SPARC independent delivery of nab-paclitaxel without depleting tumor stroma in patient-derived pancreatic cancer xenografts

التفاصيل البيبلوغرافية
العنوان: SPARC independent delivery of nab-paclitaxel without depleting tumor stroma in patient-derived pancreatic cancer xenografts
المؤلفون: Harrison Kim, Pedro P. López-Casas, Kurt R. Zinn, Joy L. Kovar, Sharon Samuel, Donald J. Buchsbaum, William E. Grizzle, Denise K. Oelschlager, Manuel Hidalgo, Jason M. Warram
سنة النشر: 2016
مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Stromal cell, Paclitaxel, Deoxycytidine, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Pancreatic tumor, Pancreatic cancer, Albumins, medicine, Animals, Humans, Trichrome stain, Osteonectin, biology, business.industry, Microcirculation, Cancer, Drug Synergism, medicine.disease, Antineoplastic Agents, Phytogenic, Xenograft Model Antitumor Assays, Gemcitabine, Tumor Burden, Pancreatic Neoplasms, Disease Models, Animal, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Immunology, Cancer research, biology.protein, Female, Stromal Cells, business, Perfusion, medicine.drug
الوصف: The study goal was to examine the relationship between nab-paclitaxel delivery and SPARC (secreted protein acidic and rich in cysteine) expression in pancreatic tumor xenografts and to determine the antistromal effect of nab-paclitaxel, which may affect tumor vascular perfusion. SPARC-positive and -negative mice bearing Panc02 tumor xenografts (n = 5–6/group) were injected with IRDye 800CW (IR800)-labeled nab-paclitaxel. After 24 hours, tumors were collected and stained with DL650-labeled anti-SPARC antibody, and the correlation between nab-paclitaxel and SPARC distributions was examined. Eight groups of mice bearing either Panc039 or Panc198 patient-derived xenografts (PDX; 4 groups/model, 5 animals/group) were untreated (served as control) or treated with gemcitabine (100 mg/kg body weight, i.p., twice per week), nab-paclitaxel (30 mg/kg body weight, i.v., for 5 consecutive days), and these agents in combination, respectively, for 3 weeks, and tumor volume and perfusion changes were assessed using T2-weighted MRI and dynamic contrast-enhanced (DCE) MRI, respectively. All tumors were collected and stained with Masson's Trichrome Stain, followed by a blinded comparative analysis of tumor stroma density. IR800-nab-paclitaxel was mainly distributed in tumor stromal tissue, but nab-paclitaxel and SPARC distributions were minimally correlated in either SPARC-positive or -negative animals. Nab-paclitaxel treatment neither decreased tumor stroma nor increased tumor vascular perfusion in either PDX model when compared with control groups. These data suggest that the specific tumor delivery of nab-paclitaxel is not directly related to SPARC expression, and nab-paclitaxel does not deplete tumor stroma in general. Mol Cancer Ther; 15(4); 680–8. ©2016 AACR.
اللغة: English
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53391946e52a182488d8b9fa0a8d45ef
https://europepmc.org/articles/PMC4873363/
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....53391946e52a182488d8b9fa0a8d45ef
قاعدة البيانات: OpenAIRE