title: Enhancement of Gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant.
abstract: BACKGROUND
  Current therapeutic options for advanced pancreatic cancer have been largely disappointing with modest results at best, and though adjuvant therapy remains controversial, most remain in agreement that Gemcitabine should stand as part of any combination study. The inhibitor of apoptosis (IAP) protein Survivin is a key factor in maintaining apoptosis resistance, and its dominant-negative mutant (Survivin-T34A) has been shown to block Survivin, inducing caspase activation and apoptosis.
  
  
  METHODS
  In this study, exosomes, collected from a melanoma cell line built to harbor a tetracycline-regulated Survivin-T34A, were plated on the pancreatic adenocarcinoma (MIA PaCa-2) cell line. Evaluation of the presence of Survivin-T34A in these exosomes followed by their ability to induce Gemcitabine-potentiative cell killing was the objective of this work.
  
  
  RESULTS
  Here we show that exosomes collected in the absence of tetracycline (tet-off) from the engineered melanoma cell do contain Survivin-T34A and when used alone or in combination with Gemcitabine, induced a significant increase in apoptotic cell death when compared to Gemcitabine alone on a variety of pancreatic cancer cell lines.
  
  
  CONCLUSIONS
  This exosomes/Survivin-T34A study shows that a new delivery method for anticancer proteins within the cancer microenvironment may prove useful in targeting cancers of the pancreas.
authors.affiliation: Division of Biochemistry & Microbiology, Department of Basic Sciences, Center for Health Disparities & Molecular Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Aspe
authors.affiliation: Division of Biochemistry & Microbiology, Department of Basic Sciences, Center for Health Disparities & Molecular Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Diaz Osterman
authors.affiliation: Division of Biochemistry & Microbiology, Department of Basic Sciences, Center for Health Disparities & Molecular Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Jessica M S
authors.initials: JM
authors.lastname: Jutzy
authors.affiliation: Division of Biochemistry & Microbiology, Department of Basic Sciences, Center for Health Disparities & Molecular Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Deshields
authors.affiliation: Division of Biochemistry & Microbiology, Department of Basic Sciences, Center for Health Disparities & Molecular Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Whang
authors.affiliation: Division of Biochemistry & Microbiology, Department of Basic Sciences, Center for Health Disparities & Molecular Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Wall
keywords: Gemcitabine; Survivin; Survivin-T34A; exosomes; pancreatic cancer