Evidence map›Paper›PMID 27231555›Full record

ArticleGynecologic oncology research and practice2014

Dasatinib (BMS-35482) potentiates the activity of gemcitabine and docetaxel in uterine leiomyosarcoma cell lines.

Micael Lopez-Acevedo, Lisa Grace, Deanna Teoh, Regina Whitaker, David J Adams, Jingquan Jia, Andrew B Nixon, Angeles Alvarez Secord

Open access · hybridAbstract read
In one paragraph

Article in Gynecologic oncology research and practice, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.8field-weighted citation impact, top 26% 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

15 citing papers in PubMed, 19 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 5 institutions in 1 country.

Micael Lopez-AcevedoDivision of Gynecologic Oncology, Duke Cancer Institute, Durham, NC 27710 USA ; DUMC 3079, Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710 USA.
Lisa GraceDivision of Gynecologic Oncology, Duke Cancer Institute, Durham, NC 27710 USA.
Deanna TeohDivision of Gynecologic Oncology, University of Minnesota, Minneapolis, MN 55455 USA.
Regina WhitakerDivision of Gynecologic Oncology, Duke Cancer Institute, Durham, NC 27710 USA.
David J AdamsDepartment of Medicine, Duke University Medical Center, Durham, NC 27710 USA.
Jingquan JiaEast Carolina University School of Medicine, Greenville, NC 27834 USA.
Andrew B NixonDepartment of Medicine, Duke University Medical Center, Durham, NC 27710 USA.
Angeles Alvarez SecordDivision of Gynecologic Oncology, Duke Cancer Institute, Durham, NC 27710 USA.
Duke Cancer InstituteDuke Medical Center · USDuke University Hospital · USEast Carolina University · USUniversity of Minnesota · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTo explore the activity of dasatinib alone and in combination with gemcitabine and docetaxel in uterine leiomyosarcoma (uLMS) cell lines, and determine if dasatinib inhibits the SRC pathway.

methodsSK-UT-1 and SK-UT-1B uLMS cells were treated with gemcitabine, docetaxel and dasatinib individually and in combination. SRC and paxcillin protein expression were determined pre- and post-dasatinib treatment using Meso Scale Discovery (MSD) multi-array immunogenicity assay. Dose-response curves were constructed and the coefficient of drug interaction (CDI) and combination index (CI) for drug interaction calculated.

resultsActivated phosphorylated levels of SRC and paxillin were decreased after treatment with dasatinib in both cell lines (p < 0.001). The addition of a minimally active concentration of dasatinib (IC25) decreased the IC50 of each cytotoxic agent by 2-4 fold. The combination of gemcitabine-docetaxel yielded a synergistic effect in SK-UT-1 (CI = 0.59) and an antagonistic effect in SK-UT-1B (CI = 1.36). Dasatinib combined with gemcitabine or docetaxel revealed a synergistic anti-tumor effect (CDI < 1) in both cell lines. The triple drug combination and sequencing revealed conflicting results with a synergistic effect in SK-UT-1B and antagonistic in SK-UT-1.

conclusionDasatinib inhibits the SRC pathway and yields a synergistic effect with the two-drug combination with either gemcitabine or docetaxel. The value of adding dasatinib to gemcitabine and docetaxel in a triple drug combination is uncertain, but may be beneficial in select uLMS cell lines. Based on our pre-clinical data and known activity of gemcitabine and docetaxel, further evaluation of dasatinib in combination with these agents for the treatment of uLMS is warranted.

Indexed as

DasatinibLeiomyosarcomaSRC pathwayTargeted agentsUterine sarcoma

Identifiers

PMID27231555
PMCPMC4877815
OpenAlexW2179680798

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.