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Anti-tumor effect of inhibition of IL-6 signaling in mucoepidermoid carcinoma
http://hdl.handle.net/10271/3359
http://hdl.handle.net/10271/3359d895d120-4afd-4ace-80fe-436a9c1f2309
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (12.4 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2018-05-09 | |||||||
| タイトル | ||||||||
| タイトル | Anti-tumor effect of inhibition of IL-6 signaling in mucoepidermoid carcinoma | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | salivary gland cancer | |||||||
| キーワード | ||||||||
| 主題 | tumorigenesis | |||||||
| キーワード | ||||||||
| 主題 | tocilizumab | |||||||
| キーワード | ||||||||
| 主題 | IL-6R | |||||||
| キーワード | ||||||||
| 主題 | tumor initiating cells | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | 粘表皮がんにおけるIL-6シグナル抑制による抗腫瘍効果 | |||||||
| 著者 |
Mochizuki, Daiki
× Mochizuki, Daiki
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| 書誌情報 |
en : Oncotarget 巻 6, p. 22822-22835, 発行日 2015-06-15 |
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| 出版者 | ||||||||
| 出版者 | Impact Journals | |||||||
| 言語 | en | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Mucoepidermoid carcinoma (MEC) is the most frequent malignant salivary gland cancer. Response to chemoradiotherapy is modest, and therefore radical surgery remains the standard-of-care. Emerging evidence suggests that Interleukin (IL)-6 signaling correlates with the survival of cancer stem cells and resistance to therapy. Here, we investigated whether inhibition of IL-6 receptor (IL-6R) signaling with tocilizumab (humanized anti-human IL-6R antibody) sensitizes MEC to chemotherapy using human mucoepidermoid carcinoma cell lines (UM-HMC) and correspondent xenograft models. In vitro, we observed that tocilizumab inhibited STAT3 phosphorylation but had no measurable effect in MEC cell viability (UM-HMC- 1,-3A,-3B). In contrast, the anti-tumor effect of single agent tocilizumab on MEC xenografts was comparable to paclitaxel or cisplatin. Combination of tocilizumab with cisplatin or paclitaxel enhanced the inhibitory effect of chemotherapy on xenograft growth (P<0.05), time to failure (P<0.01), decreased vascular endothelial growth factor (VEGF) expression and tumor microvessel density (P<0.05) without added systemic toxicities. Notably, tocilizumab decreased the fraction of MEC cancer stem cells (ALDHhighCD44high) in vitro, and prevented paclitaxel-induced increase in the fraction of cancer stem cells in vivo (P<0.05). Collectively, these findings demonstrate that tocilizumab enhances the anti-tumor effect of conventional chemotherapy in preclinical models of mucoepidermoid carcinoma, and suggest that patients might benefit from combination therapy with an inhibitor of IL-6R signaling and chemotherapeutic agent such as paclitaxel. | |||||||
| 言語 | en | |||||||
| 学位名 | ||||||||
| 学位名 | 博士（医学） | |||||||
| 学位の区分 | ||||||||
| 内容記述 | doctoral | |||||||
| 学位の分野 | ||||||||
| 内容記述 | 医学系研究科 | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 13802 | |||||||
| 学位授与機関名 | 浜松医科大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2017-07-21 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 乙第541号 | |||||||
| EISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 1949-2553 | |||||||
| PubMed番号 | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 26287605 | |||||||
| 出版社DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.18632/oncotarget.4477 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
