細胞接着分子CADM1を分子標的とする小細胞肺癌の治療法の開発

开发针对细胞粘附分子CADM1的小细胞肺癌治疗方法

• 批准号: 22K08969
• 负责人: 菊池 慎二
• 金额: $ 2.66万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K08969/
• 关键词: 小細胞肺癌; 外科手術; CADM1; スプライシングバリアント; 細胞接着分子; スプライシング

免疫グロブリン・スーパーファミリー細胞接着分子CADM1は非小細胞肺癌(NSCLC)を含む様々な上皮系の癌において腫瘍抑制に関与する．我々は，CADM1が小細胞肺癌(SCLC)において特異的なスプライシングを受けて高頻度に過剰発現し，悪性増殖能に関与することを見出した．次に，SCLCの分子生物学的特徴を検討するために，SCLC手術症例の長期治療成績の後ろ向き解析した．当院で肺切除術を行いSCLCと診断された102症例を対象としたところ，平均年齢は71.7歳，93人が男性で，99人が喫煙者であった．術式は32例が縮小手術，70例が肺葉切除術で，周術期死亡はなかった．47例に術後補助化学療法を施行し，3例に予防的全脳照射を施行した．病理病期はI/II/III/IVが51/24/26/1例で，平均観察期間は44.1ヵ月，5年生存率は56.8％であった．単変量解析ではCEA正常値（p＝0.002），組織学的pure SCLC（p＝0.002）血管侵襲陰性（p＜0.001），pStage I（p＜0.001），術後補助化学療法あり（p＝0.045）が有意な予後良好因子であった．また，手術検体の免疫組織化学染色でCADM1及び癌幹細胞マーカー候補（CD133，CD44，ALDH1）の発現を検討したところ，CADM1は71％で強陽性であり、患者の予後不良と有意な相関を示した．一方，癌幹細胞マーカー候補の発現は予後と有意な相関はなかった．以上の研究成果をまとめ，論文投稿中である．また今年度は、以上の研究成果を「第81回日本癌学会学術総会」で発表する事が出来た．

CADM1, a cell adhesion molecule, plays an important role in non-small cell lung cancer (NSCLC) and tumor suppression in epithelial cancer. CADM1 is associated with small cell lung cancer (SCLC), and is associated with high frequency and increased reproductive activity. In addition, the molecular biological characteristics of SCLC are discussed, and the long-term treatment results of SCLC surgical cases are analyzed. SCLC was performed in 102 patients with lung cancer. The average age was 71.7 years. 93 patients were male and 99 patients were smokers. 32 patients underwent reduction surgery, 70 patients underwent lobectomy, 47 patients died during surgery, and 3 patients underwent preventive total radiation. Pathological stage I/II/III/IV was 51/24/26/1 case, mean observation period was 44.1 months, 5-year survival rate was 56.8%. Quantitative analysis of CEA normal value (p=0.002), histological pure SCLC (p=0.002), negative vascular invasion (p<0.001), pStage I (p<0.001), postoperative adjuvant chemotherapy (p=0.045), intentional post-treatment good factor. Immunohistochemical staining for CADM1 and cancer stem cell candidates (CD133, CD44, ALDH1) in surgical specimens showed strong positive for CADM1 in 71% of patients. One side, cancer stem cell candidates appear after the intention to. The above research results are in the process of submission. This year, the above research results were presented at the 81st Academic Conference of the Japanese Cancer Society.

项目成果

Alaska pollock gelatin sealant shows long-term efficacy and safety in a pulmonary air leakage rat model.

阿拉斯加狭鳕明胶密封剂在肺漏气大鼠模型中显示出长期功效和安全性。

• DOI: 10.1093/ejcts/ezac497
• 发表时间: 2022
• 期刊: European Journal of Cardio-Thoracic Surgery
• 影响因子: 3.4
• 作者: Yanagihara T;Maki N;Kawamura T;Kobayashi N;Kikuchi S;Goto Y;Ichimura H;Watanabe S;Taguchi T;Sato Y
• 通讯作者: Sato Y

Efficacy of Alaska Pollock Gelatin Sealant for Pulmonary Air Leakage in Porcine Models

阿拉斯加狭鳕明胶密封剂对猪模型肺漏气的疗效

• DOI: 10.1016/j.athoracsur.2021.05.023
• 发表时间: 2022
• 期刊: The Annals of Thoracic Surgery
• 作者: Yanagihara Takahiro;Maki Naoki;Wijesinghe A.I.;Sato Shoko;Saeki Yusuke;Kitazawa Shinsuke;Yamaoka Masatoshi;Kobayashi Naohiro;Kikuchi Shinji;Goto Yukinobu;Ichimura Hideo;Watanabe Shiharu;Taguchi Tetsushi;Sato Yukio
• 通讯作者: Sato Yukio

Left thoracoscopic sympathectomy for refractory ventricular arrhythmias

左胸腔镜交感神经切除术治疗难治性室性心律失常

• DOI: 10.1007/s11748-022-01835-1
• 发表时间: 2022
• 期刊: Gen Thorac Cardiovasc Surg.
• 作者: Yanagihara T;Kobayashi N;Saeki Y;Kikuchi S;Goto Y;Sato Y.
• 通讯作者: Sato Y.

Prognostic Implication of PD-L1 Expression on Osimertinib Treatment for EGFR-mutated Non-small Cell Lung Cancer

• DOI: 10.21873/anticanres.15736
• 发表时间: 2022-05-01
• 期刊: ANTICANCER RESEARCH
• 影响因子: 2
• 作者: Shiozawa, Toshihiro;Numata, Takeshi;Hizawa, Nobuyuki
• 通讯作者: Hizawa, Nobuyuki

Surgery for small-cell lung cancer: Clinical characteristics and prognostic factors

小细胞肺癌手术：临床特征和预后因素

• 发表时间: 2022
• 作者: Shinji Kikuchi;Yasuharu Sekine;Kojiro Nakaoka;Naohiro Kobayashi;Hisashi Suzuki;Yukinobu Goto;Hideo Ichimura;Moriyuki Kiyoshima;Yukio Sato
• 通讯作者: Yukio Sato