چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده ثبت کننده مقاله | نصرت اله ضرغامی |
| مرحله جاری مقاله | تایید نهایی |
| دانشکده/مرکز مربوطه | دانشکده علوم نوین پزشکی |
| کد مقاله | 61766 |
| عنوان فارسی مقاله | RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice |
| عنوان لاتین مقاله | RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice |
| ناشر | 12 |
| آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ | خیر |
| عنوان نشریه (خارج از لیست فوق) | |
| نوع مقاله | Original Article |
| نحوه ایندکس شدن مقاله | ایندکس شده سطح یک – ISI - Web of Science |
| آدرس لینک مقاله/ همایش در شبکه اینترنت | https://www.nature.com/articles/s41598-017-05326-9.pdf |
| Induction of thrombosis in tumor vasculature represents an appealing strategy for combating 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 RGD motif on its C-terminus for cancer therapy. We demonstrated that free coagulase failed to elicit any signifcant thrombotic activity. Conversely, RGD delivery of coagulase retained coagulase activity and aforded favorable interaction of fusion proteins with prothrombin and αvβ3 endothelial cell receptors, as verifed by in silico, in vitro, and in vivo experiments. Although free coagulase elicited robust coagulase activity in vitro, only targeted coagulase (tCoa-RGD) was capable of producing extensive thrombosis, and subsequent infarction and massive necrosis of CT26 mouse colon, 4T1 mouse mammary and SKOV3 human ovarian tumors in mice. Additionally, systemic injections of lower doses of tCoa-RGD produced striking tumor growth inhibition of CT26, 4T1 and SKOV3 solid tumors in animals. Altogether, the nontoxic nature, unique shortcut mechanism, minimal efective dose, wide therapeutic window, efcient induction of thrombosis, local efects and susceptibility of human blood to coagulase suggest tCoa-RGD fusion proteins as a novel and promising anticancer therapy for human trials. |
| نویسنده | نفر چندم مقاله |
|---|---|
| نصرت اله ضرغامی | دوازدهم |
| صفر فرج نیا | هشتم |
| رعنا جهانبان اسفهلان | اول |
| خالد صیدی | دوم |
| مهران مسگری عباسی | دهم |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice.pdf | 1396/08/21 | 3754379 | دانلود |
