Evidence map›Paper›PMID 26000061›Full record

ArticleTheranostics2015

Erythropoietin improves the accumulation and therapeutic effects of carboplatin by enhancing tumor vascularization and perfusion.

Dennis Doleschel, Anne Rix, Susanne Arns, Karin Palmowski, Felix Gremse, Ruth Merkle, Florian Salopiata, Ursula Klingmüller, Michael Jarsch, Fabian Kiessling and 1 more

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

Article in Theranostics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
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  8. Review
  9. PLGA-Based Nanoparticles in Cancer Treatment.Frontiers in pharmacology · 2018
    Review
  10. Review
  11. Article
  12. Review
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  14. Article
  15. Article
  16. Emerging targets for radioprotection and radiosensitization in radiotherapy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Review
  17. Article
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 4 institutions in 2 countries.

Dennis Doleschel1. Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Anne Rix1. Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Susanne Arns1. Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Karin Palmowski1. Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany. ; 2. Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.
Felix Gremse1. Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Ruth Merkle3. Division of Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Florian Salopiata3. Division of Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany. ; 4. Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Ursula Klingmüller3. Division of Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany. ; 4. Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Michael Jarsch5. Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Penzberg, Germany.
Fabian Kiessling1. Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Wiltrud Lederle1. Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany.
RWTH Aachen University · DEGerman Cancer Research Center · DEHeidelberg University · DERoche (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recombinant human erythropoietin (rhuEpo) is currently under debate for the treatment of chemotherapy-induced anemia due to clinical trials showing adverse effects in Epo-treated patients and the discovery of the erythropoietin-receptor (EpoR) in tumor and endothelial cells. Here, using Epo-Cy5.5 as theranostic near-infrared fluorescent probe we analyzed the effects of rhuEpo as co-medication to carboplatin in non-small-cell-lung-cancer (NSCLC)-xenografts with different tumor cell EpoR-expression (H838 ~8-fold higher than A549). Nude mice bearing subcutaneous A549 and H838 NSCLC-xenografts received either only carboplatin or carboplatin and co-medication of rhuEpo in two different doses. Tumor sizes and relative blood volumes (rBV) were longitudinally measured by 3D-contrast-enhanced ultrasound (3D-US). Tumoral EpoR-levels were determined by combined fluorescence molecular tomography (FMT)/ micro computed tomography (µCT) hybrid imaging. We found that rhuEpo predominantly acted on the tumor endothelium. In both xenografts, rhuEpo co-medication significantly increased vessel densities, diameters and the amount of perfused vessels. Accordingly, rhuEpo induced EpoR-phoshorylation and stimulated proliferation of endothelial cells. However, compared with solely carboplatin-treated tumors, tumor growth was significantly slower in the groups co-medicated with rhuEpo. This is explained by the Epo-mediated vascular remodeling leading to improved drug delivery as obvious by a more than 2-fold higher carboplatin accumulation and significantly enhanced tumor apoptosis. In addition, co-medication of rhuEpo reduced tumor hypoxia and diminished intratumoral EpoR-levels which continuously increased during carboplatin (Cp) -treatment. These findings suggest that co-medication of rhuEpo in well balanced doses can be used to improve the accumulation of anticancer drugs. Doses and indications may be personalized and refined using theranostic EpoR-probes.

Indexed as

Neovascularization, PathologicAnimalsAntineoplastic AgentsCarboplatinCarcinoma, Non-Small-Cell LungCell Line, TumorDisease Models, AnimalErythropoietinFemaleHeterograftsHumansMice, NudePerfusionTherapeutic UsesAntineoplastic AgentsCarboplatinErythropoietinTherapeutic UsesAngiogenesisChemotherapyFluorescence Molecular TomographyLung cancerNon-Invasive ImagingTheranostic Agent

Identifiers

PMID26000061
PMCPMC4440446
OpenAlexW2167934217

What OpenQuestion holds

Textmetadata
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.