Evidence map›Paper›PMID 26696369›Full record

ArticleNeoplasia (New York, N.Y.)2015

Combining Optical Reporter Proteins with Different Half-lives to Detect Temporal Evolution of Hypoxia and Reoxygenation in Tumors.

Pierre Danhier, Balaji Krishnamachary, Santosh Bharti, Samata Kakkad, Yelena Mironchik, Zaver M Bhujwalla

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

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  6. Utilization of amSphere · 2024
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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

6 authors at 1 institution in 1 country.

Pierre DanhierDivision of Cancer Imaging Research, The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA.
Balaji KrishnamacharyDivision of Cancer Imaging Research, The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA.
Santosh BhartiDivision of Cancer Imaging Research, The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA.
Samata KakkadDivision of Cancer Imaging Research, The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA.
Yelena MironchikDivision of Cancer Imaging Research, The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA.
Zaver M BhujwallaDivision of Cancer Imaging Research, The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: zaver@mri.jhu.edu.
Johns Hopkins University · US

Funding

Theranostic Imaging of Metastatic Prostate CancerP50CA103175 · NCI · JOHNS HOPKINS UNIVERSITY · PI BARKER, PETER B · 2003 to 2015
$17.9M
HOSTILE ENVIRONMENTS PROMOTE INVASION AND METATASISR01CA082337 · NCI · JOHNS HOPKINS UNIVERSITY · PI BHUJWALLA, ZAVER M. · 1999 to 2024
$5.1M
FUNTIONAL IMAGING OF THE METASTATIC PHENOTYPER01CA073850 · NCI · JOHNS HOPKINS UNIVERSITY · PI BHUJWALLA, ZAVER M. · 1997 to 2014
$3.5M
NCI NIH HHS P50 CA103175NCI NIH HHS R01 CA073850NCI NIH HHS R01 CA082337NCI NIH HHS R01 CA73850NCI NIH HHS R01 CA82337
6 · The paper itself

Abstract

Here we have developed a hypoxia response element driven imaging strategy that combined the hypoxia-driven expression of two optical reporters with different half-lives to detect temporal changes in hypoxia and hypoxia inducible factor (HIF) activity. For this purpose, human prostate cancer PC3 cells were transfected with the luciferase gene fused with an oxygen-dependent degradation domain (ODD-luc) and a variant of the enhanced green fluorescent protein (EGFP). Both ODD-luciferase and EGFP were under the promotion of a poly-hypoxia-response element sequence (5xHRE). The cells constitutively expressed tdTomato red fluorescent protein. For validating the imaging strategy, cells were incubated under hypoxia (1% O2) for 48 hours and then reoxygenated. The luciferase activity of PC3-HRE-EGFP/HRE-ODD-luc/tdtomato cells detected by bioluminescent imaging rapidly decreased after reoxygenation, whereas EGFP levels in these cells remained stable for several hours. After in vitro validation, PC3-HRE-EGFP/HRE-ODD-luc/tdtomato tumors were implanted subcutaneously and orthotopically in nude male mice and imaged in vivo and ex vivo using optical imaging in proof-of-principle studies to demonstrate differences in optical patterns between EGFP expression and bioluminescence. This novel "timer" imaging strategy of combining the short-lived ODD-luciferase and the long-lived EGFP can provide a time frame of HRE activation in PC3 prostate cancer cells and will be useful to understand the temporal changes in hypoxia and HIF activity during cancer progression and following treatments including HIF targeting strategies.

Indexed as

AnimalsBlotting, WesternCell HypoxiaCell Line, TumorCycloheximideGene Expression Regulation, NeoplasticGreen Fluorescent ProteinsHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitLuciferasesLuminescent ProteinsMaleMice, NudeMicroscopy, FluorescenceOxygenCycloheximideenhanced green fluorescent proteinGreen Fluorescent ProteinsHypoxia-Inducible Factor 1, alpha SubunitLuciferasesLuminescent ProteinsOxygenProtein Synthesis InhibitorsRed Fluorescent Protein

Identifiers

PMID26696369
PMCPMC4688563
OpenAlexW2192649985

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.