Susceptibility to drug-induced seizures of Fyn tyrosine kinase-deficient mice

Neuroreport ◽  
1996 ◽  
Vol 7 (15) ◽  
pp. 2723-2726 ◽  
Author(s):  
Tsuyoshi Miyakawa ◽  
Takeshi Yagi ◽  
Kyoko Tateishi ◽  
Hiroaki Niki
2004 ◽  
Vol 48 (3) ◽  
pp. 259-267 ◽  
Author(s):  
Kayoko Hamaguchi-Hamada ◽  
Chiaki Sanbo ◽  
Shun Hamada ◽  
Takeshi Yagi

1996 ◽  
Vol 25 ◽  
pp. S60
Author(s):  
Tsuyoshi Miyakawa ◽  
Takeshi Yagi ◽  
Hiroaki Niki

2020 ◽  
Vol 22 (6) ◽  
pp. 806-818 ◽  
Author(s):  
Andrea Comba ◽  
Patrick J Dunn ◽  
Anna E Argento ◽  
Padma Kadiyala ◽  
Maria Ventosa ◽  
...  

Abstract Background High-grade gliomas are aggressive and immunosuppressive brain tumors. Molecular mechanisms that regulate the inhibitory immune tumor microenvironment (TME) and glioma progression remain poorly understood. Fyn tyrosine kinase is a downstream target of the oncogenic receptor tyrosine kinase pathway and is overexpressed in human gliomas. Fyn’s role in vivo in glioma growth remains unknown. We investigated whether Fyn regulates glioma initiation, growth and invasion. Methods We evaluated the role of Fyn using genetically engineered mouse glioma models (GEMMs). We also generated Fyn knockdown stem cells to induce gliomas in immune-competent and immune-deficient mice (nonobese diabetic severe combined immunodeficient gamma mice [NSG], CD8−/−, CD4−/−). We analyzed molecular mechanism by RNA sequencing and bioinformatics analysis. Flow cytometry was used to characterize immune cellular infiltrates in the Fyn knockdown glioma TME. Results We demonstrate that Fyn knockdown in diverse immune-competent GEMMs of glioma reduced tumor progression and significantly increased survival. Gene ontology (GO) analysis of differentially expressed genes in wild-type versus Fyn knockdown gliomas showed enrichment of GOs related to immune reactivity. However, in NSG and CD8−/− and CD4−/− immune-deficient mice, Fyn knockdown gliomas failed to show differences in survival. These data suggest that the expression of Fyn in glioma cells reduces antiglioma immune activation. Examination of glioma immune infiltrates by flow cytometry displayed reduction in the amount and activity of immune suppressive myeloid derived cells in the Fyn glioma TME. Conclusions Gliomas employ Fyn mediated mechanisms to enhance immune suppression and promote tumor progression. We propose that Fyn inhibition within glioma cells could improve the efficacy of antiglioma immunotherapies.


1994 ◽  
Vol 27 (1) ◽  
pp. 179-182 ◽  
Author(s):  
Tsuyoshi Miyakawa ◽  
Takeshi Yagi ◽  
Satoshi Watanabe ◽  
Hiroaki Niki

1998 ◽  
Vol 31 ◽  
pp. S225
Author(s):  
Kotaro Hattori ◽  
Takeshi Yagi ◽  
Osamu Kubota ◽  
Toshio Sato ◽  
Shigeki Yuasa

Neuroreport ◽  
2004 ◽  
Vol 15 (5) ◽  
pp. 819-822 ◽  
Author(s):  
Shigeki Yuasa ◽  
Kotaro Hattori ◽  
Takeshi Yagi

2021 ◽  
pp. 120347542110045
Author(s):  
Sara Mirali ◽  
Abrahim Abduelmula ◽  
Asfandyar Mufti ◽  
Muskaan Sachdeva ◽  
Jensen Yeung

Background Palmoplantar keratoderma (PPK) are a heterogenous group of hereditary and acquired disorders that are characterized by excessive epidermal thickening of the palms and/or soles. PPK has been described as a rare adverse event for some medications. The aim of this systematic review was to summarize outcomes in PPK associated with various medications. This data will assist dermatologists and other healthcare providers treating patients with drug-induced PPK. Methods EMBASE and MEDLINE databases were searched in accordance with PRISMA guidelines using the keyword “palmoplantar keratoderma.” 40 studies met the inclusion criteria. Results A total of 247 patients (mean age: 57.0 years) were included in the analysis. Among patients whose sex was reported, 60.3% ( n = 35/58) were male. PPK most frequently developed after treatment with BRAF inhibitors (73.7%, n = 182/247), BRAF inhibitors combined with MEK1/2 inhibitors (15.4%, n = 38/247), tyrosine kinase inhibitors (TKIs) (3.2%, n = 8/247), or chemotherapy (2.4%, n = 6/247). The mean latency period between initiation of the drug and onset of PPK was 7.6 months (range: 0.25-90 months). Improvement of PPK was reported in 24 cases, with 50% ( n = 12/24) achieving complete resolution and 50% ( n = 12/24) achieving partial resolution. All patients who achieved complete resolution stopped the suspected drug, with a mean resolution period of 2.4 months (range: 2 weeks-6 months). The most common treatments for PPK were keratolytic treatments ( n = 10) and topical corticosteroids ( n = 4). Conclusions PPK was most frequently associated with targeted kinase inhibitors, specifically BRAF, MEK1/2, and tyrosine kinase inhibitors.


2012 ◽  
Vol 119 (11) ◽  
pp. 1351-1359 ◽  
Author(s):  
Karl Strecker ◽  
Michael Adamaszek ◽  
Sven Ohm ◽  
Florian Wegner ◽  
Jürgen Beck ◽  
...  

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