在结果中搜索
成果类型 (Type)
- 已选条件:
MFG-E8 overexpression promotes colorectal cancer progression via AKT/MMPs signalling
Zhao, QJ;Xu, L;Sun, XY;Zhang, K;Shen, HM;Tian, YN;Sun, FK;Li, YQ
TUMOR BIOLOGY 2017年 39卷6期 页码:1-15
EPITHELIAL-MESENCHYMAL TRANSITION; GLOBULE-EGF FACTOR-8; GROWTH-FACTOR 8; APOPTOTIC CELLS; MACROPHAGES; EXPRESSION; MIGRATION; CARCINOGENESIS; METASTASIS; STATISTICS
Several studies have revealed that MFG-E8 (milk fat globule-epidermal growth factor 8) is related to tumour development and progression. However, the relationship between MFG-E8 expression and metastasis in colorectal cancer patients and the role of MFG-E8 in colorectal cancer invasion and progression remain unknown. In this study, we performed immunohistochemistry and quantitative real-time polymerase chain reaction to assess MFG-E8 expression in colorectal cancer and adjacent non-cancerous tissues. Colorectal cancer RNAseq data from The Cancer Genome Atlas project were downloaded and MFG-E8 expression was analysed. Gene set enrichment analysis was performed for gene ontology and pathway analysis associated with MFG-E8 expression. For in vitro studies, we used lentivirus-mediated MFG-E8 RNA interference and commercialized recombinant human MFG-E8 to investigate its role in colorectal cancer cell growth, migration and invasion. It seems that MFG-E8 was overexpressed in advanced colorectal cancer tissues compared with early-stage colorectal cancer tissues and adjacent non-cancerous tissues. Correlation analysis revealed that MFG-E8 expression was significantly related to plasma membrane invasion, lymph node metastasis, distant metastasis and tumour-node-metastasis stage. Survival analysis revealed that high MFG-E8 expression predicted a poorer prognosis than low MFG-E8 expression group both in our colorectal cancer cohort and The Cancer Genome Atlas colorectal cancer cohort. In vitro study suggested that MFG-E8 knockdown can suppress the growth of colorectal cancer cells without affecting the expression of the proliferation-related gene Ki67. MFG-E8 knockdown also suppressed colorectal cancer cell migration and invasion, a change accompanied by MMP-2 and MMP-9 downregulation. Moreover, MFG-E8 knockdown induced a shift from mesenchymal makers to epithelial makers, while pretreatment with rhMFG-E8 had the opposite effect. The effect of MFG-E8 on colorectal cancer cell migration, invasion and epithelial-to-mesenchymal was partially dependent on the PI3K/AKT signalling pathway. These findings provide a better understanding of the molecular mechanism underlying colorectal cancer progression and suggest a predictive role for MFG-E8 in colorectal cancer metastasis and prognosis.
Dihydroartemisinin induces endothelial cell anoikis through the activation of the JNK signaling pathway
Zhang, J;Guo, L;Zhou, X;Dong, FY;Li, LQ;Cheng, ZW;Xu, YH;Liang, JY;Xie, Q;Liu, J
ONCOLOGY LETTERS 2016年 12卷3期 页码:1896-1900
FOCAL ADHESION KINASE; N-TERMINAL KINASE; TUMOR ANGIOGENESIS; APOPTOSIS; GROWTH; CANCER; JUN; ANTIMALARIAL; SUPPRESSION; INHIBITION
Angiogenesis is required for the growth and metastasis of solid tumors. The anti-malarial agent dihydroartemisinin (DHA) demonstrates potent anti-angiogenic activity, but the underlying molecular mechanisms are not yet fully understood. During the process of angiogenesis, endothelial cells migrating from existing capillaries may undergo programmed cell death after detaching from the extracellular matrix, a process that is defined as anchorage-dependent apoptosis or anoikis. In the present study, DHA-induced cell death was compared in human umbilical vein endothelial cells (HUVECs) cultured in suspension and attached to culture plates. In suspended HUVECs, the cell viability was decreased and apoptosis was increased with the treatment of 50 mu M DHA for 5 h, while the same treatment did not affect the attached HUVECs. In addition, 50 mu M DHA increased the phosphorylation of c-Jun N-terminal kinase (JNK) in suspended HUVECs, but not in attached HUVECs, for up to 5 h of treatment. The JNK inhibitor, SP600125, reversed DHA-induced cell death in suspended HUVECs, suggesting that the JNK pathway may mediate DHA-induced endothelial cell anoikis. The data from the present study indicates a novel mechanism for understanding the anti-angiogenic effects of DHA, which may be used as a component for chemotherapy.
TIPE2 protein negatively regulates HBV-specific CD8(+) T lymphocyte functions in humans
Zhang, WQ;Zhang, J;Zhao, LY;Shao, J;Cui, J;Guo, C;Zhu, FL;Chen, YHH;Liu, SX
MOLECULAR IMMUNOLOGY 2015年 64卷1期 页码:204-209
HEPATITIS-B-VIRUS; ACUTE VIRAL-HEPATITIS; IMMUNE HOMEOSTASIS; INFECTION; CELLS; RESPONSES; MICE; EXPRESSION; CLEARANCE; EPITOPES
Cytotoxic T cell-mediated killing of virus-infected hepatocytes is an important pathogenic process of hepatitis B. However, its underlying molecular mechanisms are not fully understood. TNFAIP8L2 (TIPE2) is a newly described anti-inflammatory protein that is essential for maintaining immune homeostasis. In this study, we found that the protein levels of TIPE2 in PBMCs of hepatitis B patients were significantly reduced and negatively correlated with the sera values of aminotransferases. Importantly, TIPE2 protein was downregulated preferentially in cytotoxic CD8(+) T cells, not CD4(+) helper T cells. The CD8(+) T cells with low TIPE2 expression were more activated and produced higher levels of perforin, granzyme B, and IFN-gamma. As a result, their cytolytic activity was markedly enhanced. Interestingly, HBc(18-27) peptide stimulation could reduce TIPE2 expression in PBMCs. These results indicate that TIPE2 plays an important role in regulating HBV-specific CD8(+) T cell functions in patients with hepatitis B. (C) 2014 Elsevier Ltd. All rights reserved.
Interleukin-21 Responses in Patients with Chronic Hepatitis B
Li, J;Ren, WH;Ma, W;Zhang, J;Shi, J;Qin, CY
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 2015年 35卷2期 页码:134-142
CD8(+) T-CELLS; CHRONIC VIRAL-INFECTION; VIRUS-INFECTION; IL-21; EXPRESSION; DISEASE; HBV; PROLIFERATION; AUTOIMMUNITY; MODULATION
Interleukin (IL)-21 has been demonstrated to play a pivotal role in controlling chronic viral infections. However, little is known about the regulatory role of IL-21 in T cell immunity during the process of chronic hepatitis B (CHB). In the present study, the levels of serum IL-21 in 77 patients with various degrees of CHB in immune clearance phase (IC), 25 patients infected with hepatitis B virus (HBV) in immune tolerance phase (IT), and 25 healthy controls (HC) were measured and their potential association with major clinic indexes was examined. Peripheral blood mononuclear cells from CHB patients were stimulated with hepatitis B core antigen (HBcAg) in the presence or absence of anti-IL-21 antibody or recombinant IL-21, and the frequency of HBcAg-specific IL-21(+)CD4(+) and interferon (IFN)-gamma(+)CD8(+) T cells was characterized by flow cytometry. Our data indicated that the levels of serum IL-21 were significantly higher in the IC CHB patients than that in the other groups and were positively correlated with the levels of serum HBV DNA and HBeAg in the IC patients. There was a low frequency of HBcAg-specific IL-21(+)CD4(+) T cells in IC CHB patients. Further, IL-21 enhanced HBcAg-specific IFN-gamma(+)CD8(+) T cell proliferation, while treatment with anti-IL-21 inhibited antigen-specific IFN-gamma(+)CD8(+) T cell expansion in vitro. Our findings imply that IL-21 positively regulates proinflammatory IFN-gamma(+)CD8(+) T cell responses during the process of chronic HBV infection in humans.
Studies on immunogenetic mechanism of hepatocellular carcinoma caused by fas gene polymorphism
Mao, HT;Zhang, J;Qu, X;Yang, YM;Sun, JT;Ma, C;Gao, WJ;Liu, J
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 2012年 27卷 页码:347-347
Combination of interferon-alpha and 5-fluorouracil induces apoptosis through mitochondrial pathway in hepatocellular carcinoma in vitro
Yin, HP;Xie, FX;Zhang, J;Yang, YM;Deng, BP;Sun, JT;Wang, QJ;Qu, X;Mao, HT
CANCER LETTERS 2011年 306卷1期 页码:34-42
DIHYDROPYRIMIDINE DEHYDROGENASE EXPRESSION; CYTOCHROME-C; CELL-GROWTH; IFN-ALPHA; INTRAARTERIAL 5-FLUOROURACIL; THERAPY; FLUOROURACIL; ACTIVATION; RECEPTOR; RELEASE
Many clinical reports have proven that the combination therapy of interferon-alpha plus 5-fluorouracil is remarkably effective for advanced hepatocellular carcinoma (HCC). However, the mechanism of this therapy is not well understood. Here, we demonstrated that the combination therapy synergistically inhibited the growth of Fas-negative HCC cells, arrested cell-cycle progression and induced apoptosis. Moreover, the combination therapy significantly increased the protein expression of caspase-8, activated Bid and cytochrome c. Meanwhile, the expression of anti-apoptotic gene Bcl-xL was reduced and intracellular calcium elevated obviously during the early stage of treatment. Therefore, mitochondria] pathway was involved in the apoptosis of Fas-negative HCC cells induced by IFN-alpha/5-FU and Ca2+ partially promoted the beneficial effect against HCC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
Roles of TIPE2 in hepatitis B virus-induced hepatic inflammation in humans and mice
Xi, WJ;Hu, YJ;Liu, YG;Zhang, J;Wang, L;Lou, YW;Qu, ZH;Cui, J;Zhang, GZ;Liang, XH;Ma, CH;Gao, CJ;Chen, YH;Liu, SX
MOLECULAR IMMUNOLOGY 2011年 48卷9-10期 页码:1203-1208
CYTOTOXIC T-LYMPHOCYTES; IMMUNE HOMEOSTASIS; VIRAL-HEPATITIS; CELL-ACTIVATION; MESSENGER-RNA; IN-VIVO; LIVER; EXPRESSION; INFECTION; IMMUNOLOGY
Hepatitis B virus (HBV)-induced hepatic inflammation afflicts hundreds of millions of people worldwide and is a leading cause of hepatic cancer. While the deleterious effect of the chronic hepatitis is well recognized, the molecular mechanisms underlying the pathogenesis of HBV-induced hepatic inflammation are not well understood. We report here that the tumor necrosis factor-alpha-induced protein-8 like-2 (TIPE2 or TNFAIP8L2), a newly identified regulator of immune receptor signaling, plays an important role in controlling HBV-induced hepatitis. Patients with chronic hepatitis B had significantly reduced levels of TIPE2 expression in their peripheral blood mononuclear cells (PBMCs) as compared to healthy individuals. The TIPE2 expression negatively correlated with the blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (Tbil) as well as the HBV load of the patients. Importantly, using a murine model of HBV-induced hepatitis, we found that TIPE2-deficient mice developed significantly more severe hepatic inflammation than wild type mice. These results indicate that TIPE2 plays an important role in taming HBV-induced hepatic inflammation. (C) 2011 Elsevier Ltd. All rights reserved.
Expression of P-glycoprotein and Multidrug Resistance-associated Protein is Associated with Multidrug Resistance in Gastric Cancer
Xu, HW;Xu, L;Hao, JH;Qin, CY;Liu, H
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH 2010年 38卷1期 页码:34-42
CELLS; TRANSPORTER; INHIBITION; APOPTOSIS; SARCOMA; GRADE; GP
This study evaluated the sensitivities of gastric cancer cells to various chemotherapy drugs, and investigated the relationship between the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) and multidrug resistance. Drug sensitivities were determined using a methyl-tetrazolium assay: expression levels of P-gp and MRP were measured using immunohistochemistry. On purification culture, gastric cancer cells were found to be most sensitive to cisplatin, mitomycin and adriamycin, moderately sensitive to etoposide and 5-fluorouracil, and less sensitive to homocamptothecin and methotrexate, with sensitivities of 76.7%, 70.0%, 66.7%, 60.0%, 56.7%, 43.3% and 30.0%, respectively. Positive expression for P-gp and MRP in gastric cancer tissues was 41.7% and 29.2%, respectively; co-expression of P-gp and MRP in cancer tissue was 23%. The drug-resistant groups had higher positive expression of P-gp and MRP compared with the drug-sensitive groups. In conclusion, expression of P-gp and MRP seems to be associated with multidrug resistance in gastric cancer.
A Modified Percutaneous Transhepatic Varices Embolization With 2-Octyl Cyanoacrylate in the Treatment of Bleeding Esophageal Varices
Zhang, CQ;Liu, FL;Liang, B;Xu, HW;Xu, L;Feng, K;Liu, ZC
JOURNAL OF CLINICAL GASTROENTEROLOGY 2009年 43卷5期 页码:463-469
ENDOSCOPIC INJECTION SCLEROTHERAPY; TRANS-HEPATIC OBLITERATION; GASTRIC VARICES; GASTROESOPHAGEAL VARICES; RANDOMIZED-TRIAL; CORONARY VEIN; BAND LIGATION; MANAGEMENT; N-BUTYL-2-CYANOACRYLATE; HEMORRHAGE
Background: To evaluate the effect of a modified percutaneous transhepatic variceal embolization (PTVE) with 2-octyl cyanoacrylate (2-OCA) on the prevention and treatment of esophageal variceal bleeding.;-;Methods: Between March 2002 and December 2005, PTVE was attempted in 92 patients with esophageal varices, 74 patients with recent variceal bleeding, 18 patients with acute variceal bleeding. The 2-OCA was injected into the entire lower esophageal and periesophageal or paraesophageal varices, the cardial Submucosal, and perforating vessels.;-;Results: PTVE Was Successfully performed in 89 of 92 patients, providing a procedural Success rate of 96.7%. According to the distribution of injected 2-OCA, 3 types of variceal embolization were defined, esophagogastric obliteration (n = 42), gastric obliteration (n = 34), and main left gastric vein obliteration (n = 13). Acute variceal bleeding was immediately arrested in all 18 (100%) patients after the procedure. During the median follow-up period of 37 months, the total rebleeding rate was 19.1% (17/89), with the rate being higher in patients with main left gastric vein obliteration 46.1% (6/13) than in patients with esophagogastric obliteration 9.5% (4/42) or with gastric obliteration 20.6% (7/34, P < 0.05). Total survival rate was 74.4%, with the rate being significantly higher in patients with esophagogastric obliteration and gastric obliteration than that in patients with left gastric vein obliteration demonstrated by Kaplan-Meier analysis (P < 0.001, log-rank test). There was 1 patient with fatal bleeding at the puncture site after the PTVE procedure, and 1 patient with slight pulmonary embolism; there were no other major procedure-related complications.;-;Conclusions: The effect of PTVE with 2-OCA on esophageal varices is associated with the site and range of embolization. With the lower esophageal and periesophageal varices and/or the cardial submucosal and perforating vessels are sufficiently obliterated, PTVE with 2-OCA can improve long-term efficacy by preventing varices recurrence and rebleeding.
A modified percutaneous transhepatic variceal embolization with 2-octyl cyanoacrylate versus endoscopic ligation in esophageal variceal bleeding management: Randomized controlled trial
Zhang, CQ;Liu, FL;Liang, B;Sun, ZQ;Xu, HW;Xu, L;Feng, K;Liu, ZC
DIGESTIVE DISEASES AND SCIENCES 2008年 53卷8期 页码:2258-2267
TRANS-HEPATIC OBLITERATION; GASTRIC VARICES; INJECTION SCLEROTHERAPY; HISTOACRYL INJECTION; PORTAL-HYPERTENSION; BANDING LIGATION; GASTROESOPHAGEAL VARICES; PARAESOPHAGEAL VARICES; CORONARY VEIN; HEMORRHAGE
Background Conventional percutaneous transhepatic varices embolization (PTVE) has rarely been used in recent years due to high rates of variceal recurrence and rebleeding. Herein we report a modified PTVE with 2-octyl cyanoacrylate (2-OCA) in which the whole lower esophageal and peri or para-esophageal varices, the submucosal varices, and the advertitial plexus of the cardia and fundus were sufficiently obliterated. We compared this PTVE with endoscopic band ligation (EVL) in the treatment of esophageal variceal bleeding. Methods In this prospective randomized controlled trial, cirrhotic patients with acute or recent esophageal variceal bleeding were assigned randomly to PTVE (52 patients) or EVL (50 patients) groups. Upper gastrointestinal (UGI) rebleeding, esophageal variceal rebleeding, and survival were followed-up. Computerized tomography (CT) scanning and portal venography were used to observe 2-OCA distribution. Results During the follow-up period (median 24 and 25 months in the PTVE and EVL groups, respectively) UGI rebleeding developed in eight patients in the PTVE group and 21 patients in EVL group (P = 0.004). Recurrent bleeding from esophageal varices occurred in three patients in the PTVE group and twelve in the EVL group (P = 0.012, relative risk 0.24, 95% confidence interval 0.05-0.74). Multivariate Cox analysis indicated that the treatment was the only factor predictive of rebleeding. A Kaplan-Meier curve showed there was no significant difference between survival in the two groups (P = 0.054). Conclusions With the whole lower esophageal and peri or para-esophageal varices, the submucosal varices, and the adventitial plexus of the cardia and fundus sufficiently obliterated by 2-OCA, this modified PTVE was more effective than EVL in the management of esophageal varices recurrence and rebleeding. Survival in these two groups was not significantly different, however.
每页: 条
- <<
- <
- >
- >>