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

2006 ◽  
Vol 84 (10) ◽  
pp. 1021-1028 ◽  
Author(s):  
Bieke Lambert ◽  
Leo De Ridder ◽  
Filip De Vos ◽  
Guido Slegers ◽  
Virginie de Gelder ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dose Rate ◽  
In Vitro Model ◽  
Low Dose ◽  
High Dose ◽  
Additive Effects ◽  
Multicellular Spheroids ◽  
Low Dose Rate ◽  
Vitro Model

The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement of the effects of low dose rate (LDR) irradiation in an in vitro model for hepatocellular carcinoma. For comparison, all drugs were tested in combination with high dose rate (HDR) γ-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 (188Re), 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 188Re, the supra-additive toxicity was only transient. For topotecan and 188Re, no 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 gemcitabine 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 188Re, no lasting supra-additive effects were observed.

scholarly journals Low Dose Rate Radiosensitization of Hepatocellular Carcinoma In Vitro and in Patients

2014 ◽  
Vol 7 (4) ◽  
pp. 472-478 ◽  
Author(s):  
Kyle C. Cuneo ◽  
Mary A. Davis ◽  
Mary U. Feng ◽  
Paula M. Novelli ◽  
William D. Ensminger ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dose Rate ◽  
Low Dose ◽  
Low Dose Rate

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

2004 ◽  
Vol 82 (2) ◽  
pp. 146-152 ◽  
Author(s):  
B Lambert ◽  
L De Ridder ◽  
G Slegers ◽  
V de Gelder ◽  
R A Dierckx ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gamma Irradiation ◽  
In Vitro Model ◽  
Palliative Therapy ◽  
Cytotoxic Drugs ◽  
Treatment Modalities ◽  
Additive Effects ◽  
Vitro Model

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.Key words: hepatocellular carcinoma, cisplatin, gemcitabine, 5-fluorouracil, gamma irradiation.

LOW-DOSE-RATE OR HIGH-DOSE-RATE BRACHYTHERAPY IN COMBINATION WITH EXTERNAL BEAM RADIOTHERAPY FOR INTERMEDIATE AND HIGH-RISK PROSTATE CANCER

2018 ◽  
Vol 64 (1) ◽  
pp. 79-83
Author(s):  
Vladimir Solodkiy ◽  
Andrey Pavlov ◽  
Aleksey Tsybulskiy ◽  
Anton Ivashin
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Dose Rate ◽  
Low Dose ◽  
External Beam Radiotherapy ◽  
Combined Treatment ◽  
High Dose ◽  
External Beam ◽  
Low Dose Rate ◽  
Risk Of Progression

Introduction. One of the main problems of modem on-courology is treatment for prostate cancer of intermediate and high risk of progression. Modern radiotherapy in this category of patients has an advantage over surgical methods of treatment. One way to improve the effectiveness of radiotherapy is to escalate the dose in the prostate gland. For this purpose a combination of brachytherapy and remote radiotherapy is used. This combination allows increasing the dose of radiation, thereby providing better local control, reducing complications from neighboring organs. Purpose of the study. To conduct a comparative analysis of efficacy and safety of radical treatment of patients with prostate cancer at medium and high risk of progression using a combination of high and low dose rate brachytherapy with external beam radiotherapy. Materials and methods. 107 patients with prostate cancer of the group of medium and high risk of progression combined treatment (brachytherapy with external beam radiotherapy) was conducted. 53 patients underwent combined treatment (HDR-brachytherapy and external beam radiotherapy). 54 patients underwent combined treatment (LDR-brachytherapy and external beam radiotherapy). The observation period was 5 years. Conclusion. In a comparative analysis in groups of combined radiotherapy with the use of high-dose and low-dose-rate brachytherapy, the same effectiveness of immediate and long-term results of treatment was demonstrated. A significant reduction in early and late toxic reactions in patients with high-power brachytherapy has been demonstrated.

Activated human N-ras oncogene enhances x-irradiation repair of mammalian cells in vitro less effectively at low dose rate

1985 ◽  
Vol 8 (6) ◽  
pp. 517-522 ◽  
Author(s):  
T. J. FitzGerald ◽  
C. Daugherty ◽  
K. Kase ◽  
L. A. Rothstein ◽  
M. McKenna ◽  
...  
Keyword(s):  
Dose Rate ◽  
Mammalian Cells ◽  
Low Dose ◽  
Ras Oncogene ◽  
Low Dose Rate ◽  
X Irradiation
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