肺腺癌の転移成立を防ぐための研究

预防肺腺癌转移的研究

• 批准号: 22790367
• 负责人: SAKUMA Yuji
• 金额: $ 2.58万
• 依托单位: 地方独立行政法人神奈川県立病院機構 (2011)Kanagawa Cancer Center Research Institute (2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790367/
• 关键词: 肺腺癌; 転移; アポトーシス; EGFR; Src; EGFR遺伝子変異; がん遺伝子Src; がん遺伝子 Src; EGFR 遺伝子変異

EGFR-mutant lung adenocarcinoma cells in suspension culture system undergo massive apoptosis by treatment with EGFR tyrosine kinase inhibitors(TKIs). On the other hand, EGFR-mutant cells in monolayer culture system are much more resistant to EGFR TIKs-induced apoptosis than suspended tumor cells, although the phosphorylation of EGFR expressed in EGFR-mutant cells is completely suppressed in either culture condition. Also intrasinus floating tumor cells in metastasis-positive lymph nodes from EGFR-mutant lung adenocarcinoma patients expressed mutant specific EGFR in the same way as extracellular matrix adhesive tumor cells. These findings suggest that the tumor cells floating in vessels would be highly susceptible to EGFR TKIs.

悬浮培养系统中的EGFR突变肺腺癌细胞通过EGFR酪氨酸激酶抑制剂（TKI）处理发生大量凋亡。另一方面，在单层培养系统中的EGFR突变细胞比悬浮的肿瘤细胞对EGFR TIK诱导的凋亡更有抗性，尽管在任一培养条件下EGFR突变细胞中表达的EGFR的磷酸化被完全抑制。EGFR突变型肺腺癌患者转移阳性淋巴结中的窦内漂浮肿瘤细胞也以与细胞外基质粘附肿瘤细胞相同的方式表达突变特异性EGFR。这些发现表明，漂浮在血管中的肿瘤细胞对EGFR TKI高度敏感。

项目成果

EGFR-mutant lung adenocarcinoma cells depend critically on EGFR activation to thrive in anchorage-independent conditions

EGFR 突变型肺腺癌细胞在不依赖贴壁的条件下茁壮成长主要依赖于 EGFR 激活

• 发表时间: 2011
• 作者: Sakuma Y;Nakamura Y;Yoshihara M;Koizume S;Miyagi Y
• 通讯作者: Miyagi Y

ABT-263, a Bcl-2 inhibitor, enhances the susceptibility of lung adenocarcinoma cells treated with Src inhibitors to anoikis

• DOI: 10.3892/or.2010.1123
• 发表时间: 2011-03-01
• 期刊: ONCOLOGY REPORTS
• 影响因子: 4.2
• 作者: Sakuma, Yuji;Tsunezumi, Jun;Miyagi, Yohei
• 通讯作者: Miyagi, Yohei

ABT-263 enhances the susceptibility of lung adenocarcinoma cells treated with Src inhibitors to anoikis

ABT-263 增强 Src 抑制剂处理的肺腺癌细胞对失巢凋亡的敏感性

• 发表时间: 2010
• 作者: Sakuma Y;Nakamura Y;Yoshihara M;Koizume S;Miyagi Y.
• 通讯作者: Miyagi Y.

WZ4002, a third-generation EGFR inhibitor, can overcome anoikis resistance in EGFR-mutant lung adenocarcinomas more efficiently than Src inhibitors

• DOI: 10.1038/labinvest.2011.187
• 发表时间: 2012-03-01
• 期刊: LABORATORY INVESTIGATION
• 影响因子: 5
• 作者: Sakuma, Yuji;Yamazaki, Yukiko;Miyagi, Yohei
• 通讯作者: Miyagi, Yohei

肺腺癌におけるanoikis抵抗性の研究

肺腺癌失巢凋亡抵抗的研究

• 发表时间: 2011
• 作者: 佐久間裕司;中村圭靖;横瀬智之;亀田陽一;宮城洋平
• 通讯作者: 宮城洋平