Evidence map›Paper›PMID 25676691›Full record

ArticleCancer letters2015

VEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFβR signaling-dependent manner.

Kien Pham, Defang Luo, Dietmar W Siemann, Brian K Law, Brent A Reynolds, Parvinder Hothi, Gregory Foltz, Jeffrey K Harrison

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

Article in Cancer letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

31 citing papers in PubMed, 46 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

8 authors at 2 institutions in 1 country.

Kien PhamDepartment of Pharmacology & Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Defang LuoDepartment of Pharmacology & Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Dietmar W SiemannDepartment of Pharmacology & Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Radiation Oncology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Brian K LawDepartment of Pharmacology & Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Brent A ReynoldsDepartment of Neurosurgery, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Parvinder HothiThe Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA 98122, USA.
Gregory FoltzThe Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA 98122, USA.
Jeffrey K HarrisonDepartment of Pharmacology & Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA. Electronic address: jharriso@ufl.edu.
University of Florida · USSwedish Medical Center · US

Funding

Viral-based Chemokine Receptor AntagonistsR01AI058256 · NIAID · UNIVERSITY OF FLORIDA · PI HARRISON, JEFFREY K. · 2006 to 2010
$2.0M
NIAID NIH HHS R01 AI058256
6 · The paper itself

Abstract

The failure of standard treatment for patients diagnosed with glioblastoma (GBM) coupled with the highly vascularized nature of this solid tumor has led to the consideration of agents targeting VEGF or VEGFRs, as alternative therapeutic strategies for this disease. Despite modest achievements in survival obtained with such treatments, failure to maintain an enduring survival benefit and more invasive relapsing tumors are evident. Our study suggests a potential mechanism by which anti-VEGF/VEGFR therapies regulate the enhanced invasive phenotype through a pathway that involves TGFβR and CXCR4. VEGFR signaling inhibitors (Cediranib and Vandetanib) elevated the expression of CXCR4 in VEGFR-expressing GBM cell lines and tumors, and enhanced the in vitro migration of these lines toward CXCL12. The combination of VEGFR inhibitor and CXCR4 antagonist provided a greater survival benefit to tumor-bearing animals. The upregulation of CXCR4 by VEGFR inhibitors was dependent on TGFβ/TGFβR, but not HGF/MET, signaling activity, suggesting a mechanism of crosstalk among VEGF/VEGFR, TGFβ/TGFβR, and CXCL12/CXCR4 pathways in the malignant phenotype of recurrent tumors after anti-VEGF/VEGFR therapies. Thus, the combination of VEGFR, CXCR4, and TGFβR inhibitors could provide an alternative strategy to halt GBM progression.

Indexed as

AdultAgedAngiogenesis InhibitorsAnimalsBenzylaminesBrain NeoplasmsCell Line, TumorCell MovementCyclamsFemaleGlioblastomaHeterocyclic CompoundsHumansIndolesInterleukin-2 Receptor alpha SubunitMaleAngiogenesis InhibitorsBenzylaminescediranibCXCR4 protein, humanCyclamsHeterocyclic CompoundsIl2ra protein, mouseIndolesInterleukin-2 Receptor alpha SubunitPiperidinesplerixaforProtein Kinase InhibitorsQuinazolinesReceptors, CXCR4Receptors, Transforming Growth Factor betaReceptors, Vascular Endothelial Growth FactorvandetanibAnti-angiogenic therapyCXCR4GBMMETTGFβRVEGFR

Identifiers

PMID25676691
PMCPMC7294457
OpenAlexW2140841868

What OpenQuestion holds

Textmetadata
LicenceTDM
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.