Department of Surgery, Denver Health Medical Center, University of Colorado Denver, Denver, CO, USA.
Ann Surg Oncol. 2013 Jun;20(6):2073-7. doi: 10.1245/s10434-012-2842-0. Epub 2013 Jan 18.
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).
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.
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.
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.
在胰腺癌患者中，围手术期输血与生存率降低有关；然而，尚未确定因果机制。我们之前已经表明，储存的浓缩红细胞（pRBC）的血浆部分促进胰腺癌进展和相关发病率。我们假设这些不良影响将通过使用血红蛋白基氧载体（HBOC）得到缓解。
通过细胞因子阵列，然后通过正式的酶联免疫吸附试验（ELISA），测量储存的 pRBC 和 HBOC 的血浆部分中的细胞因子和生长因子。在免疫功能正常的小鼠模型中，通过生物发光、肿瘤重量和转移瘤数量来确定体内胰腺癌的进展。
在储存的 pRBC 的血浆部分中存在高水平的表皮生长因子（EGF）、血小板衍生生长因子 BB（PDGF-BB）和激活后正常 T 细胞表达和分泌的调节因子（RANTES），但在 HBOC 中未发现。与接受 HBOC 的小鼠相比，将血浆部分静脉内给予患有胰腺癌的小鼠可导致生物发光活性增加。与接受 HBOC 的动物相比，接受储存的 pRBC 的血浆部分的动物的转移事件和胰腺原发性肿瘤重量明显更高。
静脉内接收储存的浓缩红细胞的无细胞血浆部分可促进免疫功能正常的小鼠模型中的胰腺癌进展。这些不良事件通过使用 HBOC 得到缓解。
