Evidence map›Paper›PMID 26177294›Full record

ArticleHematology (Amsterdam, Netherlands)2016

Fasudil, a clinically safe ROCK inhibitor, decreases disease burden in a Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders.

Basem M William, Wei An, Dan Feng, Scott Nadeau, Bhopal C Mohapatra, Matthew A Storck, Vimla Band, Hamid Band

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hematology (Amsterdam, Netherlands), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact, top 98% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
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

8 authors at 1 institution in 1 country.

Basem M Williama Division of Hematology and Oncology, Department of Medicine , University of Nebraska Medical Center , Omaha , USA.
Wei Anb Department of Genetics, Cell Biology and Anatomy , University of Nebraska Medical Center , Omaha , USA.
Dan Fengc Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center , Omaha , USA.
Scott Nadeaub Department of Genetics, Cell Biology and Anatomy , University of Nebraska Medical Center , Omaha , USA.
Bhopal C Mohapatrac Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center , Omaha , USA.
Matthew A Storckc Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center , Omaha , USA.
Vimla Bandb Department of Genetics, Cell Biology and Anatomy , University of Nebraska Medical Center , Omaha , USA.
Hamid Bandb Department of Genetics, Cell Biology and Anatomy , University of Nebraska Medical Center , Omaha , USA.
University of Nebraska Medical Center · US

Funding

CHEMICAL CARCINOGENESIS &CANCER BIOLOGYT32CA009476 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Jennifer D. Black · 1988 to 2026
$6.2M
TYROSINE KINASE REGULATION VIA PROTEIN DEGRADATIONR01CA087986 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2000 to 2015
$4.2M
MOLECULAR CONTROL OF EGF RECEPTOR DOWN-REGULATIONR01CA099163 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2003 to 2012
$3.7M
Targeting Endocytic Recycling of EGF Receptor in Cancer R01CA105489 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2004 to 2014
$3.0M
A novel regulator of p53 functionR01CA096844 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, VIMLA · 2002 to 2011
$2.7M
Ecd as a regulator of cell cycle and breast oncogenesisR01CA144027 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, VIMLA · 2011 to 2015
$1.6M
ErbB2 Downregulation Through HSP90 InhibitionR01CA116552 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2007 to 2011
$1.4M
NCI NIH HHS R01 CA087986NCI NIH HHS R01 CA096844NCI NIH HHS R01 CA099163NCI NIH HHS R01 CA105489NCI NIH HHS R01 CA116552NCI NIH HHS R01 CA144027NCI NIH HHS T32 CA009476
6 · The paper itself

Abstract

objectivesMutations in Cbl or Cbl-b gene occur in 10% of myeloproliferative disorder (MPD) patients and are associated with poor prognosis. Hematopoietic Cbl/Cbl-b double knockout (DKO) leads to a disease in mice phenotypically similar to human MPDs. The aim of this study was to evaluate the anti-MPD activity of a clinically safe drug, Fasudil, identified in an in vitro kinase inhibitor as an inhibitor of proliferation of DKO mouse hematopoietic stem/progenitor cells (HSPCs).

methodsFasudil exhibited relatively selective anti-proliferative activity against Cbl/Cbl-b DKO vs. control murine bone marrow HSPCs. We established a mouse model with uniform time of MPD onset by transplanting Cbl/Cbl-b DKO HSPCs into busulfan-conditioned NOD/SCID/gamma chain-deficient mice. Four weeks post-transplant, mice were treated with 100 mg/kg fasudil (13 mice) or water (control, 8 mice) daily by oral gavage, followed by blood cell count every 2 weeks.

resultsBy 2 weeks of treatment, total white cell and monocyte counts were significantly lower in mice treated with fasudil. We observed a trend towards improved survival in fasudil-treated mice that did not reach statistical significance. Notably, prolonged survival beyond 27 weeks was observed in two fasudil-treated mice, nearly twice the 16-week average life-span in the Cbl/Cbl-b DKO MPD model.

conclusionsOur results suggest a therapeutic potential for fasudil, a clinically safe drug with promising results in vascular diseases, in the treatment of MPDs or other mutant Cbl-driven myeloid disorders.

Indexed as

Myeloproliferative Disorders1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAdaptor Proteins, Signal TransducingAnimalsDisease Models, AnimalHumansMiceMice, Inbred NODMice, KnockoutMice, SCIDProto-Oncogene Proteins c-cblrho-Associated Kinases1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAdaptor Proteins, Signal TransducingCblb protein, mouseCbl protein, mousefasudilProto-Oncogene Proteins c-cblrho-Associated KinasesCblFasudilMouse modelMyeloproliferative diseasesMyosin light chainRho kinase

Identifiers

PMID26177294
PMCPMC5555218
OpenAlexW1533080500

What OpenQuestion holds

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Registered trials

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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.