title: Hemoglobin-based oxygen carrier mitigates transfusion-mediated pancreas cancer progression.
abstract: BACKGROUND
  Perioperative blood transfusion in pancreatic cancer patients is linked to decreased survival; however, a causal mechanism has not been determined. Previously we have shown that the plasma fraction of stored packed red blood cells (pRBCs) promotes pancreas cancer progression and associated morbidity. We hypothesize these untoward effects will be mitigated by use of a hemoglobin-based oxygen carrier (HBOC).
  
  
  METHODS
  Cytokines and growth factors were measured in the plasma fraction from stored pRBCs and in an HBOC via cytokine array followed by formal enzyme-linked immunosorbent assay (ELISA). In an immunocompetent murine model, pancreas cancer progression was determined in vivo by bioluminescence, tumor weight, and number of metastases.
  
  
  RESULTS
  Elevated levels of epidermal growth factor (EGF), platelet-derived growth factor BB (PDGF-BB), and regulated upon activation, normal T cell expressed and secreted (RANTES) were present in the plasma fraction of stored pRBCs, but were not found in the HBOC. Intravenous delivery of plasma fraction to mice with pancreatic cancer resulted in increased bioluminescence activity compared with mice that received HBOC. Metastatic events and pancreatic primary tumor weights were significantly higher in animals receiving plasma fraction from stored pRBCs compared with animals receiving HBOC.
  
  
  CONCLUSIONS
  Intravenous receipt of the acellular plasma fraction of stored pRBCs promotes pancreatic cancer progression in an immunocompetent mouse model. These untoward events are mitigated by use of an HBOC.
authors: Department of Surgery, Denver Health Medical Center, University of Colorado Denver, Denver, CO, USA.
authors: Karen K
authors: KK
authors: Lo
authors: Erik A
authors: EA
authors: Bey
authors: Biswantha
authors: B
authors: Patra
authors: Douglas D
authors: DD
authors: Benson
authors: David A
authors: DA
authors: Boothman
authors: Christopher C
authors: CC
authors: Silliman
authors: Carlton C
authors: CC
authors: Barnett
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000077214:Becaplermin; D001802:Blood Substitutes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018946:Chemokine CCL5 / Q000032:analysis; D016207:Cytokines / Q000032:analysis / Q000494:pharmacology*; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000032:analysis; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000601:surgery*; D010949:Plasma / Q000737:chemistry*; D040081:Protein Array Analysis; D020574:Proto-Oncogene Proteins c-sis / Q000032:analysis
chemical_list: D001802:Blood Substitutes; D018946:Chemokine CCL5; D016207:Cytokines; D006454:Hemoglobins; C509893:PolyHeme; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D004815:Epidermal Growth Factor