Successful therapy of subcutaneously growing human hepatoblastoma xenografts with topotecan.

Abstract

BACKGROUND:

Human hepatoblastoma is an infrequent liver tumor in children. Although many hepatoblastomas can be treated adequately with well-defined treatment regimens, problems still persist with advanced and non-resectable tumors; in these cases, an effective chemotherapy is necessary to improve the patients' prognosis. This underlines the need for alternative anti-tumor agents in the treatment of human hepatoblastoma. The aim of this study was to investigate the therapeutic effects of topotecan, a water-soluble camptothecin analog (topoisomerase-I-antagonist), in an in vivo model of three human hepatoblastomas xenografted subcutaneously into nude mice.

PROCEDURE:

Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into nude mice NMRI (nu/nu). Treatment with topotecan was initiated when the tumors reached a volume between 50 and 80 mm(3). A dose of 6.6 mg/kg of topotecan were given intraperitoneally every 4 days on four occasions. The tumor volume development and alpha-fetoprotein alterations were measured and statistically analyzed. After the treatment, the tumors were investigated histologically and by immunohistochemistry.

RESULTS:

There was a significant reduction of tumor growth in all treated tumor xenografts vs. untreated control groups (mean relative volume 3.1 vs. 47.4; P = 0,0015-0,0079). Serum alpha-fetoprotein levels were reduced in all three cell lines, in two of them significantly (mean 44,535 kU/l vs. 228,883 kU/l; P = 0.005-0.246). Histologically, the tumor necrosis rates were higher and immunohistochemistry showed lower proliferation activities in the treated tumor xenografts vs. the control groups.

CONCLUSION:

The data show that topotecan is an effective agent in the treatment of human hepatoblastoma xenografts. From these results, treatment with topotecan appears to be a promising alternative in the pre- and postoperative therapy of patients suffering from human hepatoblastoma

• Authors: S W Warmann, J Fuchs, L Wilkens, K F Gratz, D von Schweinitz, H Mildenberger
• Journal: Medical and pediatric oncology (Med Pediatr Oncol) Vol. 37 Issue 5 Pg. 449-54 (Nov 2001) ISSN: 0098-1532 [Print] United States
• PMID: 11745873 (Publication Type: Journal Article)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• Antineoplastic Agents
• alpha-Fetoproteins
• Topotecan

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Cell Division (drug effects)
• Hepatoblastoma (drug therapy, pathology)
• Humans
• Immunohistochemistry
• Infant, Newborn
• Infusions, Parenteral
• Liver Neoplasms (drug therapy, pathology)
• Mice
• Mice, Nude
• Necrosis
• Neoplasms, Experimental
• Topotecan (administration & dosage, pharmacology)
• Transplantation, Heterologous
• alpha-Fetoproteins (analysis)