Study for therapeutic strategy using the target protein expressionsystem based on protein stabilization/destabilization in the cancertracing mechanism

癌症追踪机制中基于蛋白质稳定/去稳定的靶蛋白表达系统的治疗策略研究

• 批准号: 23659880
• 负责人: SAKAI Hidetaka
• 金额: $ 2.33万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659880/
• 关键词: 腫瘍治療; PETトレーサ; 遺伝子/蛋白調節; PETトレーサー; 遺伝子／蛋白調節; 遺伝子／蛋白発現調節

We studied regulations of gene/protein expression in oral squamous cell carcinoma (OSCC) cells stimulated by exogenous factors and drug-resistance of the OSCC cells in order to develop the anti-cancer therapeutic strategy using the target protein expression system based on protein stabilization/destabilization in the cancer tracing mechanism. The OSCC cells downregulated the keratinocyte differentiation-related genes and upregulated the expression of SERPINB3/4 (SCCA1/2), well-known SCC markers, following treatment with IL-22. These results indicate that IL-22 and IL-6 differentially activate the STAT-signalingpathway depending on the type of OSCC. When the OSCC cells with resistance to the V-ATPase inhibitor were treated with combination with SAHA, these cells indicated the change in STAT signaling pathway and became more susceptible to the V-ATPase inhibitor. Together these findings suggest V-ATPase could be an attractive target against OSCCs. In addition, combination with other reagents such as SAHA could help V-ATPase inhibitors to induce apoptosis in the V-ATPase inhibitor-resistant OSCC cells via change in STAT-signal pathway. Together, the regulation of STAT-signaling pathway may be a pivotal target for development of the tumor specific expression system. The accumulation of these data could lead to the development of new perspectives on this disease, and potentially new therapies with few side effects, thereby improving the treatment of patients with OSCC

我们研究了口腔鳞状细胞癌(OSCC)细胞在外源性因素刺激下的基因/蛋白表达规律和OSCC细胞的耐药性，以期在肿瘤示踪机制中利用基于蛋白质稳定/失稳的靶蛋白表达系统来制定抗癌治疗策略。经IL-22处理后，口腔鳞状细胞癌细胞下调角质形成细胞分化相关基因，上调众所周知的鳞癌标志物SERPINB3/4(SCCA1/2)的表达。这些结果表明，IL-22和IL-6激活STAT信号通路的不同取决于口腔鳞癌的类型。对V-ATPase抑制剂耐药的口腔鳞癌细胞与SAHA联合作用后，STAT信号通路发生改变，对V-ATPase抑制剂更敏感。综上所述，这些发现表明V-ATPase可能是治疗口腔鳞癌的一个有吸引力的靶点。此外，与SAHA等药物联合应用可通过改变STAT信号通路，帮助V-ATPase抑制剂诱导耐药口腔鳞癌细胞发生凋亡。总之，STAT信号通路的调控可能是肿瘤特异性表达系统发展的关键靶点。这些数据的积累可能会导致对这种疾病的新观点的发展，并有可能产生副作用很少的新疗法，从而改善口腔鳞癌患者的治疗。

项目成果

V-ATPase阻害剤Concanamycin Aによる口腔扁平上皮の細胞死誘導について

V-ATP酶抑制剂刀那霉素A诱导口腔鳞状上皮细胞死亡

• 发表时间: 2012
• 作者: 吉田寿人;清島保;永田健吾;和田裕子;藤原弘明;坂井英隆
• 通讯作者: 坂井英隆

Thymosin beta 4 のノックッダウンによる歯原性細胞の変化について

胸腺肽 β 4 敲低导致牙源细胞发生变化

• 发表时间: 2011
• 作者: 小林家吉;清島保;永田健吾;和田裕子;藤原弘明;坂井英隆
• 通讯作者: 坂井英隆

Parotid gland myoepithelioma with remarkable cystic formation: A case report.

具有显着囊性形成的腮腺肌上皮瘤：病例报告。

• DOI: 10.1016/j.ajoms.2012.05.018
• 发表时间: 2013
• 期刊: J. Oral Maxillofac. Surg. Med. Pathol.
• 作者: Kakehashi H.;Kawano S.;Kiyoshima T.;Shimizu M.;Moriyama M.;Matsubara R.;Kiyosue T.;Goto Y.;Shiratsuchi H.;Nakamura S.
• 通讯作者: Nakamura S.

Netrin-1結合部位欠失DCC遺伝子導入による癌細胞のアポトーシス誘導

通过引入缺乏 Netrin-1 结合位点的 DCC 基因诱导癌细胞凋亡

• 发表时间: 2012
• 作者: 和田裕子;清島保;小林家吉;永田健吾;藤原弘明;塩塚真帆;坂井英隆
• 通讯作者: 坂井英隆

Antimicrobial and antifungal effects of tissue conditioners containing a photocatalyst

含有光催化剂的组织调理剂的抗菌和抗真菌作用

• DOI: 10.4012/dmj.2010-203
• 发表时间: 2011
• 期刊: Dental Materials Journal
• 影响因子: 2.5
• 作者: M.Uchimaru;H.Sakai;et al
• 通讯作者: et al