Use of an antagonist of HMGB1 in mice affected by malignant mesothelioma: a preliminary ultrasound and optical imaging study

European Radiological Experimental 2022 February 8 [Link]

Massimo Venturini, Rosanna Mezzapelle, Salvatore La Marca, Laura Perani, Antonello Spinelli, Luca Crippa, Anna Colarieti, Anna Palmisano, Paolo Marra, Andrea Coppola, Federico Fontana, Giulio Carcano, Carlo Tacchetti, Marco Bianchi, Antonio Esposito, Massimo P Crippa


Background: Malignant mesothelioma (MM) is an aggressive tumor, with a poor prognosis, usually unresectable due to late diagnosis, mainly treated with chemotherapy. BoxA, a truncated form of “high mobility group box 1” (HMGB1), acting as an HMGB1 antagonist, might exert a defensive action against MM. We investigated the potential of BoxA for MM treatment using experimental 40-MHz ultrasound and optical imaging (OI) in a murine model.

Methods: Murine MM cells infected with a lentiviral vector expressing the luciferase gene were injected into the peritoneum of 14 BALB/c mice (7 × 104 AB1-B/c-LUC cells). These mice were randomized to treatment with BoxA (n = 7) or phosphate-buffered saline (controls, n = 7). The experiment was repeated with 40 mice divided into two groups (n = 20 + 20) and treated as above to confirm the result and achieve greater statistical power. Tumor presence was investigated by experimental ultrasound and OI; suspected peritoneal masses underwent histopathology and immunohistochemistry examination.

Results: In the first experiment, none of the 7 controls survived beyond day 27, whereas 4/7 BoxA-treated mice (57.1%) survived up to day 70. In the second experiment, 6/20 controls (30.0%) and 16/20 BoxA-treated mice (80.0%) were still alive at day 34 (p = 0.004). In both experiments, histology confirmed the malignant nature of masses detected using experimental ultrasound and OI.

Conclusion: In our preclinical experience on a murine model, BoxA seems to exert a protective role toward MM. Both experimental ultrasound and OI proved to be reliable techniques for detecting MM peritoneal masses.