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Gay H.A.,University of Washington | Taylor Q.Q.,Southern Maine Radiation Therapy Institute | Kiriyama F.,Southern Maine Radiation Therapy Institute | Dieck G.T.,Pocono Medical Center | And 4 more authors.
Computational and Mathematical Methods in Medicine | Year: 2013

Background. To characterize the lung tumor volume response during conventional and hypofractionated radiotherapy (RT) based on diagnostic quality CT images prior to each treatment fraction. Methods. Out of 26 consecutive patients who had received CT-on-rails IGRT to the lung from 2004 to 2008, 18 were selected because they had lung lesions that could be easily distinguished. The time course of the tumor volume for each patient was individually analyzed using a computer program. Results. The model fits of group L (conventional fractionation) patients were very close to experimental data, with a median Δ% (average percent difference between data and fit) of 5.1% (range 3.5-10.2%). The fits obtained in group S (hypofractionation) patients were generally good, with a median Δ% of 7.2% (range 3.7-23.9%) for the best fitting model. Four types of tumor responses were observed - Type A: "high" kill and "slow" dying rate; Type B: "high" kill and "fast" dying rate; Type C: "low" kill and "slow" dying rate; and Type D: "low" kill and "fast" dying rate. Conclusions. The models used in this study performed well in fitting the available dataset. The models provided useful insights into the possible underlying mechanisms responsible for the RT tumor volume response. © 2013 Hiram A. Gay et al.

Colombo V.,Laboratory of Anticancer Pharmacology | Lupi M.,Laboratory of Anticancer Pharmacology | Falcetta F.,Laboratory of Anticancer Pharmacology | Forestieri D.,Laboratory of Anticancer Pharmacology | And 2 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011

Purpose: The milk thistle extract silymarin, alone or in combined chemotherapy, is now under investigation in anticancer research, with particular interest for its possible employ in the treatment of chemoresistant tumours. So far, the consequences of a silymarin pre-treatment have not been thoroughly investigated. We studied whether silymarin pre-treatment synergized with chemotherapy, exploring the dose-dependence of the interaction in sensitive and multidrug-resistant cells. Methods: We studied cell cycle perturbations induced by silymarin in two colon carcinoma cell lines, LoVo and the multidrug-resistant isogenic LoVo/DX. Synergism/additivity/antagonism of silymarin-doxorubicin silymarin-paclitaxel combined treatments were evaluated by isobologram/ combination index analysis, in the whole spectrum of active and sub-active concentrations of all drugs. The mechanisms of silymarin interaction with the other drugs were investigated by measuring drug uptake and cell cycle perturbations. Results: Silymarin had similar antiproliferative activity against both cell lines. Pre-treatment with low silymarin concentrations synergised with both doxorubicin and paclitaxel in LoVo but not in LoVo/DX. Higher silymarin concentrations were additive with doxorubicin and paclitaxel in both cell lines. Silymarin favourably interfered with uptake and cell cycle effects of the chemotherapeutics in LoVo but not in LoVo/DX. Conclusion These findings confirm activity of silymarin against colon carcinoma, including multidrug-resistant types, at relatively high but clinically achievable concentrations. In view of its low toxicity, two schedules based on low-and high-dose silymarin pre-treatment might offer a valuable option for combined treatment. © Springer-Verlag 2010.

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