使用动态对比增强和扩散加权磁共振成像对HCC827肺癌对贝伐单抗和厄洛替尼靶向治疗的疗效进行功能评估。
Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI.
作者信息
Chen Yi-Fang, Yuan Ang, Cho Kuan-Hung, Lu Yi-Chien, Kuo Mark Yen-Ping, Chen Jyh-Horng, Chang Yeun-Chung
机构信息
Graduate Institute of Clinical Dentistry, National Taiwan University, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
出版信息
PLoS One. 2017 Nov 9;12(11):e0187824. doi: 10.1371/journal.pone.0187824. eCollection 2017.
This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive) and HCC827R (gefitinib resistant) to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agent bevacizumab using dynamic contrast enhanced (DCE) and diffusion-weighted MRI. In the HCC827 model, temporal changes in DCE-MRI derived parameters (Ktrans, kep, and iAUC90) and apparent diffusion coefficient (ADC) were significantly correlated with tumor size. Ktrans and iAUC90 significantly decreased at week 2 in the groups receiving erlotinib alone and in combination with bevacizumab, whereas kep decreased at week 1 and 2 in both treatment groups. In addition, there was a significant difference in iAUC90 between the treatment groups at week 1. Compared to the control group of HCC827, there was a significant reduction in microvessel density and increased tumor apoptosis in the two treatment group. ADC value increased in the erlotinib alone group at week 1 and week 2, and in the erlotinib combined with bevacizumab group at week 2. Enlarged areas of central tumor necrosis were associated with a higher ADC value. However, progressive enlargement of the tumors but no significant differences in DCE parameters or ADC were noted in the HCC827R model. These results showed that both erlotinib alone and in combination with bevacizumab could effectively inhibit tumor growth in the gefitinib-sensitive lung cancer mice model, and that this was associated with decreased vascular perfusion, increased ADC percentage, decreased microvessel density, and increased tumor apoptosis with a two-week treatment cycle.
本研究旨在使用动态对比增强(DCE)和扩散加权磁共振成像(MRI),研究携带腺癌HCC827(吉非替尼敏感)和HCC827R(吉非替尼耐药)的肺癌小鼠模型对表皮生长因子受体-酪氨酸激酶抑制剂厄洛替尼单独使用以及与抗血管生成剂贝伐单抗联合使用的治疗反应。在HCC827模型中,DCE-MRI衍生参数(Ktrans、kep和iAUC90)和表观扩散系数(ADC)的时间变化与肿瘤大小显著相关。单独接受厄洛替尼治疗以及与贝伐单抗联合治疗的组中,Ktrans和iAUC90在第2周时显著降低,而两个治疗组中的kep在第1周和第2周时均降低。此外,在第1周时,各治疗组之间的iAUC90存在显著差异。与HCC827对照组相比,两个治疗组的微血管密度显著降低,肿瘤凋亡增加。单独使用厄洛替尼的组在第1周和第2周时ADC值增加,厄洛替尼与贝伐单抗联合使用的组在第2周时ADC值增加。肿瘤中央坏死区域扩大与较高的ADC值相关。然而,在HCC827R模型中,肿瘤逐渐增大,但DCE参数或ADC无显著差异。这些结果表明,厄洛替尼单独使用以及与贝伐单抗联合使用均可有效抑制吉非替尼敏感的肺癌小鼠模型中的肿瘤生长,且这与血管灌注减少、ADC百分比增加、微血管密度降低以及肿瘤凋亡增加相关,治疗周期为两周。
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