Evidence map›Paper›PMID 32707866›Full record

ArticleInternational journal of molecular sciences2020

Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib.

Panagiotis Efentakis, Hendrik Doerschmann, Claudius Witzler, Svenja Siemer, Panagiota-Efstathia Nikolaou, Efstathios Kastritis, Roland Stauber, Meletios Athanasios Dimopoulos, Philip Wenzel, Ioanna Andreadou and 1 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-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

14 citing papers in PubMed, 23 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

11 authors at 2 institutions in 2 countries.

Panagiotis EfentakisLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Hendrik DoerschmannCardiology I Department, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Claudius WitzlerCardiology I Department, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Svenja SiemerMolecular and Cellular Oncology/ENT, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55101 Mainz, Germany.
Panagiota-Efstathia NikolaouLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Efstathios KastritisDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Roland StauberMolecular and Cellular Oncology/ENT, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55101 Mainz, Germany.
Meletios Athanasios DimopoulosDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Philip WenzelCardiology I Department, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.ORCID 0000-0002-5397-2781
Ioanna AndreadouLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Evangelos TerposDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.ORCID 0000-0001-5133-1422
Johannes Gutenberg University Mainz · DENational and Kapodistrian University of Athens · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCarfilzomib's (Cfz) adverse events in myeloma patients include cardiovascular toxicity. Since carfilzomib's vascular effects are elusive, we investigated the vascular outcomes of carfilzomib and metformin (Met) coadministration.

methodsMice received: (i) saline; (ii) Cfz; (iii) Met; (iv) Cfz+Met for two consecutive (acute) or six alternate days (subacute protocol). Leucocyte-derived reactive oxygen species (ROS) and serum NO

resultsAcutely, carfilzomib alone led to vascular hypo-contraction and increased ROS release. Subacutely, carfilzomib increased ROS release without vascular manifestations. Cfz+Met increased PGF2α-vasoconstriction and LC3-B-dependent autophagy in both young and aged mice. In vitro, Cfz+Met led to cytotoxicity and autophagy, while Met and Cfz+Met shifted cellular metabolism.

conclusionCarfilzomib induces a transient vascular impairment and oxidative burst. Cfz+Met increased vascular contractility and synergistically induced autophagy in all settings. Therefore, carfilzomib cannot be accredited for a permanent vascular dysfunction, while Cfz+Met exert vasoprotective potency.

Indexed as

ActinsAMP-Activated Protein Kinase KinasesAnimalsAntineoplastic AgentsAutophagyCell SurvivalCobaltDinoprostDrug Therapy, CombinationEndoplasmic ReticulumGlucoseGlycolysisHumansMaleMetforminMiceActinsAMP-Activated Protein Kinase KinasesAntineoplastic AgentscarfilzomibCobaltcobaltous chlorideDinoprostGlucoseMetforminNitric OxideOligopeptidesProteasome Endopeptidase ComplexProteasome InhibitorsProtein KinasesReactive Oxygen SpeciesTumor Suppressor Protein p53autophagycarfilzomibendoplasmatic-reticulum stressvascular smooth muscle cellsvasculature

Identifiers

PMID32707866
PMCPMC7432349
OpenAlexW3045138124

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.