<i>In vivo</i> effects of tivantinib and ZA single agent and in combination in a preventive schedule of bone metastases.

<p>(<b>A–B</b>) <i>In vivo</i> bioluminescence imaging (BLI) of 1833/TGL-i.c. injected athymic nude mice (4 week old) treated with tivantinib (120 mg/Kg; <i>n</i> = 7), ZA (100 mg/Kg; <i>n</i> = 5) and tivantinib+ZA (<i>n</i> = 5). (<b>A</b>) Ventral images from a representative nude mouse for each group 24 days after implant. Pseudocolor scale bars are consistent for all images of ventral views, in order to show relative changes at metastatic sites over time. (<b>B</b>) Average growth of bone metastasis in the hindlimbs of controls and treated mice: photon counts from the hindlimb (right and left) regions of tumor-bearing mice were quantified and displayed over time. The data are presented as mean ± SE. **, p<0.005; ***, p<0.0001. (<b>C</b>) The presence of tumor-induced osteolytic lesions were detected by weekly micro-CT scans. Representative 3D reconstruction of micro-CT images of the hindlimbs of controls and treated mice at day 24 after xenografting are reported. Similar results were obtained in the second experiment conducted independently. Red circles indicate osteolysis, the circle’s size was proportional to the extent of bone lesion. Numbers at the bottom of the images represent the number of mice. (<b>D</b>) Kaplan-Meier survival plot of the survival rate of 1833/TGL xenografted controls and treated-mice.