Evidence map›Paper›PMID 26464423›Full record

ArticleJournal of the National Cancer Institute2015

Preclinical Investigation of the Novel Histone Deacetylase Inhibitor AR-42 in the Treatment of Cancer-Induced Cachexia.

Yu-Chou Tseng, Samuel K Kulp, I-Lu Lai, En-Chi Hsu, Wei A He, David E Frankhouser, Pearlly S Yan, Xiaokui Mo, Mark Bloomston, Gregory B Lesinski and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
–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

57 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026
    Review
  4. Article
  5. Metabolomics-driven discovery of therapeutic targets for cancer cachexia.Journal of cachexia, sarcopenia and muscle · 2024
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Metabolomics and its Applications in Cancer Cachexia.Frontiers in molecular biosciences · 2022
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Yu-Chou TsengDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
Samuel K KulpDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
I-Lu LaiDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
En-Chi HsuDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
Wei A HeDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
David E FrankhouserDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
Pearlly S YanDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
Xiaokui MoDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
Mark BloomstonDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
Gregory B LesinskiDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
Guido MarcucciDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
Denis C GuttridgeDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC).
Tanios Bekaii-SaabDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC). Tanios.Saab@osumc.edu chen.844@osu.edu.
Ching-Shih ChenDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy (YCT, SKK, ILL, ECH, CSC), Department of Molecular Virology, Immunology, and Medical Genetics (WAH, DCG), Department of Surgery (MB), Department of Internal Medicine (GBL, GM, TBS), and Center for Biostatistics (XM), College of Medicine, and Genomics Shared Resource (DEF, PSY), The Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan (CSC); Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan (CSC). Tanios.Saab@osumc.edu chen.844@osu.edu.

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
Integrative Training in Biomedical SystemsT32GM068412 · NIGMS · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2005 to 2020
$2.4M
NCI NIH HHS P30 CA016058NIGMS NIH HHS T32 GM068412
6 · The paper itself

Abstract

backgroundCancer cachexia is a debilitating condition that impacts patient morbidity, mortality, and quality of life and for which effective therapies are lacking. The anticachectic activity of the novel HDAC inhibitor AR-42 was investigated in murine models of cancer cachexia.

methodsThe effects of AR-42 on classic features of cachexia were evaluated in the C-26 colon adenocarcinoma and Lewis lung carcinoma (LLC) models. Effects on survival in comparison with approved HDAC inhibitors (vorinostat, romidepsin) were determined. The muscle metabolome and transcriptome (by RNA-seq), as well as serum cytokine profile, were evaluated. Data were analyzed using mixed effects models, analysis of variance, or log-rank tests. All statistical tests were two-sided.

resultsIn the C-26 model, orally administered AR-42 preserved body weight (23.9±2.6 grams, AR-42-treated; 20.8±1.3 grams, vehicle-treated; P = .005), prolonged survival (P < .001), prevented reductions in muscle and adipose tissue mass, muscle fiber size, and muscle strength and restored intramuscular mRNA expression of the E3 ligases MuRF1 and Atrogin-1 to basal levels (n = 8). This anticachectic effect, confirmed in the LLC model, was not observed after treatment with vorinostat and romidepsin. AR-42 suppressed tumor-induced changes in inflammatory cytokine production and multiple procachexia drivers (IL-6, IL-6Rα, leukemia inhibitory factor, Foxo1, Atrogin-1, MuRF1, adipose triglyceride lipase, uncoupling protein 3, and myocyte enhancer factor 2c). Metabolomic analysis revealed cachexia-associated changes in glycolysis, glycogen synthesis, and protein degradation in muscle, which were restored by AR-42 to a state characteristic of tumor-free mice.

conclusionsThese findings support further investigation of AR-42 as part of a comprehensive therapeutic strategy for cancer cachexia.

Indexed as

AcyltransferasesAdenocarcinomaAdipose TissueAdministration, OralAnimalsCachexiaCarcinoma, Lewis LungColonic NeoplasmsCytokinesForkhead Box Protein O1Forkhead Transcription FactorsGene Expression RegulationHistone Deacetylase InhibitorsInterleukin-6Ion ChannelsLeukemia Inhibitory FactorAcyltransferasesCytokinesFbxo32 protein, mouseForkhead Box Protein O1Forkhead Transcription FactorsFoxo1 protein, mouseHistone Deacetylase InhibitorsInterleukin-6interleukin-6, mouseIon ChannelsLeukemia Inhibitory FactorLif protein, mouseLipaseMEF2 Transcription FactorsMitochondrial ProteinsMuscle ProteinsOSU-HDAC42 compoundPhenylbutyratesPNPLA2 protein, mouseReceptors, Interleukin-6SKP Cullin F-Box Protein LigasesTrim63 protein, mouseTripartite Motif ProteinsUbiquitin-Protein LigasesUcp3 protein, mouseUncoupling Protein 3

Identifiers

PMID26464423
PMCPMC6280990

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.