| Project/Area Number |
22K16528
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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 55020:Digestive surgery-related
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| Research Institution | Gunma University |
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Principal Investigator |
Osone Katasuya 群馬大学, 医学部附属病院, 助教 (30826201)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 潰瘍性大腸炎 / 炎症性発癌 / MAdCAM-1 / 炎症性大腸癌 / CD31 / Colitic cancer |
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| Outline of Research at the Start |
MAdCAM-1は免疫細胞の遊走に関与する細胞接着分子で、UCの腸管粘膜の血管上皮では異所性に高発現しており、その機序の阻害薬がUCの治療薬として臨床応用されている。希少癌であるcolitic cancerの血管内皮におけるMAdCAM-1の発現と免疫細胞の関係に着目した報告はなく、その発現意義と免疫細胞との関係を検証する。さらに炎症性大腸癌モデルマウスによりcolitic cancerに対するMAdCAM-1阻害薬の腫瘍発生の抑制効果、またICIsとMAdCAM-1阻害薬の併用により腸炎抗腫瘍効果の可能性を検討し、臨床での応用を目指す。
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| Outline of Final Research Achievements |
Using immunohistochemical staining of resected specimens from 17 cases of cancer (SCRC), MAdCAM-1, CD31 (vascular endothelium marker), and the number of immune cells in the tumor stroma were detected using various markers (tumor infiltration T marker).
lymphocytes: CD8, pan-macrophage: CD68, M2 macrophage: CD163, regulatory T cells: FOXP3). In addition, the non-cancerous epithelium was examined as normal mucosa and UC. CC mode Mice were generated as previously reported by administering azoxymethane and dextran sodium sulphate to C57BL/6 mice. CC model mice with MAdCAM-1 antibody administration group and control group We then compared various items (inflammation score, number of tumors and average tumor diameter, various proteins determined by immunostaining, and inflammatory cytokines determined by RT-PCR) between the two IgG antibody administration groups.
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| Academic Significance and Societal Importance of the Research Achievements |
MAdCAM-1阻害薬は炎症性シグナルの抑制，腫瘍発生と進展の抑
制を認めたことから抗炎症効果によりCC発生・進展を抑制する可能性がある．阻害薬は炎症性シグナルの抑制，腫瘍発生と進展の抑制を認めたことから抗炎症効果によりCC発生・進展を抑制する可能性がある．
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