Dose–response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels

Methods: Forty-eight healthy volunteers participated in the randomized, placebo-controlled, double-blind, repeated-measure study. At baseline, after 1, 2, 4 and 6 weeks, participants provided both fasting blood samples and 24-h urine

TGF beta selects for pro-stemness over pro-invasive phenotypes during cancer cell epithelial-mesenchymal transition

Transforming growth factor beta (TGF(beta) induces epithelial-mesenchymal transition (EMT), which correlates with sternness and invasiveness. Mesenchymal-epithelial transition (MET) is induced by TGF beta withdrawal and correlates with metastatic colonization. Whether TGF beta promotes sternness and invasiveness simultaneously via EMT remains unclear. We established a breast cancer cell model expressing red fluorescent protein (RFP) under the E-cadherin promoter. In 2D cultures, TGF beta induced EMT, generating RFPlow cells with a mesenchymal transcriptome, and regained RFP, with an epithelial transcriptome, after MET induced by TGF beta withdrawal. RFPlow cells generated robust mammospheres, with epithelio-mesenchymal cell surface features. Mammospheres that were forced to adhere generated migratory cells, devoid of RFP, a phenotype which was inhibited by a TGF beta receptor kinase inhibitor. Further stimulation of RFPlow mammospheres with TGF beta suppressed the generation of motile cells, but enhanced mammosphere growth. Accordingly, mammary fat-pad-transplanted mammospheres, in the absence of exogenous TGF beta treatment, established lung metastases with evident MET (RFPhigh cells). In contrast, TGF beta-treated mammospheres revealed high tumour-initiating capacity, but limited metastatic potential. Thus, the biological context of partial EMT and MET allows TGF beta to differentiate between pro-sternness and pro-invasive phenotypes.Cancer Signaling networks and Molecular Therapeutic

TGF beta selects for pro-stemness over pro-invasive phenotypes during cancer cell epithelial-mesenchymal transition

Transforming growth factor beta (TGF(beta) induces epithelial-mesenchymal transition (EMT), which correlates with sternness and invasiveness. Mesenchymal-epithelial transition (MET) is induced by TGF beta withdrawal and correlates with metastatic colonization. Whether TGF beta promotes sternness and invasiveness simultaneously via EMT remains unclear. We established a breast cancer cell model expressing red fluorescent protein (RFP) under the E-cadherin promoter. In 2D cultures, TGF beta induced EMT, generating RFPlow cells with a mesenchymal transcriptome, and regained RFP, with an epithelial transcriptome, after MET induced by TGF beta withdrawal. RFPlow cells generated robust mammospheres, with epithelio-mesenchymal cell surface features. Mammospheres that were forced to adhere generated migratory cells, devoid of RFP, a phenotype which was inhibited by a TGF beta receptor kinase inhibitor. Further stimulation of RFPlow mammospheres with TGF beta suppressed the generation of motile cells, but enhanced mammosphere growth. Accordingly, mammary fat-pad-transplanted mammospheres, in the absence of exogenous TGF beta treatment, established lung metastases with evident MET (RFPhigh cells). In contrast, TGF beta-treated mammospheres revealed high tumour-initiating capacity, but limited metastatic potential. Thus, the biological context of partial EMT and MET allows TGF beta to differentiate between pro-sternness and pro-invasive phenotypes