Evidence map›Paper›PMID 23585680›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2013

Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid.

Joseph Conlon, Dara L Burdette, Shruti Sharma, Numana Bhat, Mikayla Thompson, Zhaozhao Jiang, Vijay A K Rathinam, Brian Monks, Tengchuan Jin, T Sam Xiao and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 249 papers.

0numbers the graph read from it
0cells of the map it votes in
249citing papers in PubMed
10.0field-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

249 citing papers in PubMed, 416 citations in OpenAlex.

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189 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 4 institutions in 1 country.

Joseph ConlonDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Dara L Burdette
Shruti Sharma
Numana Bhat
Mikayla Thompson
Zhaozhao Jiang
Vijay A K Rathinam
Brian Monks
Tengchuan Jin
T Sam Xiao
Stefanie N Vogel
Russell E Vance
Katherine A Fitzgerald
University of Massachusetts Chan Medical School · USNational Institutes of Health · USUniversity of California, Berkeley · USUniversity of Maryland, Baltimore · US

Funding

The role of Listeria cyclic-di-AMP during infection and immunityP01AI063302 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI VANCE, RUSSELL E · 2004 to 2025
$45.5M
Structural Studies of Pattern Recognition ReceptorsZIAAI000960 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI XIAO, TSAN · 2009 to 2014
$6.1M
Gene Regulation in Innate ImmunityR37AI067497 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FITZGERALD, KATHERINE A. · 2015 to 2024
$4.6M
DIFFERENTIATIVE SIGNALS FOR MACROPHANGE ACTIVATIONR01AI018797 · NIAID · U.S. UNIFORMED SERVICES UNIV OF HLTH SCI · PI VOGEL, STEFANIE N. · 1985 to 2014
$3.8M
Innate Immunity Training ProgramT32AI095213 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SILVERMAN, NEAL · 2011 to 2025
$2.5M
Regulation of Type I Interferon Gene Expression in the Innate Immune ResponseR01AI067497 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FITZGERALD, KATHERINE A. · 2006 to 2010
$2.0M
DNA sensors and associated signaling pathways in the innate immune responseR01AI093752 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FITZGERALD, KATHERINE A. · 2012 to 2016
$1.7M
Macrophage transcriptional responses to Legionella pneumophilaR01AI080749 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI VANCE, RUSSELL E · 2009 to 2013
$1.6M
Distinguishing cytosolic sensing of DNA and cyclic dinucleotides in vivoR21AI103817 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI VANCE, RUSSELL E · 2013 to 2014
$430k
Regulation of Type I Interferon Gene Expression in the Innate Immune ResponseR56AI067497 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FITZGERALD, KATHERINE A. · 2012 to 2012
$415k
Mechanism of innate immune recognition of cyclic-di-GMPF32AI091100 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI BURDETTE, DARA L · 2010 to 2012
$153k
NIAID NIH HHS AI063302NIAID NIH HHS AI067497NIAID NIH HHS AI080749NIAID NIH HHS AI091100NIAID NIH HHS F32 AI091100NIAID NIH HHS P01 AI063302NIAID NIH HHS R01 AI018797NIAID NIH HHS R01 AI067497NIAID NIH HHS R01 AI080749NIAID NIH HHS R01 AI093752NIAID NIH HHS R21 AI103817NIAID NIH HHS R37 AI067497NIAID NIH HHS R56 AI067497NIAID NIH HHS T32 AI095213
6 · The paper itself

Abstract

Vascular disrupting agents such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA) represent a novel approach for cancer treatment. DMXAA has potent antitumor activity in mice and, despite significant preclinical promise, failed human clinical trials. The antitumor activity of DMXAA has been linked to its ability to induce type I IFNs in macrophages, although the molecular mechanisms involved are poorly understood. In this study, we identify stimulator of IFN gene (STING) as a direct receptor for DMXAA leading to TANK-binding kinase 1 and IFN regulatory factor 3 signaling. Remarkably, the ability to sense DMXAA was restricted to murine STING. Human STING failed to bind to or signal in response to DMXAA. Human STING also failed to signal in response to cyclic dinucleotides, conserved bacterial second messengers known to bind and activate murine STING signaling. Collectively, these findings detail an unexpected species-specific role for STING as a receptor for an anticancer drug and uncover important insights that may explain the failure of DMXAA in clinical trials for human cancer.

Indexed as

AnimalsAntineoplastic AgentsCell LineHEK293 CellsHumansInterferon-betaInterferon Regulatory Factor-3Leukocytes, MononuclearMacrophagesMembrane ProteinsMiceNeoplasmsNF-kappa BProtein Serine-Threonine KinasesSignal TransductionSTING ProteinAntineoplastic AgentsInterferon-betaInterferon Regulatory Factor-3Membrane ProteinsNF-kappa BProtein Serine-Threonine KinasesSTING1 protein, humanSting1 protein, mouseSTING ProteinTbk1 protein, mousevadimezanXanthones

Identifiers

PMID23585680
PMCPMC3647383
OpenAlexW1866003637

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.