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Assessment of supra-additive effects of cytotoxic drugs and low dose rate irradiation in an in vitro model for hepatocellular carcinoma

Bieke Lambert (UGent) , Leo De Ridder (UGent) , Filip De Vos (UGent) , Guido Slegers (UGent) , Virginie de Gelder (UGent) , Christophe Van De Wiele (UGent) and Hubert Thierens (UGent)
Author
Organization
Abstract
The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement of the effects of low dose rate (LDR) irradiation in,in in vitro model for hepatocellular carcinoma. For comparison, all drugs were tested in combination with high dose rate (HDR) gamma-irradiation as well. Multicellular spheroids of HepG2 cells were exposed to HDR or LDR irradiation by means of external beam cobalt-60 or rhenium-188 (Re-188), respectively, dissolved in the Culture medium. Secondly, exposure to irradiation was combined with the cytotoxic drug. Toxicity was evaluated by means of a quantitative spheroid outgrowth assay and histology. For 5-fluorouracil, supra-additive effects were observed in combination with HDR irradiation. With Re-188, the supra-additive toxicity was only transient. For topotecan and Re-188, 110 supra-additive effects were seen, whereas the addition of HDR irradiation at the end of the topotecan exposure yielded lasting supra-additive effects. Incubation with gemcitabine followed by exposure to HDR irradiation, induced a synergistic toxicity on the outgrowth. No supra-additive effects were observed when HDR irradiation was added at the start of the incubation with gemicitabine or combined with LDR irradiation. For all drugs tested, supra-additive effects were observed with HDR irradiation if the timing of the irradiation was appropriate. For Re-188, no lasting supra-additive effects were observed.
Keywords
TUMOR, rhenium-188, LIPIODOL, TRIAL, CHEMOTHERAPY, RADIATION, THERAPY, dose rate, TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION, hepatocellular carcinoma, CELL, RADIOIMMUNOTHERAPY, EMBOLIZATION

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MLA
Lambert, Bieke, Leo De Ridder, Filip De Vos, et al. “Assessment of Supra-additive Effects of Cytotoxic Drugs and Low Dose Rate Irradiation in an in Vitro Model for Hepatocellular Carcinoma.” CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 84.10 (2006): 1021–1028. Print.
APA
Lambert, Bieke, De Ridder, L., De Vos, F., Slegers, G., de Gelder, V., Van De Wiele, C., & Thierens, H. (2006). Assessment of supra-additive effects of cytotoxic drugs and low dose rate irradiation in an in vitro model for hepatocellular carcinoma. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 84(10), 1021–1028.
Chicago author-date
Lambert, Bieke, Leo De Ridder, Filip De Vos, Guido Slegers, Virginie de Gelder, Christophe Van De Wiele, and Hubert Thierens. 2006. “Assessment of Supra-additive Effects of Cytotoxic Drugs and Low Dose Rate Irradiation in an in Vitro Model for Hepatocellular Carcinoma.” Canadian Journal of Physiology and Pharmacology 84 (10): 1021–1028.
Chicago author-date (all authors)
Lambert, Bieke, Leo De Ridder, Filip De Vos, Guido Slegers, Virginie de Gelder, Christophe Van De Wiele, and Hubert Thierens. 2006. “Assessment of Supra-additive Effects of Cytotoxic Drugs and Low Dose Rate Irradiation in an in Vitro Model for Hepatocellular Carcinoma.” Canadian Journal of Physiology and Pharmacology 84 (10): 1021–1028.
Vancouver
1.
Lambert B, De Ridder L, De Vos F, Slegers G, de Gelder V, Van De Wiele C, et al. Assessment of supra-additive effects of cytotoxic drugs and low dose rate irradiation in an in vitro model for hepatocellular carcinoma. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY. 2006;84(10):1021–8.
IEEE
[1]
B. Lambert et al., “Assessment of supra-additive effects of cytotoxic drugs and low dose rate irradiation in an in vitro model for hepatocellular carcinoma,” CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, vol. 84, no. 10, pp. 1021–1028, 2006.
@article{413589,
  abstract     = {The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement of the effects of low dose rate (LDR) irradiation in,in in vitro model for hepatocellular carcinoma. For comparison, all drugs were tested in combination with high dose rate (HDR) gamma-irradiation as well. Multicellular spheroids of HepG2 cells were exposed to HDR or LDR irradiation by means of external beam cobalt-60 or rhenium-188 (Re-188), respectively, dissolved in the Culture medium. Secondly, exposure to irradiation was combined with the cytotoxic drug. Toxicity was evaluated by means of a quantitative spheroid outgrowth assay and histology. For 5-fluorouracil, supra-additive effects were observed in combination with HDR irradiation. With Re-188, the supra-additive toxicity was only transient. For topotecan and Re-188, 110 supra-additive effects were seen, whereas the addition of HDR irradiation at the end of the topotecan exposure yielded lasting supra-additive effects. Incubation with gemcitabine followed by exposure to HDR irradiation, induced a synergistic toxicity on the outgrowth. No supra-additive effects were observed when HDR irradiation was added at the start of the incubation with gemicitabine or combined with LDR irradiation. For all drugs tested, supra-additive effects were observed with HDR irradiation if the timing of the irradiation was appropriate. For Re-188, no lasting supra-additive effects were observed.},
  author       = {Lambert, Bieke and De Ridder, Leo and De Vos, Filip and Slegers, Guido and de Gelder, Virginie and Van De Wiele, Christophe and Thierens, Hubert},
  issn         = {0008-4212},
  journal      = {CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY},
  keywords     = {TUMOR,rhenium-188,LIPIODOL,TRIAL,CHEMOTHERAPY,RADIATION,THERAPY,dose rate,TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION,hepatocellular carcinoma,CELL,RADIOIMMUNOTHERAPY,EMBOLIZATION},
  language     = {eng},
  number       = {10},
  pages        = {1021--1028},
  title        = {Assessment of supra-additive effects of cytotoxic drugs and low dose rate irradiation in an in vitro model for hepatocellular carcinoma},
  url          = {http://dx.doi.org/10.1139/Y06-055},
  volume       = {84},
  year         = {2006},
}

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