Evidence map›Paper›PMID 30332965›Full record

ArticleCurrent cancer drug targets2019

Targeting Upstream Kinases of STAT3 in Human Medulloblastoma Cells.

Jia Wei, Ling Ma, Chenglong Li, Christopher R Pierson, Jonathan L Finlay, Jiayuh Lin

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

Article in Current cancer drug targets, 2019. 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
1.0field-weighted citation impact, top 24% 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, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
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  7. Article
  8. B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role.International journal of molecular sciences · 2020
    Article
  9. Article
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

6 authors at 3 institutions in 1 country.

Jia WeiDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Ling MaDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, United States.
Chenglong LiCollege of Pharmacy, University of Florida, Gainesville, FL 32610, United States.
Christopher R PiersonDepartment of Pathology and Laboratory Medicine, Nationwide Children's Hospital, The Department of Pathology and Department of Biomedical Education & Anatomy, The College of Medicine, The Ohio State University, Columbus, OH 43205, United States.
Jonathan L FinlayDivision of Hematology, Oncology and BMT, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43205, United States.
Jiayuh LinDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, United States.
University of Maryland, Baltimore · USThe Ohio State University · USUniversity of Florida · US

Funding

A novel STAT3-selective inhibitor for medulloblastoma therapyR01NS087213 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI LI, CHENGLONG, LIN, JIAYUH · 2015 to 2020
$1.7M
NINDS NIH HHS R01 NS087213
6 · The paper itself

Abstract

backgroundMedulloblastoma is the most common malignant brain tumor in children. Despite improvement in overall survival rate, it still lacks an effective targeted treatment strategy. The Janus family of cytoplasmic tyrosine kinases (JAKs) and Src kinases, upstream protein kinases of signal transducer and activator of transcription 3 (STAT3), play important roles in medulloblastoma pathogenesis and therefore represent potential therapeutic targets.

methodsIn this report, we examined the inhibitory efficacy of the JAK1/2 inhibitor, ruxolitinib, the JAK3 inhibitor, tofacitinib and two Src inhibitors, KX2-391 and dasatinib.

resultsThese small molecule drugs significantly reduce cell viability and inhibit cell migration and colony formation in human medulloblastoma cells in vitro. Src inhibitors have more potent efficacy than JAK inhibitors in inhibiting medulloblastoma cell migration ability. The Src inhibitors can inhibit both phosphorylation of STAT3 and Src while JAK inhibitors reduce JAK/STAT3 phosphorylation. We also investigated the combined effect of the Src inhibitor, dasatinib with cisplatin. The results show that dasatinib exerts synergistic effects with cisplatin in human medulloblastoma cells through the inhibition of STAT3 and Src.

conclusionOur results suggest that the small molecule inhibitors of STAT3 upstream kinases, ruxolitinib, tofacitinib, KX2-391, and dasatinib could be novel and attractive candidate drugs for the treatment of human medulloblastoma.

Indexed as

Drug SynergismAntineoplastic Combined Chemotherapy ProtocolsApoptosisCell MovementCell ProliferationCerebellar NeoplasmsCisplatinDasatinibHumansMedulloblastomaNitrilesPiperidinesProtein Kinase InhibitorsPyrazolesPyrimidinesPyrrolesCisplatinDasatinibNitrilesPiperidinesProtein Kinase InhibitorsPyrazolesPyrimidinesPyrrolesruxolitinibsrc-Family KinasesSTAT3 protein, humanSTAT3 Transcription Factortofacitinibcisplatindasatinib.JAK inhibitorMedulloblastomaSrc inhibitorSTAT3

Identifiers

PMID30332965
PMCPMC6533162
OpenAlexW2897864347

What OpenQuestion holds

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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.