Evidence map›Paper›PMID 27869804›Full record

ArticleNature medicine2017

Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth.

Shira L Cramer, Achinto Saha, Jinyun Liu, Surendar Tadi, Stefano Tiziani, Wupeng Yan, Kendra Triplett, Candice Lamb, Susan E Alters, Scott Rowlinson and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 318 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
318citing papers in PubMed, 3 pooled it
25.9field-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

318 citing papers in PubMed, 3 syntheses or guidelines pooled it, 530 citations in OpenAlex.

  1. Pooled it
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  3. Pooled it
  4. Significance of GSH and HRedox report : communications in free radical research · 2026
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258 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

16 authors at 4 institutions in 1 country.

Shira L CramerDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Achinto SahaDivision of Pharmacology and Toxicology and Dell Pediatric Research Institute, University of Texas at Austin, Austin, Texas, USA.
Jinyun LiuDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Surendar TadiDepartment of Nutritional Sciences, University of Texas at Austin, Austin, Texas, USA.
Stefano TizianiDepartment of Nutritional Sciences, University of Texas at Austin, Austin, Texas, USA.
Wupeng YanDepartment of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
Kendra TriplettDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Candice LambDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Susan E AltersAeglea Biotherapeutics, Austin, Texas, USA.
Scott RowlinsonAeglea Biotherapeutics, Austin, Texas, USA.
Yan Jessie ZhangDepartment of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
Michael J KeatingDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Peng HuangDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
John DiGiovanniDivision of Pharmacology and Toxicology and Dell Pediatric Research Institute, University of Texas at Austin, Austin, Texas, USA.
George GeorgiouDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Everett StoneDepartment of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
The University of Texas at Austin · USThe University of Texas MD Anderson Cancer Center · USIntegrated BioTherapeutics (United States) · USOmega Optics (United States) · US

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lei Zheng · 1991 to 2026
$59.1M
Human-Enzyme Mediated, Systemic Depletion of Cystine for Cancer Treatment.R01CA189623 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI DIGIOVANNI, JOHN, GEORGIOU, GEORGE GEORGIOU · 2014 to 2018
$2.9M
Gene-specific transcriptional silencing directed by dephosphorylation of RNAP IIR01GM104896 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI ZHANG, YAN JESSIE · 2013 to 2022
$2.4M
Novel Strategies to Target Leukemia-Stromal InteractionsR01CA172724 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI PELICANO, HELENE · 2015 to 2019
$1.8M
Engineering and Evaluation of Human L-Methionase for Cancer TherapyR01CA154754 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI GEORGIOU, GEORGE GEORGIOU, STONE, EVERETT · 2011 to 2014
$1.7M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA054174NCI NIH HHS R01 CA154754NCI NIH HHS R01 CA172724NCI NIH HHS R01 CA189623NIGMS NIH HHS R01 GM104896
6 · The paper itself

Abstract

Cancer cells experience higher oxidative stress from reactive oxygen species (ROS) than do non-malignant cells because of genetic alterations and abnormal growth; as a result, maintenance of the antioxidant glutathione (GSH) is essential for their survival and proliferation. Under conditions of elevated ROS, endogenous L-cysteine (L-Cys) production is insufficient for GSH synthesis. This necessitates uptake of L-Cys that is predominantly in its disulfide form, L-cystine (CSSC), via the xCT(-) transporter. We show that administration of an engineered and pharmacologically optimized human cyst(e)inase enzyme mediates sustained depletion of the extracellular L-Cys and CSSC pool in mice and non-human primates. Treatment with this enzyme selectively causes cell cycle arrest and death in cancer cells due to depletion of intracellular GSH and ensuing elevated ROS; yet this treatment results in no apparent toxicities in mice even after months of continuous treatment. Cyst(e)inase suppressed the growth of prostate carcinoma allografts, reduced tumor growth in both prostate and breast cancer xenografts and doubled the median survival time of TCL1-Tg:p53

Indexed as

AnimalsBlotting, WesternBreast NeoplasmsCell Line, TumorCystathionine gamma-LyaseCysteineCystineFemaleGlutathioneHumansLeukemia, Lymphocytic, Chronic, B-CellMacaca fascicularisMaleMiceMice, KnockoutMice, TransgenicCystathionine gamma-Lyasecyst(e)inase protein, humanCysteineCystineGlutathionePolyethylene GlycolsReactive Oxygen SpeciesTumor Suppressor Protein p53

Identifiers

PMID27869804
PMCPMC5218918
OpenAlexW2554956457

What OpenQuestion holds

Textmetadata
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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.