Fig. 4. In vivo activity of the new anti-LDH-A compound NHI-Glc-2 on orthotopic and subcutaneous DMPM models.

a Left panel: representative BLI images obtained with the CCD camera of orthotopic models of primary DMPM cells transduced with F-luc. Right panel: representative images showing the multiple tumour masses in the whole abdominal cavity as nodules, thus reproducing the diffusion pattern of the clinical disease in a mouse sacrificed after 2 weeks from inoculation of MesoII cells. b Representative immunohistochemical pictures (upper panel ×4, lower panel ×40 magnification) showing LDH-A overexpression in DMPM tissues obtained after orthotopic implantation of MesoII cells in mice. c Representative images of photoacoustic live imaging providing both a non-invasive anatomical image of tumours (up to 40-μm resolution) and the measurement of deep-tissue pO₂. The latter showed reduced oxygenation (in blue), suggesting that tumour nodules were characterised by hypoxic regions. d Representative H&E (upper panel), and immunohistochemical (lower panel) pictures (×4 magnification) demonstrating LDH-A overexpression that characterised subcutaneous tumours obtained by inoculation of MesoII cells in mice. e Volumes of subcutaneous tumours of mice, as shown in the representative picture, treated with gemcitabine (100 mg/kg, i.p., 2 days a week), NHI-Glc-2 (solubilised in PEG400, 50 mg/kg, 5 days a week) or their combination compared with untreated mice. Points, mean values obtained from six mice; bars, SEM. *Significantly different (P < 0.05) from the untreated animal. # and ⋆ significantly different from animals treated with gemcitabine or NHI-Glc-2 monotherapy, respectively.