selinexor and Hodgkin-Disease

This study shows the ability of sodium-glucose co-transporter-2 inhibitors to lower atrial natriuretic peptide levels and improve glycaemic control, which may benefit the cardiovascular system.. The correlation between SE and AL/CRC is stronger than that between AL or CRC alone. This suggests that in a research setting, when cycloplegic refraction is difficult to perform on 3-year-old children, AL/CRC may be the next best reference for refractive error.. In the research setting, AL/CRC may be the next best reference for refractive error over AL alone when cycloplegic refraction is unavailable in 3-year old children.

Topics: Active Transport, Cell Nucleus; Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Benzhydryl Compounds; Benzylamines; Biopsy; Blood Glucose; Blood Transfusion; Cholesterol, LDL; Combined Modality Therapy; Cyclams; Diabetes Mellitus, Type 2; Disease Progression; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Female; Glucosides; Glycated Hemoglobin; Granulocyte Colony-Stimulating Factor; Hamstring Muscles; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Heterocyclic Compounds; Hodgkin Disease; Humans; Hydrazines; Immunohistochemistry; Insulin-Secreting Cells; Leg; Male; Middle Aged; Muscle Strength; Neoplasms; Peripheral Blood Stem Cell Transplantation; Range of Motion, Articular; Recurrence; Remission Induction; Research Design; Reverse Transcriptase Polymerase Chain Reaction; Soccer; Sodium-Glucose Transport Proteins; Sodium-Glucose Transporter 2 Inhibitors; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Triazoles; Young Adult

Exportin 1 (XPO1) is the main nuclear export receptor that controls the subcellular trafficking and the functions of major regulatory proteins. XPO1 is overexpressed in various cancers and small inhibitors of nuclear export (SINEs) have been developed to inhibit XPO1. In primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin's lymphoma (cHL), the XPO1 gene may be mutated on one nucleotide and encodes the mutant XPO1

Topics: Cell Line, Tumor; Exportin 1 Protein; Hodgkin Disease; Humans; Karyopherins; Receptors, Cytoplasmic and Nuclear

Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Acrylates; Active Transport, Cell Nucleus; Adolescent; Adult; Aged; Biomarkers; Cell Line, Tumor; Exportin 1 Protein; Female; Gene Expression Profiling; Hodgkin Disease; Humans; Hydrazines; Karyopherins; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Middle Aged; Mutation; Receptors, Cytoplasmic and Nuclear; Sequence Analysis, DNA; Triazoles; Young Adult