Evidence map›Paper›PMID 26511361›Full record

ArticleRespiratory research2015

Pharmacologically-induced mitotic synchrony in airway epithelial cells as a mechanism of action of anti-inflammatory drugs.

R J Freishtat, G Nino, Y Tsegaye, S E Alcala, A S Benton, A M Watson, E K M Reeves, S K Haider, J M Damsker

2 registry-linked trialsOpen access · goldAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Respiratory research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.1field-weighted citation impact, top 52% 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.

NCT05166109 phase2completednot on this mapstarted 2022, after this paper: background citation

A Phase II Pilot Trial of Vamorolone vs. Placebo for the Treatment of Becker Muscular Dystrophy

TypeinterventionalSponsorReveraGen BioPharma, Inc.Ran2022 to 2025Enrolled46ConditionsBecker Muscular DystrophyArmsVamorolone, Placebo
NCT05185622 phase2completednot on this mapstarted 2022, after this paper: background citation

A Phase II Open-Label, Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of Vamorolone in Boys Ages 2 to <4 Years and 7 to <18 Years With Duchenne Muscular Dystrophy (DMD)

TypeinterventionalSponsorSanthera PharmaceuticalsRan2022 to 2024Enrolled54ConditionsDuchenne Muscular DystrophyArmsVamorolone
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Structural insights into glucocorticoid receptor function.Biochemical Society transactions · 2021
    Review
  4. Review
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

9 authors at 3 institutions in 1 country.

R J FreishtatDivision of Emergency Medicine, Children's National Health System, Washington, DC, USA. rfreishtat@childrensnational.org.
G NinoDepartment of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA. gnino@childrensnational.org.
Y TsegayeGeorge Washington University School of Medicine and Health Sciences, Washington, DC, USA. ytsegaye@gwmail.gwu.edu.
S E AlcalaGeorge Washington University School of Medicine and Health Sciences, Washington, DC, USA. sda@gwmail.gwu.edu.
A S BentonChildren's National Health System, Washington, DC, USA. asbenton@gmail.com.
A M WatsonGeorge Washington University School of Medicine and Health Sciences, Washington, DC, USA. augie95@gmail.com.
E K M ReevesReveraGen Biopharma, Inc., Silver Spring, MD, USA. Erica.Reeves@reveragen.com.
S K HaiderDivision of Pulmonary and Sleep Medicine, Children's National Health System, Washington, DC, USA. suraiyakureshi@yahoo.com.
J M DamskerDepartment of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA. Jesse.Damsker@reveragen.com.
George Washington University · USChildren's National · USReveraGen BioPharma (United States) · US

Funding

NCMRR-DC Core Molecular & Functional Outcome Measures in Rehabilitation MedicineR24HD050846 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI KNOBLACH, SUSAN M · 2005 to 2014
$8.6M
RNA fidelity and protein function of Becker-like in-frame deletionsP50AR060836 · NIAMS · CHILDREN'S RESEARCH INSTITUTE · PI PARTRIDGE, TERENCE A · 2011 to 2015
$7.8M
Preclinical dosing optimization: Dosing schedule, tissueU54HD071601 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI JOSE, PEDRO A. · 2011 to 2015
$4.0M
Anti-inflammatory and Mitotic Properties of Non-hormonal Steroids in Lung EpithelR41HL104939 · NHLBI · REVERAGEN BIOPHARMA, INC. · PI REEVES, ERICA · 2010 to 2010
$375k
Preclinical drug trial in mouse models of inflammationK26RR032082 · NCRR · CHILDREN'S RESEARCH INSTITUTE · PI NAGARAJU, KANNEBOYINA · 2011 to 2011
$106k
NCRR NIH HHS K26 RR032082NHLBI NIH HHS R41 HL104939NHLBI NIH HHS R41HL104939NIAMS NIH HHS P50 AR060836NICHD NIH HHS U54 HD071601
6 · The paper itself

Abstract

backgroundMitotic synchrony is the synchronous progression of a population of cells through the cell cycle and is characteristic of non-diseased airway epithelial cells. However, we previously showed that asthmatic airway epithelial cells are characterized by mitotic asynchrony and are pro-inflammatory as a result. Glucocorticoids can induce mitotic synchrony that in turn suppresses the pro-inflammatory state of diseased cells, suggesting a novel anti-inflammatory mechanism of action. Herein, we benchmarked traditional glucocorticoids against the ability of a new clinical-stage dissociative steroidal drug, VBP15, for mitotic resynchronization and associated anti-inflammatory activity in asthmatic airway epithelial cells.

methodsPrimary airway epithelial cells differentiated at air-liquid interface were exposed to VBP15, dexamethasone or vehicle following in vitro mechanical injury. Basolateral cytokine secretions (TGF-β1, IL-6, IL-10, IL-13, and IL-1β) were analyzed at different time points using cytometric bead assays and mitosis was examined by flow cytometry.

resultsVBP15 improved mitotic synchrony of proliferating asthmatic cells in air-liquid interface cultures compared to vehicle-exposed cultures. VBP15 also significantly reduced the basolateral secretion of pro-inflammatory (i.e. IL-1β) and pro-fibrogenic cytokines (i.e. TGF-β1) in air-liquid interface-differentiated asthmatic epithelial cultures following mechanical injury.

conclusionVBP15 improves mitotic asynchrony and injury-induced pro-inflammatory and fibrogenic responses in asthmatic airway epithelial cultures with efficacy comparable to traditional glucocorticoids. As it is predicted to show superior side effect profiles compared to traditional glucocorticoids, VBP15 holds potential for treatment of asthma and other respiratory conditions.

Indexed as

Anti-Inflammatory AgentsAsthmaCase-Control StudiesCells, CulturedCytokinesDexamethasoneEpithelial CellsGlucocorticoidsHumansInflammation MediatorsLungMitosisPregnadienediolsPulmonary FibrosisTime FactorsAnti-Inflammatory AgentsCytokinesDexamethasoneGlucocorticoidsInflammation MediatorsPregnadienediolsVBP15 compound

Identifiers

PMID26511361
PMCPMC4625853
OpenAlexW1906167331

What OpenQuestion holds

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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.