膵癌の術後早期転移再発予測をめざした転移前土壌形成に関わる細胞外小胞の単離解析

分离和分析参与转移前土壤形成的细胞外囊泡，用于预测胰腺癌术后早期转移复发

• 批准号: 22K15958
• 负责人: 石垣 和祥
• 金额: $ 2.91万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K15958/
• 关键词: 膵がん; 細胞外小胞

膵癌治療において術前化学療法が予後改善に寄与していることは臨床的に明らかであるが、一部の症例では術後早期に転移再発する。このような症例に対しては、切除は身体的負担になるばかりか、限られた予後の生活の質を落とす要因にもなる。もし『術前化学療法後・切除前』に『術後』の早期転移再発が予測できれば、不要な外科的切除を回避でき、その恩恵は患者側にも医療者側にも大きい。本研究は、『術前化学療法後・切除前』に、『術後の予後』を推定するマーカーを、血中の細胞外小胞に着目して探索する。具体的に、第一には、「術前化学療法前後における血中の細胞外小胞内の変異kRas頻度の変化」と「術後の予後」の相関の有無を検証する。第二には、細胞外小胞の特異的サブセットが「pre-metastatic niche」の形成に関与するという「seed and soil 仮説」に立脚して、膵癌由来の細胞外小胞サブセットの中から転移巣形成に関わるサブセットを探索し、その定量を『術前化学療法前後』で行い『術後の予後』との相関を検討する。本年度は切除可能病変または切除可能境界病変を持つ膵癌患者のNAC前の血清とNAC後術前の血清をから、サイズ除去クロマトグラフィー法で血中の細胞外小胞を一括で収集したのちRNAを抽出し逆転写後、野生型kRasと変異型kRasの存在比をdigital PCRでの定量を試み、今後の多数検体での解析の基盤を樹立した。今後、想定どおりの結果が得られた場合は新規症例30例に対して前向きにvalidation を行って堅牢性を担保し、当初の目的である『NAC後・術前』に「術後の早期転移再発」を予測し不必要な手術を除外する方法として確立していく。

After the treatment of cancer, the chemical method before the treatment of cancer was used to improve the information sent to the hospital bed, and the disease was moved again in the early stage after the treatment. The symptoms of the disease, the removal of the body, the loss of the body, the loss of life, the loss of life, the loss of the body, the removal of the body, the loss of the body, and the loss of life. Chemical surgery before and after resection was performed in the early stage and then was transferred to the patients before and after the operation. No surgical excision was required. In this study, "pre-operative chemical therapy and post-resection", "pre-operative chemical therapy and post-surgical resection", "pre-operative chemical therapy and post-surgical resection", "pre-operative chemical therapy and post-resection", "pre-operative chemical therapy and post-resection", "pre-operative chemical therapy", "pre-operative chemical resection" and "post-surgical resection". The specific drug, the first drug, and the chemical method before and after the operation were used to determine the concentration of extracellular kRas in the blood. The second, the extracellular small cell (ECC) is characterized by the formation of "pre-metastatic niche", the formation of the "seed and soil", the formation of the cancer, the formation of the extracellular cell, the formation of the tumor, the formation of the cancer, the formation of the tumor, the formation of the cancer, the formation of the tumor, the formation This year, the serum of patients with cancer before NAC, the serum of patients with cancer before surgery, the serum of patients with cancer before NAC, the serum of patients with cancer before operation, the serum of patients with cancer before operation, the serum of patients with cancer before operation, the serum of patients with cancer before NAC, the serum of patients with cancer before surgery, the serum of patients with cancer before In the future, the majority of people will analyze the basis of the analysis. In the future, it was concluded that 30 cases of new regulations were confirmed by clinical practice. In 30 cases of validation, the original intention was to obtain a safe sex guarantee before and after NAC surgery, and to treat unnecessary surgical procedures except that they were not required to do so.

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

Smaller extracellular vesicles are released from pancreatic cancer cells by the alteration of the lipid composition under low glucose conditions

在低葡萄糖条件下，通过脂质成分的改变，胰腺癌细胞释放出较小的细胞外囊泡

• DOI: 10.1016/j.bbrc.2022.11.040
• 发表时间: 2022
• 期刊: Biochemical and Biophysical Research Communications
• 影响因子: 3.1
• 作者: Shibata Chikako;Otsuka Motoyuki;Seimiya Takahiro;Ishigaki Kazunaga;Miyakawa Yu;Kishikawa Takahiro;Fujishiro Mitsuhiro
• 通讯作者: Fujishiro Mitsuhiro