Evidence map›Paper›PMID 34008339›Full record

ArticleJournal of cachexia, sarcopenia and muscle2021

Activated mast cells in skeletal muscle can be a potential mediator for cancer-associated cachexia.

D Brooke Widner, Chun Liu, Qingxia Zhao, Sarah Sharp, Matthew R Eber, Sun H Park, D Clark Files, Yusuke Shiozawa

Open access · goldAbstract read
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Immunoregulation in cancer-associated cachexia.Journal of advanced research · 2024
    Review
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  11. Review
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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.

D Brooke WidnerDepartment of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Chun LiuInternal Medicine-Sections in Pulmonary and Critical Care Medicine and Geriatrics and the Critical Illness Injury and Recovery Research Center, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Qingxia ZhaoDepartment of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Sarah SharpDepartment of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Matthew R EberDepartment of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Sun H ParkDepartment of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
D Clark FilesInternal Medicine-Sections in Pulmonary and Critical Care Medicine and Geriatrics and the Critical Illness Injury and Recovery Research Center, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Yusuke ShiozawaDepartment of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC, USA.ORCID 0000-0001-9814-9230
Wake Forest University · US

Funding

Tumor Tissue CoreP30CA012197 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Ruben A. Mesa · 1985 to 2026
$55.4M
CDK8/19 inhibitors for therapy of advanced prostate cancerR44CA203184 · NCI · SENEX BIOTECHNOLOGY, INC. · PI CHEN, MENGQIAN, LILLY, MICHAEL B · 2020 to 2021
$2.0M
The contributions of sensory nerves to bone metastasis and associated bone painR01CA238888 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SHIOZAWA, YUSUKE · 2020 to 2024
$1.8M
CDK8/19 inhibitors for therapy of advanced prostate cancerR43CA203184 · NCI · SENEX BIOTECHNOLOGY, INC. · PI PORTER, DONALD C. · 2015 to 2015
$241k
NCI NIH HHS P30 CA012197NCI NIH HHS R01 CA238888NCI NIH HHS R43 CA203184NCI NIH HHS R44 CA203184
6 · The paper itself

Abstract

backgroundEighty per cent of United States advanced cancer patients faces a worsened prognosis due to cancer-associated cachexia. Inflammation is one driver of muscle atrophy in cachexia, and skeletal muscle-resident immune cells could be a source of inflammation. This study explores the efficacy of cancer activated skeletal muscle-resident mast cells as a biomarker and mediator of cachexia.

methodsIndividual gene markers for immune cells were assessed in a publicly available colon carcinoma cohort of normal (n = 3), moderate cachexia (n = 3), and severe cachexia (n = 4) mice. Lewis lung carcinoma (LL/2) cells induced cachexia in C57BL/6 mice, and a combination of toluidine blue staining, immunofluorescence, quantitative polymerase chain reaction, and western blots measured innate immune cell expression in hind limb muscles. In vitro measurements included C2C12 myotube diameter before and after treatment with media from primary murine mast cells activated with LL/2 conditioned media. To assess translational potential in human samples, innate immune cell signatures were assessed for correlation with skeletal muscle atrophy and apoptosis, dietary excess, and cachexia signatures in normal skeletal muscle tissue. Gene set enrichment analysis was performed with innate immune cell signatures in publicly available cohorts for upper gastrointestinal (GI) cancer and pancreatic ductal adenocarcinoma (PDAC) patients (accession: GSE34111 and GSE130563, respectively).

resultsIndividual innate immunity genes (TPSAB1 and CD68) showed significant increases in severe cachexia (weight loss > 15%) mice in a C26 cohort (GSE24112). Induction of cachexia in C57BL/6 mice with LL/2 subcutaneous injection significantly increased the number of activated skeletal muscle-resident degranulating mast cells. Murine mast cells activated with LL/2 conditioned media decreased C2C12 myotube diameter (P ≤ 0.05). Normal human skeletal muscle showed significant positive correlations between innate immune cell signatures and muscle apoptosis and atrophy, dietary excess, and cachexia signatures. The mast cell signature was up-regulated (positive normalized enrichment score and false discovery rate ≤ 0.1) in upper GI cachectic patients (n = 12) compared with control (n = 6), as well as in cachectic PDAC patients (n = 17) compared with control patients (n = 16).

conclusionsActivated skeletal muscle-resident mast cells are enriched in cachectic muscles, suggesting skeletal-muscle resident mast cells may serve as a biomarker and mediator for cachexia development to improve patient diagnosis and prognosis.

Indexed as

CachexiaPancreatic NeoplasmsAnimalsHumansMast CellsMiceMice, Inbred C57BLMuscle, SkeletalCancer-associated cachexiaDegranulationInnate immunityMast cellsSkeletal muscle

Identifiers

PMID34008339
PMCPMC8350201
OpenAlexW3160016211

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.