Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells.
Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells.
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DOI：
10.4143/crt.2020.585
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发表时间：
2021-04
影响因子：
4.6
通讯作者：
Wongprasert K
中科院分区：
文献类型：
--
作者：
Boonsri B;Yacqub-Usman K;Thintharua P;Myint KZ;Sae-Lao T;Collier P;Suriyonplengsaeng C;Larbcharoensub N;Balasubramanian B;Venkatraman S;Egbuniwe IU;Gomez D;Mukherjee A;Kumkate S;Janvilisri T;Zaitoun AM;Kuakpaetoon T;Tohtong R;Grabowska AM;Bates DO;Wongprasert K
表皮生长因子受体（ErbB）家族成员作为胆管癌（CCA）药物靶点的潜力尚未得到广泛关注。尽管III期临床试验显示厄洛替尼对晚期CCA患者没有生存益处，但CCA的标准治疗化疗吉西他滨/顺铂的结果令人沮丧，因此我们确定了其他ErbB受体抑制剂单独或联合治疗的效果CCA细胞中的化疗。ErbB受体表达测定CCA患者组织的免疫组化和数字滴聚合酶链反应，并在原代细胞和细胞系的免疫印迹。在CCA细胞系中进行使用ErbB抑制剂与化疗药物的组合疗法对细胞活力和细胞周期分布的影响。然后采用原代CCA细胞的3D培养物来评估在更接近于体内细胞环境的环境中的药物作用。CCA肿瘤表现出更高的表达所有ErbB受体相比，切除边缘。原代和CCA细胞系具有不同的erbB受体表达。CCA细胞系在接受化疗药物（吉西他滨和5-氟尿嘧啶）以及ErbB抑制剂（特别是阿法替尼）和联合治疗时显示细胞活力降低。吉西他滨与阿法替尼序贯治疗特别有效。CCA原代细胞与癌症相关成纤维细胞的共培养降低了对化疗的敏感性，但对阿法替尼敏感。阿法替尼是一种潜在的表皮生长因子受体靶向药物，用于CCA治疗，可以在CCA患者中探索吉西他滨和阿法替尼的序贯治疗方案。
The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in patients with advanced CCA, the outcome of the standard-of-care chemotherapy treatment for CCA, gemcitabine/cisplatin, is discouraging so we determined the effect of other ErbB receptor inhibitors alone or in conjunction with chemotherapy in CCA cells. ErbB receptor expression was determined in CCA patient tissues by immunohistochemistry and digital-droplet polymerase chain reaction, and in primary cells and cell lines by immunoblot. Effects on cell viability and cell cycle distribution of combination therapy using ErbB inhibitors with chemotherapeutic drugs was carried out in CCA cell lines. 3D culture of primary CCA cells was then adopted to evaluate the drug effect in a setting that more closely resembles in vivo cell environments. CCA tumors showed higher expression of all ErbB receptors compared with resection margins. Primary and CCA cell lines had variable expression of erbB receptors. CCA cell lines showed decreased cell viability when treated with chemotherapeutic drugs (gemcitabine and 5-fluorouracil) but also with ErbB inhibitors, particularly afatinib, and with a combination. Sequential treatment of gemcitabine with afatinib was particularly effective. Co-culture of CCA primary cells with cancer-associated fibroblasts decreased sensitivity to chemotherapies, but sensitized to afatinib. Afatinib is a potential epidermal growth factor receptor targeted drug for CCA treatment and sequential treatment schedule of gemcitabine and afatinib could be explored in CCA patients.
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影响因子：
3.8
作者：
Moehler, Markus;Maderer, Annett;Thomaidis, Thomas
通讯作者：
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影响因子：
3.5
作者：
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影响因子：
4.6
作者：
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通讯作者：
Sun JM
影响因子：
4.3
作者：
Sripa, Banchob;Leungwattanawanit, Saman;Miwa, Masanao
通讯作者：
Miwa, Masanao
泛素肽酶 UCHL1 通过稳定 p53 诱导 G0/G1 细胞周期停滞和凋亡，并且在乳腺癌中经常沉默
影响因子：
3.7
作者：
Xiang T;Li L;Yin X;Yuan C;Tan C;Su X;Xiong L;Putti TC;Oberst M;Kelly K;Ren G;Tao Q
通讯作者：
Tao Q