AIM： To characterize the expression and genomic amplification of decoy receptor 3 （DcR3） in hepatocellular carcinoma （HCC） and to evaluate the role of DcR3 in apoptosis.METHODS： We examined 48 cases of HCC for D...AIM： To characterize the expression and genomic amplification of decoy receptor 3 （DcR3） in hepatocellular carcinoma （HCC） and to evaluate the role of DcR3 in apoptosis.METHODS： We examined 48 cases of HCC for DcR3 expression by RT-PCR and DcR3 gene amplification by quantitative genomic PCR. DcR3 protein was detected by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick and labeling （TUNEL） was used to identify the apoptosis cells in tissues. Primary hepatoma cell culture and MTT test were used to evaluate the protection against FasL- and chemicalinduced apoptosis by DcR3 expression. RESULTS： DcR3 mRNA overexpression was detected in 60% HCC （29/48） patients. The occurrence of HCC was not associated with amplification of the gene. One sample base substitution was found in three sites as a sequence in Genbank. The expression of DcR3 in HCC was associated with the apoptotic index （0.067±0.04 vs 0.209±0.12, P〈0. 01）, size of mass, stage, and infiltration or metastasis （41.2% vs71.0%, 40% vs75%, 51.8% vs84.6%, P〈0. 05）. DcR3 expression could protect hepatoma cells against apoptosis induced by FasL, but not by chemicals. CONCLUSION： These data suggest that in addition to gene amplification there may be another mechanism underlying DcR3 overexpression. The effect of overexpression of DcR3 on the apoptosis of cancer cells may have direct therapeutic implications for the management of HCC.展开更多
Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morpho- genesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apoptosis ...Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morpho- genesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apoptosis in many tissues. Wnts bind to a membrane receptor complex comprised of a frizzled （FZD） G-protein-coupled receptor and a low-density lipoprotein （LDL） receptor-related protein （LRP）. The formation of this ligand-receptor complex initiates a number of signaling cascades that include the canonical/beta-catenin pathway as well as several noncanonical pathways. In recent years, canonical Wnt signaling has been reported to play a significant role in the control of bone formation. Clinical studies have found that mutations in LRP-5 are associated with reduced bone mineral density （BMD） and fractures. Investigations of knockout and transgenic mouse models of Wnt pathway components have shown that canonical Wnt signaling modulates most aspects ofosteoblast physiology including proliferation, differentiation, function and apoptosis. Transgenic mice expressing a gain of function mutant of LRP-5 in bone, or mice lacking the Wnt antagonist secreted frizzled-related protein-l, exhibit elevated BMD and suppressed osteoblast apoptosis. In addition, preclinical studies with pharmacologic compounds such as those that inhibit glycogen synthase kinase-3β support the importance of the canonical Wnt pathway in modulation of bone formation and osteoblast apoptosis.展开更多
Objective： The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress- related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset ...Objective： The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress- related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset of action to promote hemostasis and relieve the symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor, omeprazole 20 mg, and an H2-receptor antagonist, roxatidine 75 mg. Methods： Ten Heficobacterpylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 h after single oral admini- stration of omeprazole 20 mg and roxatidine 75 mg. Each administration was separated by a 7-d washout period. Results： During the 6-h study period, the average pH after administration of roxatidine was higher than that after administration of omeprazole （median： 4.45 vs. 2.65; P=0.0367）. Also during the 6-h study period, a longer duration of maintenance at pH above 2, 5, and 6 was observed after administration of roxatidine 75 mg than after administration of omeprazole 20 mg （median： 90.6% vs. 55.2%, P=-0.0284; 43.7% vs. 10.6%, P=0.0125; 40.3% vs. 3.3%, P=0.0125; respectively）. Conclusions： In Helicobacter pylori-negative healthy male subjects, oral administration of roxatidine 75 mg increased the intragastric pH more rapidly than that of omeprazole 20 mg.展开更多
文摘AIM： To characterize the expression and genomic amplification of decoy receptor 3 （DcR3） in hepatocellular carcinoma （HCC） and to evaluate the role of DcR3 in apoptosis.METHODS： We examined 48 cases of HCC for DcR3 expression by RT-PCR and DcR3 gene amplification by quantitative genomic PCR. DcR3 protein was detected by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick and labeling （TUNEL） was used to identify the apoptosis cells in tissues. Primary hepatoma cell culture and MTT test were used to evaluate the protection against FasL- and chemicalinduced apoptosis by DcR3 expression. RESULTS： DcR3 mRNA overexpression was detected in 60% HCC （29/48） patients. The occurrence of HCC was not associated with amplification of the gene. One sample base substitution was found in three sites as a sequence in Genbank. The expression of DcR3 in HCC was associated with the apoptotic index （0.067±0.04 vs 0.209±0.12, P〈0. 01）, size of mass, stage, and infiltration or metastasis （41.2% vs71.0%, 40% vs75%, 51.8% vs84.6%, P〈0. 05）. DcR3 expression could protect hepatoma cells against apoptosis induced by FasL, but not by chemicals. CONCLUSION： These data suggest that in addition to gene amplification there may be another mechanism underlying DcR3 overexpression. The effect of overexpression of DcR3 on the apoptosis of cancer cells may have direct therapeutic implications for the management of HCC.
文摘Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morpho- genesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apoptosis in many tissues. Wnts bind to a membrane receptor complex comprised of a frizzled （FZD） G-protein-coupled receptor and a low-density lipoprotein （LDL） receptor-related protein （LRP）. The formation of this ligand-receptor complex initiates a number of signaling cascades that include the canonical/beta-catenin pathway as well as several noncanonical pathways. In recent years, canonical Wnt signaling has been reported to play a significant role in the control of bone formation. Clinical studies have found that mutations in LRP-5 are associated with reduced bone mineral density （BMD） and fractures. Investigations of knockout and transgenic mouse models of Wnt pathway components have shown that canonical Wnt signaling modulates most aspects ofosteoblast physiology including proliferation, differentiation, function and apoptosis. Transgenic mice expressing a gain of function mutant of LRP-5 in bone, or mice lacking the Wnt antagonist secreted frizzled-related protein-l, exhibit elevated BMD and suppressed osteoblast apoptosis. In addition, preclinical studies with pharmacologic compounds such as those that inhibit glycogen synthase kinase-3β support the importance of the canonical Wnt pathway in modulation of bone formation and osteoblast apoptosis.
文摘Objective： The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress- related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset of action to promote hemostasis and relieve the symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor, omeprazole 20 mg, and an H2-receptor antagonist, roxatidine 75 mg. Methods： Ten Heficobacterpylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 h after single oral admini- stration of omeprazole 20 mg and roxatidine 75 mg. Each administration was separated by a 7-d washout period. Results： During the 6-h study period, the average pH after administration of roxatidine was higher than that after administration of omeprazole （median： 4.45 vs. 2.65; P=0.0367）. Also during the 6-h study period, a longer duration of maintenance at pH above 2, 5, and 6 was observed after administration of roxatidine 75 mg than after administration of omeprazole 20 mg （median： 90.6% vs. 55.2%, P=-0.0284; 43.7% vs. 10.6%, P=0.0125; 40.3% vs. 3.3%, P=0.0125; respectively）. Conclusions： In Helicobacter pylori-negative healthy male subjects, oral administration of roxatidine 75 mg increased the intragastric pH more rapidly than that of omeprazole 20 mg.
