http://www3.interscience.wiley.com/cgi-bin/abstract/110506993/ABSTRACT
Research Article
Role of heat treatment in childhood cancers: Distinct resistance
profiles of solid tumor cell lines towards combined thermochemotherapy
Anette Debes, PhD 1, Reinhart Willers, PhD 2, Ulrich Göbel, MD 1,
Rüdiger Wessalowski, MD 1 *
1 Clinic of Pediatric Oncology, Hematology and Immunology,
Heinrich-Heine-University, Düsseldorf, Germany
2 Computer Center, Heinrich-Heine-University Düsseldorf, Düsseldorf,
Germany
email: Rüdiger Wessalowski (wessalowski@med.uni-duesseldorf.de)
*Correspondence to Rüdiger Wessalowski, Clinic of Pediatric Oncology,
Hematology and Immunology, Heinrich-Heine-University, Moorenstreet 5,
40225 Düsseldorf, Germany.
Funded by:
Elterninitiative Kinderkrebsklinik e.V. Düsseldorf
Keywords
chemosensitivity • pediatric tumors • thermosensitivity • XTT-assay
Abstract
Background
Since information on the efficacy of hyperthermia in combination with
chemotherapy on pediatric tumors is limited, we performed a systematic
analysis on the synergistic effects of a combined application of heat
and chemotherapy on 20 tumor cell lines derived from patients with
neuroblastomas, Ewing tumors, germ cell tumors (GCT), and osteosarcomas.
Methods
Cisplatin (cDDP), a cross-linking agent, and etoposide (VP-16), a
topoisomerase II inhibitor, were examined either alone or in
combination with heat (42°C, 43°C) by using the XTT-assay [1].
Results
Our data demonstrate that heat stress at 43°C for 1 hr, but not at
42°C, leads to a notable cytotoxic effect on the different tumor cells.
The comparison of mean survival fractions reveals values between 62%
for neuroblastoma cells and 76% for Ewing tumor cells. Analyzing the
sensitivity to chemotherapy alone, our results show that cDDP (5 g/ml)
reduces cell growth to 47% in Ewing tumor cells, to 61% in
neuroblastoma cells, to 75% in GCT cells, and to 76% in osteosarcoma
cells. Treatment with VP-16 (10 g/ml) decreases cell survival to mean
values between 58% (neuroblastomas) and 77% (osteosarcomas).
Simultaneous application of heat and chemotherapy enhances
synergistically cDDP cytotoxicity in all tumor types tested, whereas
the efficacy of VP-16 is only slightly influenced by additional
application of hyperthermia. The cytotoxicity of cDDP (5 g/ml) can be
increased by a factor of between 1.5 and 2.5 at 42°C and from 2.6 to
14.0 at 43°C. Furthermore, the results show that the sensitivity to
heat (43°C) as well as the sensitivity to chemotherapy and combined
thermochemotherapy varies considerably between cell lines of the same
tumor group.
Conclusions
Simultaneous application of hyperthermia synergistically enhances the
cytotoxicity of the alkylating agent cDDP, but not of the topoisomerase
II inhibitor VP-16, in a defined spectrum of cell lines from different
pediatric tumor entities.
© 2005 Wiley-Liss, Inc.