Skip to main content
Top
Published in: Annals of Surgical Oncology 6/2013

01-06-2013 | Pancreatic Tumors

Hemoglobin-Based Oxygen Carrier Mitigates Transfusion-Mediated Pancreas Cancer Progression

Authors: Karen K. Lo, MD, Erik A. Bey, PhD, Biswantha Patra, PhD, Douglas D. Benson, MD, David A. Boothman, PhD, Christopher C. Silliman, PhD, Carlton C. Barnett Jr., MD

Published in: Annals of Surgical Oncology | Issue 6/2013

Login to get access

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.
Literature
1.
go back to reference American Red Cross Blood Facts and Statistics. 2006. American Red Cross Blood Facts and Statistics. 2006.
2.
go back to reference Opelz G, Teraski P. Improvement of kidney-graft survival with increased numbers of blood transfusions. N Engl J Med. 1978;299: 799–803.PubMedCrossRef Opelz G, Teraski P. Improvement of kidney-graft survival with increased numbers of blood transfusions. N Engl J Med. 1978;299: 799–803.PubMedCrossRef
4.
go back to reference Yeh JJ GM, Tomlinson JS, Idrees K, Brennan MF, Fong Y. Effect of blood transfusion on outcome after pancreaticoduodenectomy for exocrine tumour of the pancreas. Br J Surg. 2007;94: 466–472.PubMedCrossRef Yeh JJ GM, Tomlinson JS, Idrees K, Brennan MF, Fong Y. Effect of blood transfusion on outcome after pancreaticoduodenectomy for exocrine tumour of the pancreas. Br J Surg. 2007;94: 466–472.PubMedCrossRef
5.
go back to reference Park SJ KS, Jang JY, Lee KU, Park YH. Intraoperative transfusion: is it a real prognostic factor of periampullary cancer following pancreatoduodenectomy? World J Surg. 2002;26: 487–492.PubMedCrossRef Park SJ KS, Jang JY, Lee KU, Park YH. Intraoperative transfusion: is it a real prognostic factor of periampullary cancer following pancreatoduodenectomy? World J Surg. 2002;26: 487–492.PubMedCrossRef
6.
go back to reference Barnett CC, Jr., Beck AW, Holloway SE, et al. Intravenous delivery of the plasma fraction of stored packed erythrocytes promotes pancreatic cancer growth in immunocompetent mice. Cancer. 2010;116: 3862–3874.PubMedCrossRef Barnett CC, Jr., Beck AW, Holloway SE, et al. Intravenous delivery of the plasma fraction of stored packed erythrocytes promotes pancreatic cancer growth in immunocompetent mice. Cancer. 2010;116: 3862–3874.PubMedCrossRef
7.
go back to reference Yao HS, Wang Q, Wang WJ, Hu ZQ. Intraoperative allogeneic red blood cell transfusion in ampullary cancer outcome after curative pancreatoduodenectomy: a clinical study and meta-analysis. World J Surg. 2008;32: 2038–2046.PubMedCrossRef Yao HS, Wang Q, Wang WJ, Hu ZQ. Intraoperative allogeneic red blood cell transfusion in ampullary cancer outcome after curative pancreatoduodenectomy: a clinical study and meta-analysis. World J Surg. 2008;32: 2038–2046.PubMedCrossRef
8.
go back to reference Technical Manual. American association of blood banks, Bethesda. 2003. Technical Manual. American association of blood banks, Bethesda. 2003.
9.
go back to reference Silliman CC, Clay KL, Thurman GW et al. Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase. J Lab Clin Med. 1994;124: 684–694.PubMed Silliman CC, Clay KL, Thurman GW et al. Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase. J Lab Clin Med. 1994;124: 684–694.PubMed
10.
go back to reference Holloway S, Davis M, Jaber R, Fleming J. A clinically relevant model of human pancreatic adenocarcinoma identifies patterns of metastasis associated with alterations of the TGF-beta/Smad4 signaling pathway. Int J Gastrointest Cancer. 2003;33: 61–69.PubMedCrossRef Holloway S, Davis M, Jaber R, Fleming J. A clinically relevant model of human pancreatic adenocarcinoma identifies patterns of metastasis associated with alterations of the TGF-beta/Smad4 signaling pathway. Int J Gastrointest Cancer. 2003;33: 61–69.PubMedCrossRef
11.
go back to reference Contag CH, Bachmann MH. Advances in in vivo bioluminescence imaging of gene expression. Ann Rev Biomed Eng. 2002;4: 235–260.CrossRef Contag CH, Bachmann MH. Advances in in vivo bioluminescence imaging of gene expression. Ann Rev Biomed Eng. 2002;4: 235–260.CrossRef
12.
go back to reference Animal resources body weight study of 1993. In: The Jackson Labs 1993. Animal resources body weight study of 1993. In: The Jackson Labs 1993.
13.
go back to reference Morikawa K, Walker SM, Jessup JM, Fidler IJ. In vivo selection of highly metastatic cells from surgical specimens of different primary human colon carcinomas implanted into nude mice. Cancer Res. 1988;48: 1943–1948.PubMed Morikawa K, Walker SM, Jessup JM, Fidler IJ. In vivo selection of highly metastatic cells from surgical specimens of different primary human colon carcinomas implanted into nude mice. Cancer Res. 1988;48: 1943–1948.PubMed
14.
go back to reference Silliman CC, Clay KL, Thurman GW, et al. Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase. J Lab Clin Med. 1994;124: 684–694.PubMed Silliman CC, Clay KL, Thurman GW, et al. Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase. J Lab Clin Med. 1994;124: 684–694.PubMed
15.
go back to reference Partrick DA, Moore FA, Moore EE, et al. Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure. New Horizons. 1996;4: 194–210.PubMed Partrick DA, Moore FA, Moore EE, et al. Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure. New Horizons. 1996;4: 194–210.PubMed
16.
go back to reference Johnson JL, Moore EE, Gonzalez RJ, et al. Alteration of the postinjury hyperinflammatory response by means of resuscitation with a red cell substitute. J Trauma. 2003;54: 133–139; discussion 139–140.PubMedCrossRef Johnson JL, Moore EE, Gonzalez RJ, et al. Alteration of the postinjury hyperinflammatory response by means of resuscitation with a red cell substitute. J Trauma. 2003;54: 133–139; discussion 139–140.PubMedCrossRef
17.
go back to reference Johnson JL, Moore EE, Offner PJ, et al. Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function. J Trauma. 2001;50: 449–455; discussion 456. Johnson JL, Moore EE, Offner PJ, et al. Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function. J Trauma. 2001;50: 449–455; discussion 456.
18.
go back to reference Silliman C, Kelher M, Masuno T, Moore EE, Damle S, Cheng A. A two-event in vivo model of transfusion-related acute lung injury. Blood. 2006;108(suppl): 10a. Silliman C, Kelher M, Masuno T, Moore EE, Damle S, Cheng A. A two-event in vivo model of transfusion-related acute lung injury. Blood. 2006;108(suppl): 10a.
19.
go back to reference Silliman CC, Bjornsen AJ, Wyman TH, et al. Plasma and lipids from stored platelets cause acute lung injury in an animal model. Transfusion 2003;43: 633–640.PubMedCrossRef Silliman CC, Bjornsen AJ, Wyman TH, et al. Plasma and lipids from stored platelets cause acute lung injury in an animal model. Transfusion 2003;43: 633–640.PubMedCrossRef
20.
go back to reference Silliman CC, Voelkel NF, Allard JD, et al. Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model. J Clin Invest. 1998;101: 1458–1467.PubMedCrossRef Silliman CC, Voelkel NF, Allard JD, et al. Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model. J Clin Invest. 1998;101: 1458–1467.PubMedCrossRef
Metadata
Title
Hemoglobin-Based Oxygen Carrier Mitigates Transfusion-Mediated Pancreas Cancer Progression
Authors
Karen K. Lo, MD
Erik A. Bey, PhD
Biswantha Patra, PhD
Douglas D. Benson, MD
David A. Boothman, PhD
Christopher C. Silliman, PhD
Carlton C. Barnett Jr., MD
Publication date
01-06-2013
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 6/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2842-0

Other articles of this Issue 6/2013

Annals of Surgical Oncology 6/2013 Go to the issue