Study on a new combination chemotherapy for head and neck squamous cell carcinomas

头颈鳞癌新型联合化疗方案的研究

• 批准号: 21390543
• 负责人: KUBOTA Eiro
• 金额: $ 11.65万
• 依托单位: Kanagawa Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390543/
• 关键词: ケモカイン; BRAK; メチル化; EGFR阻害剤; 頭頸部扁平上皮癌; CXCL14; EGFR; SCC; Gefitinib; DAC; microarray; transcription

BRAK/CXCL14 is a chemokine that is expressed in normal tissues, and is important for maintaining homeostasis. BRAK has many functions such as inhibition of angiogenesis and chemotaxis of monocytes as well as macrophaghes. BRAK is absent from or expressed at very low levels in head and neck squamous cell carcinoma(HNSCC), and this is closely correlated with tumorigenesis and progression of HNSCC. Forced expression of BRAK chemokine by the gene transfection into HNSCC or BRAK transgenic mice reduced the tumorigenicity of the cells in xenografts, and BRAK was considered to be a target molecule for the cancer treatment. In the present study, we elucidated that low expression of BRAK in HNSCC was due to mutation of BRAK promotor region by methylation. The low expression level of BRAK in HNSCC is restored by treatment of the cells with anti-methylation drug. HNSCC overexpressed BRAK by EGF receptor antagonist(gefitinib) and anti-methylation drug gave rise to susceptible to tumor regression. The anti-tumor effect using gefitinib and anti-cancer drugs is thus feasible for combination chemotherapy in HNSCC.

BRAK/CXCL 14是一种在正常组织中表达的趋化因子，对维持体内平衡很重要。BRAK具有抑制血管生成、抑制单核细胞和巨噬细胞趋化等多种功能。在头颈部鳞状细胞癌（HNSCC）中，BRAK表达水平很低或缺失，与肿瘤的发生、发展密切相关。通过基因转染到HNSCC或BRAK转基因小鼠中强制表达BRAK趋化因子降低了异种移植物中细胞的致瘤性，并且BRAK被认为是癌症治疗的靶分子。在本研究中，我们阐明了在HNSCC中BRAK的低表达是由于BRAK启动子区甲基化引起的突变。通过用抗甲基化药物处理细胞来恢复HNSCC中BRAK的低表达水平。EGF受体拮抗剂（吉非替尼）和抗甲基化药物可使HNSCC过度表达BRAK，使其易发生肿瘤消退。因此，吉非替尼联合抗癌药物的抗肿瘤作用对于HNSCC的联合化疗是可行的。

项目成果

EGF受容体阻害剤とデシタビンを用いた併用療法の基礎的研究

EGF受体抑制剂与地西他滨联合治疗的基础研究

• 发表时间: 2009
• 作者: 小澤重幸;生駒丈晴;鈴木健司;久保田英朗
• 通讯作者: 久保田英朗

Functional Analysis of Promoter of Human BRAK/CXCL14, A Tumor Suppressor

人肿瘤抑制因子BRAK/CXCL14启动子的功能分析

• 发表时间: 2009
• 作者: Komori R;Ozawa S;Kato Y;Shinji H;Kimoto S;Hata R
• 通讯作者: Hata R

Restoration of BRAK/CXCL14 gene expression by gefitinib is associated with antitumor efficacy of the drug in head and neck squamous cell carcinoma

• DOI: 10.1111/j.1349-7006.2009.01281.x
• 发表时间: 2009-11-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Ozawa, Shigeyuki;Kato, Yasumasa;Hata, Ryu-Ichiro
• 通讯作者: Hata, Ryu-Ichiro

ケモカインBRAK/CXCL14をマーカー分子とした頭頸部扁平上皮癌への新たな併用療法の試み

以趋化因子BRAK/CXCL14为标记分子的头颈鳞状细胞癌新联合疗法试验

• 发表时间: 2009
• 作者: 小澤重幸;加藤靖正;伊藤慎;小森令賀;椎木直人;槻木恵一;前畑洋次郎;田口亨秀;石黒-今川由香利;佃守;畑隆一郎;久保田英朗
• 通讯作者: 久保田英朗

ケモカインCXCL14/BRAKと扁平上皮細胞の分化レベルとの関連性

趋化因子CXCL14/BRAK与鳞状细胞分化水平的关系

• 发表时间: 2011
• 作者: 頭司雄介;野口一馬;山村倫世;高岡一樹;瀬川英美;岸本裕充;浦出雅裕;生駒丈晴
• 通讯作者: 生駒丈晴