It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated...It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since α-1,6 Fucosyltransferase (α-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by α-1,6 FucT targeted RNAi and transfecting α-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E- cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after α-1,6 FucT over expression. Our data indicated that α-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asym- metry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.展开更多
Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid （SUA） levels w...Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid （SUA） levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. Methods Two hundred and seventy six elderly patients affected by advanced atherosclerosis （217 males and 59 females; aged 71.2 ±7.8 years） were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ±11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral isehemia, myocardial and/or peripheral revascularization and death. Results Mean SUA level was 5.47 ±1.43 mg/dL; then we further divided the population in two groups, according to the median value （5.36 mg/dL）. During a median follow up of 31 months （5 to 49 months）, 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events （HR： 1.867, P = 0.014, 95% CI： 1.134-3.074）, The same patients showed a significant increased risk of cancer-related death （HR： 4.335, P = 0.025, 95% CI： 1.204-15.606）. Conclusions Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.展开更多
AIM： To assess whether CCL2 or interactions between this chemokine and its receptor （CCR2） are associated with outcomes of chronic hepatitis C and with responses to antiviral therapy. METHODS： Two hundred and eigh...AIM： To assess whether CCL2 or interactions between this chemokine and its receptor （CCR2） are associated with outcomes of chronic hepatitis C and with responses to antiviral therapy. METHODS： Two hundred and eighty-four patients with chronic hepatitis C and 193 non-infected matched controls were included in this study. Patients were categorized according to their Scheuer score of hepatic fibrosis as F0-F2 （/7 = 202） or F3-F4 （/7 = 82） and according to their response to anti-Hepatitis C virus （HCV） therapy as sustained response （SR, n = 201） or non-sustained response （NSR, n = 98）. Genotyping of the -2518 （A/G） CCL2 was performed using PCR-RFLP, genotyping of the 190 （A/G） CCR2 using a PCR-ARMS system, and genotyping of the rs3138042 （G/A） CCR2 using Taqman probes. RESULTS： Univariate analyses identified 4 parameters （infection duration time, viral genotype, gender and AST levels） that tended to influence fibrosis and 7 parameters （CCL2G, CCL2ACCR2A, viremia levels, fibrosis stage, viral genotype, infection duration time and AST levels） that significantly influenced or tended to influence response to treatment. Multivariate analysis identified gender and AST levels as parameters that independently influenced fibrosis stage and viral genotype and infection duration time were the two parameters that independently influenced response to treatment. CONCLUSION： Our results indicate that the mutations studied in the gene pair CCL2/CCR2 do not play a major role in the outcome and response to treatment for HCV infection in the Spanish population.展开更多
基金supported by the National Nature Science Foundation of China(No.30070183,No.30470398)Key Subject Foundation of Shanghai Municipal Education Committee(No.B9808010).
文摘It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since α-1,6 Fucosyltransferase (α-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by α-1,6 FucT targeted RNAi and transfecting α-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E- cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after α-1,6 FucT over expression. Our data indicated that α-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asym- metry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.
文摘Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid （SUA） levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. Methods Two hundred and seventy six elderly patients affected by advanced atherosclerosis （217 males and 59 females; aged 71.2 ±7.8 years） were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ±11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral isehemia, myocardial and/or peripheral revascularization and death. Results Mean SUA level was 5.47 ±1.43 mg/dL; then we further divided the population in two groups, according to the median value （5.36 mg/dL）. During a median follow up of 31 months （5 to 49 months）, 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events （HR： 1.867, P = 0.014, 95% CI： 1.134-3.074）, The same patients showed a significant increased risk of cancer-related death （HR： 4.335, P = 0.025, 95% CI： 1.204-15.606）. Conclusions Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.
基金Supported by Plan Andaluz de Investigacion (PAI, grupos CTS-0197 and CTS-0102)Fundacion Reina Mercedes. MA Montes-Cano is the recipient of a fellowship from Instituto de Salud Carlos III (04/0146)
文摘AIM： To assess whether CCL2 or interactions between this chemokine and its receptor （CCR2） are associated with outcomes of chronic hepatitis C and with responses to antiviral therapy. METHODS： Two hundred and eighty-four patients with chronic hepatitis C and 193 non-infected matched controls were included in this study. Patients were categorized according to their Scheuer score of hepatic fibrosis as F0-F2 （/7 = 202） or F3-F4 （/7 = 82） and according to their response to anti-Hepatitis C virus （HCV） therapy as sustained response （SR, n = 201） or non-sustained response （NSR, n = 98）. Genotyping of the -2518 （A/G） CCL2 was performed using PCR-RFLP, genotyping of the 190 （A/G） CCR2 using a PCR-ARMS system, and genotyping of the rs3138042 （G/A） CCR2 using Taqman probes. RESULTS： Univariate analyses identified 4 parameters （infection duration time, viral genotype, gender and AST levels） that tended to influence fibrosis and 7 parameters （CCL2G, CCL2ACCR2A, viremia levels, fibrosis stage, viral genotype, infection duration time and AST levels） that significantly influenced or tended to influence response to treatment. Multivariate analysis identified gender and AST levels as parameters that independently influenced fibrosis stage and viral genotype and infection duration time were the two parameters that independently influenced response to treatment. CONCLUSION： Our results indicate that the mutations studied in the gene pair CCL2/CCR2 do not play a major role in the outcome and response to treatment for HCV infection in the Spanish population.
