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Screening for supra-additive effects of cytotoxic drugs and gamma irradiation in an in vitro model for hepatocellular carcinoma

Bieke Lambert (UGent) , Leo De Ridder, Guido Slegers (UGent) , Virginie de Gelder (UGent) , Rudi Dierckx (UGent) and Hubert Thierens (UGent)
Author
Organization
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. A wide variety of treatment modalities is available for palliative therapy of HCC, although there is no strong evidence that these treatments can have a significant impact on survival. The aim of this work was to screen cytotoxic drugs relevant in the treatment of HCC for enhancement of the effect of irradiation in an in vitro model. As the majority of patients presenting with HCC suffer reduced liver function, attention was paid to low-dose effects of the cytotoxic drugs tested. To reflect this situation in vivo, multicellular tumor aggregates or "spheroids" of HepG2 cells were cultured and exposed to gamma irradiation alone or in combination with cisplatin for 4 h, gemcitabin for 4 or 24 h, or 5-fluorouracil for 4 h. In one experiment, the spheroids were cultured for 4 weeks in multiwell plates that allowed adhesion. Measurement of two-dimensional spheroid outgrowth was made every week for each spheroid. This kind of growth depends on the proliferation and motility of the cells that form the spheroid. In a second experiment, toxicity was evaluated by comparative growth curves by means of a three-dimensional growth assay and by histology. Supra-additive effects lasting for 4 weeks were observed for all drugs tested in combination with a gamma irradiation of 10 Gy.
Keywords
TRIAL, CELL, CANCER, CHEMOTHERAPY, THERAPY, MULTICELLULAR TUMOR SPHEROIDS, TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION, gamma irradiation, 5-fluorouracil, gemcitabine, cisplatin, hepatocellular carcinoma

Citation

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MLA
Lambert, Bieke, Leo De Ridder, Guido Slegers, et al. “Screening for Supra-additive Effects of Cytotoxic Drugs and Gamma Irradiation in an in Vitro Model for Hepatocellular Carcinoma.” CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 82.2 (2004): 146–152. Print.
APA
Lambert, Bieke, De Ridder, L., Slegers, G., de Gelder, V., Dierckx, R., & Thierens, H. (2004). Screening for supra-additive effects of cytotoxic drugs and gamma irradiation in an in vitro model for hepatocellular carcinoma. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 82(2), 146–152. Presented at the 6th International symposium of Fundamental and Applied Radiobiology.
Chicago author-date
Lambert, Bieke, Leo De Ridder, Guido Slegers, Virginie de Gelder, Rudi Dierckx, and Hubert Thierens. 2004. “Screening for Supra-additive Effects of Cytotoxic Drugs and Gamma Irradiation in an in Vitro Model for Hepatocellular Carcinoma.” Canadian Journal of Physiology and Pharmacology 82 (2): 146–152.
Chicago author-date (all authors)
Lambert, Bieke, Leo De Ridder, Guido Slegers, Virginie de Gelder, Rudi Dierckx, and Hubert Thierens. 2004. “Screening for Supra-additive Effects of Cytotoxic Drugs and Gamma Irradiation in an in Vitro Model for Hepatocellular Carcinoma.” Canadian Journal of Physiology and Pharmacology 82 (2): 146–152.
Vancouver
1.
Lambert B, De Ridder L, Slegers G, de Gelder V, Dierckx R, Thierens H. Screening for supra-additive effects of cytotoxic drugs and gamma irradiation in an in vitro model for hepatocellular carcinoma. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY. 2004;82(2):146–52.
IEEE
[1]
B. Lambert, L. De Ridder, G. Slegers, V. de Gelder, R. Dierckx, and H. Thierens, “Screening for supra-additive effects of cytotoxic drugs and gamma irradiation in an in vitro model for hepatocellular carcinoma,” CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, vol. 82, no. 2, pp. 146–152, 2004.
@article{218180,
  abstract     = {{Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. A wide variety of treatment modalities is available for palliative therapy of HCC, although there is no strong evidence that these treatments can have a significant impact on survival. The aim of this work was to screen cytotoxic drugs relevant in the treatment of HCC for enhancement of the effect of irradiation in an in vitro model. As the majority of patients presenting with HCC suffer reduced liver function, attention was paid to low-dose effects of the cytotoxic drugs tested. To reflect this situation in vivo, multicellular tumor aggregates or "spheroids" of HepG2 cells were cultured and exposed to gamma irradiation alone or in combination with cisplatin for 4 h, gemcitabin for 4 or 24 h, or 5-fluorouracil for 4 h. In one experiment, the spheroids were cultured for 4 weeks in multiwell plates that allowed adhesion. Measurement of two-dimensional spheroid outgrowth was made every week for each spheroid. This kind of growth depends on the proliferation and motility of the cells that form the spheroid. In a second experiment, toxicity was evaluated by comparative growth curves by means of a three-dimensional growth assay and by histology. Supra-additive effects lasting for 4 weeks were observed for all drugs tested in combination with a gamma irradiation of 10 Gy.}},
  author       = {{Lambert, Bieke and De Ridder, Leo and Slegers, Guido and de Gelder, Virginie and Dierckx, Rudi and Thierens, Hubert}},
  issn         = {{0008-4212}},
  journal      = {{CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY}},
  keywords     = {{TRIAL,CELL,CANCER,CHEMOTHERAPY,THERAPY,MULTICELLULAR TUMOR SPHEROIDS,TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION,gamma irradiation,5-fluorouracil,gemcitabine,cisplatin,hepatocellular carcinoma}},
  language     = {{eng}},
  location     = {{Batz sur Mer, France}},
  number       = {{2}},
  pages        = {{146--152}},
  title        = {{Screening for supra-additive effects of cytotoxic drugs and gamma irradiation in an in vitro model for hepatocellular carcinoma}},
  url          = {{http://dx.doi.org/10.1139/Y04-008}},
  volume       = {{82}},
  year         = {{2004}},
}

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