| Project/Area Number |
19K18963
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
NGUYEN THAO 広島大学, 病院(医), 研究員 (40733837)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Liver / metabolism / bile acids / Senescence / Invasion / cancer / Liver cancer / Metabolism / Bile acids / Cancer / invasion / Gastroenterology / hepatocellular carcinoma / Deoxycholic acid / Selenomonas Noxia |
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| Outline of Research at the Start |
Selenomonas noxia, salivary microbiology, increases secondary bile acid deoxycholic acid (DCA) in liver. The elevated of DCA stimulates senescence-associated secretory phenotypes (SASP) in hepatic stellate cells (HSCs), which accelerate the secretion of various tumor promoting factors in the liver.
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| Outline of Final Research Achievements |
This study aimed to examine the effect of DCA on hepatic stellate cells (HSCs), a major component of nonparenchymal cells in the liver, and its subsequent indirect effect on HCC cells. LX2 cells, a human HSC line, were treated with DCA in vitro. Then, HuH7 cells, a human hepatoma cell line, were incubated in conditioned media of DCA-treated LX2 to investigate the subsequent effect focusing on malignant behaviors. DCA resulted in cellular senescence in LX2 with the decreased cell proliferation via cell cycle and the induction of senescence-associated secretory phenotype (SASP) factors. HCC cells were treated with DCA treated LX2-conditioned media, that promoted cell migration and invasion via induction of epithelial mesenchymal transition. These changes were attenuated in the presence of neutralizing antibody against IL8 or TGFb. Pathological analysis of surgical specimens from HCC patients revealed that senescent HSCs were detected in the stroma surrounding HCC.
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| Academic Significance and Societal Importance of the Research Achievements |
Our study provided the new insights into the molecular genetics of liver cancer under effects of Deoxycholic acid. In addition, we proposed a novel therapeutic strategy against HCC development, including interventions targeting senescent HSCs and SASP factors, particularly IL8 and TGFβ.
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