Evaluation of different pharmacokinetically guided IV busulfan exposure ranges on adult patient outcomes after hematopoietic stem cell transplantation.

Conditioning intensity contributes significantly to outcomes in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We evaluated two myeloablative conditioning dosing ranges of intravenous (IV) busulfan (Bu) in combination with fludarabine in 70 patients. In 2015, our practice changed to target busulfan area under the curve (AUC) of ≥ 19.

Impact of Next-Generation Sequencing Cell-free Pathogen DNA Test on Antimicrobial Management in Adults with Hematological Malignancies and Transplant Recipients with Suspected Infections.

Infections in adult patients with hematological malignancies (HM) and stem cell transplant (SCT) recipients are a significant cause of morbidity and mortality. A timely diagnosis of infections can have a major impact on outcomes. Tools that help rule out infectious causes of fever can decrease antibiotic use, toxicities, hospitalization costs, and potentially decrease antibiotic resistance in the long term.

Conditioning regimen intensity and low-dose azacitidine maintenance after allogeneic hematopoietic cell transplantation for acute myeloid leukemia.

Azacitidine (AZA) maintenance following allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) may reduce relapse risk and improve survival. Given logistic and toxicity-related challenges, identifying subgroups appropriate for this approach is an unmet need. Using data from two centers, we retrospectively compared event-free survival (EFS) and overall survival (OS) of AML and MDS patients who received AZA maintenance ( = 59) with historic controls ( = 90).

Eltrombopag for Treating Thrombocytopenia after Allogeneic Stem Cell Transplantation.

Thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-SCT) can pose significant problems in management of patients. Eltrombopag is a small-molecule thrombopoietin receptor agonist that has been approved for use in immune thrombocytopenic purpura and aplastic anemia; but its use after allo-SCT is limited. Between 2014 and 2017, we treated 13 patients with eltrombopag for poor platelet engraftment without evidence of relapse at the time of initiation, including 6 patients with primary platelet engraftment failure and 7 with secondary platelet engraftment failure.

Aryl hydrocarbon receptor regulates the cholesterol biosynthetic pathway in a dioxin response element-independent manner.

Unlabelled: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. Activation of AhR mediates the expression of target genes (e.g.

Ah receptor represses acute-phase response gene expression without binding to its cognate response element.

Repression of the nuclear factor-kappaB (NF-kappaB) pathway has been extensively researched because of its pivotal role in inflammation. We investigated the potential of the aryl hydrocarbon receptor (AHR) to suppress NF-kappaB regulated-gene expression, especially acute-phase genes, such as serum amyloid A (Saa). Using AHR mutants, it was determined that nuclear translocation and heterodimerization with AHR-nuclear translocator are essential, but DNA binding is not involved in AHR-mediated Saa repression.

12(R)-Hydroxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic acid [12(R)-HETE], an arachidonic acid derivative, is an activator of the aryl hydrocarbon receptor.

The aryl hydrocarbon receptor (AHR) is a ligand-regulated transcription factor that can be activated by structurally diverse chemicals, ranging from environmental carcinogens to dietary metabolites. Evidence supporting a necessary role for the AHR in normal biology has been established; however, identification of key endogenous ligand/activator remains to be established. Here, we report the ability of 12(R)-hydroxy-5(Z),8(Z),10(E), 14(Z)-eicosatetraenoic acid [12(R)-HETE], an arachidonic acid metabolite produced by either a lipoxygenase or cytochrome P-450 pathway, to act as a potent indirect modulator of the AHR pathway.

Evidence for an aryl hydrocarbon receptor-mediated cytochrome p450 autoregulatory pathway.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor responsible for mediating the cellular response to the toxic compound 2,3,7,8,-tetrachlorodibenzo-p-dioxin. An essential role for the AhR in cellular biology has been established previously, but no high-affinity endogenous ligand has yet been identified. We have confirmed the presence of a putative endogenous ligand(s) in CV-1 cells through transient transfection with various cytochrome P450 isoforms.

Aryl-hydrocarbon receptor activation regulates constitutive androstane receptor levels in murine and human liver.

Unlabelled: The aryl-hydrocarbon receptor (AhR) is a basic helix-loop-helix/Per-Arnt-Sim transcription factor that can be activated by exogenous as well as endogenous ligands. AhR is traditionally associated with xenobiotic metabolism. In an attempt to identify novel target genes, C57BL/6J mice were treated with beta-naphthoflavone (BNF), a known AhR ligand, and genome-wide expression analysis studies were performed using high-density microarrays.

Endogenous hepatic expression of the hepatitis B virus X-associated protein 2 is adequate for maximal association with aryl hydrocarbon receptor-90-kDa heat shock protein complexes.

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that acts as an environmental sensor by binding to a variety of xenobiotics. AHR activation serves to combat xenotoxic stress by inducing metabolic enzyme expression in the liver. The hepatitis B virus X-associated protein (XAP2) is a component of the cytosolic AHR complex and modulates AHR transcriptional properties in vitro and in cell culture and yeast systems.

The aryl hydrocarbon receptor directly regulates expression of the potent mitogen epiregulin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to cause a large number of adverse effects, mediated largely by its binding to the aryl-hydrocarbon receptor (AhR) and subsequent modulation of gene expression. It is thought that AhR mediates these effects through the untimely and disproportionate expression of specific genes. However, the exact mechanism, or the genes involved, through which TCDD leads to these effects is still unknown.