Evidence map›Paper›PMID 33456713›Full record

ArticleOncotarget2021

The noradrenergic profile of plasma metanephrine in neuroblastoma patients is reproduced in xenograft mice models and arise from PNMT downregulation.

Karim Abid, Maja Beck Popovic, Katia Balmas Bourloud, Jacqueline Schoumans, Joana Grand-Guillaume, Eric Grouzmann, Annick Mühlethaler-Mottet

Abstract read
In one paragraph

Article in Oncotarget, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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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

2 citing papers in PubMed.

  1. Article
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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

7 authors.

Karim AbidCatecholamine and Peptides Laboratory, Service of Clinical Pharmacology and Toxicology, Lausanne University Hospital and University of Lausanne, Switzerland.
Maja Beck PopovicPediatric Hematology-Oncology Unit, Woman-Mother-Child Department, Lausanne University Hospital and University of Lausanne, Switzerland.
Katia Balmas BourloudPediatric Hematology-Oncology Research Laboratory, Woman-Mother-Child Department, Lausanne University Hospital and University of Lausanne, Switzerland.
Jacqueline SchoumansOncogenomics Laboratory, Hematology Service, Laboratory Medicine and Pathology Department, Lausanne University Hospital and University of Lausanne, Switzerland.
Joana Grand-GuillaumeCatecholamine and Peptides Laboratory, Service of Clinical Pharmacology and Toxicology, Lausanne University Hospital and University of Lausanne, Switzerland.
Eric GrouzmannCatecholamine and Peptides Laboratory, Service of Clinical Pharmacology and Toxicology, Lausanne University Hospital and University of Lausanne, Switzerland.
Annick Mühlethaler-MottetPediatric Hematology-Oncology Research Laboratory, Woman-Mother-Child Department, Lausanne University Hospital and University of Lausanne, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metanephrines (MNs; normetanephrine (NMN), metanephrine (MN) and methoxytyramine (MT)) detected in urine or plasma represent the best biomarker for neuroblastoma (NB) diagnosis, however the metabolism of both catecholamine (CAT) and MNs remains enigmatic in NB. Using patient-derived xenograft (PDX) models derived from primary NB cells, we observed that the plasma levels of MNs in NB-PDX-bearing mice were comparable as in patients. Interestingly, murine plasma displayed an elevated fraction of glucuronidated forms of MNs relative to human plasma where sulfonated forms prevail. In tumors, the concentration ranges of MNs and CAT and the expression levels of the main genes involved in catecholamine metabolism were similar between NB-PDX and human NB tissues. Likewise, plasma and intratumoral profiles of individual MNs, with increased levels of MT and NMN relative to MN, were also conserved in mouse models as in patients. We further demonstrated the downregulation of the Phenylethanolamine N-Methyltransferase gene in NB biopsies and in NB-PDX explaining this biochemical phenotype, and giving a rational to the low levels of epinephrine and MN measured in NB affected patients. Thus, our subcutaneous murine NB-PDX models not only reproduce the phenotype of primary NB tumors, but also the metabolism of catecholamine as observed in patients. This may potentially open new avenues in preclinical studies for the follow up of novel therapeutic options for NB through the quantification of plasma MNs.

Indexed as

metanephrinemouse modelneuroblastomapatient-derived xenograftPhenylethanolamine N-Methyltransferase

Identifiers

PMID33456713
PMCPMC7800772

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