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Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically(More)
In heart failure (HF), Ca(2+)/calmodulin kinase II (CaMKII) expression is increased. Altered Na(+) channel gating is linked to and may promote ventricular tachyarrhythmias (VTs) in HF. Calmodulin regulates Na(+) channel gating, in part perhaps via CaMKII. We investigated effects of adenovirus-mediated (acute) and Tg (chronic) overexpression of cytosolic(More)
The transcription factor SOX2 (3q26.3-q27) is a key regulator of foregut development and an embryonic stem cell factor cooperating during induction of pluripotency in terminally differentiated somatic cells. Recently, we found SOX2 to be amplified in a subset of squamous cell lung and esophageal cancers. The aim of this study was to explore the prognostic(More)
BACKGROUND Restitution kinetics and alternans of ventricular action potential duration (APD) have been shown to be important determinants of cardiac electrical stability. In this study, we tested the hypothesis that APD restitution and alternans properties differ between normal and diseased human ventricular myocardium. METHODS AND RESULTS Monophasic(More)
BACKGROUND Voltage-gated sodium channels composed of pore-forming alpha and auxiliary beta subunits are responsible for the rising phase of the action potential in cardiac muscle, but their localizations have not yet been clearly defined. METHODS AND RESULTS Immunocytochemical studies show that the principal cardiac alpha subunit isoform Na(v)1.5 and the(More)
Voltage-gated Na(+) channels are composed of pore-forming alpha and auxiliary beta subunits. The majority of Na(+) channels in the heart contain tetrodotoxin (TTX)-insensitive Na(v)1.5 alpha subunits, but TTX-sensitive brain-type Na(+) channel alpha subunits are present and functionally important in the transverse tubules of ventricular myocytes. Sinoatrial(More)
Voltage-gated sodium channels composed of pore-forming alpha and auxiliary beta subunits are responsible for the rising phase of the action potential in cardiac muscle, but the functional roles of distinct sodium channel subtypes have not been clearly defined. Immunocytochemical studies show that the principal cardiac pore-forming alpha subunit isoform(More)
The majority of Na+ channels in the heart are composed of the tetrodotoxin (TTX)-resistant (KD, 2-6 microm) Nav1.5 isoform; however, recently it has been shown that TTX-sensitive (KD, 1-10 nm) neuronal Na+ channel isoforms (Nav1.1, Nav1.3 and Nav1.6) are also present and functionally important in the myocytes of the ventricles and the sinoatrial (SA) node.(More)
In neurons, voltage-gated sodium channel beta subunits regulate the expression levels, subcellular localization, and electrophysiological properties of sodium channel alpha subunits. However, the contribution of beta subunits to sodium channel function in heart is poorly understood. We examined the role of beta1 in cardiac excitability using Scn1b null(More)
BACKGROUND Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias. We hypothesized that CaMKII contributes to arrhythmias and underlying cellular events and that inhibition of CaMKII reduces cardiac arrhythmogenesis in vitro and in vivo. METHODS AND RESULTS Under(More)