Evidence map›Paper›PMID 27259276›Full record

ArticleOncotarget2016

Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs.

Rafael Barreto, David L Waning, Hongyu Gao, Yunlong Liu, Teresa A Zimmers, Andrea Bonetto

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed, 3 pooled it
10.7field-weighted citation impact, top 1% 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

138 citing papers in PubMed, 3 syntheses or guidelines pooled it, 195 citations in OpenAlex.

  1. Pooled it
  2. Exercise on quality of life and cancer-related fatigue for lymphoma survivors: a systematic review and meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2019
    Pooled it
  3. Barriers and facilitators of exercise experienced by cancer survivors: a mixed methods systematic review.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2018
    Pooled it
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  12. Chemotherapy induces tissue NADbioRxiv : the preprint server for biology · 2026
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78 more citing papers are in PubMed but not listed here.

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

6 authors at 3 institutions in 1 country.

Rafael BarretoDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
David L WaningSimon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Hongyu GaoDepartment of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Yunlong LiuDepartment of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Teresa A ZimmersDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Andrea BonettoDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Indiana University School of MedicineIndiana University Health · USIndiana University – Purdue University Indianapolis · US

Funding

Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
Manipulation of STAT3 Signaling for Muscle Preservation in Cancer CachexiaR01CA122596 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ZIMMERS, TERESA A · 2010 to 2015
$1.6M
PQB3: Mechanisms & Targeting of Sonic Hedgehog Signaling in Muscle Wasting of Cancer CachexiaR01CA194593 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI ZIMMERS, TERESA A · 2015 to 2018
$1.4M
(PQB-3) Roles of skeletal muscle mass in chemotherapy-associated cachexiaR21CA190028 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI BONETTO, ANDREA · 2014 to 2015
$373k
NCATS NIH HHS UL1 TR001108NCI NIH HHS R01 CA122596NCI NIH HHS R01 CA194593NCI NIH HHS R21 CA190028
6 · The paper itself

Abstract

Cachexia affects the majority of cancer patients, with currently no effective treatments. Cachexia is defined by increased fatigue and loss of muscle function resulting from muscle and fat depletion. Previous studies suggest that chemotherapy may contribute to cachexia, although the causes responsible for this association are not clear. The purpose of this study was to investigate the mechanism(s) associated with chemotherapy-related effects on body composition and muscle function. Normal mice were administered chemotherapy regimens used for the treatment of colorectal cancer, such as Folfox (5-FU, leucovorin, oxaliplatin) or Folfiri (5-FU, leucovorin, irinotecan) for 5 weeks. The animals that received chemotherapy exhibited concurrent loss of muscle mass and muscle weakness. Consistently with previous findings, muscle wasting was associated with up-regulation of ERK1/2 and p38 MAPKs. No changes in ubiquitin-dependent proteolysis or in the expression of TGFβ-family members were detected. Further, marked decreases in mitochondrial content, associated with abnormalities at the sarcomeric level and with increase in the number of glycolytic fibers were observed in the muscle of mice receiving chemotherapy. Finally, ACVR2B/Fc or PD98059 prevented Folfiri-associated ERK1/2 activation and myofiber atrophy in C2C12 cultures. Our findings demonstrate that chemotherapy promotes MAPK-dependent muscle atrophy as well as mitochondrial depletion and alterations of the sarcomeric units. Therefore, these findings suggest that chemotherapy potentially plays a causative role in the occurrence of muscle loss and weakness. Moreover, the present observations provide a strong rationale for testing ACVR2B/Fc or MEK1 inhibitors in combination with anticancer drugs as novel strategies aimed at preventing chemotherapy-associated muscle atrophy.

Indexed as

Activin Receptors, Type IIAnimalsAntineoplastic Combined Chemotherapy ProtocolsBody CompositionCachexiaCamptothecinCell LineColorectal NeoplasmsFlavonoidsFluorouracilHumansLeucovorinMaleMAP Kinase Kinase 1MAP Kinase Signaling SystemMice2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-oneActivin Receptors, Type IIactivin receptor type II-BCamptothecinFlavonoidsFluorouracilLeucovorinMap2k1 protein, mouseMAP Kinase Kinase 1Mitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mstn protein, mouseMyostatinOrganoplatinum Compoundsp38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorscachexiachemotherapyMAPKsmitochondriamuscle wasting

Identifiers

PMID27259276
PMCPMC5190036
OpenAlexW2413238603

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.