Tumor-associated macrophages (TAMs) are candidate histological factors in invasive ductal carcinoma (IDC) of the pancreas. Tumorassociated macrophages can be affected by cancer-related inflammation and pancreatitis and interact with important invasive behavior in a recurrent manner in pancreatic IDC. These features may help elucidate the aggressiveness of pancreatic IDC. The aim of this study was to characterize TAMs in pancreatic IDC in comparison with chronic pancreatitis (CP) and to reveal TAM-related factors and the clinical impact of TAMs. CD68 (a pan-macrophage marker) and CD204 (an M2 macrophage marker) immunohistochemistry was carried out in pancreas head specimens from 107 IDC cases and 11 CP cases. Immunopositive cell areas were calculated at the periphery and center of the tumor. The distributions of macrophages in IDC and CP and the relationship between TAMs and histological tumor factors, survival, and recurrence were evaluated. Macrophages were more frequently observed in the lesion periphery than the center in IDC and CP. The density of macrophages was elevated in IDC compared to CP. Dense M2 macrophages at the tumor periphery were frequently seen in large tumors and showed an independent impact on overall survival and disease-free time. Early recurrence in the liver or the local manipulated area was associated with high accumulation of peripheral M2 macrophages. More M2 macrophages were seen in IDC than in CP in both the periphery and the center. High numbers of peripheral M2 macrophages were associated with large tumor size, early recurrence in the liver, local recurrence, and shortened survival time in patients with pancreatic IDC. (Cancer Sci 2012; 103: 2012-2020 T he prognosis of patients undergoing resection for pancreatic invasive ductal carcinoma (IDC) remains poor.(1-5) Histological studies have been carried out to elucidate the aggressiveness of pancreatic IDC and have revealed prognostic factors including tumor size, lymph node involvement, nerve plexus invasion, positive resected margin, and low tumor grade.(1-8)Tumor-associated macrophages (TAMs) have recently been reported as a candidate factor in poor prognosis. (9) Macrophages are the most abundant cancer stromal cells involved in the host immune system, (10) and TAMs have been found to play important roles in tumorigenesis, angiogenesis, matrix remodeling, and metastasis.(11-13) Tumor-associated macrophages have a prognostic impact in prostate, breast, and lung cancers, as well as pancreatic IDC.(9,14-16) The heterogeneity of macrophages has been discussed with regard to their different responses to various microenvironmental stimuli. Macrophages are classically activated towards the M1 phenotype by lipopolysaccharide and interferon-c. M1 macrophages are characterized by high expression of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-12, and tumor necrosis factor. Alternatively, macrophages are activated towards the M2 phenotype by IL-4, IL-13, and IL-10. M2 macrophages are characterized by high expression of ...
Carbohydrate-deficient transferrin (CDT) has been established as a valuable biological marker for detecting chronic alcohol abuse. To improve the diagnostic efficiency, we studied new CDT determination procedures involving the use of lectin affinity chromatography with Allomyrina dichotoma agglutinin (allo A) and Trichosanthes japonica agglutinin I (TJA-I) to isolate the CDT isoforms CDT-allo A and CDT-TJA, respectively. These procedures, based on detection of the CDT-allo A and CDT-TJA isoforms in sera, showed high sensitivity (100% and 98%, respectively) and high specificity (93% and 85%, respectively). These results demonstrate that the new procedures involving the use of lectin affinity chromatography are more useful for isolating markers in the CDT test than the conventional charge-based separation method.z 1999 Federation of European Biochemical Societies.
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