Evidence map›Paper›PMID 33006443›Full record

ArticleJournal of cachexia, sarcopenia and muscle2020

Brain metabolites in cholinergic and glutamatergic pathways are altered by pancreatic cancer cachexia.

Paul T Winnard, Santosh Kumar Bharti, Raj Kumar Sharma, Balaji Krishnamachary, Yelena Mironchik, Marie-France Penet, Michael G Goggins, Anirban Maitra, Ihab Kamel, Karen M Horton and 2 more

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

Article in Journal of cachexia, sarcopenia and muscle, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 16% 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

12 citing papers in PubMed, 20 citations in OpenAlex.

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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

12 authors at 2 institutions in 1 country.

Paul T WinnardDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Santosh Kumar BhartiDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Raj Kumar SharmaDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Balaji KrishnamacharyDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yelena MironchikDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Marie-France PenetDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael G GogginsSol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Anirban MaitraSidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ihab KamelDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Karen M HortonDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael A JacobsDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zaver M BhujwallaDivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-6617-9360
Johns Hopkins University · USThe University of Texas MD Anderson Cancer Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
Using markers to improve pancreatic cancer screening and surveillance: a multi-center studyU01CA210170 · NCI · JOHNS HOPKINS UNIVERSITY · PI Michael G. Goggins · 2016 to 2026
$9.3M
Molecular Imaging and Theranostics of CancerR35CA209960 · NCI · JOHNS HOPKINS UNIVERSITY · PI BHUJWALLA, ZAVER M. · 2017 to 2023
$6.5M
HOSTILE ENVIRONMENTS PROMOTE INVASION AND METATASISR01CA082337 · NCI · JOHNS HOPKINS UNIVERSITY · PI BHUJWALLA, ZAVER M. · 1999 to 2024
$5.1M
Molecular Imaging of Cachexia in Pancreatic CancerR01CA193365 · NCI · JOHNS HOPKINS UNIVERSITY · PI BHUJWALLA, ZAVER M., HORTON, KAREN M · 2016 to 2020
$1.6M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA082337NCI NIH HHS R01 CA193365NCI NIH HHS R35 CA209960NIH HHS R01 CA193365NIH HHS R01 CA82337NIH HHS R35 CA209960NIH HHS U01 CA210170
6 · The paper itself

Abstract

backgroundCachexia is a major cause of morbidity in pancreatic ductal adenocarcinoma (PDAC) patients. Our purpose was to understand the impact of PDAC-induced cachexia on brain metabolism in PDAC xenograft studies, to gain new insights into the causes of cachexia-induced morbidity. Changes in mouse and human plasma metabolites were characterized to identify underlying causes of brain metabolic changes.

methodsWe quantified metabolites, detected with high-resolution

resultsThe brain metabolic signature of cachexia-inducing PDAC was characterized by a significant depletion of choline of -27% and -21% as well as increases of glutamine of 13% and 9% and formate of 21% and 14%, relative to normal controls and non-cachectic tumour-bearing mice, respectively. Good to moderate correlations with percent weight change were found for choline (r = 0.70), glutamine (r = -0.58), and formate (r = -0.43). Significant choline depletion of -38% and -30%, relative to normal controls and non-cachectic tumour-bearing mice, respectively, detected in the plasma of cachectic mice likely contributed to decreased brain choline in cachectic mice. Similarly, relative to normal controls and patients with benign disease, choline levels in human plasma samples of PDAC patients were significantly lower by -12% and -20% respectively. A comparison of plasma metabolites from PDAC patients with and without weight loss identified significant changes in glutamine metabolism.

conclusionsDisturbances in metabolites of the choline/cholinergic and glutamine/glutamate/glutamatergic neurotransmitter pathways may contribute to morbidity. Metabolic normalization may provide strategies to reduce morbidity. The human plasma metabolite changes observed may lead to the development of companion diagnostic markers to detect PDAC and PDAC-induced cachexia.

Indexed as

BrainCarcinoma, Pancreatic DuctalPancreatic NeoplasmsAnimalsCachexiaCholinergic AgentsHumansMiceCholinergic AgentsBrain and plasma 1H MR spectroscopyCachexiaHuman pancreatic cancer xenograftsHuman plasmaMetabolites

Identifiers

PMID33006443
PMCPMC7749557
OpenAlexW3090470026

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.