Tumor-inhibition effect of levetiracetam in combination with temozolomide in glioblastoma cells.

• Material Type: 博士論文
• Title: Tumor-inhibition effect of levetiracetam in combination with temozolomide in glioblastoma cells.
• Author/Editor: Marutani, Akiko; Nakamura, Mitsutoshi; Nishimura, Fumihiko; Nakazawa, Tsutomu; Matsuda, Ryosuke; Hironaka, Yasuo; Nakagawa, Ichiro; Tamura, Kentaro; Takeshima, Yasuhiro; Motoyama, Yasushi; Boku, Eishu; Ouji, Yukiteru; Yoshikawa, Masahide; Nakase, Hiroyuki
• Author Heading: Marutani, Akiko; Nakamura, Mitsutoshi; Nishimura, Fumihiko; Nakazawa, Tsutomu; Matsuda, Ryosuke; Hironaka, Yasuo; Nakagawa, Ichiro; Tamura, Kentaro; Takeshima, Yasuhiro; Motoyama, Yasushi; Boku, Eishu; Ouji, Yukiteru; Yoshikawa, Masahide; Nakase, Hiroyuki
• Publication, Distribution, etc.: Springer
• Publication Date: 2017-01
• Publication Date (W3CDTF): 2017-01
• Alternative Title: 膠芽腫細胞株におけるテモゾロミド併用によるレベチラセタムの抗腫瘍効果
• Periodical title: Neurochemical Journal
• No. or year of volume/issue: 11 1
• Volume: 11
• Issue: 1
• Pages: 43-49
• ISSN (Periodical Title): ISSN : 1819-7124
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2017-03-15
• Dissertation Number: 甲第667号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: temozolomide; levetiracetam; premature senescence; glioblastoma
• Target Audience: 一般
• Note (General): type:Thesis; Glioblastoma (GBM) is a malignant brain tumor with a poor prognosis. The standard postoperative chemotherapy is temozolomide (TMZ), which does not greatly improve survival. The DNA repair gene O-6-methylguanine-DNA methyltransferase (MGMT) contributes to the response of TMZ-induced DNA damage. The commonly prescribed antiepileptic drug levetiracetam (LEV) has been shown to enhance TMZ’s antitumor effect via inhibition of histone deacetylases (HDACs), but the therapeutic advantages of the LEV and TMZ combination remain poorly understood. Mechanisms of response to chemotherapy include apoptosis and mitotic catastrophe, and recent studies have suggested that premature senescence may also be invoked when cancer cells are exposed to therapeutic agents. In our study, we evaluated cell proliferation and premature senescence after single and combined treatments of TMZ and LEV in two GBM cell lines that differ in TMZ sensitivity caused by the absence (A172) or presence (T98) of the MGMT protein. Both LEV and TMZ reduced cell proliferation in a dose-dependent manner in A172 cells. A senescent-like phenotype, as determined by β-galactosidase activity, was induced by both TMZ and LEV. Overall, there was a greater effect following combined treatment compared to the monotherapy groups. Thus, LEV appears to have a tumor-suppressive effect and induces cellular senescence, and combined treatment of LEV and TMZ enhanced these effects. because LEV treatment results in few adverse effects, its use in GBM treatment may allow for reduction of the TMZ dose to enhance the clinical efficacy of TMZ chemotherapy and improve quality of life.; 博士（医学）・甲第667号・平成29年3月15日; © Pleiades Publishing, Ltd. 2017; The final publication is available at Springer via http://dx.doi.org/10.1134/S1819712416040073; identifier:Neurochemical Journal Vol.11 No.1 p.43-49 (2017 Jan); identifier:18197124; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3320; identifier:Neurochemical Journal, 11(1): 43-49
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1134/S1819712416040073
• 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

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3320/1/01_%e7%94%b2667%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3320/2/02_%e7%94%b2667%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3320/10/03%20%e7%94%b2667%e6%9c%ac%e6%96%87.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3320/11/04%20%e7%94%b2667Figures01-03.pdf fulltext