Evidence map›Paper›PMID 30742098›Full record

ArticleOncogene2019

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis.

Alejandro Torres-Hernandez, Wei Wang, Yuri Nikiforov, Karla Tejada, Luisana Torres, Aleksandr Kalabin, Yue Wu, Muhammad Israr Ul Haq, Mohammed Y Khan, Zhen Zhao and 11 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

21 citing papers in PubMed, 43 citations in OpenAlex.

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  19. Role of spleen tyrosine kinase in liver diseases.World journal of gastroenterology · 2020
    Review
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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

21 authors at 1 institution in 1 country.

Alejandro Torres-HernandezS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Wei WangS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Yuri NikiforovS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Karla TejadaS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Luisana TorresS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Aleksandr KalabinS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Yue WuS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Muhammad Israr Ul HaqS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Mohammed Y KhanS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Zhen ZhaoS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Wenyu SuS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Jimmy CamargoS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Mautin HundeyinS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Brian DiskinS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Salma AdamS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Juan A Kochen RossiS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Emma KurzS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Berk AykutS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Sorin A A ShadaloeyS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
Joshua LeinwandS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA.
George MillerS.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, 450 East 29th Street, New York, NY, 10016, USA. george.miller@nyumc.org.
New York University · US

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) CA155649Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) CA168611NCI NIH HHS P30 CA016087
6 · The paper itself

Abstract

Liver fibrosis and fibrosis-associated hepatocarcinogenesis are driven by chronic inflammation and are leading causes of morbidity and death worldwide. SYK signaling regulates critical processes in innate and adaptive immunity, as well as parenchymal cells. We discovered high SYK expression in the parenchymal hepatocyte, hepatic stellate cell (HSC), and the inflammatory compartments in the fibrotic liver. We postulated that targeting SYK would mitigate hepatic fibrosis and oncogenic progression. We found that inhibition of SYK with the selective small molecule inhibitors Piceatannol and PRT062607 markedly protected against toxin-induced hepatic fibrosis, associated hepatocellular injury and intra-hepatic inflammation, and hepatocarcinogenesis. SYK inhibition resulted in increased intra-tumoral expression of the p16 and p53 but decreased expression of Bcl-xL and SMAD4. Further, hepatic expression of genes regulating angiogenesis, apoptosis, cell cycle regulation, and cellular senescence were affected by targeting SYK. We found that SYK inhibition mitigated both HSC trans-differentiation and acquisition of an inflammatory phenotype in T cells, B cells, and myeloid cells. However, in vivo experiments employing selective targeted deletion of SYK indicated that only SYK deletion in the myeloid compartment was sufficient to confer protection against fibrogenic progression. Targeting SYK promoted myeloid cell differentiation into hepato-protective TNFα

Indexed as

Signal TransductionAnimalsCarcinogenesisCarcinoma, HepatocellularCell TransdifferentiationCyclohexylaminesFemaleFibrosisHepatic Stellate CellsHumansInterleukin-8Lectins, C-TypeLiverLiver CirrhosisLiver NeoplasmsMale3,3',4,5'-tetrahydroxystilbene4-(3-(2H-1,2,3-triazol-2-yl)phenylamino)-2-(2-aminocyclohexylamino)pyrimidine-5-carboxamideCyclohexylaminesInterleukin-8Lectins, C-TypeMannose-Binding LectinsMannose ReceptorPyrimidinesReceptors, Cell SurfaceStilbenesSyk KinaseSYK protein, humanSyk protein, mouse

Identifiers

PMID30742098
OpenAlexW2912857566

What OpenQuestion holds

Textmetadata
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.