Function of Cortactin/N-cadherin signal axis in pathological myocardial hypertrophy / 中国药理学通报

Aim To investigate the regulatory effect of Cortaetin on pathological myocardial hypertrophy induced by isoprenaline (ISO) and the underlying mechanism. Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h, and myocardial hypertrophy model was established at the cellular level. C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level. RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content. Immunofluorescence was used to measure the subcellular location of Cortaetin and the change of its expression. The overex-pression of Cortaetin by adenovirus infection and the knockdown of Cortaetin by transfection of small interfering RNA were studied. Results On the cellular and animal levels, ISO-induced myocardial hypertrophy models were successfully established, and it was observed that ISO caused the decrease of Cortaetin and N-cadherin protein levels. Overexpression of Cortaetin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO. Knockdown of Cortaetin showed the opposite effect. Conclusion Cortaetin, in combination with N-cadherin, may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.

GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

Relationship of E-cadherin, Beta-catenin, N-cadherin, ZEB1 and ?SMA as Epithelial Mesenchymal Transition markers with prognostic factors in early and advanced stage laryngeal squamous cell carcinomas

Aims: To investigate the relationship between E-cadherin, beta-catenin, N-cadherin, ZEB1, and ?SMA as epithelial-mesenchymal transformation markers with tumor stage, lymph node metastasis (LNM), and overall survival (OS) in laryngeal squamous cell carcinomas (LSCC). Materials and Methods: A total of 100 cases diagnosed with LSCC were included in the study. Data about the lymphovascular invasion (LVI), perineural invasion (PNI), necrosis, and LNM were recorded by evaluating hematoxylin-eosin–stained slides. Markers of E-cadherin, beta-catenin, N-cadherin, ZEB1, and ?SMA were applied to the sections prepared from paraffin blocks of tumor samples. Results: Ninety-five male and five female patients were included in the study, and 38 of them exited. A significant relationship was observed between OS with advanced tumor stage, presence of LNM and PNI. A significant relationship was found between increased tumor Zeb1 expression and advanced tumor stage. In univariate and multivariate analyses, a significant negative relationship with OS, and increased Zeb1 expression in tumor and tumor stroma was seen. Any relationship was not observed between E-cadherin, beta-catenin, N-cadherin, and ?SMA and OS. Conclusion: Among the EMT markers, we evaluated in our study, it was seen that Zeb1, which is an EMT transcription factor, is associated with tumor stage, LNM, and OS. Remarkably, Zeb1 expression observed in tumor stroma was also significant for OS. Any similar data reported for LSCCs have not been encountered in the literature, and it was thought that it would be appropriate to support our findings with further studies to be performed on this subject.

Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells, Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice / 神经科学通报·英文版

Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders (NDDs) that exhibit delayed speech development, intellectual disability, and congenital abnormalities. The etiology of NDDs is unclear. Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells (RGCs), respectively, in the mouse neocortex during early gestation. Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone (VZ). Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ. The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs. The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions, the loss of which leads to periventricular heterotopias. We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.

Effects of RhoA silencing on the migration and invasion of salivary adenoid cystic carcinoma / 口腔疾病防治

Objective@# To explore whether RhoA plays a role in the migration and invasion of the salivary adenoid cystic carcinoma cell lines SACC-LM and SACC-83.@*Methods@#Total RNA and total protein were extracted from 20 salivary adenoid cystic carcinoma (SACC) and normal adjacent tissues frozen in liquid nitrogen to detect RhoA expression. RhoA-siRNA was constructed to transfect two cell lines (SACC-LM and SACC-83) for cytological experiments. The research included an experimental group (RhoA-siRNA transfection), negative control group (siRNA-NC transfection) and blank group by transient transfection with liposomes. Expression of RhoA mRNA and protein as well as the protein expression of biomarkers of epithelial-mesenchymal transition (EMT) were analyzed, including E-cadherin, N-cadherin, and Vimentin. Furthermore, the changes in invasion and migration of cells in each group were analyzed by comparing the number of transmembrane cells in the Transwell assay and the results of the scratch test.@*Results@#Compared with normal adjacent tissues, RhoA protein and mRNA levels increased in SACC tissues. Compared with the control group, the relative expression levels of RhoA mRNA and protein decreased (P < 0.01), the relative expression levels of E-cadherin protein increased, and the relative expression levels of N-cadherin and vimentin protein increased in the experimental group (P < 0.01). Additionally, the trial results revealed that RhoA knockdown restrained cell migration and invasion (P < 0.01).@*Conclusion @#RhoA expression increased in SACC tissue. Silencing RhoA in vitro could effectively restrain cell migration and invasion in SACC-LM and SACC-83 cells through the regulation of EMT signaling pathways.

Effects of N-cadherin silencing on the proliferation and migration of human dental pulp stem cells / 口腔疾病防治

Objective @#To investigate the effects of N-cadherin silencing on the proliferation and migration of human dental pulp stem cells (DPSCs) and to provide experimental evidence for DPSCs-based dental pulp regeneration.@* Methods@# DPSCs were transfected with N-cadherin shRNA lentivirus, and the knockdown efficiency of N-cadherin at both the mRNA and protein levels was confirmed by qRT-PCR and Western blot. The experiment included a negative control group (shRNA -NC) and an N-cadherin shRNA silencing group. Cell proliferation was detected by the CCK-8 method. Cell cycle and apoptosis were assessed by flow cytometry, and cell migration was detected using the Transwell method.@*Results@#N-cadherin shRNA significantly reduced the expression levels of N-cadherin mRNA and protein in DPSCs (P<0.001). The proliferation activity of the N-cadherin shRNA group was significantly greater than that of the shRNA-NC group on the 3rd and 4th days after cell inoculation and lower than that of the shRNA-NC group from the 6th to 8th days (P<0.05). On the 3rd day after cell inoculation, the proportion of cells in S phase and G2 phase in the N-cadherin shRNA group was greater than that in the shRNA-NC group (P<0.05). On the 6th day after cell inoculation, the proportion of cells in S phase and G2 phase in the N-cadherin shRNA group was lower than that in the shRNA-NC group (P<0.05), and the proportion of apoptotic cells in the N-cadherin shRNA group was greater than that in the shRNA-NC group (P<0.01). Low densities cells and high densities cells were inoculated into Transwell upper chamber for 20 h, the number of cells passing through the membrane pores of upper chamber in the N-cadherin shRNA group was greater than that in the shRNA-NC group (P<0.001).@*Conclusion@#Silencing N-cadherin expression can promote the early proliferation and migration of DPSCs.

Association of N-cadherin (CDH2) polymorphisms with schizophrenia susceptibility and clinical symptoms in Han Chinese population / 中华行为医学与脑科学杂志

Objective:A case-control association analysis was performed to investigate if the single nucleotide polymorphisms (SNPs) of N-cadherin(CDH2) gene is implicated in schizophrenia in a Han Chinese population.Methods:A total of 528 patients with paranoid schizophrenia and 528 healthy controls were recruited from northern Henan province to analyze 25 SNPs located in CDH2 gene.The clinical symptoms of 267 first-episode schizophrenia patients were evaluated with positive and negative syndrome scale (PANSS), and the correlation between CDH2 gene and clinical symptoms was analyzed by SNPStats software online.Results:Allele frequencies of rs9951577 and rs1231268 were significantly correlated with schizophrenia( P<0.05), genotype frequency of rs1639387 was significantly correlated with schizophrenia( P=0.044). After gender classification, SNPs rs1789470 and rs28365328 were found to be significantly correlated with schizophrenia in female patients ( P=0.044, 0.019). In addition, the study found that CDH2 was correlated with the clinical characteristics of schizophrenia( P<0.05), and the negative factor score of patients between GG type rs1231268 and the other two genotypes (AG+ AA) ((21.12±8.41) vs (18.87±7.52)) was statistically significant ( P<0.05). Conclusion:CDH2 gene may be one of the susceptibility genes to SZ, and has definite correlation with clinical negative symptoms.

Modified Wenjingtang Affects Caspase-8， MMP-9， N-cadherin and E-cadherin in Local Microenvironment of EM Rats with Kidney Deficiency and Blood Stasis / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect and mechanism of modified Wenjingtang on endometriosis （EM） rats with kidney deficiency and blood stasis. Method:Healthy non-pregnant female Sprague-Dawley （SD） rats of SPF grade were randomly divided into the blank group and experimental group. After being modeled via soaking in ice water and subcutaneous injection of epinephrine hydrochloride， the ones in the experimental group were further divided into the sham operation group and EM model group， with the former only undergoing laparotomy and the latter further receiving autologous endometrial transplant for triggering EM. The successfully modeled rats with EM due to kidney deficiency and blood stasis were randomized into the positive drug （danazol， 63 mg·kg^-1） group and low- （5 g·kg^-1）， medium- （10 g·kg^-1）， and high-dose （20 g·kg^-1） modified Wenjingtang groups. The corresponding drugs were administered by gavage， once per day， for four weeks. Then the ectopic and eutopic endometrial tissues were stained with hematoxylin-eosin （HE） to observe the histopathological changes. The protein and mRNA expression levels of cysteinyl aspartate-specific proteinase-8 （Caspase-8）， matrix metalloproteinase-9 （MMP-9）， N-cadherin， and E-cadherin were detected by immunohistochemistry （IHC）， Western blotting， and real-time polymerase chain reaction （Real-time PCR）， respectively. Result:The IHC and Western blot revealed that the protein expression levels of MMP-9 and N-cadherin in eutopic and ectopic endometrial tissues of the model group were significantly increased as compared with those in the sham operation group （<italic>P</italic><0.01）， while the levels of Caspase-8 and E-cadherin was significantly decreased （<italic>P</italic><0.01）. Compared with the model group， the danazol and low-， medium-， and high-dose modified Wenjingtang groups exhibited obviously down-regulated MMP-9 and N-cadherin protein expression in eutopic and ectopic endometrial tissues （<italic>P</italic><0.05，<italic>P</italic><0.01）， but up-regulated Caspase-8 and E-cadherin （<italic>P</italic><0.05， <italic>P</italic><0.01）. Real-time PCR uncovered that the mRNA expression levels of MMP-9 and N-cadherin in eutopic and ectopic endometrial tissues of the model group were significantly elevated as compared with those in the sham operation group （<italic>P</italic><0.01）， whereas the levels of Caspase-8 and E-cadherin significantly declined （<italic>P</italic><0.01）. The comparison with the eutopic endometrial tissue in the model group showed that the mRNA expression levels of MMP-9 and N-cadherin in the danazol group and high- and medium-dose modified Wenjingtang groups were significantly down-regulated， while those of Caspase-8 and E-cadherin were significantly up-regulated （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Modified Wenjingtang alleviates the immunosuppression and blocks the angiogenesis in EM rats with kidney deficiency and blood stasis syndrome by regulating the expression of such cytokines as Caspase-8， MMP-9， N-cadherin， and E-cadherin， thus exerting the therapeutic effect against EM. The above-mentioned micro-indicators are potential markers reflecting the disease （EM）， syndrome （kidney deficiency and blood stasis）， and pathological mechanisms （immunosuppression and angiogenesis）.

Effects of polygonatum polysaccharide on p38 MAPK/N-cadherin in zebrafish with Alzheimer disease / 中国药理学与毒理学杂志

OBJECTIVE To study the effect of polygonatum polysaccharide on zebrafish with Alzheimer disease. METHODS Zebrafish were trained in T maze for 7 d. The 40 zebrafish successfully trained were divided into 4 groups:blank group, model group, positive group and polygonatum polysaccharide group. Model group, positive group and polygonatum polysaccharide group were put in AlCl3100μg·L-1 for 6 d. The positive group was exposed to Huperzine A solution 4μg·L-1, and the polygonatum polysaccharide group was exposed to polygonatum polysaccharide solution 6 g·L-1 for 6 d. The model group was not treated, and the blank group was not treated. Each stage of zebrafish was recorded by video, and the time of each group in the EC region was analyzed. After administration, the brain tissue was taken out and the expression of N-cadherin, P38 and p-P38 protein factors was determined by Western blotting. RESULTS In behavior, the analysis of the time spent in the EC area, the blank group, the positive group and the polygonatum polysac?charide group were compared with the model group, respectively, there were statistically significant differences (P<0.05). At the protein level, compared with the model group, the P38 and p-P38 proteins in the positive group and the polygonatum polysaccharide group were down-regulated, while the N-cadherin protein was up-regulated, with statistical difference (P<0.05). CONCLUSION Polygonatum polysaccharide can improve the learning and memory ability of zebrafish with Alzheimer disease by up regulating the protein level of N-cadherin and hindering P38 phosphorylation.

Effect of N-cadherin on Proliferation，Migration and Invasion of Retinal Pigment Epithelial Cells / 中山大学学报(医学科学版)

@#【Objective】To clarify the role of neuro-cadherin（N-cadherin）in epithelial-mesenchymal transition of diabetic retinopathy，and to investigate the effect of N-cadherin on proliferation ，migration and invasion of retinal pigment epithelial cells.【Methods】Cells were turned into over-expressed or silenced N-cadherin by using Ad-N-cadherin （Ad-N-cad）and Ad-si N-cadherin（si N-cad）. Glucose（25 mmol/L）was used to simulate high glucose（HG）condi⁃ tions. Cell Counting Kit-8（CCK-8）kit was used to detect cell proliferation. Transwell chamber was used to detect the vertical migration and invasion of cells.【Results】Transwell assay showed N-cadherin over-expression increased the num⁃ ber of cells migrated to the transwell subventricular chamber. The difference was statistically significant（P < 0.05）. The number of ARPE19 cells that migrated to or invaded the transwell subventricular chamber increased after high glucose treatment. N-cadherin knockdown suppressed high glucose-induced migration and invasion（P < 0.05）. CCK8 results showed N-cadherin knockdown could inhibit cell proliferation induced by high glucose（P < 0.05）.【Conclusion】N-cad⁃ herin may promote cell migration，and down-regulation of N-cadherin can inhibit cell proliferation，migration and inva⁃ sion induced by high glucose.

Expression of ubiquitin-conjugating enzyme E2S in malignant melanoma and its effect on the biological behavior of melanoma cells / 中华皮肤科杂志

Objective To determine the expression of ubiquitin-conjugating enzyme E2S (UBE2S) in malignant melanoma (MM),and to evaluate its effect on the biological behavior of melanoma cells.Methods Immunohistochemical study was performed to determine the UBE2S expression in 128 primary MM tissue chips,64 metastatic MM tissue chips,16 non-tumor tissue chips (8 paralesional normal skin tissues and 8 normal epidermal tissues).Real-time quantitative RCR was conducted to determine the UBE2S mRNA expression in the melanoma cell lines A375,MUM-2B and MUM-2C.The melanoma cell lines A375 and MUM-2B were divided into 2 groups separately:interference group transfected with a lentiviral vector carrying UBE2S RNA interference sequence,and control group transfected with a lentiviral vector carrying control sequence.After 72 hours,real-time quantitative RCR was performed to determine the UBE2S mRNA expression in the melanoma cell lines A375 and MUM-2B.Caspase-3/7 activity in the groups was assessed by using kits,and cell apoptosis and cell cycle distribution were detected by flow cytometry.The effect of UBE2S knockdown on the migratory and invasive abilities of and N-cadherin expression in A375 cells were evaluated by Transwell assay and Western blot analysis respectively.Statistical analysis was carried out with SPSS 22.0 software by using independent sample t-test for the comparison of normally distributed data between two groups,chi-square test for enumeration data,MannWhitney U test for the comparison of non-normally distributed data,and Spearman's coefficient for assessment of the correlation of UBE2S expression with T staging of melanoma.Results UBE2S was highly expressed in 98 (51.0％) MM tissues,but lowly expressed in 16 non-tumor tissues,and the UBE2Sexpression rate significantly differed between the above two kinds of tissues (x2 =11.905,P ＜ 0.01).UBE2S expression was negatively correlated with T staging of melanoma (ρ =-0.210,P =0.043).The relative mRNA expression of UBE2S significantly differed among the A375,MUM-2B,and MUM-2C cells (F =817.228,P ＜ 0.01).After UBE2S knockdown,the caspase-3/7 activity was significantly up-regulated in the A375 interference group (t =17.572,P ＜ 0.01) and MUM-2B interference group (t =24.552,P ＜0.01) compared with the A375 and MUM-2B control groups respectively.Compared with the control group,the A375 interference group showed significantly increased proportion of A375 cells at G1 phase (t =7.365,P ＜ 0.01),decreased proportion at S phase (t =-9.190,P ＜ 0.01),and no change in the proportion of A375 cells at G2/M phase (t =-0.227,P ＞ 0.05).The MUM-2B interference group showed significantly increased proportions of MUM-2B cells at G1 (t =12.676,P ＜ 0.01) and G2/M phases (t =13.045,P ＜0.01),but significantly decreased proportion at S phase (t =-15.718,P ＜ 0.01) compared with the control group.Transwell assay revealed decreased migratory and invasive abilities of A375 cells in the interference group compared with the control group (t =-35.727,-125.000,P ＜ 0.05,＜ 0.01,respectively).Western blot analysis showed down-regulated expression of N-cadherin protein in A375 cells in the interference group compared with the control group.Conclusions UBE2S is over-expressed in melanoma tissues,whose expression is associated with the T staging of melanoma.Knockdown of UBE2S affects the apoptosis,cell cycle,migration and invasion of melanoma cells,and may promote the metastasis of MM cells by regulating N-cadherin expression.

Expressions of N-cadherin, E-cadherin and P63 Protein in Hepatocellular Carcinoma and Their Clinical Significance / 医学研究杂志

Objective To explore the expressions of N-cadherin,E-cadherin,and P63 protein in hepatocellular carcinoma (HCC) tissues,and the relationship between their expressions and clinicopathologic factors.Methods Immuohistochemistry was used to detect the expressions of N-cadherin,E-cadherin,and P63 protein in 60 normal liver tissues,60 HCC tissues and their peficancerous tissues,and then the relationship between their expressions and clinicopathologic factors were analyzed.Results The positive expression rates of N-cadherin in normal liver tissue,peficancerous tissues and HCC tissue were gradually decreased,the difference was statistically significant (P ＜ 0.05).And The positive expression rates of E-cadherin in normal liver tissue,peficanceroustissues and HCC tissue were gradually increased,the difference was statistically significant (P ＜ 0.05).The expression of P63 in normal liver tissue was significantly higher than that in peficancerous tissues and HCC tissue,and the differences wcrc all significant(P ＜ 0.05).The positive rates of expression of N-cadherin were related with clinical stage,portal vein invasion,metastasis and pathological grading.The positive rates of expression of E-cadherin were related with clinical stage,portal vein invasion and pathological grading.The positive rates of expression of P63 were related with clinical stage,tumor sizeand pathological grading.Spearman rank correlation analysis showed that the expression of P63was positively correlated with the expression of E-cadherin,but negatively correlated with the expression of N-cadherin.Conclusion The high expression of N-cadherin and low expression of P63 protein,E-cadherin of HCC tissues may play a role in tumor metastasis and carcinogenesis.

Effect of soyasaponin on drug resistance of ovarian cancer cells / 中国药理学通报

Aim To screen the most effective soyasa-ponins for reversing the drug resistance of ovarian cancer cells, and investigate the possible mechanism. Methods Cell viability assay was used to analyze the drug resistance of A2780/PTX cells treated with four different common soyasaponins respectively,in order to screen out the most effective soyasaponin. Then, the most effective soyasaponin was used to detect the ex-pression of epithelial-mesenchymal transition ( EMT)-related marker proteins, including N-cadherin and E-cadherin,with Western blot and confocal microsco-py. Finally, transwell assay and wound healing assay were applied to observe effect of soyasaponin on regula-ting cancer cell migration. Results Compared with other soyasaponins,soyasaponin Ac most effectively re-versed the drug resistance of A2780/PTX cells. The expression of N-cadherin decreased while that of E-cadherin increased in A2780/PTX cells when treated with soyasaponin Ac for 48 h. The results of transwell and wound healing assay suggested that soyasaponin Ac also reduced the migration of A2780/PTX cells. Con-clusion Soyasaponin Ac can decrease the drug resist-ance via EMT pathway and weaken the migration abili-ty of ovarian cancer cells.

Clinical study on expressions of transcription factor Snail and its related proteins in non-small cell lung cancer / 肿瘤研究与临床

Objective To detect the expressions of transcription factor Snail,E-cadherin(E-cad)and N-cadherin(N-cad)in non-small cell lung cancer(NSCLC),and explore their correlations.Methods The expression patterns of Snail,E-cad and N-cad in human lung tissues were detected by immunohistochemistry,from 59 untreated NSCLC patients in Affiliated Cancer Hospital of Xinjiang Medical University from January 2014 to December 2015 for whom clinical data were available,with adjacent tissues and 31 benign lesions as control.The expression patterns of Snail,E-cad,N-cad and clinicopathological factors were analyzed.Results The positive rate of Snail and N-cad in NSCLC was significantly higher than those in the control tissues [81.4％(48/59)vs.37.3％(22/59)vs.12.9％(4/31),χ2=9.782,P <0.05; 76.3％(45/59)vs.33.9％(20/59)vs.12.9％(4/31),χ2= 7.445,P< 0.05].The positive rate of E-cad in NSCLC was significantly lower than those in the control tissues [20.3％(12/59)vs.55.9％(33/59)vs.93.5％(29/31),χ2= 45.107,P< 0.01].The expressions of Snail and E-cad were related to lymph node metastasis and TNM stage [snail: 97.5％(39/40)vs.47.4％(9/19),χ2=7.734,P <0.05; 12.5％(1/8)vs.81.0％(17/21)vs.100.0％(30/30),χ2=7.723,P<0.05; E-cad: 95.0％(38/40)vs.36.8％(7/19),χ 2=7.190,P<0.05; 100.0％(8/8)vs.19.0％(4/21)vs.0(0/30),χ 2= 12.311,P < 0.01].The expression of N-cad was related to lymph node metastasis,histological grade and TNM stage [97.5％(39/40)vs.47.4％(9/19),χ2=11.231,P <0.01; 28.6％(2/7)vs.63.6％(14/22)vs.96.7％(29/30),χ2=9.564,P <0.05; 12.5％(1/8)vs.85.7％(18/21)vs.86.7％(26/30),χ 2= 11.664,P<0.01].The positive correlation was found between Snail and N-cad(r=0.373,P<0.01),the negative correlation was found between the expression of Snail and E-cad,N-cad and E-cad(r =-0.667,P= 0.00;r=-0.297,P=0.01).Conclusion Snail,E-cad and N-cad are involved in the development,progression and metastasis of NSCLC,and combined detection can predict tumor invasion,metastasis and prognosis.

Analysis of the Epithelium-Mesenchymal Transition Process on Oral Squamous Cell Carcinomas

Abstract The aim of this study is to evaluate the immunohistochemical expression of E-cadherin, N-cadherin and Bmi-1, and their association with clinical parameters and with the degree of histopathological differentiation in oral squamous cell carcinomas. 65 squamous cell carcinoma samples were used for constructing a tissue microarray block, and then immunohistochemistry was performed for different markers. A semi-quantitative analysis of the amount of positive tumor cells was performed by two blind and calibrated observers (Kappa>0.75). The statistical Mann-Whitney and Kruskal-Wallis tests were used to evaluate the data. The correlation between variables was investigated by the Spearman test, and the significance level set at p<0.05. We observed higher expression of Bmi-1 in tumors located in the palate (p<0.0001). In addition, poorly differentiated tumors had a greater amount of Bmi-1 positive cells (p=0.0011). Regarding the other correlations between variables, no significant associations were detected. In conclusion, poorly differentiated squamous cell carcinomas located in the palate have higher immunostaining of Bmi-1, which can characterize activation of the Epithelial-Mesenchymal Transition process in these tumors.

Resumo O objetivo deste estudo foi avaliar a associação entre a expressão imunoistoquímica de E-caderina, N-caderina e Bmi-1, com os parâmetros clínicos e o grau de diferenciação em carcinomas espinocelulares bucais. Sessenta e cinco amostras foram selecionadas para a construção de um bloco de microarranjo tecidual, e a técnica de imunoistoquímica foi realizada para os diferentes marcadores. Uma análise semi-quantitativa das células tumorais positivas foi realizada por dois observadores calibrados e cegos (Kappa>0.75). Os testes estatísticos Mann-Whitney e Kruskal-Wallis foram utilizados para a análise dos dados e a correlação entre as variáveis foi investigada com o teste de Spearman. O nível de significância foi determinado em p <0.05. Observamos maior expressão de Bmi-1 em tumores localizados em palato (p <0.0001). Além disso, tumores pobremente diferenciados apresentaram maior quantidade de células positivas para Bmi-1 (p=0.0011). Não encontramos outras correlações ou associações significativas. Em conclusão, carcinomas espinocelulares pobremente diferenciados e localizados no palato apresentam maior marcação imunoistoquímica de Bmi-1, o que pode caracterizar a ativação do processo de transição epitélio-mesênquima nesses tumores.

The expression changes observation of N-Cadherin and Bax in myocardial tissue after sudden cardiac death and evaluation / 中国法医学杂志

Objective To investigate the expression changes of victims suffering from sudden cardiac death(SCD), eurological calcium adhesion proteins (N-Cadherin) and Bax and explore their significance in forensic medicine. Methods Separately select 33 samples of myocardial tissue suffering from sudden cardiac death and 29 samples of myocardial tissue from the cases which were diagnosed not dying of heart disease as SCD and controls. Histological methods were used to examine the morphologic changes in myocardial tissue, examining the expression changes of N-Cadherin and Bax and analyzing them in a statistic way. Results N-Cadherin was weakly positively expressed in myocardial tissue of group SCD and the cells shew disordered arrangement, which is obviously lower than the controls. The cells exhibited obvious features ordered arrangement in control group. The positive expression of Bax was detected in myocardial tissue of group SCD, which is obviously higher than the controls. Conclusion The expression changes observation of N-Cadherin and Bax will make a difference to the sudden cardiac death.

Effects of bisphenol A on the expression of N-cadherin, Vimentin and FSHR in rat Sertoli cells / 中华劳动卫生职业病杂志

Objective@#To explore the effects of BPA on the expression of N-cadherin, Vimentin and FSHR in rat Sertoli cells.@*Methods@#Primary Sertoli cells collected from prepuberty rats (18-21 d) were cultured for 48 h, and then they were treated with 0, 30, 50, 70 μmol/L BPA respectively for 24 h. The methods of MTT, real-time quantitative PCR and Western blotting were utilized to measure the cell ability of Sertoli cells, the mRNA and protein expression levels of N-cadherin, Vimentin and FSHR respectively.@*Results@#Compared with control, the cell abilities of Sertoli cells in 50 μmol/L BPA group and 70 μmol/L BPA group increased significantly (P<0.05) . The cell abilities of Sertoli cells decreased with the increases of exposure doses of BPA. Compared with control, the expression of N-cadherin mRNA only increased in 30 μmol/L BPA group (P<0.05) , the expression of Vimentin mRNA decreased significantly in all doses group of BPA (P<0.05) , the expression of FSHR mRNA increased in all doses group of BPA (P<0.05) . Compared with the control, the protein levels of N-cadherin increased significantly in 50 μmol/L BPA group (P<0.05) , the protein levels of Vimentin decreased significantly in all doses group of BPA (P<0.05) , the protein levels of FSHR decreased significantly in 50 μmol/L BPA group and 70 μmol/L BPA group (P<0.05) .@*Conclusion@#The mechanism of testicular toxicity from BPA might be the alterations of N-cadherin, Vimentin and FSHR by disturbing normal spermatogenesis.

Expression and Clinicopathological Significance of N-cadherin in the Ovarian Carcinoma / 现代生物医学进展

Objective:To explore the expression of N-cadherin and its correlations with the clinicopathological features of human ovarian carcinoma.Methods:The expression of N-cadherin in 281 cases of ovarian carcinoma tissues were determined by immunohistochemical method.The correlations of N-cadherin expression with the clinicopathological features of human ovarian carcinoma were analyzed.Results:There was higher expression of N-cadherin in the metastatic lesions than its paired primary lesions (P =0.018).The expression level of N-cadherin in ovarian carcinoma was correlated with the FIGO stage (P =0.034),histological type (P ＜0.001) and tumor grade (P =0.004).Conclusions:High expression of N-cadherin might positively correlate with the invasion and migration ability of ovarian carcinoma cells,which was more common in the the advanced (FIGO Ⅱ-Ⅳ) ovarian carcinoma,high-grade serous carcinoma,and high grade ovarian carcinoma.N-cadherin might be useful in estimating the biological behavior of human ovarian carcinoma.

Effects of Capsaicin on Proliferation,Migration and Invasion of Human Large Cell Carcinoma NCI-H460 / 医药导报

Objective To investigate effects of capsaicin on proliferation,migration and invasion of human large cell carcinoma NCI-H460 and discuss the possible mechanisms by which capsaicin inhibits non-small cell lung cancer. Methods NCI-H460 cells were cultured in vitro and treated with capsaicin at various concentrations. Colony formation assay,wound healing assay,and transwell chamber invasion assay were used to detect the effects of capsaicin on proliferation,migration and invasion of NCI-H460 cells. Western blotting was used to detect the protein expression of E-cadherin,N-cadherin,Vimentin and Snail. Results The rate of colony formation of 100,200,300 μmol.L-1 of capsaicin were (91.17±24.38)%,(43.22±12.91)% and (15.71±4.26)%,respectively,the control group was (99.53±21.25)%.the rate of migration of NCI-H460 cells of 25,50, 100 μmol.L-1 of capsaicin were (85.83±17.43)%,(37.92±10.16)% and(21.08±6.39)%,respectively,the control group was (93.04±20.23)%.The number of invasion of NCI-H460 cells of 25,50,100 μmol.L-1 of capsaicin were (99±18.2),(75± 17.9) and( 52 ± 14. 1 ) , respectively, the control group was ( 107 ± 20. 4 ) . The middle and high-dose capsaicincould inhibit proliferation,migration and invasion of NCI-H460 cells ( P<0.05) ,and E-cadherin expression level was significantly up-regulated and N-cadherin, Vimentin, Snail expression level was significantly down-regulated ( P<0. 05 ) . Conclusion Capsaicin can inhibit proliferation,migration and invasion of NCI-H460 cells,the mechanism may be related to up-regulation of E-cadherin and down-regulation of N-cadherin,Vimentin and Snail expression levels.

Research progress of application of E-cadherin, N-cadherin and vimentin in tumor metastasis / 肿瘤研究与临床

The invasion and metastasis of tumor as the primary cause of death in cancer increases not only the patient's suffering, but also the difficulty of clinical treatment. It is an important guiding to find the molecular biological tumor markers and gene targets of antirecurrence and antimetastasis for clinical treatment. The invasion and metastasis of tumor is a complex process including the biological characteristics of the cancer, interaction among host cells, extracellular matrix and cancer cells, etc. Recently, epithelial mesenchymal transition (EMT) is becoming a hot spot in oncology research by virtue of its effect on genesis and development of tumor. Currently, the known markers of EMT include epithelial marker proteins mainly containing E-cadherin and interstitial marker proteins mainly containing N-cadherin and vimentin. It is necessary to make a summary among the studies on three proteins.