title: Cellular and plasma uptake of parenteral omega-3 rich lipid emulsion fatty acids in patients with advanced pancreatic cancer.
abstract: OBJECTIVE
  Omega-3 rich fatty acids (n-3FA) have powerful anti-inflammatory and anti-neoplastic properties. Previous studies have investigated plasma and cellular uptake of oral and parenteral n-3FA regimens. These have shown that n-3FA undergo rapid uptake into cells which is sustained for the length of the treatment course. The aim of this study was to investigate long-term uptake of prolonged, regular treatment courses of parenteral n-3FA which has not been previously reported.
  
  
  METHODS
  As part of a phase II single-arm trial, patients with advanced pancreatic cancer were treated with gemcitabine plus parenteral n-3FA rich lipid emulsion (up to 100 g) each week for three consecutive weeks with a subsequent rest week. This was repeated for up to six months in total for each patient. Pre-treatment serum and erythrocyte cell membrane (ECM) pellet samples were obtained each week for the entire treatment course of each patient. Post-treatment samples were obtained for the first two cycles only to assess rapid uptake. Fatty acid methyl esters (FAME) were produced and analysed using gas chromatography. FAME proportions as a total of sample lipid composition for each class were plotted and the results analysed using a linear regression coefficient model.
  
  
  RESULTS
  There was rapid and significant uptake of EPA and DHA FAME into plasma Non-Esterified Fatty Acids (NEFA) and EPA into ECM pellets in post-treatment samples (median increase of 1.06%, 0.65% and 0.05% respectively). There was significant reduction in n-6 fatty acid FAMEs and DHA in ECM pellets (decrease of 0.31% and 0.8% respectively- p = 0.031 for all). There was significant sustained uptake of EPA and DHA FAME into ECM pellets over the cohort's pooled treatment course with corresponding reduction in the n-6:n-3 ratio.
  
  
  CONCLUSIONS
  Prolonged regular parenteral n-3FA administration results in rapid and sustained cellular uptake. This regimen is appropriate for therapies aimed at increasing n-3FA content of cellular membranes and reduction of the n-6:n-3 ratio.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. Electronic address: ali.arshad@doctors.org.uk.
authors.forename: A
authors.initials: A
authors.lastname: Arshad
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
authors.forename: W Y
authors.initials: WY
authors.lastname: Chung
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
authors.forename: J
authors.initials: J
authors.lastname: Isherwood
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Mann
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
authors.forename: D
authors.initials: D
authors.lastname: Al-Leswas
authors.affiliation: Department of Medical Oncology, University Hospitals of Leicester, Leicester, UK.
authors.forename: W P
authors.initials: WP
authors.lastname: Steward
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Metcalfe
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Dennison
mesh_terms: D000284:Administration, Oral; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004655:Emulsions; D006801:Humans; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D004655:Emulsions; D003841:Deoxycytidine; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D000093542:Gemcitabine
keywords: Cancer; Parenteral; Uptake; n-3FA