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Fig 1.

Temperature profile of the incubator during heat-up phase to 42°C steady-state hyperthermia.

Dots represent temperature read off the incubator display over three independent runs, and lines represent the temperature recorded by a sensor placed in the culture dish, immersed in medium during those same runs.

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Fig 2.

Effect of thermoradiotherapy treatment on clonogenic cell survival of cancer cells.

Clonogenic cell survival curves of human (A, B) and canine (C-H) cancer cell lines. The corresponding LQ parameters along with their enhancement factors are given in a Table (I). Unpaired t-test. Mean of at least three independent experiments ±SEM is shown.

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Fig 3.

Different conditions of hyperthermia pre-treatment affect radiation-sensitivity of A549 cells.

Effect of the time gap between hyperthermia and radiation on clonogenic cell survival (A). Influence of the hyperthermia temperature of 41, 42 and 43°C in combination with radiation on A549 clonogenic cell survival (B). Treatment with hyperthermia (42°C, 1 h) first versus radiation first affects clonogenic cell survival of A549 cells (C). One-way ANOVA with Dunnett’s multiple comparison test. Mean of at least three independent experiments ±SEM is shown.

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Fig 4.

Analysis of DNA damage and apoptosis/necrosis in hyperthermia, radiation and combined thermoradiotherapy-treated A549 cells.

DNA damage (tail intensity analyzed by Comet assay) in A549 cells (A). Apoptosis (B) and necrosis (C) in A549 cells 48 h after treatment. Luminescent/fluorescent signal intensity values were normalized by the number of cells (coupled luminescence assay) in each well. Mixed model ANOVA with Tukey’s multiple comparison test. Mean of three independent experiments ±SEM is shown.

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Fig 5.

Levels of HSP70 and Rad51 in control and thermoradiotherapy-treated human and canine cancer cell lines.

Cell lysates analyzed by immunoblotting for HSP70 and Rad51 and β-actin in control (-) and thermoradiotherapy (+; (42°C, heat-up plus 1 h) followed by ionizing radiation (6 Gy))-treated cells (A). Representative experiment of three experiments performed independently is shown. Quantification of HSP70 and Rad51 immunoblot signal normalized to β-actin (B). Mean of three independent experiments ±SEM is shown.

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Fig 6.

HSP70 knockdown in A549 cells.

Efficiency of HSP70 downregulation 48 h after transfection in A549 cells; immunoblot (upper panel) and relative quantification of HSP70 normalized to β-actin (lower panel) and normalized to non-transfected cells, mean of three independent experiments ±SEM is shown (A). Effect of HSP70 knockdown on clonogenic cell survival of A549 cells treated with radiation or combined thermoradiotherapy (B). A control siRNA (siCtrl) was used versus HSP70-KD cells. The corresponding LQ parameters along with their enhancement factors are given in a table (lower panel). Unpaired t-test.

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