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Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer
The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the… Expand
Metabolic Modulation of Glioblastoma with Dichloroacetate
- E. Michelakis, G. Sutendra, +10 authors K. Petruk
- Medicine, Biology
- Science Translational Medicine
- 12 May 2010
Dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase, shifts metabolism away from aerobic glycolysis in glioblastoma tumor cells and may have clinical efficacy in patients. Metabolic… Expand
Diversity in Mitochondrial Function Explains Differences in Vascular Oxygen Sensing
Renal arteries (RAs) dilate in response to hypoxia, whereas the pulmonary arteries (PAs) constrict. In the PA, O2 tension is detected by an unidentified redox sensor, which controls K+ channel… Expand
The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted
- S. Bonnet, G. Rochefort, +6 authors E. Michelakis
- Biology, Medicine
- Proceedings of the National Academy of Sciences
- 3 July 2007
In pulmonary arterial hypertension (PAH), antiapoptotic, proliferative, and inflammatory diatheses converge to create an obstructive vasculopathy. A selective down-regulation of the Kv channel Kv1.5… Expand
A Nuclear Pyruvate Dehydrogenase Complex Is Important for the Generation of Acetyl-CoA and Histone Acetylation
DNA transcription, replication, and repair are regulated by histone acetylation, a process that requires the generation of acetyl-coenzyme A (CoA). Here, we show that all the subunits of the… Expand
Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension.
- M. McMurtry, S. Archer, +6 authors E. Michelakis
- The Journal of clinical investigation
- 1 June 2005
Pulmonary arterial hypertension (PAH) is characterized by genetic and acquired abnormalities that suppress apoptosis and enhance cell proliferation in the vascular wall, including downregulation of… Expand
Phosphodiesterase Type 5 Is Highly Expressed in the Hypertrophied Human Right Ventricle, and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility
Background— Sildenafil was recently approved for the treatment of pulmonary arterial hypertension. The beneficial effects of phosphodiesterase type 5 (PDE5) inhibitors in pulmonary arterial… Expand
Differential distribution of electrophysiologically distinct myocytes in conduit and resistance arteries determines their response to nitric oxide and hypoxia.
The cellular mechanisms that determine differences in reactivity of arteries of varying size and origin are unknown. We evaluated the hypothesis that there is diversity in the distribution of K+… Expand
Vascular Endothelial Growth Factor Gene Therapy Increases Survival, Promotes Lung Angiogenesis, and Prevents Alveolar Damage in Hyperoxia-Induced Lung Injury: Evidence That Angiogenesis Participates…
Background— Bronchopulmonary dysplasia (BPD) and pulmonary emphysema, both significant global health problems, are characterized by a loss of alveoli. Vascular endothelial growth factor (VEGF) is a… Expand
The metabolic basis of pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease of the lungs resulting in heart failure and premature death. Although, until recently, it was thought that PAH pathology is… Expand