Cytoplasmic expression of LGR5 in pancreatic adenocarcinoma.

Background: CD133 has been identified as a cancer stem cell (CSC) marker for pancreatic ductal adenocarcinoma. Although leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5), a marker of intestinal stem cells, has been shown to be on a higher level of the stem cell hierarchy than CD133, the expression and function of LGR5 in pancreatic cancer tissue remains unclear. This study investigated tissue expression of LGR5 and CD133 in resected pancreatic cancer tissue.Methods: LGR5 and CD133 expression was immunohistochemically examined in 9 patients with pancreatic ductal adenocarcinoma who underwent resection.Results: LGR5 was expressed in the cytoplasm of pancreatic cancer cells in 4 of 9 cases. CD133 was not detected in cancerous tissue. In non-neoplastic tissue, LGR5 was expressed in the basolateral membrane of a subset of endocrine cells. Conversely, CD133 was expressed in the apical membrane of small duct cells. Co-localization of LGR5 and CD133 was not found in either neoplastic or non-neoplastic tissue. LGR5 expression in pancreatic cancer cells showed no statistically significant correlation with survival after surgery.Conclusion: We have demonstrated that LGR5 is expressed in the cytoplasm of pancreatic adenocarcinoma cells, and the basolateral membrane of a subset of endocrine cells of the human pancreas. Further investigation is required to clarify any prognostic significance of LGR5 expression

発展途上国の女子教育と社会経済開発に関する総合的研究

研究期間:平成11-12年度 ; 研究種目: 基盤研究A2 ; 課題番号:1169102

Persistent high levels of plasma oxidized low-density lipoprotein after acute myocardial infarction predict stent restenosis

Recently, elevated levels of plasma oxidized low-density lipoprotein (LDL) have been shown to relate to plaque instability in human atherosclerotic lesions. We investigated prospectively patients admitted with acute myocardial infarction (AMI) who underwent primary coronary stenting to evaluate whether the 6-month outcome could be predicted by measuring plasma oxidized LDL (ox-LDL) levels at the time of hospital discharge. Plasma ox-LDL levels were measured in 102 patients with AMI undergoing primary coronary stenting using a highly sensitive ELISA method. Measurements were taken on admission and at discharge, and the findings related to the clinical outcome. At 6-month follow-up, angiographic stent restenosis occurred in 25 (25%) of the 102 AMI patients. Plasma ox-LDL levels at discharge were significantly (P=0.0074) higher in the restenosis group than those in the no-restenosis group (1.03+/-0.65 versus 0.61+/-0.34 ng/5 microg LDL protein). Multiple regression analysis showed that only plasma ox-LDL levels at discharge were a statistically significant independent predictor for late lumen loss after stenting (beta=0.645; P <0.0001). This prospective study demonstrates that persistence of an increased level of plasma ox-LDL at discharge is a strong independent predictor of stent restenosis at 6-month follow-up in AMI patient

Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study

Calcification is a common finding in human coronary arteries; however, the relationship between calcification patterns, plaque morphology, and patterns of remodeling of culprit lesions in a comparison of patients with acute coronary syndromes (ACS) and those with stable conditions has not been documented. Preinterventional intravascular ultrasound (IVUS) images of 178 patients were studied, 61 with acute myocardial infarction (AMI), 70 with unstable angina pectoris (UAP), and 47 with stable angina pectoris (SAP). The frequency of calcium deposits within an arc of less than 90 degrees for all calcium deposits was significantly different in culprit lesions of patients with AMI, UAP, and SAP (P <0.0001). Moreover, the average number of calcium deposits within an arc of <90 degrees per patient was significantly higher in AMI than in SAP (P <0.0005; mean+/-SD, AMI 1.4+/-1.3, SAP 0.5+/-0.8). Conversely, calcium deposits were significantly longer in SAP patients (P <0.0001; mean+/-SD, AMI 2.2+/-1.6, UAP 1.9+/-1.8, and SAP 4.3+/-3.2 mm). In AMI patients, the typical pattern was spotty calcification, associated with a fibrofatty plaque and positive remodeling. In ACS patients showing negative remodeling, no calcification was the most frequent observation. Conversely, SAP patients had the highest frequency of extensive calcification. Our observations show that IVUS allows the identification of vulnerable plaques in coronary arteries, not only by identifying a fibrofatty plaque and positive remodeling, but also by identifying a spotty pattern of calcificatio

Elevated levels of neopterin are associated with carotid plaques with complex morphology in patients with stable angina pectoris

Neopterin is an activation marker for monocytes/macrophages, and circulating levels of neopterin are elevated in patients with coronary complex lesions in unstable angina pectoris. We investigated the possible association between neopterin and complex carotid plaques which may be associated with the risk of ischemic stroke in patients with stable angina pectoris (SAP). We measured plasma levels of neopterin in 102 patients with SAP and carotid ultrasound was performed for evaluation of the presence of carotid plaques and plaque surface characteristics categorized as complex or noncomplex. In addition, endarterectomy specimens of extracranial high-grade carotid stenosis with complex plaques from five patients with SAP were immunohistochemically examined with antibodies to smooth muscle cells, endothelial cells, platelets, macrophages, and T cells. Plasma neopterin levels were significantly higher in patients with complex carotid plaques than in those with noncomplex plaques (median [interquartile range]: 24.2 [19.2-39.3]nmol/L vs. 19.4 [11.9-25.1]nmol/L; P=0.01) or without any plaques (18.8 [14.9-23.6]nmol/L; P=0.001). On multivariate logistic analyses after adjustment for traditional atherosclerotic risk factors, multi-vessel coronary disease and high sensitivity C-reactive protein, neopterin levels were independently associated with the presence of complex carotid plaques (adjusted OR 2.21 per SD increase, 95%CI 1.13-4.33, P=0.02). Immunohistochemical staining revealed abundant neopterin-positive macrophages in carotid complex lesions. These findings demonstrate that carotid plaques with complex morphology have increased circulating neopterin levels and immunohistochemical localization of neopterin in patients with SAP. Neopterin can be considered an important biomarker of plaque destabilization in carotid artery atherosclerotic lesions in this populatio