دورية أكاديمية

SPARC independent drug delivery and antitumour effects of nab-paclitaxel in genetically engineered mice.

التفاصيل البيبلوغرافية
العنوان: SPARC independent drug delivery and antitumour effects of nab-paclitaxel in genetically engineered mice.
المؤلفون: Neesse, Albrecht, Frese, Kristopher K, Chan, Derek S, Bapiro, Tashinga E, Howat, William J, Richards, Frances M, Ellenrieder, Volker, Jodrell, Duncan I, Tuveson, David A
بيانات النشر: BMJ
//dx.doi.org/10.1136/gutjnl-2013-305559
Gut
سنة النشر: 2014
المجموعة: Apollo - University of Cambridge Repository
مصطلحات موضوعية: Pancreatic Cancer, Adenocarcinoma, Albumin-Bound Paclitaxel, Albumins, Animals, Genetically Modified, Antineoplastic Agents, Phytogenic, Collagen, Dose-Response Relationship, Drug, Mice, Osteonectin, Paclitaxel, Pancreatic Neoplasms, Pharmaceutical Vehicles, Polyethylene Glycols, Xenograft Model Antitumor Assays
الوصف: DESIGN: Pharmacokinetic and pharmacodynamic parameters of cremophor-paclitaxel, nab-paclitaxel (human-albumin-bound paclitaxel, Abraxane) and a novel mouse-albumin-bound paclitaxel (m-nab-paclitaxel) were evaluated in genetically engineered mouse models (GEMMs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS), histological and biochemical analysis. Preclinical evaluation of m-nab-paclitaxel included assessment by three-dimensional high-resolution ultrasound and molecular analysis in a novel secreted protein acidic and rich in cysteine (SPARC)-deficient GEMM of pancreatic ductal adenocarcinoma (PDA). RESULTS: nab-Paclitaxel exerted its antitumoural effects in a dose-dependent manner and was associated with less toxicity compared with cremophor-paclitaxel. SPARC nullizygosity in a GEMM of PDA, Kras(G12D);p53(flox/-);p48Cre (KPfC), resulted in desmoplastic ductal pancreas tumours with impaired collagen maturation. Paclitaxel concentrations were significantly decreased in SPARC null plasma samples and tissues when administered as low-dose m-nab-paclitaxel. At the maximally tolerated dose, SPARC deficiency did not affect the intratumoural paclitaxel concentration, stromal deposition and the immediate therapeutic response. CONCLUSIONS: nab-Paclitaxel accumulates and acts in a dose-dependent manner. The interaction of plasma SPARC and albumin-bound drugs is observed at low doses of nab-paclitaxel but is saturated at therapeutic doses in murine tumours. Thus, this study provides important information for future preclinical and clinical trials in PDA using nab-paclitaxel in combination with novel experimental and targeted agents.
نوع الوثيقة: article in journal/newspaper
وصف الملف: Print-Electronic; application/pdf
اللغة: English
العلاقة: https://www.repository.cam.ac.uk/handle/1810/302077Test
DOI: 10.17863/CAM.49152
الإتاحة: https://doi.org/10.17863/CAM.49152Test
https://www.repository.cam.ac.uk/handle/1810/302077Test
حقوق: Attribution-NonCommercial 4.0 International ; https://creativecommons.org/licenses/by-nc/4.0Test/
رقم الانضمام: edsbas.A0157286
قاعدة البيانات: BASE