Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug ZHER2:V2-pemetrexed in lung adenocarcinoma Xenografts
Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug ZHER2:V2-pemetrexed in lung adenocarcinoma Xenografts
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HER2靶向化疗药物ZHER2:V2-培美曲塞治疗肺腺癌异种移植的疗效及影像学评估
DOI：
10.1007/s10637-019-00876-3
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Jianfang Wang
中科院分区：
文献类型：
--
作者：
Jingya Han;Yan Zhao;Xinming Zhao;Tuo Ma;Tiancheng Hao;Jiaohui Liu;Zhaoqi Zhang;Jingmian Zhang;Jianfang Wang
化疗一直是晚期非小细胞肺癌（NSCLC）患者不可治疗的致癌基因突变的首选治疗方案。然而，化疗已经证明成功有限，并且与严重的副作用有关。本研究旨在研究新型靶向化疗药物ZHER 2：V2-培美曲塞偶联物的抗肿瘤疗效和细胞毒安全性。在这种情况下，使用ZHER 2：V2-培美曲塞、培美曲塞或生理盐水处理人表皮生长因子受体2（HER 2）+ A549肺异种移植物。使用99 mTc标记的ZHER 2：V2-培美曲塞偶联物通过单光子发射计算机断层扫描（SPECT）成像监测治疗效果，并通过使用流式细胞术分析和苏木精-伊红（H&E）染色进行细胞凋亡测定进一步证实。为了评估肿瘤组织中HER 2的表达，进行免疫组织化学，并使用流式细胞术进行定量分析。还进行了毒理学评价。99 mTc-ZHER 2：V2-培美曲塞成像显示，在HER 2 + A549模型中，ZHER 2：V2-培美曲塞显示出比培美曲塞更好的抑制作用。与培美曲塞相比，ZHER 2：V2-培美曲塞对A549肿瘤细胞具有较高的抗肿瘤活性，可诱导肿瘤细胞坏死、凋亡和细胞周期阻滞。此外，ZHER 2：V2-培美曲塞给药组的毒性临床体征较培美曲塞给药组减少。这些数据表明，ZHER 2：V2-培美曲塞偶联物具有针对HER 2阳性肺腺癌的靶向抗肿瘤活性，且与培美曲塞相比副作用降低。因此，ZHER 2：V2-培美曲塞偶联物可作为一种新型分子药物，在HER 2阳性肺腺癌的诊断和治疗中具有巨大的临床突破潜力。
Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and cytotoxic safety of the conjugate ZHER2:V2-pemetrexed, a novel targeted chemotherapeutic drug. In this context, human epidermal growth factor receptor 2 (HER2) + A549 lung xenografts were treated using ZHER2:V2-pemetrexed, pemetrexed or physiological saline. Therapeutic efficacy was monitored by single photon emission computed tomography (SPECT) imaging using the99mTc-labeled ZHER2:V2-pemetrexed conjugate and further confirmed by performing apoptosis assays using flow cytometry analysis and hematoxylin-eosin (H&E) staining. To evaluate the expression of HER2 in tumor tissues, immunohistochemistry was performed, accompanied by quantitative analysis using flow cytometry. A toxicological evaluation was also conducted. Imaging with99mTc-ZHER2:V2-pemetrexed demonstrated that in HER2+ A549 models, ZHER2:V2-pemetrexed showed better antineoplastic effects than pemetrexed. Compared with pemetrexed, the results from the pathological and flow cytometry analyses also revealed that ZHER2:V2-pemetrexed exhibits high antitumor activity against A549 tumors, inducing necrosis, apoptosis and cell cycle arrest. In addition, the clinical signs of toxicity in the ZHER2:V2-pemetrexed treated group were reduced compared with those in the pemetrexed treated group. These data revealed that the ZHER2:V2-pemetrexed conjugate encompasses promising targeted antitumor activity against HER2-positive lung adenocarcinoma, with reduced side effects compared with pemetrexed. Thus, the ZHER2:V2-pemetrexed conjugate may serve as a novel molecular agent with tremendous clinical breakthrough potential in the diagnosis and treatment of HER2-positive lung adenocarcinoma.
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DOI：
10.1016/j.jtho.2017.11.113
发表时间：
2018-04
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
A. Costantini;J. Cadranel
通讯作者：
A. Costantini;J. Cadranel
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
45.3
作者：
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通讯作者：
Gandara, David
DOI：
10.1007/s00432-019-02941-z
发表时间：
2019-07-01
影响因子：
3.6
作者：
Park, Ji Hyun;Kwon, Byoung Soo;Lee, Jae Cheol
通讯作者：
Lee, Jae Cheol
DOI：
10.1186/s13046-019-1133-z
发表时间：
2019-04-05
影响因子：
11.3
作者：
Liu, Tianze;Jin, Lizi;Chen, Hongtao
通讯作者：
Chen, Hongtao