanashi
T
T
Uematsu
K
K
Okamoto
E
E
Toyosaka
A
A
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002675:Child, Preschool; D003510:Cyclohexanes; D005260:Female; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D000509:alpha-Fetoproteins / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000509:alpha-Fetoproteins; D000077609:O-(Chloroacetylcarbamoyl)fumagillol