Evidence map›Paper›PMID 27568980›Full record

ArticleOncogene2017

Antiangiogenic and tumour inhibitory effects of downregulating tumour endothelial FABP4.

U Harjes, E Bridges, K M Gharpure, I Roxanis, H Sheldon, F Miranda, L S Mangala, S Pradeep, G Lopez-Berestein, A Ahmed and 3 more

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

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 11% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 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

13 authors at 7 institutions in 2 countries.

U HarjesHypoxia and Growth Factor Group, WIMM, Department of Oncology, University of Oxford, Oxford, UK.
E BridgesHypoxia and Growth Factor Group, WIMM, Department of Oncology, University of Oxford, Oxford, UK.
K M GharpureDepartment of Gynecologic Oncology, University of Texas, Austin, TX, USA.
I RoxanisDepartment of Cellular Pathology, Oxford University Hospitals and NIHR Biomedical Research Centre Oxford, John Radcliffe Hospital, Oxford, UK.
H SheldonHypoxia and Growth Factor Group, WIMM, Department of Oncology, University of Oxford, Oxford, UK.
F MirandaOvarian Cancer Cell Laboratory, WIMM, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
L S MangalaDepartment of Gynecologic Oncology, University of Texas, Austin, TX, USA.
S PradeepDepartment of Gynecologic Oncology, University of Texas, Austin, TX, USA.
G Lopez-BeresteinCenter for RNA Interference and Non-Coding RNA, MD Anderson Cancer Center, Department of Gynecologic Oncology, University of Texas, Austin, TX, USA.
A AhmedOvarian Cancer Cell Laboratory, WIMM, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
B FieldingDepartment of Nutritional Sciences, University of Surrey, Surrey, UK.
A K SoodDepartment of Gynecologic Oncology, University of Texas, Austin, TX, USA.
A L HarrisHypoxia and Growth Factor Group, WIMM, Department of Oncology, University of Oxford, Oxford, UK.
Oxford Research Group · GBThe University of Texas at Austin · USUniversity of Oxford · GBJohn Radcliffe Hospital · GBTexas Oncology · USThe University of Texas System · USUniversity of Surrey · GB

Funding

UNIVERSITY OF TEXAS MD ANDERSON SPORE IN OVARIAN CANCERP50CA083639 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BAST, ROBERT C · 1999 to 2015
$33.0M
Targeting the PI3K Signaling Pathway in Endometrial CarcinomaP50CA098258 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BROADDUS, RUSSELL R · 2003 to 2020
$32.0M
Ovarian Cancer: Mechanisms of Neuroendocrine RegulationR01CA109298 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SOOD, ANIL K · 2005 to 2017
$4.5M
Novel extra cellular RNA-based combinatorial RNA inhibition therapyUH2TR000943 · NCATS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CALIN, GEORGE A., LOPEZ-BERESTEIN, GABRIEL · 2013 to 2014
$1.1M
Cancer Research UK 11359Cancer Research UK 16466Cancer Research UK 18974Medical Research Council G0300648Medical Research Council G0902418NCATS NIH HHS UH2 TR000943NCI NIH HHS P50 CA083639NCI NIH HHS P50 CA098258NCI NIH HHS R01 CA109298
6 · The paper itself

Abstract

Fatty acid binding protein 4 (FABP4) is a fatty acid chaperone, which is induced during adipocyte differentiation. Previously we have shown that FABP4 in endothelial cells is induced by the NOTCH1 signalling pathway, the latter of which is involved in mechanisms of resistance to antiangiogenic tumour therapy. Here, we investigated the role of FABP4 in endothelial fatty acid metabolism and tumour angiogenesis. We analysed the effect of transient FABP4 knockdown in human umbilical vein endothelial cells on fatty acid metabolism, viability and angiogenesis. Through therapeutic delivery of siRNA targeting mouse FABP4, we investigated the effect of endothelial FABP4 knockdown on tumour growth and blood vessel formation. In vitro, siRNA-mediated FABP4 knockdown in endothelial cells led to a marked increase of endothelial fatty acid oxidation, an increase of reactive oxygen species and decreased angiogenesis. In vivo, we found that increased NOTCH1 signalling in tumour xenografts led to increased expression of endothelial FABP4 that decreased when NOTCH1 and VEGFA inhibitors were used in combination. Angiogenesis, growth and metastasis in ovarian tumour xenografts were markedly inhibited by therapeutic siRNA delivery targeting mouse endothelial FABP4. Therapeutic targeting of endothelial FABP4 by siRNA in vivo has antiangiogenic and antitumour effects with minimal toxicity and should be investigated further.

Indexed as

Angiogenesis InhibitorsAnimalsApoptosisBiomarkers, TumorCell MovementCell ProliferationCystadenocarcinoma, SerousFatty Acid-Binding ProteinsFemaleFollow-Up StudiesHumansHuman Umbilical Vein Endothelial CellsMiceMice, NudeNeoplasm GradingNeoplasm InvasivenessAngiogenesis InhibitorsBiomarkers, TumorFABP4 protein, humanFatty Acid-Binding ProteinsNOTCH1 protein, humanReceptor, Notch1Vascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID27568980
PMCPMC5318662
OpenAlexW2514592417

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Registered trials

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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.