Evidence map›Paper›PMID 21266355›Full record

ArticleCancer research2011

In vivo profiling of hypoxic gene expression in gliomas using the hypoxia marker EF5 and laser-capture microdissection.

Diane Marotta, Jayashree Karar, W Timothy Jenkins, Monika Kumanova, Kevin W Jenkins, John W Tobias, Donald Baldwin, Artemis Hatzigeorgiou, Panagiotis Alexiou, Sydney M Evans and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

35 citing papers in PubMed, 52 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

14 authors at 4 institutions in 2 countries.

Diane MarottaDepartment of Radiation Oncology, University of Pennsylvania, Pennsylvania, USA.
Jayashree Karar
W Timothy Jenkins
Monika Kumanova
Kevin W Jenkins
John W Tobias
Donald Baldwin
Artemis Hatzigeorgiou
Panagiotis Alexiou
Sydney M Evans
Rodolfo Alarcon
Amit Maity
Cameron Koch
Constantinos Koumenis
KCI (United States) · USAlexander Fleming Biomedical Sciences Research Center · GRUniversity of Pennsylvania · USMolecular Oncology (United States) · US

Funding

Role of elF2a phosphorylation and ER stress in hypoxia tolerance and tumor growthR01CA094214 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI KOUMENIS, CONSTANTINOS · 2002 to 2016
$3.6M
NCI NIH HHS R01 CA094214
6 · The paper itself

Abstract

Hypoxia is a key determinant of tumor aggressiveness, yet little is known regarding hypoxic global gene regulation in vivo. We used the hypoxia marker EF5 coupled with laser-capture microdissection to isolate RNA from viable hypoxic and normoxic regions of 9L experimental gliomas. Through microarray analysis, we identified several mRNAs (including the HIF targets Vegf, Glut-1, and Hsp27) with increased levels under hypoxia compared with normoxia both in vitro and in vivo. However, we also found striking differences between the global in vitro and in vivo hypoxic mRNA profiles. Intriguingly, the mRNA levels of a substantial number of immunomodulatory and DNA repair proteins including CXCL9, CD3D, and RAD51 were found to be downregulated in hypoxic areas in vivo, consistent with a protumorigenic role of hypoxia in solid tumors. Immunohistochemical staining verified increased HSP27 and decreased RAD51 protein levels in hypoxic versus normoxic tumor regions. Moreover, CD8(+) T cells, which are recruited to tumors upon stimulation by CXCL9 and CXCL10, were largely excluded from viable hypoxic areas in vivo. This is the first study to analyze the influence of hypoxia on mRNA levels in vivo and can be readily adapted to obtain a comprehensive picture of hypoxic regulation of gene expression and its influence on biological functions in solid tumors.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsCell HypoxiaEtanidazoleFluorocarbonsGene Expression ProfilingGliomaHSP27 Heat-Shock ProteinsHydrocarbons, FluorinatedMaleMicrodissectionRad51 RecombinaseRatsRats, Inbred F344RNA, MessengerRNA, Neoplasm2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamideEtanidazoleFluorocarbonsHSP27 Heat-Shock ProteinsHspb1 protein, ratHydrocarbons, FluorinatedRad51 protein, ratRad51 RecombinaseRNA, MessengerRNA, Neoplasm

Identifiers

PMID21266355
PMCPMC3071295
OpenAlexW2092282215

What OpenQuestion holds

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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.