排序方式: 共有18条查询结果,搜索用时 31 毫秒
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Breuhahn K Vreden S Haddad R Beckebaum S Stippel D Flemming P Nussbaum T Caselmann WH Haab BB Schirmacher P 《Cancer research》2004,64(17):6058-6064
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Yang ZQ Moffa AB Haddad R Streicher KL Ethier SP 《International journal of cancer. Journal international du cancer》2007,121(6):1265-1273
Breast cancer development is associated with gene amplification and over expression that is believed to have a causative role in oncogenesis. Previous studies have demonstrated that over expression of TC-1(C8orf4) mRNA occurs in approximately 50% of breast cancer cell lines and primary tumor specimens. Here, we show that TC-1 has transforming properties in human mammary epithelial (HME) cells and its expression is mechanistically linked to FGFR signaling cascades. In vitro experiments demonstrate that TC-1 over expression mediates both anchorage-independent and growth factor-independent proliferation of HME cells. TC-1 was down regulated by the FGFR inhibitor PD173074 in the breast cancer cell line SUM-52 that also has an FGFR2 gene amplification and over expression. Furthermore, forced expression of FGFR2 in HME cells increased the level of expression of endogenous TC-1 mRNA. TC-1 has been implicated as a modulator of Wnt/beta-catenin signaling in 293 cells and in gastric cancer cells. However, while we did find increased expression of a subset of beta-catenin target genes in TC-1 over expressing cells, we did not find an association of TC-1 with global expression of beta-catenin target genes in our cells. Taken together, our data suggest that TC-1 over expression is transforming and may link with the FGFR pathway in a subset of breast cancer. 相似文献
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Sauer V Siaj R St?ppeler S Bahde R Spiegel HU K?hler G Zibert A Schmidt HH 《Liver transplantation》2012,18(2):248-259
The outcome of consecutive hepatocyte transplants was explored in a rat model of Wilson's disease before the onset of fulminant hepatitis without preconditioning regimens. Rats received a high-copper diet in order to induce a rapid induction of liver failure. Sham-operated rats (15/15) developed jaundice and fulminant hepatitis, and they died within 4 weeks of first transplantation. Despite the continuation of a high dietary copper challenge, long-term survival was observed for a notable proportion of the transplanted animals (7/18). All survivors displayed normalized levels of hepatitis-associated serum markers and ceruloplasmin oxidase activity by posttransplant days 50 and 98, respectively. The liver copper concentrations, the liver histology, and the expression of marker genes were significantly restored within 4 months of transplantation in comparison with the control group. The high expression of a copper transporter gene (ATPase Cu++ transporting beta polypeptide) in the livers of the survivors indicated a high rate of repopulation by donor hepatocytes. Our data suggest that repeated cell transplantation can overcome the limitations of a single therapy session in rats with severe hepatic disease by functionally restoring the host liver without preconditioning. 相似文献
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Ramsi Siaj Vanessa Sauer Sandra St?ppeler Hans-Ullrich Spiegel Gabriele K?hler Andree Zibert Hartmut HJ Schmidt 《World journal of gastroenterology : WJG》2012,18(39):5542-5550
AIM:To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS:The Long-Evans cinnamon (LEC) rat model of Wilson's disease (WD) was used to study the impact of high dietary copper (hCu) on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults (month 5) for three months. Animals that received reduced dietary copper (rCu) throughout their lifetime served as a control. Hepatitis-associated serum markers (alanine aminotransferase, aspartate transaminase, bilirubin) were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis (Vegfa), fat metabolism (Srebf1), ex-tracellular matrix (Timp1), oxidative stress (Hmox1), and the cell cycle (Cdkn1a) were analyzed by real-time polymerase chain reaction. RESULTS:Regardless of the time point when hCu was started, LEC rats (35/36) developed fulminant hepatitis and died. Animals receiving rCu (36/36) remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals (477 ± 75 μg/g). With regard to start of hCu, onset of fulminant hepatitis was significantly (P 0.001) earlier in adults (35 ± 9 d) that showed pre-accumulation of liver copper as compared to the pup group (77 ± 15 d). Hepatitis-associated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats receiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION:Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper suggests that there is a critical threshold of liver copper which is important to trigger the course of WD. 相似文献
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Ramsi Siaj Vanessa Sauer Sandra St?ppeler Joachim Ger? Hans-Ullrich Spiegel Gabriele K?hler Andree Zibert Hartmut H.-J. Schmidt 《Hepatology International》2012,6(4):770-777
Purpose
MicroRNA-122 (miR-122) has recently been shown to represent a novel biomarker of liver disease. However, the presence of serum miR-122 after liver injury was mostly studied at singular time points. The course of serum miR-122 was determined at consecutive time points during the onset of disease.Methods
Fulminant hepatitis was induced by a high-copper diet in Long-Evans Cinnamon (LEC) rats that were used as models for Wilson??s disease (WD). Levels of serum miR-122, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and liver histology were determined.Results
Toxic copper given to isolated hepatocytes induced release of miR-122 into the tissue culture medium. Levels of serum miR-122 were highly elevated (21.9?±?5) in LEC rats after high-copper diet in fulminant hepatitis, whereas healthy rats showed low (<0.6) baseline levels of miR-122. Levels of miR-122 in the serum of LEC rats after high-copper diet continuously increased for about 4?weeks prior to the onset of fulminant hepatitis. In most of the animals (77.8%), significantly increased levels of miR-122 were detected about 2?weeks (13.7?±?2?days) earlier as compared to hepatitis-associated serum markers ALT, AST, and bilirubin. Analysis of miR-122 in survivors after cell-based therapy of WD demonstrated a rapid decrease of miR-122 levels following hepatocyte transplantation. miR-122 expression in the serum was normalized to baseline levels in most of the (4/5) survivors.Conclusion
Our results suggest that longitudinal analysis of miR-122 allows detection of severe liver disease at an early stage and might be excellently suited to monitor therapy, at least when severe liver disease can be restored as observed after cell-based therapy of WD. 相似文献7.
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Effect of Curcuma longa L. extract on the AP1 expression in rat cochlear fibroblasts under noise conditions
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Tengku Siti Hajar Haryuna Ramsi Lutan Faathir Agung Ainul Taufika Ratna Anggraeni Tengku Siti Harilza Zubaidah 《中国药学》2016,25(9):690-694
Noise-induced cellular stress can cause damage to fibroblasts within the cochlear supporting tissues and lateral wall. In the present study, we aimed to evaluate the role of curcumin as the safe and effective therapeutic agent in the prevention and treatment of this condition according to the expression of activator protein-1 (AP1). A total of 24 Rattus norvegicus were randomly divided into four groups (n = 6). Group 1: control; group 2: noise (+); group 3: noise (+), 50 mg/day curcumin (+); group 4: noise (+), 100 mg/day curcumin (+). All groups (except for group 1) were subjected to a sound pressure level (SPL) of 100 dB for 2 h/day during 2 weeks. Curcumin used in this study was derived from Curcuma longa L. (Turmeric), and it was orally administered for 2 weeks. All samples were immunohistochemistrically examined for the expression of AP1 in cochlear fibroblasts. The results showed that there were significant differences for the AP1 expression (P<0.05) among all groups, except for between groups 1 and 3, or between groups 1 and 4. Our data proved that curcumin was potentially effective in the prevention and treatment of damage of fibroblasts within the cochlear supporting tissues and lateral wall due to the decreased AP1 expression following noise exposure. 相似文献
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