Aiming to applying to gene therapy for peritoneal dissemination of ovarian cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11263
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Hirosaki University
• Principal Investigator: Yokoyama Yoshihito 弘前大学, 医学研究科, 教授 (90261453)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 卵巣癌腹膜播種 / Carbonyl reductase 1 / 遺伝子治療 / 人工ヒト腹膜組織 / ネクローシス

Outline of Final Research Achievements

Cancer cells perforated the mesothelium, leaving normal mesothelium intact. However, the cells proliferated between the layers of the mesothelium, forming a mass. After 24 h, cancer cells had invaded the lymphatics, and after 48 to 72 h cancer cells had invaded deep into the mesothelium, where they formed a mass. Invasion of the peritoneum by cancer cells in a murine model of peritoneal carcinomatosis resembled that in a model using Artificial human peritoneal tissue (AHPT), and results substantiated the reproducibility of peritoneal carcinomatosis in AHPT. Proliferation of cells transfected with carbonyl reductase 1(CR1) DNA was significantly inhibited on AHPT, and necrosis was evident. Nevertheless, cancer cell invasion deep into the mesothelium was not inhibited. CR1 DNA does not play a role in inhibiting invasion of the mesothelium during peritoneal metastasis, but it affects cancer cell proliferation. Results suggested that CR1 DNA inhibits cancer cell proliferation via necrosis.

Free Research Field

産科婦人科学

Academic Significance and Societal Importance of the Research Achievements

卵巣癌患者へ応用するために行った3次元ヒト人工腹膜を用いた研究において、卵巣癌細胞を播種させCBR1 DNA/デンドリマー複合体を添加すると、24時間後から癌細胞の接着・増殖・中皮層への浸潤が有意に抑制された。これはマウス生体内での播種巣にCBR1 DNA/デンドリマー複合体を投与した場合と同様の動態であった。この結果はCBR1 DNA/デンドリマー複合体のヒト卵巣癌治療への応用ができるものと大いに期待される。