title: SPARC-Independent Delivery of Nab-Paclitaxel without Depleting Tumor Stroma in Patient-Derived Pancreatic Cancer Xenografts.
abstract: 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.
authors.affiliation: Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama. hyunkikim@uabmc.edu djb@uab.edu.
authors.forename: Harrison
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Sharon
authors.initials: S
authors.lastname: Samuel
authors.affiliation: Gastrointestinal Cancer Clinical Research Unit, Clinical Research Program, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Lopez-Casas
authors.affiliation: Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama. Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: William
authors.initials: W
authors.lastname: Grizzle
authors.affiliation: Gastrointestinal Cancer Clinical Research Unit, Clinical Research Program, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.affiliation: LI-COR Biosciences, Lincoln, Nebraska.
authors.forename: Joy
authors.initials: J
authors.lastname: Kovar
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Denise
authors.initials: D
authors.lastname: Oelschlager
authors.affiliation: Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Kurt
authors.initials: K
authors.lastname: Zinn
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Jason
authors.initials: J
authors.lastname: Warram
authors.affiliation: Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama. Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama. hyunkikim@uabmc.edu djb@uab.edu.
authors.forename: Donald
authors.initials: D
authors.lastname: Buchsbaum
mesh_terms: D000418:Albumins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D015676:Osteonectin / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D015676:Osteonectin; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine
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