HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Hokkaido University Hospital >
Peer-reviewed Journal Articles, etc >

cAMP Signaling Pathway Prevents Dasatinib-Induced Vascular Hyperpermeability

Files in This Item:

The file(s) associated with this item can be obtained from the following URL:

Title: cAMP Signaling Pathway Prevents Dasatinib-Induced Vascular Hyperpermeability
Authors: Aoyama, Tsuyoshi Browse this author
Kuriyama, Hiroki Browse this author
Sato, Yuki Browse this author
Imai, Shungo Browse this author
Kashiwagi, Hitoshi Browse this author
Sugawara, Mitsuru Browse this author
Takekuma, Yoh Browse this author →KAKEN DB
Keywords: dasatinib
pleural effusion
vascular endothelial (VE)-cadherin
cell morphology
Issue Date: Aug-2021
Publisher: The Pharmaceutical Society of Japan (日本薬学会)
Journal Title: Biological & pharmaceutical bulletin
Volume: 44
Issue: 8
Start Page: 1101
End Page: 1110
Publisher DOI: 10.1248/bpb.b21-00270
Abstract: Dasatinib is a first- line pharmacotherapeutic treatment for chronic myeloid leukemia (CML). It is more effective than traditional treatments but causes adverse effects such as pleural effusion that limits its effective treatment cycle. Since pleural effusion is caused by vascular hyperpermeability and causes discontinuation of treatment with dasatinib, it is important to explore the mechanism of pleural effusion caused by dasatinib and how to prevent it. In this study, we investigated how dasatinib increase vascular permeability, and how it can be prevented. Cytotoxicity was observed in vascular endothelial cells or epithelial cells were exposed to high concentrations of dasatinib. Thus, it was observed in vascular endothelial cells such as human umbilical vascular endothelial cell (HUVEC). Vascular endothelial (VE)-cadherin is one of the important factors that control vascular permeability. When VE-cadherin expression decreases, vascular permeability increases, but it did not change with tyrosine kinase inhibitor exposure. Monolayer permeability significantly increased only with high concentration of dasatinib, but this increase was prevented by cAMP activation. Furthermore, dasatinib affects the cell morphology of HUVEC, with increased inter celluar space compared to control and bosutinib, which were also attenuated by cAMP activation. Dasatinib significantly affected permeability control of vascular endothelial cells compared to bosutinib and imatinib. These results indicated that the cAMP signaling pathway may be involved in the pleural effusion caused by dasatinib in CML patients.
Type: article
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University