دورية أكاديمية
Systemic effects of angiogenesis inhibition alter pharmacokinetics and intratumoral delivery of nab-paclitaxel
| العنوان: | Systemic effects of angiogenesis inhibition alter pharmacokinetics and intratumoral delivery of nab-paclitaxel |
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| المؤلفون: | Anne Steins, Eva A. Ebbing, Marcel C. M. Pistorius, Cynthia Waasdorp, Kausilia K. Krishnadath, Jan Paul Medema, Johanna W. Wilmink, Ron A. A. Mathôt, Maarten F. Bijlsma, Hanneke W. M. van Laarhoven |
| المصدر: | Drug Delivery, Vol 24, Iss 1, Pp 1801-1810 (2017) |
| بيانات النشر: | Taylor & Francis Group, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | angiogenesis, anti-angiogenic therapy, esophagogastric adenocarcinoma, nab-paclitaxel, pharmacokinetics, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | Angiogenesis is critical to the growth of tumors. Vascularization-targeting agents, with or without cytotoxic drugs, are widely used for the treatment of several solid tumors including esophagogastric adenocarcinoma. However, little is known about the systemic effects of anti-angiogenic therapies and how this affects the pharmacokinetics and intratumoral delivery of cytotoxic agents. In this study, patient-derived xenograft mouse models of esophageal adenocarcinoma were used to identify the effects of DC101, a murine vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor, on the pharmacokinetics and the intratumoral uptake of nab-paclitaxel (NPTX). We showed that DC101 had large systemic effects resulting in decreased vasculature of intraperitoneally located organs. As a consequence, after intraperitoneal administration of NPTX, plasma uptake (5.029 ± 4.35 vs. 25.85 ± 2.27 µM) and intratumoral delivery (5.48 ± 5.32 vs. 38.49 ± 2.805 pmol/mg) of NPTX were greatly impaired in DC101-treated animals compared to control animals. Additionally, routes of NPTX elimination were altered upon angiogenesis inhibition; unchanged renal clearance and intraperitoneal accumulation of NPTX were observed, but NPTX levels were significantly lower in the liver. Histological examination of the intestine revealed a reduced thickness of the intestinal wall following DC101 therapy and suggested seepage of intraperitoneally injected NTPX through the intestinal wall to explain its reduced uptake in liver, plasma, and tumor tissue. These data explain several adverse effects observed in the clinic when using anti-angiogenic therapies and also imply that the combined use of anti-angiogenesis and cytotoxic agents in both preclinical and clinical setting is still suboptimal. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1071-7544 1521-0464 10717544 97794996 |
| العلاقة: | https://doaj.org/toc/1071-7544Test; https://doaj.org/toc/1521-0464Test |
| DOI: | 10.1080/10717544.2017.1406559 |
| الوصول الحر: | https://doaj.org/article/9f977949965842869376a58d9500847dTest |
| رقم الانضمام: | edsdoj.9f977949965842869376a58d9500847d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10717544 15210464 97794996 |
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| DOI: | 10.1080/10717544.2017.1406559 |