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Thursday 01 November 2001

Successful therapy of subcutaneously growing human hepatoblastoma xenografts with topotecan.

By: Warmann SW, Fuchs J, Wilkens L, Gratz KF, von Schweinitz D, Mildenberger H.

Med Pediatr Oncol 2001 Nov;37(5):449-54

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 Copyright 2001 Wiley-Liss, Inc.

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