後天的ゲノム修飾による膵腫瘍環境リモデリング機構の検証

通过获得性基因组修饰验证胰腺肿瘤环境重塑机制

• 批准号: 21K07886
• 负责人: 中井 陽介
• 金额: $ 2.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K07886/
• 关键词: 膵癌; エピジェネテイクス

膵癌においては変異などの遺伝子異常のみならず、エピジェネテイクス環境が特異的に構築されている。エピジェネテイクス制御とはDNAメチル化やヒストン修飾の総称であり、細胞分化、代謝状態や免疫応答と関連して多彩な機序で癌の性質に影響を及ぼしうる。実際にエピジェネテイクス修飾酵素のゲノム変異が膵癌で見出され、その重要性が示唆されている。膵癌の特徴的な線維性間質による微小環境においては、癌随伴性線維芽細胞（CAF）が膠原線維などの基質や増殖因子を産生し、免疫細胞とのせめぎあいの中で癌の進展や治療に対する抵抗性を誘導する。免疫細胞のプロファイルも腫瘍進展に直結するが、最近報告された膵癌細胞内オートファジー依存性MHC-1分子の分解による免疫回避など、未知の免疫応答機序が示唆される。前研究で膵癌組織内CAFの活性化とエピジェネテイクス制御について報告したが、免疫細胞プロファイルを含めた微小環境リモデリングの分子機構には未知の点が多い。本研究ではエピジェネテイクス制御化合物によって生じる影響の解析を通して、多様なCAFおよび免疫細胞リモデリングの分子機構と腫瘍生物学的意義を検討する。倫理委員会承認のもと、内視鏡的生検検体から患者微量検体を増幅培養し、その特性および腫瘍内多様性を維持したまま解析可能なオルガノイドとゼノグラフトシステムを構築した。それらは原発巣の性質を良く再現・維持し、既報通りin vitro オルガノイド培養も原発巣の腺管構造を維持していた。このシステムは患者各々の膵癌組織の解析を可能とした。前検討では、このヒト膵癌オルガノイド培養系3ラインを用いて、約100種類のエピゲノム阻害合物の抗腫瘍効果のスクリーニングを行った。その結果から膵癌に対する抗腫瘍効果を持つ化合物とその作用機序について解析する。

In the case of cancer, please do not know what to do with the environment. In order to control the development of DNA, we need to modify the diagnosis of cancer, cell differentiation and immune response. The sequence is cancer, cancer, and cancer. In the international market, we need to know that the enzyme is used to treat cancer, and that the importance of cancer is important. The characteristics of cancer are sensitive to microenvironment, cancer-associated germ cells (CAF) are associated with the production of reproductive factors, and immune cells are involved in the progressive treatment of cancer and the induction of cancer resistance. The immune response of the immunized mice was significantly higher than that of the normal controls. Recently, it was reported that the tumor cells of the cancer cells showed that the MHC-1 molecules were dependent on each other. The immune avoidance tests and the unknown immune response machine sequence showed that the immune responses were not clear. In the previous study, the activation of CAF in cancer tissue is very important for the preparation and control of cancer reports, and the immune system contains a large number of molecular mechanisms for the detection of microenvironment. The purpose of this study is to analyze the meaning of biology in the molecular mechanism of immune cell immune system. The purpose of this study is to analyze the molecular mechanism of the control of chemical compounds. The committee will recognize that there is a significant increase in the number of patients who are born and treated in the hospital, and that the characteristics and characteristics of the patients may be different from each other. In order to improve the quality of sex, it is reported that the in vitro should be used to maintain the quality of the glandular canal. The cancer tissue of each patient may be affected by the analysis of the cancer tissue. In the first half of the year, the number of anti-cancer products in the first half of the year, in the first half of the year, was used in the first half of the year, and about 100 percent of them were used to prevent the disease. Results the results showed that the anti-tumor effect of anti-cancer was confirmed by sequence analysis of the mechanism of antitumor action of compounds.

项目成果

Clinical Outcomes of Intraductal Papillary Mucinous Neoplasms With Dilatation of the Main Pancreatic Duct

伴有主胰管扩张的导管内乳头状粘液性肿瘤的临床结果

• DOI: 10.1016/j.cgh.2023.01.032
• 发表时间: 2023
• 期刊: Clinical Gastroenterology and Hepatology
• 影响因子: 12.6
• 作者: Hamada Tsuyoshi;Oyama Hiroki;Nakai Yousuke;Tateishi Keisuke;Ushiku Tetsuo;Hasegawa Kiyoshi;Fujishiro Mitsuhiro
• 通讯作者: Fujishiro Mitsuhiro

MNX1-HNF1B Axis Is Indispensable for Intraductal Papillary Mucinous Neoplasm Lineages

• DOI: 10.1053/j.gastro.2021.12.254
• 发表时间: 2022-03-15
• 期刊: GASTROENTEROLOGY
• 影响因子: 29.4
• 作者: Kato, Hiroyuki;Tateishi, Keisuke;Koike, Kazuhiko
• 通讯作者: Koike, Kazuhiko