Ex vivo-expanded highly purified natural killer cells in combination with temozolomide induce antitumor effects in human glioblastoma cells in vitro.

• Material Type: 博士論文
• Title: Ex vivo-expanded highly purified natural killer cells in combination with temozolomide induce antitumor effects in human glioblastoma cells in vitro.
• Author/Editor: Tanaka, Yoshitaka; Nakazawa, Tsutomu; Nakamura, Mitsutoshi; Nishimura, Fumihiko; Matsuda, Ryosuke; Omoto, Koji; Shida, Yoichi; Murakami, Toshiharu; Nakagawa, Ichiro; Motoyama, Yasushi; Morita, Hiromichi; Tsujimura, Takahiro; Nakase, Hiroyuki
• Author Heading: Tanaka, Yoshitaka; Nakazawa, Tsutomu; Nakamura, Mitsutoshi; Nishimura, Fumihiko; Matsuda, Ryosuke; Omoto, Koji; Shida, Yoichi; Murakami, Toshiharu; Nakagawa, Ichiro; Motoyama, Yasushi; Morita, Hiromichi; Tsujimura, Takahiro; Nakase, Hiroyuki
• Publication, Distribution, etc.: Public Library of Science
• Publication Date: 2019-03-06
• Publication Date (W3CDTF): 2019-03-06
• Alternative Title: 高純度natural killer細胞及びtemozolomide併用によるヒト膠芽腫細胞に対する抗腫瘍効果の研究
• Periodical title: PloS one
• No. or year of volume/issue: 14 3
• Volume: 14
• Issue: 3
• Pages: Article No.e0212455-
• ISSN (Periodical Title): ISSN : 1932-6203
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2019-06-26
• Dissertation Number: 甲第715号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Target Audience: 一般
• Note (General): type:Thesis; Glioblastoma is the leading malignant glioma with a poor prognosis. This study aimed to investigate the antitumor effects of natural killer cells in combination with temozolomide as the standard chemotherapeutic agent for glioblastoma. Using a simple, feeder-less, and chemically defined culture method, we expanded human peripheral blood mononuclear cells and assessed the receptor expression, natural killer cell activity, and regulatory T cell frequency in expanded cells. Next, using the standard human glioblastoma cell lines (temozolomide-sensitive U87MG, temozolomide-resistant T98G, and LN-18), we assessed the ligand expressions of receptors on natural killer cells. Furthermore, the antitumor effects of the combination of the expanded natural killer cells and temozolomide were assessed using growth inhibition assays, apoptosis detection assays, and senescence-associated β-galactosidase activity assays in the glioblastoma cell lines. Novel culture systems were sufficient to attain highly purified (>98%), expanded (>440-fold) CD3-/CD56+ peripheral blood-derived natural killer cells. We designated the expanded population as genuine induced natural killer cells. Genuine induced natural killer cells exhibited a high natural killer activity and low regulatory T cell frequency compared with lymphokine-activated killer cells. Growth inhibition assays revealed that genuine induced natural killer cells inhibited the glioblastoma cell line growth but enhanced temozolomide-induced inhibition effects in U87MG. Apoptosis detection assays revealed that genuine induced natural killer cells induced apoptosis in the glioblastoma cell lines. Furthermore, senescence-associated β-galactosidase activity assays revealed that temozolomide induced senescence in U87MG. Genuine induced natural killer cells induce apoptosis in temozolomide-sensitive and temozolomide-resistant glioblastoma cells and enhances temozolomide-induced antitumor effects in different mechanisms. Hence, the combination of genuine induced natural killer cells and temozolomide may prove to be a promising immunochemotherapeutic approach in patients with glioblastoma if the antitumor effects in vivo can be demonstrated.; 博士（医学）・甲第715号・令和元年6月26日; Copyright: © 2019 Tanaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.; identifier:PloS one Vol.14 No.3 Article No.e0212455 (2019 Mar); identifier:19326203; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3588; identifier:PloS one, 14(3): Article No.e0212455
• Source: comment：fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3588/1/01%e7%94%b2715%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3588/2/02%e7%94%b2715%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3588/3/03%e7%94%b2715%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1371/journal.pone.0212455
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU