Evidence map›Paper›PMID 28654865›Full record

ArticleNeoplasia (New York, N.Y.)2017

Molecular Effects of Doxorubicin on Choline Metabolism in Breast Cancer.

Menglin Cheng, Asif Rizwan, Lu Jiang, Zaver M Bhujwalla, Kristine Glunde

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.1field-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

29 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Article
  3. Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Cellular Lactate Spectroscopy Using 1.5 Tesla Clinical Apparatus.International journal of molecular sciences · 2022
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  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

5 authors at 3 institutions in 1 country.

Menglin ChengDivision of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Asif RizwanDivision of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lu JiangDivision of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zaver M BhujwallaDivision of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kristine GlundeDivision of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: kglunde@mri.jhu.edu.
Johns Hopkins Medicine · USSidney Kimmel Comprehensive Cancer Center · USJohns Hopkins University · US

Funding

Hypoxia-derived molecular MSI signatures to predict breast cancer outcomeR01CA213492 · NCI · JOHNS HOPKINS UNIVERSITY · PI GLUNDE, KRISTINE, HEEREN, RON · 2017 to 2021
$2.1M
Molecular studies of the MR-detectable oncometabolite glycerophosphocholineR01CA213428 · NCI · JOHNS HOPKINS UNIVERSITY · PI GLUNDE, KRISTINE · 2017 to 2021
$1.9M
Multi-scale Molecular Imaging of the Degradome in Breast TumorsR01CA154725 · NCI · JOHNS HOPKINS UNIVERSITY · PI GLUNDE, KRISTINE · 2011 to 2015
$1.7M
Imaging hypoxia-driven signaling pathways in the breast tumor microenvironmentR01CA134695 · NCI · JOHNS HOPKINS UNIVERSITY · PI GLUNDE, KRISTINE · 2008 to 2012
$1.5M
NCI NIH HHS R01 CA134695NCI NIH HHS R01 CA154725NCI NIH HHS R01 CA213428NCI NIH HHS R01 CA213492
6 · The paper itself

Abstract

Abnormal choline phospholipid metabolism is a hallmark of cancer. The magnetic resonance spectroscopy (MRS) detected total choline (tCho) signal can serve as an early noninvasive imaging biomarker of chemotherapy response in breast cancer. We have quantified the individual components of the tCho signal, glycerophosphocholine (GPC), phosphocholine (PC) and free choline (Cho), before and after treatment with the commonly used chemotherapeutic drug doxorubicin in weakly metastatic human MCF7 and triple-negative human MDA-MB-231 breast cancer cells. While the tCho concentration did not change following doxorubicin treatment, GPC significantly increased and PC decreased. Of the two phosphatidylcholine-specific PLD enzymes, only PLD1, but not PLD2, mRNA was down-regulated by doxorubicin treatment. For the two reported genes encoding GPC phosphodiesterase, the mRNA of GDPD6, but not GDPD5, decreased following doxorubicin treatment. mRNA levels of choline kinase α (ChKα), which converts Cho to PC, were reduced following doxorubicin treatment. PLD1 and ChKα protein levels decreased following doxorubicin treatment in a concentration dependent manner. Treatment with the PLD1 specific inhibitor VU0155069 sensitized MCF7 and MDA-MB-231 breast cancer cells to doxorubicin-induced cytotoxicity. Low concentrations of 100 nM of doxorubicin increased MDA-MB-231 cell migration. GDPD6, but not PLD1 or ChKα, silencing by siRNA abolished doxorubicin-induced breast cancer cell migration. Doxorubicin induced GPC increase and PC decrease are caused by reductions in PLD1, GDPD6, and ChKα mRNA and protein expression. We have shown that silencing or inhibiting these genes/proteins can promote drug effectiveness and reduce adverse drug effects. Our findings emphasize the importance of detecting PC and GPC individually.

Indexed as

Antibiotics, AntineoplasticBreast NeoplasmsCell Line, TumorCell MovementCell ProliferationCell SurvivalCholineCholine KinaseDoxorubicinFemaleGene SilencingHumansMetabolic Networks and PathwaysPhospholipase DPhospholipasesAntibiotics, AntineoplasticCHKA protein, humanCholineCholine KinaseDoxorubicinGPCPD1 protein, humanPhospholipase Dphospholipase D1Phospholipases

Identifiers

PMID28654865
PMCPMC5487306
OpenAlexW2682166989

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.