Evidence map›Paper›PMID 26483043›Full record

ArticleBMC cancer2015

The Aplidin analogs PM01215 and PM02781 inhibit angiogenesis in vitro and in vivo.

Bojana Borjan, Normann Steiner, Silvia Karbon, Johann Kern, Andrés Francesch, Martin Hermann, Wolfgang Willenbacher, Eberhard Gunsilius, Gerold Untergasser

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

Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

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  9. Plitidepsin: design, development, and potential place in therapy.Drug design, development and therapy · 2017
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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

9 authors at 3 institutions in 2 countries.

Bojana BorjanDepartment of Internal Medicine V, Innsbruck Medical University, Innrain 66, 6020, Innsbruck, Austria. bojana.borjan@i-med.ac.at.
Normann SteinerDepartment of Internal Medicine V, Innsbruck Medical University, Innrain 66, 6020, Innsbruck, Austria. normann.steiner@i-med.ac.at.
Silvia KarbonDepartment of Internal Medicine V, Innsbruck Medical University, Innrain 66, 6020, Innsbruck, Austria. silvia.carbon@i-med.ac.at.
Johann KernOncotyrol GmbH, Karl Kapfererstrasse 5, 6020, Innsbruck, Austria. johann.kern@oncotyrol.at.
Andrés FranceschPharmamar, R&D Department, Avda de los Reyes 1, 28770, Colmenar Viejo, Madrid, Spain. afrancesch@pharmar.com.
Martin HermannDepartment of Anesthesiology & Critical Care Medicine, Innsbruck Medical University, Innsbruck, Austria. martin.hermann@uki.at.
Wolfgang WillenbacherDepartment of Internal Medicine V, Innsbruck Medical University, Innrain 66, 6020, Innsbruck, Austria. wolfgang.willenbacher@uki.at.
Eberhard GunsiliusDepartment of Internal Medicine V, Innsbruck Medical University, Innrain 66, 6020, Innsbruck, Austria. eberhard.gunsilius@i-med.ac.at.
Gerold UntergasserDepartment of Internal Medicine V, Innsbruck Medical University, Innrain 66, 6020, Innsbruck, Austria. gerold.untergasser@i-med.ac.at.
Innsbruck Medical University · ATPharmaMar (Spain) · ESTyrolean Cancer Research Institute · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNovel synthesized analogs of Aplidin, PM01215 and PM02781, were tested for antiangiogenic effects on primary human endothelial cells in vitro and for inhibition of angiogenesis and tumor growth in vivo.

methodsAntiangiogenic activity of both derivatives was evaluated by real-time cell proliferation, capillary tube formation and vascular endothelial growth factor (VEGF)-induced spheroid sprouting assays. Distribution of endothelial cells in the different phases of the cell cycle was analyzed by flow cytometry. Aplidin analogs were tested in vivo in chicken chorioallantoic membrane (CAM) assays.

resultsBoth derivatives inhibited angiogenic capacities of human endothelial cells (HUVECs) in vitro at low nanomolar concentrations. Antiangiogenic effects of both analogs were observed in the CAM. In addition, growth of human multiple myeloma xenografts in vivo in CAM was significantly reduced after application of both analogs. On the molecular level, both derivatives induced cell cycle arrest in G1 phase. This growth arrest of endothelial cells correlated with induction of the cell cycle inhibitor p16(INK4A) and increased senescence-associated beta galactosidase activity. In addition, Aplidin analogs induced oxidative stress and decreased production of the vascular maturation factors Vasohibin-1 and Dickkopf-3.

conclusionsFrom these findings we conclude that both analogs are promising agents for the development of antiangiogenic drugs acting independent on classical inhibition of VEGF signaling.

Indexed as

Antineoplastic AgentsBlotting, WesternBortezomibCell CycleCell MovementCell ProliferationDepsipeptidesEndothelium, VascularEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHumansMicroscopy, ConfocalMultiple MyelomaNeovascularization, PathologicNeovascularization, PhysiologicAntineoplastic AgentsBortezomibDepsipeptidesPeptides, Cyclicplitidepsin

Identifiers

PMID26483043
PMCPMC4615365
OpenAlexW2102259487

What OpenQuestion holds

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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.