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| 脱氢环氧甲基醌霉素，一种新的NF-κB抑制剂,可增强紫杉烷类对甲状腺未分化癌的抗肿瘤活性 |
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| Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, enhances antitumor activity of taxanes in anaplastic thyroid cancer cells |
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| Meng Z., Mitsutake N., Nakashima M., Starenki D., Matsuse M., Takakura S., Namba H., Saenko V., Umezawa K., Ohtsuru A., Yamashita S. 2009/5/29 18:38:57 |
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Endocrinology, 2008, Volume 149, Issue 11
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| Nuclear factor κB (NF-κB), as an antiapoptotic factor, crucially affects the outcomes of cancer treatments, being one of the major culprits of resistance to chemotherapy. In this study, we investigated whether dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-κB inhibitor, can enhance antitumor activities of taxanes in anaplastic thyroid cancer (ATC) cells. Taxanes induced NF-κB activation in ATC cells, which could compromise the therapeutic effect of the drugs. However, DHMEQ, by inhibiting the nuclear translocation of NF-κB, completely suppressed the DNA binding capacities of NF-κB and lowered the levels of nuclear NF-κB protein. Compared with single treatment (either taxane or DHMEQ), the combined treatment strongly potentiated apoptosis, confirmed by cell survival assay; Western blotting for poly (ADPribose) polymerase, caspase 3, X-linked inhibitor of apoptosis, and survivin; and flow cytometry for annexin V. Furthermore, we also demonstrate for the first time that the combined treatment showed significantly greater inhibitory effect on tumor growth in a nude mice xenograft model. These findings suggest that taxanes are able to induce NF-κB activation in ATC cells, which could attenuate antitumor activities of the drugs, but inhibition of NF-κB by DHMEQ creates a chemosensitive environment and greatly enhances apoptosis in taxanes-treated ATC cells in vitro and in vivo. Thus, DHMEQ may emerge as an attractive therapeutic strategy to enhance the response to taxanes in ATCs. Copyright © 2008 by The Endocrine Society. |
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| Correspondence Address: Mitsutake, N.; Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; email: mitsu@nagasaki-u.ac.jp |
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 疾病资源中心
摘自：《西氏内科学》，第23版
患者女性，21岁，因干咳、间歇性气促2个月到急诊科就诊。开始症状为上呼吸道感染引起的鼻塞、流涕和咳嗽。医生检查后开了抗生素。服药后鼻部症状缓解，但仍有轻微干咳和呼吸困难。其他症状包括疲劳和焦虑。否认发热、体重减轻、胸痛、端坐呼吸、气喘、鼻后滴漏、胃灼热以及神经系统症状。
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