Evidence map›Paper›PMID 25428224›Full record

Trial reportBlood2015

Histone deacetylase inhibition regulates inflammation and enhances Tregs after allogeneic hematopoietic cell transplantation in humans.

Sung Won Choi, Erin Gatza, Guoqing Hou, Yaping Sun, Joel Whitfield, Yeohan Song, Katherine Oravecz-Wilson, Isao Tawara, Charles A Dinarello, Pavan Reddy

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03167437 (An Open-Label, Proof of Concept Study of Vorinostat for the Treatment of Moderate-to-Severe Crohn's Disease, Ulcerative Colitis, and Chronic Granulomatous Disease Colitis Patients and Maintenance Therapy With Ustekinumab), which is not on this map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03167437 phase1 / phase2recruitingnot on this mapstarted 2017, after this paper: background citation

An Open-Label, Proof of Concept Study of Vorinostat for the Treatment of Moderate-to-Severe Crohn's Disease, Ulcerative Colitis, and Chronic Granulomatous Disease Colitis Patients and Maintenance Therapy With Ustekinumab

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2017 to 2035Enrolled35ConditionsCrohn's DiseaseArmsVorinostat, Ustekinumab
3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 102 citations in OpenAlex.

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  15. Review
  16. Mucosal microbiotas and their role in stem cell transplantation.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2022
    Review
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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Sung Won ChoiDepartment of Pediatrics.
Erin GatzaDepartment of Pediatrics.
Guoqing HouDepartment of Pediatrics.
Yaping SunDepartment of Internal Medicine, Division of Hematology-Oncology, Blood and Marrow Transplantation Program, and.
Joel WhitfieldImmunology Core, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI;
Yeohan SongDepartment of Pediatrics.
Katherine Oravecz-WilsonDepartment of Internal Medicine, Division of Hematology-Oncology, Blood and Marrow Transplantation Program, and.
Isao TawaraDepartment of Hematology-Oncology, Mie University Hospital, Tsu, Mie, Japan; and.
Charles A DinarelloDepartment of Medicine, Division of Infectious Diseases, University of Colorado, Aurora, CO.
Pavan ReddyDepartment of Internal Medicine, Division of Hematology-Oncology, Blood and Marrow Transplantation Program, and.
Pediatrics and Genetics · USMichigan Center for Translational Pathology · USMie University Hospital · JPUniversity of Colorado Anschutz Medical Campus · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8M
Yeast-based HTS Assay Technologies for ProteasesR01AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1985 to 2025
$8.5M
Development of a Novel Strategy to Prevent Experimental GVHDR01CA143379 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI REDDY, PAVAN · 2010 to 2014
$739k
Phase II Trial of Vorinostat plus Tacrolimus and Mycophenolate to Prevent GVHDK23AI091623 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHOI, SUNG WON · 2011 to 2015
$658k
Pathogenesis of Fever in ManR56AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 2016 to 2016
$311k
PATHOGENESIS OF FEVER IN HUMANSR37AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1988 to 1998
–
NCATS NIH HHS UL1 TR000043NCATS NIH HHS UL1TR00043NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA143379NCI NIH HHS R01CA143379NIAID NIH HHS 1K23AI091623NIAID NIH HHS AI-15614NIAID NIH HHS K23 AI091623NIAID NIH HHS R01 AI015614NIAID NIH HHS R56 AI015614
6 · The paper itself

Abstract

We examined immunological responses in patients receiving histone deacetylase (HDAC) inhibition (vorinostat) for graft-versus-host disease prophylaxis after allogeneic hematopoietic cell transplant. Vorinostat treatment increased histone acetylation in peripheral blood mononuclear cells (PBMCs) from treated patients, confirming target HDAC inhibition. HDAC inhibition reduced proinflammatory cytokine levels in plasma and from PBMCs and decreased ex vivo responses of PBMCs to proinflammatory TLR-4 stimuli, but did not alter the number or response of conventional T cells to nonspecific stimuli. However, the numbers of regulatory T cells (Tregs) were increased, which revealed greater demethylation of the Foxp3 T regulatory-specific demethylation region. Vorinostat-treated patients showed increased expression of CD45RA and CD31 on Tregs, and these Tregs demonstrated greater suppression on a per cell basis. Consistent with preclinical findings, HDAC inhibition also increased signal transducer and activator of transcription 3 acetylation and induced indoleamine-2,3-dioxygenase. Our data demonstrate that HDAC inhibition reduces inflammatory responses of PBMC but enhances Tregs after allo-HCT.

Indexed as

Hematopoietic Stem Cell TransplantationAcetylationAdultAgedCytokinesFemaleForkhead Transcription FactorsGene Expression RegulationGraft vs Host DiseaseHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHumansHydroxamic AcidsIndoleamine-Pyrrole 2,3,-DioxygenaseInflammationCytokinesForkhead Transcription FactorsFOXP3 protein, humanHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHydroxamic AcidsIndoleamine-Pyrrole 2,3,-DioxygenaseLeukocyte Common AntigensPlatelet Endothelial Cell Adhesion Molecule-1STAT3 protein, humanSTAT3 Transcription FactorTLR4 protein, humanToll-Like Receptor 4Vorinostat

Identifiers

PMID25428224
PMCPMC4311228
OpenAlexW2087590696

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.