Evidence map›Paper›PMID 21778190›Full record

ArticleNeuro-oncology2011

AR42, a novel histone deacetylase inhibitor, as a potential therapy for vestibular schwannomas and meningiomas.

Matthew L Bush, Janet Oblinger, Victoria Brendel, Griffin Santarelli, Jie Huang, Elena M Akhmametyeva, Sarah S Burns, Justin Wheeler, Jeremy Davis, Charles W Yates and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 2 pooled it
3.2field-weighted citation impact, top 8% 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

49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Fimepinostat Promotes Apoptosis and Decreases Cytokine Secretion inInternational journal of molecular sciences · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. The molecular biology of NF2/Merlin on tumorigenesis and development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. [Research progress on non-surgical treatment of vestibular schwannomas].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2022
    Review
  19. [Prospects of Drug Therapy of Vestibular Schwannoma].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022
    Review
  20. 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

16 authors at 3 institutions in 1 country.

Matthew L BushDepartment of Otolaryngology–Head and Neck Surgery, The Ohio State University, Columbus, OH 43212, USA.
Janet Oblinger
Victoria Brendel
Griffin Santarelli
Jie Huang
Elena M Akhmametyeva
Sarah S Burns
Justin Wheeler
Jeremy Davis
Charles W Yates
Abhik R Chaudhury
Samuel Kulp
Ching-Shih Chen
Long-Sheng Chang
D Bradley Welling
Abraham Jacob
University of Toledo · USNationwide Children's Hospital · USThe Ohio State University · US

Funding

Phenotypic Determinants of Vestibular SchwannomasR01DC005985 · NIDCD · OHIO STATE UNIVERSITY · PI WELLING, D BRADLEY · 2005 to 2009
$1.7M
Preclinical testing of a novel PDK1 inhibitor for treating vestibular schwannomaK08DC009644 · NIDCD · UNIVERSITY OF ARIZONA · PI JACOB, ABRAHAM · 2009 to 2013
$1.2M
NIDCD NIH HHS 3R01DC005985-05S11NIDCD NIH HHS K08 DC009644-01A1NIDCD NIH HHS R01 DC005985
6 · The paper itself

Abstract

Neurofibromatosis type 2 (NF2) is an autosomal-dominant disease that results in the formation of bilateral vestibular schwannomas (VSs) and multiple meningiomas. Treatment options for NF2-associated tumors are limited, and to date, no medical therapies are FDA approved. The ideal chemotherapeutic agent would inhibit both VS and meningiomas simultaneously. The objectives of this study are (1) to test the efficacy of AR42, a novel histone deacetylase inhibitor, to inhibit VS and meningioma growth and (2) to investigate this drug's mechanisms of action. Primary cultures of human VS and meningioma cells were established. Nf2-deficient mouse schwannoma and benign human meningioma Ben-Men-1 cells were also cultured. Cells were treated with AR42, and the drug's effects on proliferation and the cell cycle were analyzed using a methanethiosulfonate assay and flow cytometry, respectively. Human phospho-kinase arrays and Western blots were used to evaluate the effects of AR42 on intracellular signaling. The in vivo efficacy of AR42 was investigated using schwannoma xenografts. Tumor volumes were quantified using high-field, volumetric MRI, and molecular target analysis was performed using immunohistochemistry. AR42 inhibited the growth of primary human VS and Nf2-deficient mouse schwannoma cells with a half maximal inhibitory concentration (IC(50)) of 500 nM and 250-350 nM, respectively. AR42 also inhibited primary meningioma cells and the benign meningioma cell line, Ben-Men-1, with IC(50) values of 1.5 µM and 1.0 µM, respectively. AR42 treatment induced cell-cycle arrest at G(2) and apoptosis in both VS and meningioma cells. Also, AR42 exposure decreased phosphorylated Akt in schwannoma and meningioma cells. In vivo treatment with AR42 inhibited the growth of schwannoma xenografts, induced apoptosis, and decreased Akt activation. The potent growth inhibitory activity of AR42 in schwannoma and meningioma cells suggests that AR42 should be further evaluated as a potential treatment for NF2-associated tumors.

Indexed as

AnimalsApoptosisBlotting, WesternCell CycleCell Line, TumorCell ProliferationDisease Models, AnimalFluorescent Antibody TechniqueHistone Deacetylase InhibitorsHumansImmunoenzyme TechniquesMagnetic Resonance ImagingMeningeal NeoplasmsMeningiomaMiceMice, KnockoutHistone Deacetylase InhibitorsNeurofibromin 2OSU-HDAC42 compoundPhenylbutyratesProto-Oncogene Proteins c-akt

Identifiers

PMID21778190
PMCPMC3158011
OpenAlexW2139681340

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.