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811.
Discovery of novel tumor markers of pancreatic cancer using global gene expression technology 总被引:20,自引:0,他引:20
812.
Prognostic significance of maspin in pancreatic ductal adenocarcinoma: tissue microarray analysis of 223 surgically resected cases. 总被引:1,自引:0,他引:1
Dengfeng Cao Qian Zhang Lee Shun-Fune Wu Safia N Salaria Jordan W Winter Ralph H Hruban Michael S Goggins James L Abbruzzese Anirban Maitra Linus Ho 《Modern pathology》2007,20(5):570-578
Maspin (SERPINB5), a serine proteinase inhibitor, was first identified as a potential tumor suppressor on the basis of its differential expression between normal mammary epithelial cells and human breast carcinoma cell lines. Recent studies have shown that maspin might be a prognostic tumor marker. Pancreatic ductal adenocarcinoma acquires maspin expression through hypomethylation of the maspin promoter. However, no study has investigated the prognostic significance of maspin expression in pancreatic ductal adenocarcinomas. In this study, we investigated maspin protein expression in a large series of 223 surgically resected pancreatic ductal adenocarcinomas using immunohistochemical staining and high throughput tissue microarrays. Maspin expression was correlated with postoperative survival and other clinicopathologic factors. Maspin was detected in 209 of these 223 (94% cases) pancreatic ductal adenocarcinomas including 39 (18% cases) focal (5-50% tumor cells) and 170 (76% cases) diffuse (>50% tumor cells). Fourteen (or 6% cases) pancreatic ductal adenocarcinomas did not show maspin expression by immunohistochemical staining (<5% tumor cells). Normal ductal epithelium is not labeled with maspin. Overexpression of maspin in pancreatic ductal adenocarcinoma is associated with worse postoperative survival especially in patients whose tumors exhibit diffuse expression of maspin. After adjusting other clinicopathologic factors, maspin expression remains to be an independent adverse prognosticator for postoperative survival. Maspin expression is not associated with patient age, gender, tumor size, tumor pathologic stage, lymph node status, and vascular invasion or perineural invasion. Nuclear labeling of maspin is associated with better tumor differentiation although this staining pattern is not associated with a better prognosis. In addition, maspin overexpression is also observed in 48% low-grade (grades 1a and 1b) pancreatic intraepithelial neoplasias (PanINs) and 78% high-grade (grades 2 and 3) PanINs, suggesting that maspin upregulation occurs early during the multi-step progression model of pancreatic ductal adenocarcinoma. 相似文献
813.
814.
Steinhardt AA Gayyed MF Klein AP Dong J Maitra A Pan D Montgomery EA Anders RA 《Human pathology》2008,39(11):1582-1589
The Hippo signaling pathway is a highly conserved potent regulator of cell growth, division, and apoptosis. Yes-associated protein (YAP), the nuclear effector of the Hippo pathway, is a highly conserved component of this pathway in mammalian systems. In humans, amplification of the chromosome region containing the YAP gene (11q22) has been reported in several tumor types. This study was performed to determine if YAP expression was present in 4 common types of malignant tumors that have the highest lifetime risk of causing cancer death among men and women in the United States. The YAP expression intensity and distribution were evaluated in normal tissues and compared to the most frequently occurring malignant tumors in these tissues (colonic adenocarcinoma, lung adenocarcinoma, ovarian serous cystadenocarcinoma, and ductal carcinoma of the breast). For each tissue, the nuclear and cytoplasmic YAP expression intensity was scored as negative, low, or high. We found focal expression of YAP in the progenitor and reparative cellular compartments of normal tissue. In contrast, there was strong and diffuse nuclear and cytoplasmic YAP expression in colonic adenocarcinoma, lung adenocarcinoma, and ovarian serous cystadenocarcinoma. We concluded that the potent Hippo growth regulatory pathway shows markedly different expression patterns in normal tissues of the colon, lung, and ovary compared to the 3 common malignant tumor types we examined in these tissues. Our findings suggest that activation of the Hippo signaling pathway may occur through YAP as part of cell proliferation in normal tissue homeostasis and also might be a frequently activated oncogenic pathway in 3 common malignant tumor types. 相似文献
815.
Objective
To assess maternal cardiovascular function using echocardiography in normal and preeclamptic women in the third trimester of pregnancy.Methods
40 subjects, 20 with preeclampsia and 20 normotensive controls with >34 weeks gestation and singleton pregnancy were recruited. Baseline characteristics, maternal and fetal outcome were studied with systolic and diastolic parameters on echocardiography.Results
The following parameters were higher in preeclamptic subjects as compared to normotensive controls–mean cardiac output (66.85 ± 4.56 ml/min vs. 56.1 ± 1.77 ml/min); mean LV diastolic mass (131.15 ± 16.85 vs. 104.90 ± 23.17 g); systolic mass (88.5 ± 7.34 vs. 83.33 ± 23.84 g); total vascular resistance (1396.85 ± 150.2 vs. 1204.5 ± 71.182 dyne, s cm5). Women with preeclampsia delivered smaller babies (2410 ± 426.16 g) as compared to normotensive controls (2895 ± 276.20 g). Student ‘t’ test was used as a test of significance.Conclusion
Women with preeclampsia have significant systolic and diastolic dysfunction compared to normotensive controls. Blood pressure monitoring alone is insufficient to identify effectively, risk of cardiovascular complications in these subjects. 相似文献816.
Interleukin-12 (IL-12) p70 and IL-23 are bioactive cytokines and their biological functions are becoming clear. Increased expression of IL-7 in the central nervous system as well as in peripheral immune cells is associated with multiple sclerosis and experimental allergic encephalomyelitis. Here, we describe the induction of IL-7 in primary mouse and human microglia, BV-2 microglial cells, mouse peritoneal macrophages and astrocytes by IL-12p70. Interestingly, IL-12 strongly induced the expression of IL-7 whereas IL-23 and other p40 family members remained weak inducers of IL-7 in these cell types. Consistently, IL-12, but not IL-23 and other p40 family members, induced IL-7 promoter-driven luciferase activity in microglial cells. Among various stimuli tested, IL-12 emerged as the most potent stimulus followed by bacterial lipopolysaccharide and HIV-1 gp120 in inducing the activation of IL-7 promoter in microglial cells. Furthermore, increase in IL-7 mRNA expression by over-expression of IL-12p35 subunit, but not p40 and IL-23 p19 subunit, confirm that p35, but not p40 and p19, is responsible for the induction of IL-7. Finally, by using primary microglia from IL-12 receptor β1-deficient (IL-12Rβ1−/−) and IL-12Rβ2−/− mice, we demonstrate that IL-12 induces the expression of IL-7 in microglia and macrophages via both IL-12Rβ2 and IL-12Rβ1. These studies delineate a novel biological function of IL-12 that is absent in IL-23 and other p40 family members. 相似文献
817.
Loss of Dpc4 expression in colonic adenocarcinomas correlates with the presence of metastatic disease 总被引:30,自引:0,他引:30 下载免费PDF全文
Maitra A Molberg K Albores-Saavedra J Lindberg G 《The American journal of pathology》2000,157(4):1105-1111
DPC4 is a candidate tumor suppressor gene on chromosome 18q21, a region that shows high frequencies of allelic losses in pancreatic and colorectal adenocarcinomas. Biallelic inactivation of DPC4 has been reported in half of pancreatic cancers, but are relatively infrequent in other tumor types. The role of DPC4 inactivation in colorectal neoplasms has not been fully characterized. An immunohistochemical assay for Dpc4 protein expression has been recently developed and shown to be a sensitive and specific surrogate for alterations in the DPC4 gene. In this study we examined the expression of Dpc4 protein in formalin-fixed archival tissue from 83 colorectal lesions, including 19 adenomas and 64 sporadic adenocarcinomas (11 stage I, 13 stage II, 17 stage III, and 23 stage IV cancers). None of the adenomas or stage I adenocarcinomas showed loss of Dpc4 expression, whereas one of 13 (8%) stage II, one of 17 (6%) stage III, and five of 23 (22%) of stage IV cancers showed loss of Dpc4 expression. There was a borderline significant difference in loss of Dpc4 reactivity in colorectal tumors with distant metastasis at presentation (22%) versus primary tumors without distant metastasis (5%) (Fisher's exact test, P = 0.05; chi(2) = 0.04). Poorly differentiated histology or status of pericolonic lymph nodes did not affect Dpc4 expression. Alterations in DPC4 are involved in the progression of a subset of colorectal carcinomas, especially those that present with advanced disease. In the sequential pathogenesis of colorectal tumors, inactivation of DPC4 is likely to be a late event. 相似文献