Evidence map›Paper›PMID 24914410›Full record

ArticleVascular cell2014

Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

Edmund Chinchar, Kristina L Makey, John Gibson, Fang Chen, Shelby A Cole, Gail C Megason, Srinivassan Vijayakumar, Lucio Miele, Jian-Wei Gu

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

Article in Vascular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
8.7field-weighted citation impact, top 2% 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

42 citing papers in PubMed, 77 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

9 authors at 2 institutions in 1 country.

Edmund ChincharCancer Institute, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA ; Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Kristina L MakeyCancer Institute, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA ; Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
John GibsonCancer Institute, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA.
Fang ChenCancer Institute, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA ; Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Shelby A ColeCancer Institute, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA ; Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Gail C MegasonCancer Institute, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA ; Children's Cancer Center, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Srinivassan VijayakumarCancer Institute, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA.
Lucio MieleCancer Institute, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA.
Jian-Wei GuCancer Institute, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA ; Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
State Street (United States) · USUniversity of Mississippi Medical Center · US

Funding

Targeting y-secretase in GVHDP01CA166009 · NCI · UNIVERSITY OF MASSACHUSETTS AMHERST · PI OSBORNE, BARBARA A · 2013 to 2017
$4.9M
NCI NIH HHS P01 CA166009
6 · The paper itself

Abstract

The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an innovative therapeutic strategy in TNBC therapy by using sunitinib plus γ-secretase inhibitor to simultaneously target angiogenesis and CSC.

Indexed as

AngiogenesisApoptosisBasal-like triple-negative breast cancerBreast cancer stem cellMigrationNotch-1ProliferationSunitinibXenografts

Identifiers

PMID24914410
PMCPMC4049452
OpenAlexW2128777602

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.