Overcoming chemoresistance of small-cell lung cancer through stepwise HER2-targeted antibody-dependent cell-mediated cytotoxicity and VEGF-targeted antiangiogenesis.
Overcoming chemoresistance of small-cell lung cancer through stepwise HER2-targeted antibody-dependent cell-mediated cytotoxicity and VEGF-targeted antiangiogenesis.
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DOI：
10.1038/srep02669
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发表时间：
2013
影响因子：
4.6
通讯作者：
Kumanogoh, Atsushi
中科院分区：
文献类型：
--
作者：
Minami, Toshiyuki;Kijima, Takashi;Kohmo, Satoshi;Arase, Hisashi;Otani, Yasushi;Nagatomo, Izumi;Takahashi, Ryo;Miyake, Kotaro;Higashiguchi, Masayoshi;Morimura, Osamu;Ihara, Shoichi;Tsujino, Kazuyuki;Hirata, Haruhiko;Inoue, Koji;Takeda, Yoshito;Kida, Hiroshi;Tachibana, Isao;Kumanogoh, Atsushi
小细胞肺癌（SCLC）容易复发，具有多药耐药表型。然而，复发性SCLC的标准治疗策略仍未建立。我们发现，人表皮生长因子受体2（HER 2）不仅在预处理的人小细胞肺癌标本中表达，而且当HER 2阳性小细胞肺癌细胞获得化疗耐药性时也上调。曲妥珠单抗对HER 2阳性SCLC细胞诱导不同水平的抗体依赖性细胞介导的细胞毒性（ADCC）。此外，作为ADCC水平差异的机制，我们已经揭示了SCLC细胞上细胞内粘附分子（ICAM）-1的共表达对于促进和加速曲妥珠单抗介导的ADCC至关重要。尽管缺乏ICAM-1表达的SN-38耐药SCLC细胞仍然对曲妥珠单抗无效，但贝伐珠单抗治疗显著抑制了其体内生长，这是由于依赖于其独特且丰富的血管内皮生长因子产生。总的来说，曲妥珠单抗和贝伐珠单抗的逐步治疗对于治疗化学抗性SCLC是有希望的。
Small-cell lung cancer (SCLC) easily recurs with a multidrug resistant phenotype. However, standard therapeutic strategies for relapsed SCLC remain unestablished. We found that human epidermal growth factor receptor 2 (HER2) is not only expressed in pretreated human SCLC specimens, but is also upregulated when HER2-positive SCLC cells acquire chemoresistance. Trastuzumab induced differential levels of antibody-dependent cell-mediated cytotoxicity (ADCC) to HER2-positive SCLC cells. Furthermore, as a mechanism of the differential levels of ADCC, we have revealed that coexpression of intracellular adhesion molecule (ICAM)-1 on SCLC cells is essential to facilitate and accelerate the trastuzumab-mediated ADCC. Although SN-38–resistant SCLC cells lacking ICAM-1 expression were still refractory to trastuzumab, their in vivo growth was significantly suppressed by bevacizumab treatment due to dependence on their distinctive and abundant production of vascular endothelial growth factor. Collectively, stepwise treatment with trastuzumab and bevacizumab is promising for the treatment of chemoresistant SCLC.
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影响因子：
15.9
作者：
Cascone, Tina;Herynk, Matthew H.;Heymach, John V.
通讯作者：
Heymach, John V.
DOI：
10.1073/pnas.0604946103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Chen, Xueni;Hyatt, Brian A.;Shannon, John M.
通讯作者：
Shannon, John M.
影响因子：
45.3
作者：
Burris, Howard A., III;Rugo, Hope S.;O'Shaughnessy, Joyce A.
通讯作者：
O'Shaughnessy, Joyce A.
影响因子：
3.6
作者：
Hanna, Nasser H;Einhorn, Lawrance H
通讯作者：
Einhorn, Lawrance H
影响因子：
5.3
作者：
Moore, AM;Einhorn, LH;Hanna, NH
通讯作者：
Hanna, NH