Evidence map›Paper›PMID 22952426›Full record

ArticleNeoplasia (New York, N.Y.)2012

Localized hypoxia results in spatially heterogeneous metabolic signatures in breast tumor models.

Lu Jiang, Tiffany R Greenwood, Dmitri Artemov, Venu Raman, Paul T Winnard, Ron M A Heeren, Zaver M Bhujwalla, Kristine Glunde

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2012. 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
2.0field-weighted citation impact, top 14% 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, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Magnetic Resonance Spectroscopy Studies of Mouse Models of Cancer.Methods in molecular biology (Clifton, N.J.) · 2018
    Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2015
    Review
  12. Article
  13. 18F-FAZA PET imaging response tracks the reoxygenation of tumors in mice upon treatment with the mitochondrial complex I inhibitor BAY 87-2243.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Mass spectrometric imaging of red fluorescent protein in breast tumor xenografts.Journal of the American Society for Mass Spectrometry · 2013
    Article
  19. Emerging targets in lipid-based therapy.Biochemical pharmacology · 2013
    Review
  20. Article
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 4 institutions in 2 countries.

Lu JiangThe Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, Division of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Tiffany R Greenwood
Dmitri Artemov
Venu Raman
Paul T Winnard
Ron M A Heeren
Zaver M Bhujwalla
Kristine Glunde
Imaging Center · USJohns Hopkins Medicine · USJohns Hopkins University · USInstitute for Atomic and Molecular Physics · NL

Funding

Imaging hypoxia-driven signaling pathways in the breast tumor microenvironmentR01CA134695 · NCI · JOHNS HOPKINS UNIVERSITY · PI GLUNDE, KRISTINE · 2008 to 2012
$1.5M
Request for Zeiss LSM 510 MP Multiphoton Imaging SystemS10RR024550 · NCRR · JOHNS HOPKINS UNIVERSITY · PI KUO, SCOT CHARLES · 2008 to 2008
$500k
NCI NIH HHS R01 CA134695NCRR NIH HHS S10 RR024550
6 · The paper itself

Abstract

Tumor hypoxia triggers signaling cascades that significantly affect biologic outcomes such as resistance to radiotherapy and chemotherapy in breast cancer. Hypoxic regions in solid tumor are spatially heterogeneous. Therefore, delineating the origin and extent of hypoxia in tumors is critical. In this study, we have investigated the effect of hypoxia on different metabolic pathways, such as lipid and choline metabolism, in a human breast cancer model. Human MDA-MB-231 breast cancer cells and tumors, which were genetically engineered to express red fluorescent tdTomato protein under hypoxic conditions, were used to investigate hypoxia. Our data were obtained with a novel three-dimensional multimodal molecular imaging platform that combines magnetic resonance (MR) imaging, MR spectroscopic imaging (MRSI), and optical imaging of hypoxia and necrosis. A higher concentration of noninvasively detected total choline-containing metabolites (tCho) and lipid CH3 localized in the tdTomato-fluorescing hypoxic regions indicated that hypoxia can upregulate tCho and lipid CH3 levels in this breast tumor model. The increase in tCho under hypoxia was primarily due to elevated phosphocholine levels as shown by in vitro MR spectroscopy. Elevated lipid CH3 levels detected under hypoxia were caused by an increase in mobile MR-detectable lipid droplets, as demonstrated by Nile Red staining. Our findings demonstrate that noninvasive MRSI can help delineate hypoxic regions in solid tumors by means of detecting the metabolic outcome of tumor hypoxia, which is characterized by elevated tCho and lipid CH3.

Indexed as

Lipid MetabolismBreast NeoplasmsCell HypoxiaCell Line, TumorCholineFemaleHumansMagnetic Resonance ImagingMagnetic Resonance SpectroscopyOptical ImagingSignal TransductionCholine

Identifiers

PMID22952426
PMCPMC3431180
OpenAlexW1928656802

What OpenQuestion holds

Textmetadata
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.