Evidence map›Paper›PMID 28415808›Full record

ArticleOncotarget2017

IKK inhibition by BMS-345541 suppresses breast tumorigenesis and metastases by targeting GD2+ cancer stem cells.

Venkata Lokesh Battula, Khoa Nguyen, Jeff Sun, Mary Kathryn Pitner, Bin Yuan, Chandra Bartholomeusz, Numsen Hail, Michael Andreeff

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.1field-weighted citation impact, top 27% 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

25 citing papers in PubMed, 33 citations in OpenAlex.

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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 1 institution in 1 country.

Venkata Lokesh BattulaDepartment of Leukemia, Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Khoa NguyenDepartment of Leukemia, Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jeff SunDepartment of Leukemia, Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mary Kathryn PitnerDepartment of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bin YuanDepartment of Leukemia, Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chandra BartholomeuszDepartment of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Numsen HailDepartment of Leukemia, Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael AndreeffDepartment of Leukemia, Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

We have identified that the ganglioside GD2 is a marker for breast cancer stem cells (BCSCs), and that targeting the enzyme GD3 synthase (GD3S, which regulates GD2 biosynthesis) reduces breast tumorigenesis. The pathways regulating GD2 expression, and their anomalous functions in BCSC, are unclear. Proteomic analysis of GD2+ and GD2- cells from breast cancer cell lines revealed the activation of NFκB signaling in GD2+ cells. Dose- and time-dependent suppression of NFκB signaling by the small molecule inhibitor BMS-345541 reduced GD2+ cells by > 90%. Likewise, BMS-345541 inhibited BCSC GD3S expression, mammosphere formation, and cell migration/invasion in vitro. Breast tumor-bearing mice treated with BMS-345541 showed a statistically significant decrease in tumor volume and exhibited prolonged survival compared to control mice, with a median survival of 78 d for the BMS-345541-treated group vs. 58 d for the controls. Moreover, in an experimental metastases model, treatment with BMS-345541 reduced the lung metastases by > 5-fold. These data suggest that GD2 expression and function,and NFκB signaling, are related, and they control BCSCs tumorigenic characteristics. Thus, the suppression of NFκB signaling by BMS-345541 is a potentially important advance in controlling breast cancer growth and metastases.

Indexed as

Xenograft Model Antitumor AssaysAnimalsBreast NeoplasmsCarcinogenesisCell Line, TumorGangliosidesGene Expression Regulation, NeoplasticHumansI-kappa B KinaseImidazolesMice, Inbred NODMice, KnockoutMice, SCIDNeoplasm MetastasisNeoplastic Stem CellsQuinoxalines4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxalinealpha-N-acetylneuraminate alpha-2,8-sialyltransferaseganglioside, GD2GangliosidesI-kappa B KinaseImidazolesQuinoxalinesSialyltransferasesbreast cancercancer stem cellsGD2GD3 synthaseNFκB

Identifiers

PMID28415808
PMCPMC5514883
OpenAlexW2596930495

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.