Evidence map›Paper›PMID 25795306›Full record

ArticleNeuro-oncology2015

Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma.

Melissa M Singh, Blake Johnson, Avinashnarayan Venkatarayan, Elsa R Flores, Jianping Zhang, Xiaoping Su, Michelle Barton, Frederick Lang, Joya Chandra

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Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
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

45 citing papers in PubMed.

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  16. Prognostic role of CD11bArchives of medical science : AMS · 2023
    Article
  17. Review
  18. Review
  19. Review
  20. Epigenetic Deregulation of the Histone MethyltransferaseFrontiers in cell and developmental biology · 2021
    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

9 authors.

Melissa M SinghDepartment of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, Texas (M.M.S., B.J., J.C.); Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (A.V., E.R.F.); Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas (M.B., J.C.); Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z., X.S.); Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (B.J., F.L.); Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas (A.V., E.R.F., M.B., F.L., J.C.).
Blake JohnsonDepartment of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, Texas (M.M.S., B.J., J.C.); Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (A.V., E.R.F.); Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas (M.B., J.C.); Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z., X.S.); Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (B.J., F.L.); Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas (A.V., E.R.F., M.B., F.L., J.C.).
Avinashnarayan VenkatarayanDepartment of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, Texas (M.M.S., B.J., J.C.); Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (A.V., E.R.F.); Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas (M.B., J.C.); Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z., X.S.); Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (B.J., F.L.); Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas (A.V., E.R.F., M.B., F.L., J.C.).
Elsa R FloresDepartment of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, Texas (M.M.S., B.J., J.C.); Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (A.V., E.R.F.); Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas (M.B., J.C.); Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z., X.S.); Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (B.J., F.L.); Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas (A.V., E.R.F., M.B., F.L., J.C.).
Jianping ZhangDepartment of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, Texas (M.M.S., B.J., J.C.); Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (A.V., E.R.F.); Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas (M.B., J.C.); Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z., X.S.); Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (B.J., F.L.); Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas (A.V., E.R.F., M.B., F.L., J.C.).
Xiaoping SuDepartment of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, Texas (M.M.S., B.J., J.C.); Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (A.V., E.R.F.); Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas (M.B., J.C.); Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z., X.S.); Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (B.J., F.L.); Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas (A.V., E.R.F., M.B., F.L., J.C.).
Michelle BartonDepartment of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, Texas (M.M.S., B.J., J.C.); Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (A.V., E.R.F.); Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas (M.B., J.C.); Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z., X.S.); Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (B.J., F.L.); Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas (A.V., E.R.F., M.B., F.L., J.C.).
Frederick LangDepartment of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, Texas (M.M.S., B.J., J.C.); Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (A.V., E.R.F.); Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas (M.B., J.C.); Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z., X.S.); Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (B.J., F.L.); Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas (A.V., E.R.F., M.B., F.L., J.C.).
Joya ChandraDepartment of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, Texas (M.M.S., B.J., J.C.); Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (A.V., E.R.F.); Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas (M.B., J.C.); Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z., X.S.); Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (B.J., F.L.); Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas (A.V., E.R.F., M.B., F.L., J.C.).

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Tropism Enhanced Oncolytic Adenovirus for the Treatment of Brain TumorsP50CA127001 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Juan Fueyo · 2008 to 2026
$41.2M
Dual LSD1 and HDAC Inhibition for Cancer TherapyF32CA150610 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SINGH, MELISSA MARIE · 2011 to 2013
$166k
NCI NIH HHS F32 CA150610NCI NIH HHS F32CA150610NCI NIH HHS P30CA016672NCI NIH HHS P50 CA127001
6 · The paper itself

Abstract

backgroundGlioblastoma (GBM) is the most common and aggressive form of brain cancer. Our previous studies demonstrated that combined inhibition of HDAC and KDM1A increases apoptotic cell death in vitro. However, whether this combination also increases death of the glioma stem cell (GSC) population or has an effect in vivo is yet to be determined. Therefore, we evaluated the translational potential of combined HDAC and KDM1A inhibition on patient-derived GSCs and xenograft GBM mouse models. We also investigated the changes in transcriptional programing induced by the combination in an effort to understand the induced molecular mechanisms of GBM cell death.

methodsPatient-derived GSCs were treated with the combination of vorinostat, a pan-HDAC inhibitor, and tranylcypromine, a KDM1A inhibitor, and viability was measured. To characterize transcriptional profiles associated with cell death, we used RNA-Seq and validated gene changes by RT-qPCR and protein expression via Western blot. Apoptosis was measured using DNA fragmentation assays. Orthotopic xenograft studies were conducted to evaluate the effects of the combination on tumorigenesis and to validate gene changes in vivo.

resultsThe combination of vorinostat and tranylcypromine reduced GSC viability and displayed efficacy in the U87 xenograft model. Additionally, the combination led to changes in apoptosis-related genes, particularly TP53 and TP73 in vitro and in vivo.

conclusionsThese data support targeting HDACs and KDM1A in combination as a strategy for GBM and identifies TP53 and TP73 as being altered in response to treatment.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBrain NeoplasmsCell Line, TumorCell ProliferationCell SurvivalDNA FragmentationFemaleGlioblastomaHigh-Throughput Nucleotide SequencingHistone Deacetylase InhibitorsHistone DemethylasesHumansHydroxamic AcidsImmunoblottingHistone Deacetylase InhibitorsHistone DemethylasesHydroxamic AcidsKDM1A protein, humanTranylcypromineVorinostatepigeneticsglioblastomaHDAC inhibitorsKDM1ALSD1lysine demethylasesorthotopic GBM modelstranylcypromine

Identifiers

PMID25795306
PMCPMC4648298

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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.