Sodium dichloroacetate attenuates the growth of B16-F10 melanoma in vitro and in vivo: an opportunity for drug repurposing.

Sodium dichloroacetate (DCA) is a metabolic regulator used to treat diabetes. Since DCA inhibits pyruvate dehydrogenase kinase, decreasing lactic acid formation, it can reverse the Warburg effect in cancer cells, promoting apoptosis. Therefore, this study aimed to investigate the potential of DCA as a drug repurposing candidate for the treatment of melanoma. For the in-vitro assay, murine B16-F10 melanoma cells were treated with 0.5, 1, 5, 10, 20 or 50 mM DCA for 3 days, analyzed with the crystal violet method. The in-vivo effect of DCA was evaluated in B16-F10 tumor-bearing C57BL/6 mice treated with different doses of DCA (0, 25, 75 or 150 mg/kg) by gavage for 10 days, followed by measurement of tumor volume. Upon necropsy, representative slices of lung, liver, kidney, spleen and intestine were collected, processed and submitted for histopathological examination. The DCA concentrations of 10, 20 and 50 mM reduced B16-F10 cell viability after 48 and 72 h of treatment, whereas 20 and 50 mM were effective after 24 h of treatment. A significant reduction in tumor growth was observed in B16-F10 melanoma bearing mice at all doses, with no change in body weight or histology. DCA attenuates the growth of B16-F10 melanoma in vitro and in vivo, without systemic toxic effects. Therefore, DCA is a candidate for drug repurposing against melanomas.

Canine visceral hemangiosarcoma treated with surgery alone or surgery and doxorubicin: 37 cases (2005-2014).

The purpose of this retrospective study was to determine survival times and prognostic factors of dogs with visceral hemangiosarcoma (HSA) treated with surgery alone or surgery and doxorubicin. Medical records from 2 hospitals from 2005 to 2014 were searched for dogs with histopathologically confirmed visceral HSA. Data relevant to patient demographics, tumor characteristics, and outcomes were abstracted. The most common primary organ affected was the spleen; however, primary tumor location had no influence on prognosis. Twenty-three dogs were treated with surgery alone, while 14 dogs were treated with surgery and doxorubicin. There was a significant difference in survival times between dogs treated with surgery alone and with surgery followed by doxorubicin (66 days versus 274 days). Dogs with stage I tumors (196 days) had a longer median survival time (MST) than dogs with stage II (117 days) and stage III (23 days) disease. The overall MST was 179 days with a 1-year survival rate of 29.2%.

Hémangiosarcome viscéral canin traité par la chirurgie seule et la doxorubicine : 37 cas (2005­2014). Le but de cette étude rétrospective consistait à déterminer les temps de survie et les facteurs de pronostic des chiens atteints d'un hémangiosarcome (HSE) viscéral traités à l'aide de la chirurgie seule ou de la chirurgie et de la doxorubicine. Les dossiers médicaux de deux cliniques de 2005 à 2014 ont été fouillés pour trouver des chiens avec un HSE viscéral confirmé par histopathologie. Les données pertinentes pour les données démographiques du patient, les caractéristiques de la tumeur et les résultats ont été extraits des dossiers. L'organe primaire le plus couramment affecté était la rate. Cependant, l'emplacement primaire de la tumeur n'avait aucune influence sur le pronostic. Vingt-trois chiens ont été traités par la chirurgie seule, tandis que 14 chiens ont été traités par la chirurgie et la doxorubicine. Il y avait une différence importante dans les temps de survie entre les chiens traités par la chirurgie seule et la chirurgie suivie de la doxorubicine (66 jours contre 274 jours). Les chiens ayant des tumeurs de stade I (196 jours) avaient un temps de survie médian (TSM) plus long que les chiens atteints d'une maladie de stade II (117 jours) et de stade III (23 jours). Le TSM général était de 179 jours avec un taux de survie après 1 an de 29,2 %.(Traduit par Isabelle Vallières).