Evidence map›Paper›PMID 20145128›Full record

ArticleCancer research2010

Noninvasive detection of target modulation following phosphatidylinositol 3-kinase inhibition using hyperpolarized 13C magnetic resonance spectroscopy.

Christopher S Ward, Humsa S Venkatesh, Myriam M Chaumeil, Alissa H Brandes, Mark Vancriekinge, Hagit Dafni, Subramaniam Sukumar, Sarah J Nelson, Daniel B Vigneron, John Kurhanewicz and 3 more

Open access · bronzeAbstract readEvaluation Study
In one paragraph

Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed
8.5field-weighted citation impact, top 1% 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

96 citing papers in PubMed, 150 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. HyperpolarizedMetabolites · 2021
    Article
  12. Article
  13. Article
  14. Hyperpolarized [1-Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. HyperpolarizedACS chemical neuroscience · 2018
    Article

36 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Christopher S WardDepartment of Radiology and Biomedical Imaging , University of California at San Francisco, San Francisco, California 94158, USA.
Humsa S Venkatesh
Myriam M Chaumeil
Alissa H Brandes
Mark Vancriekinge
Hagit Dafni
Subramaniam Sukumar
Sarah J Nelson
Daniel B Vigneron
John Kurhanewicz
C David James
Daphne A Haas-Kogan
Sabrina M Ronen
Neurological Surgery · USUniversity of California, San Francisco · US

Funding

UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Phosphocholine modulation by oncognenic signaling - MRS studies of mechanismR01CA130819 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RONEN, SABRINA MIRIAM · 2008 to 2011
$1.3M
Non-invasive molecular MR spectroscopic imaging of histone deacetylase activityR21CA120010 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RONEN, SABRINA MIRIAM · 2007 to 2008
$339k
NCI NIH HHS CA097257NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA130819NCI NIH HHS R21 CA120010NCI NIH HHS R21 CA120010-01A1NCRR NIH HHS UL1 RR024131NCRR NIH HHS UL1 RR024131-01
6 · The paper itself

Abstract

Numerous mechanism-based anticancer drugs that target the phosphatidylinositol 3-kinase (PI3K) pathway are in clinical trials. However, it remains challenging to assess responses by traditional imaging methods. Here, we show for the first time the efficacy of hyperpolarized (13)C magnetic resonance spectroscopy (MRS) in detecting the effect of PI3K inhibition by monitoring hyperpolarized [1-(13)C]lactate levels produced from hyperpolarized [1-(13)C]pyruvate through lactate dehydrogenase (LDH) activity. In GS-2 glioblastoma cells, PI3K inhibition by LY294002 or everolimus caused hyperpolarized lactate to drop to 42 +/- 12% and to 76 +/- 5%, respectively. In MDA-MB-231 breast cancer cells, hyperpolarized lactate dropped to 71 +/- 15% after treatment with LY294002. These reductions were correlated with reductions in LDH activity to 48 +/- 4%, 63 +/- 4%, and 69 +/- 12%, respectively, and were associated with a drop in levels of LDHA mRNA and LDHA and hypoxia-inducible factor-1alpha proteins. Supporting these findings, tumor growth inhibition achieved by everolimus in murine GS-2 xenografts was associated with a drop in the hyperpolarized lactate-to-pyruvate ratio detected by in vivo MRS imaging, whereas an increase in this ratio occurred with tumor growth in control animals. Taken together, our findings illustrate the application of hyperpolarized (13)C MRS of pyruvate to monitor alterations in LDHA activity and expression caused by PI3K pathway inhibition, showing the potential of this method for noninvasive imaging of drug target modulation.

Indexed as

Carbon IsotopesPhosphoinositide-3 Kinase InhibitorsAnimalsChromonesDrug Delivery SystemsEnzyme InhibitorsEverolimusGlioblastomaHumansLactic AcidMagnetic Resonance SpectroscopyMiceMice, NudeMonitoring, PhysiologicMorpholinesNeoplasms2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneCarbon IsotopesChromonesEnzyme InhibitorsEverolimusLactic AcidMorpholinesPhosphoinositide-3 Kinase InhibitorsSirolimus

Identifiers

PMID20145128
PMCPMC2822895
OpenAlexW2162755211

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.