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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

Interaction of the histone-like nucleoid structuring protein and the general stress response regulator RpoS at Vibrio cholerae promoters that regulate motility and hemagglutinin/protease expression.

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The bacterium Vibrio cholerae colonizes the human small intestine and secretes cholera toxin (CT) to cause the rice-watery diarrhea characteristic of this illness. The ability of this pathogen to colonize the small bowel, express CT, and return to the aquatic environment is controlled by a complex

Core histone genes of Giardia intestinalis: genomic organization, promoter structure, and expression.

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BACKGROUND Giardia intestinalis is a protist found in freshwaters worldwide, and is the most common cause of parasitic diarrhea in humans. The phylogenetic position of this parasite is still much debated. Histones are small, highly conserved proteins that associate tightly with DNA to form chromatin

Toxicological evaluation of an apicidin derivative, histone deacetylase inhibitor SD-2007 in mice.

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SD-2007 is a new derivative of apicidin, an anti-parasitic agent and a histone deacetylase (HDAC) inhibitor. A subacute toxicological evaluation of SD-2007 was investigated for 2 weeks in ICR mice. After oral administration of SD-2007 (0, 0.2, 1, 5 or 25 mg/mouse), the clinical signs, mortalities,

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

A Highly Potent and Selective Histone Deacetylase 6 Inhibitor Prevents DSS-Induced Colitis in Mice.

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Inflammatory bowel disease (IBD) is a refractory illness with remarkably increasing incidence rate all over the world. However, no desirable treatment scheme is available. Therefore, research and development of new drugs for treating IBD are urgently needed. Histone deacetylase 6 (HDAC6) is

Clinical developments in the treatment of relapsed or relapsed and refractory multiple myeloma: impact of panobinostat, the first-in-class histone deacetylase inhibitor.

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BACKGROUND Panobinostat is a new agent for the treatment of relapsed and refractory multiple myeloma (rrMM) as part of a combination regimen. This article presents an overview of the mechanism of action, pharmacokinetics, safety, efficacy, patient care strategies, and role of the agent in treating

CTXφ Replication Depends on the Histone-Like HU Protein and the UvrD Helicase.

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The Vibrio cholerae bacterium is the agent of cholera. The capacity to produce the cholera toxin, which is responsible for the deadly diarrhea associated with cholera epidemics, is encoded in the genome of a filamentous phage, CTXφ. Rolling-circle replication (RCR) is central to the life cycle of

Inhibition of attachment of virions of Norwalk virus to mammalian cells by soluble histone molecules.

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Viral infection is usually initiated by the binding of virus particles to specific receptor molecule(s) on the host cell surface. Blocking of this step prevents the following step, penetration into the cell. In the present study, we investigated the virus-cell interactions of virions of Norwalk

Combined inhibitors of angiogenesis and histone deacetylase: efficacy in rat hepatoma.

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OBJECTIVE To evaluate the antitumoral effect of combined inhibitors of angiogenesis and histone deacetylases in an experimental rat hepatoma model. METHODS MH7777A hepatoma cells were injected into the liver of male Buffalo rats. After 7 d treatment with the vascular endothelial growth factor

Porcine epidemic diarrhea virus nucleoprotein contributes to HMGB1 transcription and release by interacting with C/EBP-β.

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Porcine epidemic diarrhea is a devastating swine enteric disease, which is caused by porcine epidemic diarrhea virus (PEDV) infection. Our studies demonstrated that PEDV infection resulted in the up-regulation of proinflammatory cytokines. Meanwhile, PEDV infection and overexpression of viral

Molecular characterizations of cytolethal distending toxin produced by Providencia alcalifaciens strains isolated from patients with diarrhea.

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Cytolethal distending toxins (CDTs), which block eukaryotic cell proliferation by acting as inhibitory cyclomodulins, are produced by diverse groups of Gram-negative bacteria. Active CDT is composed of three polypeptides--CdtA, CdtB, and CdtC--encoded by the genes cdtA, cdtB, and cdtC, respectively.

Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies.

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OBJECTIVE To document the toxicity and activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with pretreated hematologic malignancies. METHODS Two formulations of SAHA (intravenous [IV] and oral) have been assessed in two consecutive phase I trials. In both

Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes.

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Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor active clinically in cutaneous T-cell lymphoma and preclinically in leukemia. A phase 1 study was conducted to evaluate the safety and activity of oral vorinostat 100 to 300 mg twice or thrice daily for 14 days

Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas.

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OBJECTIVE Chidamide (CS055/HBI-8000) is a new benzamide class of histone deacetylase inhibitor with marked anti-tumor activity. This study reports the phase I results. METHODS Patients with advanced solid tumors or lymphomas received oral doses of 5, 10, 17.5, 25, 32.5, or 50 mg chidamide either

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