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Effects of irradiation and cisplatin on human glioma spheroids: inhibition of cell proliferation and cell migration

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Abstract

Purpose: Investigation of cell migration and proliferation of human glioma cell line spheroids (CLS) and evaluation of morphology, apoptosis, and immunohistochemical expression of MIB-1, p53, and p21 of organotypic muticellular spheroids (OMS) following cisplatin (CDDP) and irradiation (RT). Material and methods: Spheroids of the GaMg glioma cell line and OMS prepared from biopsy tissue of six glioblastoma patients were used. Radiochemosensitvity (5 μg/ml CDDP followed by RT) was determined using migration and proliferation assays on CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21 expression were examined 24 and 48 h following treatment. Results: Combination treatment led to a migration inhibition of 38% (CDDP 13%; RT 27%) and specific growth delay of 2.6 (CDDP 1.3; RT 2.1) in CLS. Cell cycle analysis after combination treatment showed an accumulation of cells in the G2/M phase. In OMS, apoptosis increased, cell proliferation decreased, and p53/p21 expression increased more pronounced following CDDP+RT. No morphological damage was observed. Conclusion: CDDP can lead to enhancement of the RT effect in spheroids of both human glioma cell line spheroids and biopsy spheroids from glioblastoma specimens. The exerted effect is additive rather than synergistic.

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Acknowledgments

The authors acknowledge Dr. R. Bjerkvig (Department of Anatomy and Cell Biology, University of Bergen, Norway) for his hospitality during the laboratory visit of Dr. F. Fehlauer in Bergen and his critical comments on the manuscript. We also wish to thank the members of the European Cancer Centre (ECC) Neuro-Oncology Group for their collaborations, insightful discussions and encouragement. Dr. F. Fehlauer was research fellow and supported by a grand of the Deutsche Forschungsgemeinschaft (Bonn, Germany) and the ECC (Amsterdam, The Netherlands). Furthermore, we thank Dr. Dr. A.J. Terzis (Department of Neurosurgery, University of Luebeck, Germany) for providing the GaMg cell line.

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Authors and Affiliations

  1. Department of Radiation Oncology, Universitätsklinikum Eppendorf, University of Hamburg, Martinistr. 52, 20254, Hamburg, Germany

    Fabian Fehlauer, Martina Muench & Dirk Rades

  2. Department of Radiation Oncology, AMC University of Amsterdam, Amsterdam, The Netherlands

    Fabian Fehlauer & Lukas J. A. Stalpers

  3. Department of Neurosurgery, AMC University of Amsterdam, Amsterdam, The Netherlands

    Sieger Leenstra

  4. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

    Fabian Fehlauer & Paul van der Valk

  5. Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands

    Ben Slotman, Ernst J. Smid & Peter Sminia

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  1. Fabian Fehlauer
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Correspondence to Fabian Fehlauer.

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Fehlauer, F., Muench, M., Rades, D. et al. Effects of irradiation and cisplatin on human glioma spheroids: inhibition of cell proliferation and cell migration. J Cancer Res Clin Oncol 131, 723–732 (2005). https://doi.org/10.1007/s00432-005-0014-3

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  • DOI: https://doi.org/10.1007/s00432-005-0014-3

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