日本毒性学会学術年会
第48回日本毒性学会学術年会
セッションID: O-34
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口演
慢性的活性酸素種からヒト治療耐性胃がんへ至る有害性発現経路の開発及び分子ネットワーク解析
*田邊 思帆里Sabina QUADER小野 竜一Horacio CABRAL青柳 一彦広瀬 明彦Ed PERKINS横崎 宏佐々木 博己
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会議録・要旨集 フリー

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Molecular signaling pathway networks are regulated in epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which exhibit anti-cancer drug resistant features. To reveal the mechanism of human treatment-resistant gastric cancer (GC) and the relationship between oxidative stress response and GC, analysis on oxidative stress response and molecular networks in diffuse- and intestinal-type GC has been performed. The network pathways of GC were analyzed by Ingenuity Pathway Analysis (IPA). NRF2-mediated oxidative stress response network included molecules related to Regulation of EMT by growth factors pathway and Production of nitric oxide and reactive oxygen species in macrophages such as PI3K and AKT. We have developed the Adverse Outcome Pathway (AOP) on chronic reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer consists of Molecular Initiating Event (MIE) as chronic ROS, followed by Key Event (KE)1 as sustained tissue damage / macrophage activation / porcupine-induced Wnt secretion, KE2 as proliferation / beta-catenin activation, KE3 as EMT, and AO as human treatment-resistant GC. Updates on the AOP development will be introduced.

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