کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10914753 | 1088810 | 2014 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Establishment of a human 3D lung cancer model based on a biological tissue matrix combined with a Boolean in silico model
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
3D Tumor ModelTGFβ1TKIMUC1EGFRThree-dimensionalTem - این استTransforming growth factor-β1 - تبدیل فاکتور رشد β1Invasion - تهاجمEMT - تکنسین فوریتهای پزشکیTargeted therapy - درمان هدفمندtwo-dimensional - دو بعدیProliferation index - شاخص تکثیرBoolean model - مدل بولینSEM - مدل معادلات ساختاری / میکروسکوپ الکترونی روبشیTyrosine kinase inhibitor - مهار کننده تیروزین کینازmucin-1 - موین-1Scanning electron microscopy - میکروسکوپ الکترونی روبشیTransmission electron microscopy - میکروسکوپ الکترونی عبوریPersonalized medicine - پزشکی شخصیEpithelial–mesenchymal transition - گذار اپیتلیال-مزانشیمیEpidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Establishment of a human 3D lung cancer model based on a biological tissue matrix combined with a Boolean in silico model Establishment of a human 3D lung cancer model based on a biological tissue matrix combined with a Boolean in silico model](/preview/png/10914753.png)
چکیده انگلیسی
For the development of new treatment strategies against cancer, understanding signaling networks and their changes upon drug response is a promising approach to identify new drug targets and biomarker profiles. Pre-requisites are tumor models with multiple read-out options that accurately reflect the clinical situation. Tissue engineering technologies offer the integration of components of the tumor microenvironment which are known to impair drug response of cancer cells. We established three-dimensional (3D) lung carcinoma models on a decellularized tissue matrix, providing a complex microenvironment for cell growth. For model generation, we used two cell lines with (HCC827) or without (A549) an activating mutation of the epidermal growth factor receptor (EGFR), exhibiting different sensitivities to the EGFR inhibitor gefitinib. EGFR activation in HCC827 was inhibited by gefitinib, resulting in a significant reduction of proliferation (Ki-67 proliferation index) and in the induction of apoptosis (TUNEL staining, M30-ELISA). No significant effect was observed in conventional cell culture. Results from the 3D model correlated with the results of an in silico model that integrates the EGFR signaling network according to clinical data. The application of TGFβ1 induced tumor cell invasion, accompanied by epithelial-mesenchymal transition (EMT) both in vitro and in silico. This was confirmed in the 3D model by acquisition of mesenchymal cell morphology and modified expression of fibronectin, E-cadherin, β-catenin and mucin-1. Quantitative read-outs for proliferation, apoptosis and invasion were established in the complex 3D tumor model. The combined in vitro and in silico model represents a powerful tool for systems analysis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Oncology - Volume 8, Issue 2, March 2014, Pages 351-365
Journal: Molecular Oncology - Volume 8, Issue 2, March 2014, Pages 351-365
نویسندگان
Anna T. Stratmann, David Fecher, Gaby Wangorsch, Claudia Göttlich, Thorsten Walles, Heike Walles, Thomas Dandekar, Gudrun Dandekar, Sarah L. Nietzer,