Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date.
Adrenal Cortex Hormones ; Biomarkers, Tumor ; CA-19-9 Antigen ; Chemotherapy, Adjuvant ; Humans ; Inflammation* ; Pancreatic Neoplasms* ; Radiodermatitis

BACKGROUNDThe extracellular release of the danger signal high mobility group box-1 (HMGB1) has been implicated in the pathogenesis and outcomes of sepsis. Understanding the mechanisms responsible for HMGB1 release can lead to the identification of targets that may inhibit this process. The transcription factor interferon regulatory factor-1 (IRF-1) is an important mediator of innate immune responses and has been shown to participate in mortality associated with endotoxemia; however, its role in mediating the release of HMGB1 in these settings is unknown.

METHODSMale IRF-1 knockout (KO) and age matched C57BL/6 wild type (WT) mice were given intraperitoneal (IP) injections of lipopolysaccharide (LPS). In some experiments, 96 hours survival rates were observed. In other experiments, mice were sacrificed 12 hours after LPS administration and sera were harvested for future analysis. In in vitro study, RAW 264.7 murine monocyte/macrophage-like cells or primary peritoneal macrophage obtained from IRF-1 KO and WT mice were cultured for LPS mediated HMGB1 release analysis. And the mechanism for HMGB1 release was analyzed by immune-precipitation.

RESULTSIRF-1 KO mice experienced less mortality, and released less systemic HMGB1 compared to their WT counterparts. Exogenous administration of recombinant HMGB1 to IRF-1 KO mice returned the mortality rate to that seen originally in IRF-1 WT mice. Using cultures of peritoneal macrophages or RAW264.7 cells, in vitro LPS stimulation induced the release of HMGB1 in an IRF-1 dependent manner. And the janus associated kinase (JAK)-IRF-1 signal pathway appeared to participate in the signaling mechanisms of LPS-induced HMGB1 release by mediating acetylation of HMGB1.

CONCLUSIONIRF-1 plays a role in LPS induced release of HMGB1 and therefore may serve as a novel target in sepsis.

Animals ; Cell Line ; Cells, Cultured ; Endotoxemia ; chemically induced ; metabolism ; HMGB1 Protein ; genetics ; metabolism ; Immunoprecipitation ; Interferon Regulatory Factor-1 ; genetics ; metabolism ; Lipopolysaccharides ; toxicity ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Reverse Transcriptase Polymerase Chain Reaction