Evidence map›Paper›PMID 30135222›Full record

ArticlemSphere2018

Spleen Tyrosine Kinase Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of Epstein-Barr Virus-Associated Lymphoma.

Osman Cen, Karuppiah Kannan, Jessica Huck Sappal, Jie Yu, Mengkun Zhang, Muzaffer Arikan, Ali Ucur, Duran Ustek, Yeter Cen, Leo Gordon and 1 more

Open access · goldAbstract read
In one paragraph

Article in mSphere, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. New insights into SYK targeting in solid tumors.Trends in pharmacological sciences · 2024
    Review
  2. [Transcriptome sequencing for identification of the genes associated with restenosis of venous grafts in rabbits].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Role of spleen tyrosine kinase in liver diseases.World journal of gastroenterology · 2020
    Review
  8. Article
  9. 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

11 authors at 3 institutions in 2 countries.

Osman CenDepartment of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Karuppiah KannanTakeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.
Jessica Huck SappalTakeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.
Jie YuTakeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.
Mengkun ZhangTakeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.
Muzaffer ArikanIstanbul University, Institute of Experimental Medicine, Istanbul, Turkey.
Ali UcurIstanbul University, Institute of Experimental Medicine, Istanbul, Turkey.
Duran UstekIstanbul University, Institute of Experimental Medicine, Istanbul, Turkey.
Yeter CenDepartment of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Leo GordonDepartment of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.ORCID 0000-0003-1666-7064
Richard LongneckerDepartment of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA r-longnecker@northwestern.edu.ORCID 0000-0001-7175-6217
Northwestern University · USTakeda (United States) · USIstanbul University · TR

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1993 to 2026
$153.9M
In Vivo Model of Epstein-Barr Virus LatencyR01CA073507 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LONGNECKER, RICHARD M · 1997 to 2018
$6.1M
Discovery of New Treatment Options for EBV-associated Lymphoma and PTLDR01CA133063 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LONGNECKER, RICHARD M · 2008 to 2012
$1.9M
NCI NIH HHS P30 CA060553NCI NIH HHS R01 CA073507NCI NIH HHS R01 CA133063
6 · The paper itself

Abstract

Epstein-Barr virus (EBV) is associated with several B and epithelial cell cancers. EBV-encoded latent membrane protein 2A (LMP2A) contributes to cellular transformation by mimicking B cell receptor signaling. LMP2A/MYC double transgenic mice develop splenomegaly and B cell lymphoma much faster than MYC transgenic mice do. In this study, we explored the potential therapeutic efficacy of a novel spleen tyrosine kinase (SYK) and FLT3 inhibitor TAK-659 for development of a treatment option for EBV-associated malignancies. In our transgenic model, TAK-659 treatment totally abrogated splenomegaly and tumor development in LMP2A/MYC mice in both pretumor and tumor cell transfer experiments. TAK-659 treatment killed tumor cells, but not host cells within the spleen and tumors. Furthermore, TAK-659 treatment abrogated metastasis of tumor cells into bone marrow. Our data also show that TAK-659 inhibits SYK phosphorylation and induces apoptosis in LMP2A/MYC tumor cells at low nanomolar concentrations. Therefore, TAK-659 may provide an effective therapeutic option for treatment of LMP2A-positive EBV-associated malignancies and should be explored further in clinical trials.

Indexed as

AnimalsApoptosisCell Line, TumorCell Transformation, NeoplasticDisease Models, AnimalEpstein-Barr Virus InfectionsHerpesvirus 4, HumanLymphomaMiceMice, TransgenicPyrimidinesPyrrolidinonesSplenomegalySyk KinasePyrimidinesPyrrolidinonesSyk KinaseTAK-659Burkitt’s lymphomaEBV-related cancerLMP2ASYKTAK-659

Identifiers

PMID30135222
PMCPMC6106053
OpenAlexW2888431611

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.