We previously developed SKI-178 (N'-[(1E)-1-(3,4-dimethoxyphenyl)ethylidene]-3-(4-methoxxyphenyl)-1H-pyrazole-5-carbohydrazide) as a novel sphingosine kinase-1 (SphK1) selective inhibitor and, herein, sought to determine the mechanism-of-action of SKI-178-induced cell death. Using human acute myeloid leukemia (AML) cell lines as a model, we present evidence that SKI-178 induces prolonged mitosi...

Transforming growth factor-beta (TGF-β) signaling pathways contain both tumor suppressor and tumor promoting activities. We have demonstrated that Nodal, another member of the TGF-β superfamily, and its receptors are expressed in prostate cancer cells. Nodal and TGF-β exerted similar biological effects on prostate cells; both inhibited proliferation in WPE, RWPE1 and DU145 cells, whereas neithe...

Ski injury research is traditionally studied on small-scale observational studies where risk factors from univariate and multivariate statistical models are extracted. In this article, a large-scale ski injury observational study was conducted by analyzing skier transportation data from six consecutive seasons. Logistic regression and chi-square automatic interaction detection decision tree mod...

OBJECTIVES To examine the incidence and patterns of snow sports injuries at the three largest commercial ski areas in Scotland and to identify factors associated with injury risk. METHODS A prospective case-control study of all injured people at Cairngorm, Glenshee, and Nevis Range ski areas during the 1999-2000 winter season. Personal details, snow sports related variables, diagnosis, and tr...

c-ski gene product is a nuclear protein with myogenesis-promoting and transforming activities. We have analysed the effects of c-ski transfection on the promoter/enhancer activity of the upstream region of the myogenin gene during in vitro myogenesis using CAT reporter assay. When co-transfected with c-ski into myogenic C2C12 cells, promoter/enhancer activity was efficiently suppressed in proli...

The N-CoR/SMRT complex containing mSin3 and histone deacetylase (HDAC) mediates transcriptional repression by nuclear hormone receptors and Mad. The proteins encoded by the ski proto-oncogene family directly bind to N-CoR/SMRT and mSin3A, and forms a complex with HDAC. c-Ski and its related gene product Sno are required for transcriptional repression by Mad and thyroid hormone receptor (TRbeta)...

INTRODUCTION This case report describes an unusual injury to the neck, caused by a ski stick, sustained by a skier on a dry ski slope. The majority of equipment-related skiing injuries involve the ankle, knee and lower leg and are influenced by skiing experience and quality of ski binding; Young et al (1976). Johnson et al (1980) found that 80% of lower extremity injuries were equipment related...

Overexpression of the oncoprotein SKI correlates with the progression of human melanoma in vivo. SKI is known to curtail the growth inhibitory activity of tumor growth factor through the formation of repressive transcriptional complexes with Smad2 and Smad3 at the p21 promoter. Here, we show that SKI also stimulates growth by activating the Wnt signaling pathway. From a yeast two-hybrid screen ...

The ski/sno protooncogenes encode nuclear proteins that may act as transcription factors. We examined ski and sno mRNA expression in hemolymphopoietic lineages. The ski protooncogene is expressed in B- and T-lineage cells, mature macrophages, and mast cells. In normal murine marrow-derived progenitors analyzed by single-cell reverse transcription-polymerase chain reaction (RT-PCR), ski expressi...