histone/fatigue

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Phase I trial of induction histone deacetylase and proteasome inhibition followed by surgery in non-small-cell lung cancer.

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BACKGROUND Despite complete surgical resection survival in early-stage non-small-cell lung cancer (NSCLC) remains poor. On the basis of prior preclinical evaluations, we hypothesized that combined induction proteasome and histone deacetylase inhibitor therapy, followed by tumor resection, is

A phase 1 pharmacokinetic and pharmacodynamic study of the histone deacetylase inhibitor belinostat in patients with advanced solid tumors.

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OBJECTIVE To determine the safety, dose-limiting toxicity, maximum tolerated dose, and pharmacokinetic and pharmacodynamic profiles of the novel hydroxamate histone deacetylase inhibitor belinostat (previously named PXD101) in patients with advanced refractory solid tumors. METHODS Sequential

Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with previously treated chronic lymphocytic leukaemia.

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MGCD0103, an orally available class I histone deacetylase (HDAC) inhibitor, was examined for pre-clinical activity in chronic lymphocytic leukaemia (CLL). A phase II clinical trial was performed, starting at a dose of 85 mg/d, three times per week. Dose escalation to 110 mg or the addition of

A phase I pharmacokinetic and pharmacodynamic study of CHR-3996, an oral class I selective histone deacetylase inhibitor in refractory solid tumors.

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OBJECTIVE This clinical trial investigated the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profile of CHR-3996, a selective class I histone deacetylase inhibitor. METHODS CHR-3996 was administered orally once a day. This phase I trial used a 3+3 dose-escalation design. PK

Anti-chromatin and anti-histone antibodies in Egyptian patients with systemic lupus erythematosus.

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There has been a renewed interest in anti-chromatin and anti-histone antibodies in the last few years. To assess the prevalence of anti-chromatin and anti-histone antibodies in patients with systematic lupus erythematosus (SLE) and to correlate serum levels of these antibodies with clinical features

Phase I and pharmacodynamic study of an orally administered novel inhibitor of histone deacetylases, SB939, in patients with refractory solid malignancies.

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BACKGROUND The objective of this study was to assess the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary efficacy of SB939, a novel histone deacetylase (HDAC) inhibitor, in patients with advanced solid malignancies. METHODS Dose-escalating cohorts of three

Presence of Citrullinated Histone H3-Positive Neutrophils in Microscopic Polyangiitis from the Early Phase: An Autopsy Proven Case.

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A 76-year-old man was admitted with general fatigue, weight loss, fever, headache, renal failure, and a high serum level of myeloperoxidase-antineutrophil cytoplasmic antibody. Biopsy revealed citrullinated histone H3 (citH3)-positive neutrophils adherent to the temporal artery endothelium. Three

Synthesis and biochemical analysis of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-N-hydroxy-octanediamides as inhibitors of human histone deacetylases.

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Inhibition of human histone deacetylases (HDACs) has emerged as a novel concept in the chemotherapeutic treatment of cancer. Two chemical entities, SAHA (ZOLINZA, Merck) and romidepsin (Istodax, Celgene) have been recently approved by the FDA as first-in-class drugs against cutaneous T-cell

Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS).

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The inhibition of histone deacetylase (HDAC) can induce differentiation, growth arrest, and apoptosis in cancer cells. This phase II multicenter study was undertaken to estimate the efficacy of belinostat, a potent inhibitor of both class I and class II HDAC enzymes, for the treatment of

Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome.

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Hypocortisolism is a frequent finding in individuals with chronic fatigue syndrome (CFS) with other research findings implying potential dysregulation of glucocorticoid signaling. Glucocorticoid signaling is under the influence of several pathways, several of which are of interest in the study of

Efficacy and tolerability of the histone deacetylase inhibitor panobinostat in clinical practice.

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The histone deacetylase inhibitor panobinostat has shown efficacy in phase-II and phase-III trials for multiple myeloma and has recently received market approval in combination with bortezomib and dexamethasone. Here, we retrospectively report our single center experience with

[Several properties of 3':5'-AMP-dependent skeletal muscle protein kinases in normal rats and following physical exertion to fatigue].

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Three fractions of rat adenosine-3',5'-monophosphate-dependent protein kinase were isolated, partially purified in buffer concentration gradient at normal state and after long-term physical loading and studied. It is found that first two fractions of protein kinases at normal state and after

Therapy with the histone deacetylase inhibitor pracinostat for patients with myelofibrosis.

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Approximately half of the patients with myelofibrosis (MF) carry mutant JAK2(V617F) proteins. JAK2(V617F) has been recently shown to translocate to the nucleus and modify specific histones, thus regulating transcription. We report on a phase II study testing the activity and tolerability of the

A phase I first-in-human study with tefinostat - a monocyte/macrophage targeted histone deacetylase inhibitor - in patients with advanced haematological malignancies.

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Tefinostat (CHR-2845) is a monocyte/macrophage targeted histone deacetylase inhibitor (HDACi). This first-in-human, standard 3 + 3 dose escalating trial of oral, once daily tefinostat was conducted to determine the safety, tolerability, pharmacokinetic and pharmacodynamic profile of tefinostat in

Phase I clinical, pharmacokinetic and pharmacodynamic study of SB939, an oral histone deacetylase (HDAC) inhibitor, in patients with advanced solid tumours.

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BACKGROUND SB939 is an orally available, competitive histone deacetylase (HDAC) inhibitor selective for class I, II and IV histone deacetylases. Preclinical evaluation of SB939 revealed a profile suggesting improved efficacy compared to other HDAC inhibitors. This phase I study was carried out to

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