Evidence map›Paper›PMID 27286797›Full record

ArticleNeuro-oncology2016

Limited role for transforming growth factor-β pathway activation-mediated escape from VEGF inhibition in murine glioma models.

Davide Mangani, Michael Weller, Emad Seyed Sadr, Edith Willscher, Katharina Seystahl, Guido Reifenberger, Ghazaleh Tabatabai, Hans Binder, Hannah Schneider

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

Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 34 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

9 authors at 2 institutions in 2 countries.

Davide ManganiLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (D.M., M.W., E.S.S., K.S., G.T., H.S.); Center for Neuroscience, University of Zurich, Zurich, Switzerland (M.W., G.T.); Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany (E.W., H.B.); Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany (G.R.); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site, Essen/Düsseldorf, Germany (G.R.).
Michael WellerLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (D.M., M.W., E.S.S., K.S., G.T., H.S.); Center for Neuroscience, University of Zurich, Zurich, Switzerland (M.W., G.T.); Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany (E.W., H.B.); Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany (G.R.); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site, Essen/Düsseldorf, Germany (G.R.).
Emad Seyed SadrLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (D.M., M.W., E.S.S., K.S., G.T., H.S.); Center for Neuroscience, University of Zurich, Zurich, Switzerland (M.W., G.T.); Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany (E.W., H.B.); Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany (G.R.); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site, Essen/Düsseldorf, Germany (G.R.).
Edith WillscherLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (D.M., M.W., E.S.S., K.S., G.T., H.S.); Center for Neuroscience, University of Zurich, Zurich, Switzerland (M.W., G.T.); Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany (E.W., H.B.); Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany (G.R.); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site, Essen/Düsseldorf, Germany (G.R.).
Katharina SeystahlLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (D.M., M.W., E.S.S., K.S., G.T., H.S.); Center for Neuroscience, University of Zurich, Zurich, Switzerland (M.W., G.T.); Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany (E.W., H.B.); Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany (G.R.); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site, Essen/Düsseldorf, Germany (G.R.).
Guido ReifenbergerLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (D.M., M.W., E.S.S., K.S., G.T., H.S.); Center for Neuroscience, University of Zurich, Zurich, Switzerland (M.W., G.T.); Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany (E.W., H.B.); Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany (G.R.); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site, Essen/Düsseldorf, Germany (G.R.).
Ghazaleh TabatabaiLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (D.M., M.W., E.S.S., K.S., G.T., H.S.); Center for Neuroscience, University of Zurich, Zurich, Switzerland (M.W., G.T.); Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany (E.W., H.B.); Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany (G.R.); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site, Essen/Düsseldorf, Germany (G.R.).
Hans BinderLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (D.M., M.W., E.S.S., K.S., G.T., H.S.); Center for Neuroscience, University of Zurich, Zurich, Switzerland (M.W., G.T.); Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany (E.W., H.B.); Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany (G.R.); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site, Essen/Düsseldorf, Germany (G.R.).
Hannah SchneiderLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (D.M., M.W., E.S.S., K.S., G.T., H.S.); Center for Neuroscience, University of Zurich, Zurich, Switzerland (M.W., G.T.); Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany (E.W., H.B.); Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany (G.R.); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site, Essen/Düsseldorf, Germany (G.R.).
Leipzig University · DEUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β pathways regulate key biological features of glioblastoma. Here we explore whether the TGF-β pathway, which promotes angiogenesis, invasiveness, and immunosuppression, acts as an escape pathway from VEGF inhibition.

methodsThe role of the TGF-β pathway in escape from VEGF inhibition was assessed in vitro and in vivo and by gene expression profiling in syngeneic mouse glioma models.

resultsWe found that TGF-β is an upstream regulator of VEGF, whereas VEGF pathway activity does not alter the TGF-β pathway in vitro. In vivo, single-agent activity was observed for the VEGF antibody B20-4.1.1 in 3 and for the TGF-β receptor 1 antagonist LY2157299 in 2 of 4 models. Reduction of tumor volume and blood vessel density, but not induction of hypoxia, correlated with benefit from B20-4.1.1. Reduction of phosphorylated (p)SMAD2 by LY2157299 was seen in all models but did not predict survival. Resistance to B20 was associated with anti-angiogenesis escape pathway gene expression, whereas resistance to LY2157299 was associated with different immune response gene signatures in SMA-497 and GL-261 on transcriptomic profiling. The combination of B20 with LY2157299 was ineffective in SMA-497 but provided prolongation of survival in GL-261, associated with early suppression of pSMAD2 in tumor and host immune cells, prolonged suppression of angiogenesis, and delayed accumulation of tumor infiltrating microglia/macrophages.

conclusionsOur study highlights the biological heterogeneity of murine glioma models and illustrates that cotargeting of the VEGF and TGF-β pathways might lead to improved tumor control only in subsets of glioblastoma.

Indexed as

Angiogenesis InhibitorsAnimalsBevacizumabBrain NeoplasmsCell Line, TumorCell SurvivalDisease Models, AnimalGliomaLymphotoxin-alphaPhosphorylationPyrazolesQuinolinesSignal TransductionSmad2 ProteinVascular Endothelial Growth Factor AAngiogenesis InhibitorsBevacizumabLY-2157299Lymphotoxin-alphaPyrazolesQuinolinesSmad2 ProteinSmad2 protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mousecoinhibitionescape mechanismglioblastomaTGF-βVEGF

Identifiers

PMID27286797
PMCPMC6693192
OpenAlexW2413772354

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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.