چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده ثبت کننده مقاله | رعنا جهانبان اسفهلان |
| مرحله جاری مقاله | تایید نهایی |
| دانشکده/مرکز مربوطه | دانشکده علوم نوین پزشکی |
| کد مقاله | 64502 |
| عنوان فارسی مقاله | NGR-DIRECTED DELIVERY OF COAGULASE TO TUMOR VASCULATURE INDUCE INFARCTION OF TUMORS IN MICE |
| عنوان لاتین مقاله | NGR-DIRECTED DELIVERY OF COAGULASE TO TUMOR VASCULATURE INDUCE INFARCTION OF TUMORS IN MICE |
| نوع ارائه | سخنرانی |
| عنوان کنگره / همایش | (International Conference of Current Cancer Medicine (I4CM |
| نوع کنگره / همایش | بین المللی |
| کشور محل برگزاری کنگره/ همایش | Poland |
| شهر محل برگزاری کنگره/ همایش | warsaw |
| سال انتشار/ ارائه شمسی | 1397 |
| سال انتشار/ارائه میلادی | 2017 |
| تاریخ شمسی شروع و خاتمه کنگره/همایش | 1396/06/16 الی 1396/06/16 |
| آدرس لینک مقاله/ همایش در شبکه اینترنت | http://i4cm.net/ngr-directed-delivery-of-coagulase-to-tumor-vasculature-induce-infarction-of-tumors-in-mice/ |
| آدرس علمی (Affiliation) نویسنده متقاضی | Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran |
| نویسنده | نفر چندم مقاله |
|---|---|
| نصرت اله ضرغامی | پنجم |
| رعنا جهانبان اسفهلان | دوم |
| خالد صیدی | اول |
| عنوان | متن |
|---|---|
| خلاصه مقاله | ABSTRACT REGISTRATION VENUE SPONSORSHIPGUIDELINES CONTACTS JUNE 2, 2017 NGR-DIRECTED DELIVERY OF COAGULASE TO TUMOR VASCULATURE INDUCE INFARCTION OF TUMORS IN MICE No Comments in Article By Khaled Seidi Purpose: Induction of selective thrombosis and infarction in tumor-feeding vessels represents an attractive strategy to combat cancer. Herein, we combined unique intrinsic coagulation properties of staphylocoagulase with new acquired functional potentials introduced by genetic engineering, to generate a novel bi-functional fusion protein consisting of truncated coagulase (tCoa) bearing an NGR motif for cancer therapy. Materials and methods: Full Coagulase gene (AN: KX914667.1) was isolated from S. aureus (ATCC: 29213). Using specific primers, gene constructs encoding tCoa and tCoa-NGR were constructed and cloned into pet28 vector, and expressed in Ecoli BL21 (DE3). Recombinant proteins were purified by Ni-NTA and FPLC chromatography and identified by western blotting. Dual binding capacity of tCoa-RGD with prethrombin, and αvβ3 receptors were assessed by molecular modeling, docking and dynamics simulation. Binding potential to αvβ3 integrins was verified by ELISA, FACS, and whole body animal imaging using FITC-tagged fusion proteins. Mice bearing 4T1, CT26 and SKOV3 xenografts were established to evaluate thrombogenic activity and tumor growth inhibition potential of the novel fusion proteins. Results: We demonstrated that coupling of NGR sequence to the C-terminus of truncated coagulase (tCoa) retained its proper binding with prothrombin and avβ3 integrins, as verified in silico (molecular modeling (MD), docking, and simulation), and in vitro (clotting test, enzyme activity, ELISA, and FACS). Accordingly, biodistribution studies demonstrated selective accumulation of FITC labeled tCoa-NGR fusion protein at the subcutaneously implanted PC3 tumor xenografts in C57BL/6 nude mice. In vivo studies in mice bearing 4T1 mouse mammary tumors and PC3 human prostate xenografts, revealed that systemic administration of tCoa-NGR resulted in striking tumor growth inhibition of both 4T1 and PC3 solid tumors. Significant tumor shrinkage was accompanied by massive thrombotic occlusion of small and large tumor vessels, tumor infarction and subsequent necrosis of cancer cells, as verified by H&E and Masson’s trichrome staining of histological sections. Conclusion: In conclusion, we consider NGR-directed delivery of tCoa to tumor neovasculature as a novel, and promising anti-cancer strategy |
| کلمات کلیدی | tCoa-NGR; coagulase; tumor vascular infarction; 4T1 mammary cancer; PC3 prostate carcinoma; tumor regression |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| (38) Oncogene.pdf | 1397/08/11 | 9175584 | دانلود |
| img117.pdf | 1397/08/11 | 804341 | دانلود |
