Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma

Whereas the prevalence of several cancer types is decreasing, skin malignancies are growing more common every year. Malignant melanoma is the most aggressive form of skin cancer with high metastatic capacity. In most cases, malignant melanoma shows acquired therapy resistance. We evaluated the ability of Ocoxin, a natural compound-based antioxidant and anti-inflammatory nutritional complement, to exert an antitumor effect in melanoma. To do so, the cytotoxicity of Ocoxin in a panel of BRAF-mutated murine and human melanoma cell lines was tested alone and in combination with BRAF inhibitor Vemurafenib. Our results revealed a potent cytotoxic effect of Ocoxin against melanoma cells and a synergic effect when combined with Vemurafenib, reducing viability and increasing apoptosis. Besides, Ocoxin interferes with the cell cycle, impairs the inherent and fibroblast-mediated melanoma cell migration, and reduces resistance to BRAF inhibition. Proteomic analysis revealed reduced tumor secretion of inflammatory factors Galectin-1, Osteopontin, CCL5, and CCL9 upon treatment with Ocoxin. Moreover, RNASeq showed that Ocoxin downregulated the cell cycle and proliferation-related genes. In vivo, Ocoxin reduced the number of lung metastasis of YUMM-1.7 melanoma cells. Therefore, Ocoxin arises as a good candidate for clinical trials analyzing the beneficial effects in patients suffering from this cutaneous malignancy.This research was partly funded by Catalysis S.L

Growth Differentiation Factor 15: A Biomarker with High Clinical Potential in the Evaluation of Kidney Transplant Candidates

Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. For this purpose, 395 kidney transplant recipients with pretransplant stored serum samples were included. The median GDF-15 was 5331.3 (50.49–16242.3) pg/mL. After a mean of 90.6 ± 41.5 months of follow-up, 82 (20.8%) patients died. Patients with higher GDF-15 levels (high risk tertile) had a doubled risk of mortality after adjustment by clinical characteristics (p = 0.009). After adjustment by EPTS (Estimated Post Transplant Survival score) the association remained significant for medium hazards ratios (HR) 3.24 95%CI (1.2–8.8), p = 0.021 and high risk tertiles HR 4.3 95%CI (1.65–11.54), p = 0.003. GDF-15 improved the prognostic accuracy of EPTS at 1-year (ΔAUC = 0.09, p = 0.039) and 3-year mortality (ΔAUC = 0.11, p = 0.036). Our study suggests an independent association between higher GDF-15 levels and mortality after kidney transplant, adding accuracy to the EPTS score, an established risk prediction model currently used in kidney transplant candidates