Evidence map›Paper›PMID 26006023›Full record

ArticleLaboratory investigation; a journal of technical methods and pathology2015

The hepatocyte growth factor receptor as a potential therapeutic target for dedifferentiated liposarcoma.

Kate Lynn J Bill, Jeannine Garnett, Xiaoyan Ma, Caitlin D May, Svetlana Bolshakov, Alexander J Lazar, Dina C Lev, Raphael E Pollock

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Laboratory investigation; a journal of technical methods and pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

11 citing papers in PubMed, 13 citations in OpenAlex.

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  11. Liposarcoma: molecular targets and therapeutic implications.Cellular and molecular life sciences : CMLS · 2016
    Review
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 2 institutions in 2 countries.

Kate Lynn J Bill1] Department of Surgical Oncology, University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA [3] The Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [4] Department of Surgical Oncology, Comprehensive Cancer Center, The Ohio State University (OSU), Columbus, OH, USA.
Jeannine Garnett1] Department of Surgical Oncology, University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA [2] The Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xiaoyan Ma1] Department of Surgical Oncology, University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA [2] The Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Caitlin D May1] Department of Surgical Oncology, University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA [3] The Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Svetlana Bolshakov1] Department of Surgical Oncology, University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA [2] The Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alexander J Lazar1] Department of Surgical Oncology, University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA [2] The Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [3] Department of Pathology, University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA.ORCID 0000000263954499
Dina C LevDepartment of Surgery, The Sheba Medical Center, Tel Aviv, Israel.
Raphael E Pollock1] Department of Surgical Oncology, University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA [2] The Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [3] Department of Surgical Oncology, Comprehensive Cancer Center, The Ohio State University (OSU), Columbus, OH, USA.
The University of Texas MD Anderson Cancer Center · USSheba Medical Center · IL

Funding

Tissue and Pathology ResourcesU54CA168512 · NCI · SARC · PI BAKER, LAURENCE HOWARD, POLLOCK, RAPHAEL E. · 2012 to 2016
$11.0M
NCI NIH HHS U54 CA168512NCI NIH HHS U54CA168512
6 · The paper itself

Abstract

Dedifferentiated liposarcomas (DDLPS) are highly resistant to conventional chemo- and radiotherapies, with surgical resection remaining the classic treatment strategy; therefore, there is a pressing need for novel anti-DDLPS-targeted chemotherapeutics. Hepatocyte growth factor receptor (Met) expression is elevated in DDLPS, but the functional role of Met signaling in this disease is not known. We found that the in vitro stimulation of DDLPS cells with hepatocyte growth factor (HGF) elevated the degree of PI3K/AKT and MAPK pathway signaling, and that pro-tumorigenic phenotypes such as cell proliferation, invasion, and migration were significantly enhanced. Conversely, Met knockdown using shRNA-mediated interference decreased HGF-induced Met signaling, the invasive and migratory nature of DDLPS cells in vitro, and the tumorigenicity of DDLPS cells in vivo. These data strongly support the role for Met as a DDLPS therapeutic target. To that end, using EMD1214063, an ATP-competitive kinase inhibitor that targets Met more specifically than other kinases, inhibited Met-dependent signaling, reduced the oncogenicity of DDLPS cells in vitro, and significantly increased the survival of nude mice bearing subcutaneous DDLPS xenografts. These findings support further investigations of HGF-induced Met signaling inhibition in DDLPS, as a potential strategy to enhance clinical outcomes for this disease.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationFemaleGene Knockdown TechniquesHepatocyte Growth FactorHumansLiposarcomaMiceProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-metPyridazinesPyrimidinesAntineoplastic AgentsEMD1214063Hepatocyte Growth FactorMET protein, humanProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-metPyridazinesPyrimidines

Identifiers

PMID26006023
PMCPMC4520775
OpenAlexW1515069445

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.