Bioenergetic modulation with dichloroacetate reduces the growth of melanoma cells and potentiates their response to BRAF^V600E inhibition

BACKGROUND: Advances in melanoma treatment through targeted inhibition of oncogenic BRAF are limited owing to the development of acquired resistance. The involvement of BRAF(V600E) in metabolic reprogramming of melanoma cells provides a rationale for co-targeting metabolism as a therapeutic approach. METHODS: We examined the effects of dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, on the growth and metabolic activity of human melanoma cell lines. The combined effect of DCA and the BRAF inhibitor vemurafenib was investigated in BRAF(V600E) -mutated melanoma cell lines. Vemurafenib-resistant cell lines were established in vitro and their sensitivity to DCA was tested. RESULTS: DCA induced a reduction in glycolytic activity and intracellular ATP levels, and inhibited cellular growth. Co-treatment of BRAF(V600E)-mutant melanoma cells with DCA and vemurafenib induced a greater reduction in intracellular ATP levels and cellular growth than either compound alone. In addition, melanoma cells with in vitro acquired resistance to vemurafenib retained their sensitivity to DCA. CONCLUSIONS: These results suggest that DCA potentiates the effect of vemurafenib through a cooperative attenuation of energy production. Furthermore, the demonstration of retained sensitivity to DCA in melanoma cells with acquired resistance to vemurafenib could have implications for melanoma treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0247-5) contains supplementary material, which is available to authorized users

Studerendes udvikling af professionsidentitet gennem musikpædagogi

Der er stor kropslig diversitet blandt børn i danske dagtilbud, og hermed et pædagogisk behov for at kunne skabe deltagelsesmuligheder for alle børn. I et aktionsforskningsstudie undersøger vi, hvordan studerendes arbejde med børns deltagelsesmuligheder i musikaktiviteter understøtter deres professionsidentitet. Artiklen peger på, at studerendes erfaringer forankrer sig kropsligt som særligt meningsfulde, når de erfarer øjeblikke af at forbinde sig til og afstemme børns udtryk og behov musikalsk. Et musikalsk repertoire med fokus på samskabelse kan understøtte disse erfaringer. Når studerende deler erfaringer og udviklingsmuligheder omkring pædagogiske situationer i refleksive fællesskaber, kan det give studerende mulighed for at integrere opnåede kropslige erfaringer i deres forståelse af sig selv som kommende pædagoger