上皮钙黏素/链接素黏附复合体在鼻咽癌组织中的表达及意义

目的探讨鼻咽癌组织中上皮钙黏素(E-CAD)、β-链接素(β-CAT)和α-链接素(α-CAT)的表达情况及与临床病理特征的关系。方法应用免疫组化SP法检测52例鼻咽非角化癌及其癌旁黏膜组织中E-CAD、β-CAT和α-CAT的表达。结果鼻咽癌组织中E-CAD、β-CAT及α-CAT的异常表达率分别为48.1%、32.7%及34.6%,而全部52例癌旁黏膜上皮中均正常表达E-CAD、β-CAT和α-CAT,癌组织的异常表达率显著高于癌旁组织(P<0.05)。鼻咽癌的E-CAD、β-CAT、α-CAT表达之间呈正相关(P<0.05)。α-CAT正常表达的鼻咽癌患者外周血中抗EB病毒病毒壳抗原IgA(VCA-IgA)滴度高于异常表达者(P<0.01)。E-CAD、β-CAT、α-CAT的表达与其他临床病理特征无相关性。结论鼻咽非角化癌中E-CAD/β-CAT/α-CAT黏附复合体明显异常表达,三者表达具有一致性。E-CAD、β-CAT、α-CAT表达下调与鼻咽癌临床分期和淋巴结转移缺乏必然联系。     

Prognostic significance of E-cadherin/catenin complex expression in gastric cancer

Abnormal expression of E-cadherin/catenin complex in cancer has been associated with poor differentiation and acquisition of invasiveness, suggesting a possible role of this protein as an invasion suppressor. In this study, we conducted an immunohistochemical investigation of all components of the E-cadherin/catenin complex in 65 gastric cancer patients. Abnormal expression of E-cadherin and, alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal type of gastric cancer, and correlated with poor differentiation. Abnormal expression of E-cadherin and beta-catenin correlated with poor survival. Abnormal expression of all four components of the complex was associated with poorly differentiated and diffuse-type carcinoma, and poor survival. In the multivariate analysis, abnormal expression of the E-cadherin/catenin complex was not an independent prognostic factor. These results suggest that the E-cadherin/catenin complex may be a useful marker of differentiation and prognosis in gastric cancer. Further studies are warranted to clarify the impact of the E-cadherin/catenin complex on prognostic factor of gastric cancer.     

Reduced expression of the cadherin–catenin complex in oesophageal adenocarcinoma correlates with poor prognosis

The E-cadherin–catenin complex is important for cell–cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. Oesophageal adenocarcinomas causes early metastases, progress rapidly, and consequently have a poor prognosis. By means of immunohistochemistry, the expression of E-cadherin and alpha- and beta-catenin was studied in 65 oesophageal adenocarcinomas and 15 lymph node metastases. Expression of these proteins was evaluated with respect to clinico-pathological parameters and patient survival. Expression of the proteins was strongly correlated. In carcinomas, reduced expression of E-cadherin, alpha-catenin, and beta-catenin was found in 74, 60, and 72 per cent, respectively. Expression of E-cadherin and alpha-catenin correlated significantly with stage and grade of the carcinomas, whereas expression of beta-catenin correlated only with grade. Reduced expression of all three proteins correlated with shorter patient survival. In contrast to grade, E-cadherin and beta-catenin were significant prognosticators for survival, independent of disease stage. We conclude that in oesophageal adenocarcinomas, decreased expression of E-cadherin, alpha-catenin and beta-catenin are related events. Furthermore, expression of at least E-cadherin and beta-catenin is significantly correlated with poor prognosis. © 1997 John Wiley & Sons, Ltd.     

Linear head displacement measured by the otoliths can be reproduced through the saccadic system

Fifty-nine Purkinje cells that responded to electrical stimulation of the glossopharyngeal (IXth) nerve with complex and/or simple spikes were isolated in the frog cerebellum. For these 59 Purkinje cells, changes in the complex and simple spike activity during taste stimulation of the tongue (42 cells for NaCl and 17 for quinine) were investigated. Of 42 Purkinje cells, 23 (54.8%) showed excitatory changes in simple and/or complex spike discharge rate during NaCl stimulation, and the remaining 19 (45.2%) showed no response. On the contrary, only a few Purkinje cells (2 of 17 cells, 11.8%) showed an excitatory change in simple or complex spike discharge rate during quinine stimulation. These results demonstrate that gustatory information influences cerebellar Purkinje cell activity.     

Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours.

AIMS: Compelling evidence from cell culture studies implicates cadherins in the neoplastic progression of melanocytic tumours but few reports describe the expression of cadherins and the related transmembrane proteins, catenins, in a full range of benign and malignant excised melanocytic tumours. METHODS: Using immunohistochemistry and western blotting after tissue fractionation, the pattern of expression of cadherins/catenins was studied in a range of surgically excised melanocytic tumours, from dysplastic naevi to stage III cutaneous metastatic malignant melanoma. RESULTS: Appropriate membranous expression of E-cadherins and P-cadherins is seen in dysplastic naevocytes with an epithelioid phenotype and is largely maintained with malignant transformation to radial growth phase melanoma and primary vertical growth phase malignant melanoma. Loss of membranous E-cadherin is seen in a small number of vertical growth phase melanomas only when metastasis has occurred. However, there is a concomitant dramatic loss of membranous P-cadherin expression in all melanomas at the same stage. A minority of metastatic melanomas show de novo membranous N-cadherin expression in comparison with dysplastic naevi and primary melanoma. Membranous expression of the desmosomal cadherin, desmoglein, was not seen in any tumour studied. Frequently, beta catenin is aberrantly produced in the cytoplasm of cells in dysplastic naevi and metastatic malignant melanoma, with an implied compromise to adhesive function. Furthermore, membranous gamma catenin expression was not seen in any of the 70 melanocytic tumours studied, implying obligatory transmembrane binding of cadherins to beta catenin for maintenance of adhesive function. CONCLUSIONS: The most important alterations in membranous cadherin and catenin expression are seen late in the biological progression of melanocytic tumours at the stage of "in transit" or regional lymph node metastasis, with implications for tumour growth, invasion, and dissemination.     

Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours.

AIMS: Compelling evidence from cell culture studies implicates cadherins in the neoplastic progression of melanocytic tumours but few reports describe the expression of cadherins and the related transmembrane proteins, catenins, in a full range of benign and malignant excised melanocytic tumours. METHODS: Using immunohistochemistry and western blotting after tissue fractionation, the pattern of expression of cadherins/catenins was studied in a range of surgically excised melanocytic tumours, from dysplastic naevi to stage III cutaneous metastatic malignant melanoma. RESULTS: Appropriate membranous expression of E-cadherins and P-cadherins is seen in dysplastic naevocytes with an epithelioid phenotype and is largely maintained with malignant transformation to radial growth phase melanoma and primary vertical growth phase malignant melanoma. Loss of membranous E-cadherin is seen in a small number of vertical growth phase melanomas only when metastasis has occurred. However, there is a concomitant dramatic loss of membranous P-cadherin expression in all melanomas at the same stage. A minority of metastatic melanomas show de novo membranous N-cadherin expression in comparison with dysplastic naevi and primary melanoma. Membranous expression of the desmosomal cadherin, desmoglein, was not seen in any tumour studied. Frequently, beta catenin is aberrantly produced in the cytoplasm of cells in dysplastic naevi and metastatic malignant melanoma, with an implied compromise to adhesive function. Furthermore, membranous gamma catenin expression was not seen in any of the 70 melanocytic tumours studied, implying obligatory transmembrane binding of cadherins to beta catenin for maintenance of adhesive function. CONCLUSIONS: The most important alterations in membranous cadherin and catenin expression are seen late in the biological progression of melanocytic tumours at the stage of "in transit" or regional lymph node metastasis, with implications for tumour growth, invasion, and dissemination.     

Stromal CD10 expression and relationship to the E‐cadherin/β‐catenin complex in breast carcinoma

Kim H‐S, Kim G Y, Kim Y W, Park Y‐K, Song J‐Y & Lim S‐J
(2010) Histopathology 56, 708–719
Stromal CD10 expression and relationship to the E‐cadherin/β‐catenin complex in breast carcinoma Aims: Previous investigations have indicated that stromal CD10 expression, and altered levels of both E‐cadherin and β‐catenin, are associated with the biological aggressiveness of human carcinoma. The aim was to evaluate stromal CD10 expression and the association of stromal CD10 with E‐cadherin and β‐catenin in breast carcinoma. Methods and results: The expression of CD10, E‐cadherin and β‐catenin was immunohistochemically analysed in tissue microarrays containing 104 cases of invasive ductal carcinoma (IDC) and 10 cases of ductal carcinoma in situ (DCIS). Stromal CD10 was detected in 49.5% (50/101) of the IDC. No immunoreactivity was identified in the stromal cells of normal breast, DCIS or intraductal components of IDC. Accumulation of the cytoplasmic β‐catenin was found in 87.0% (87/100) of the IDC. Stromal CD10 expression in IDC was significantly correlated with tumour size (P = 0.027), stage (P < 0.001) and histological grade (P = 0.006), the presence of nodal (P = 0.048) and distant (P = 0.015) metastases, oestrogen receptor‐negative status (P = 0.016), cytoplasmic β‐catenin accumulation (P = 0.031) and lower overall survival rate (P = 0.041). Conclusions: Stromal CD10 expression in IDC may constitute an important prognostic marker. Stromal CD10 expression with associated aggressive features might be related to aberrant β‐catenin expression.     

Age-related decline in cold tolerance can be retarded by brain stimulation

The sharp decline in capacity of old C57BL/6J male mice to maintain body temperature during 3-hr cold exposure can be delayed and even partly restored after 15, 30-min, daily sessions of hypothalamic self-stimulation. In control experiments it was demonstrated that electrical stimulation of “rewarding” areas of hypothalamus itself is sufficient for improvement of the age-related deterioration of thermoregulatory ability.     

水通道蛋白-4 mRNA沉默可抑制离体缺氧星形胶质细胞水通道蛋白-4的表达

目的:研究水通道蛋白-4(AQP4) mRNA沉默对体外缺氧星形胶质细胞AQP4表达的影响.方法: 用氯化钴诱导体外星形胶质细胞缺氧,建立AQP4 mRNA沉默缺氧星形胶质细胞模型.随机分为正常组、对照组、缺氧组和干扰组,观察星形胶质细胞形态,免疫细胞化学、荧光定量PCR、免疫印迹法检测AQP4 mRNA 及蛋白表达....     

Angiogenesis-related gene expression analysis in celiac disease

Celiac Disease (CD) involves disturbance of the small-bowel mucosal vascular network, and transglutaminase autoantibodies (TGA) have been related to angiogenesis disturbance, a complex phenomenon probably also influenced by common genetic variants in angiogenesis-related genes. A set of genes with “angiogenesis” GO term identified in a previous expression microarray experiment (SCG2, STAB1, TGFA, ANG, ERBB2, GNA13, PML, CASP8, ECGF1, JAG1, HIF1A, TNFSF13 and TGM2) was selected for genetic and functional studies. SNPs that showed a trend for association with CD in the first GWAS were genotyped in 555 patients and 541 controls. Gene expression of all genes was quantified in 15 pairs of intestinal biopsies (diagnosis vs. GFD) and in three-dimensional HUVEC and T84 cell cultures incubated with TGA-positive and negative serum. A regulatory SNP in TNFSF13 (rs11552708) is associated with CD (p = 0.01, OR = 0.7). Expression changes in biopsies pointed to TGM2 and PML as up-regulated antiangiogenic genes and to GNA13, TGFA, ERBB2 and SCG2 as down-regulated proangiogenic factors in CD. TGA seem to enhance TGM2 expression in both cell models, but PML expression was induced only in T84 enterocytes while GNA13 and ERBB2 were repressed in HUVEC endothelial cells, with several genes showing discordant effects in each model, highlighting the complexity of gene interactions in the pathogenesis of CD. Finally, cell culture models are useful tools to help dissect complex responses observed in human explants.     

Angiogenesis-related gene expression analysis in celiac disease

Celiac disease (CD) involves disturbance of the small-bowel mucosal vascular network, and transglutaminase autoantibodies (TGA) have been related to angiogenesis disturbance, a complex phenomenon probably also influenced by common genetic variants in angiogenesis-related genes. A set of genes with "angiogenesis" GO term identified in a previous expression microarray experiment (SCG2, STAB1, TGFA, ANG, ERBB2, GNA13, PML, CASP8, ECGF1, JAG1, HIF1A, TNFSF13 and TGM2) was selected for genetic and functional studies. SNPs that showed a trend for association with CD in the first GWAS were genotyped in 555 patients and 541 controls. Gene expression of all genes was quantified in 15 pairs of intestinal biopsies (diagnosis vs. GFD) and in three-dimensional HUVEC and T84 cell cultures incubated with TGA-positive and negative serum. A regulatory SNP in TNFSF13 (rs11552708) is associated with CD (p = 0.01, OR = 0.7). Expression changes in biopsies pointed to TGM2 and PML as up-regulated antiangiogenic genes and to GNA13, TGFA, ERBB2 and SCG2 as down-regulated proangiogenic factors in CD. TGA seem to enhance TGM2 expression in both cell models, but PML expression was induced only in T84 enterocytes while GNA13 and ERBB2 were repressed in HUVEC endothelial cells, with several genes showing discordant effects in each model, highlighting the complexity of gene interactions in the pathogenesis of CD. Finally, cell culture models are useful tools to help dissect complex responses observed in human explants.     

Comparison of integrin,cadherin, and catenin expression in squamous cell carcinomas of the oral cavity

In addition to their role in maintenance of tissue integrity, cell adhesion molecules regulate the growth and differentiation of stratified squamous epithelia. Reduced expression of E-cadherin and the α₂β₁, α₃β₁ and α₆β₄ integrins is already reported to correlate with poor histological differentiation in oral squamous cell carcinomas. However, it is not clear how closely cadherin and integrin loss are related in any given tumour, nor whether cadherin loss is correlated with changes in expression of the cytoplasmic regulatory proteins known as catenins. Double-label immunofluorescence has been used to stain a panel of 22 oral squamous cell carcinomas with antibodies to ten proteins, including E- and P-cadherin, the major keratinocyte integrin subunits, and α-, β- and γ-catenin. Overall, E-cadherin expression and integrin expression correlated well with tumour grade, while P-cadherin staining was more variable. All tumours, regardless of differentiation status, showed reduced staining for at least two of the catenins, implying that the adhesive function of E- and P-cadherin could be impaired even when cadherin expression is normal. It is concluded that in all squamous cell carcinomas, regardless of degree of histological differentiation, there is some perturbed expression of cell adhesion molecules and that integrin and E-cadherin loss are closely related. © 1998 John Wiley & Sons, Ltd.     

Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma.

AIMS: To investigate alpha catenin expression in surgically resected human colorectal cancers to evaluate its prognostic value during long term follow up. METHODS: Immunohistochemistry was used to compare the expression of alpha catenin with conventional prognostic factors in 187 colorectal cancer patients treated in Kuopio University Hospital and followed up for a mean of 14 years. The hypothesis that the intensity of expression of alpha catenin and its distribution in cancer cells is correlated with survival was tested with the long-rank test, hazard ratios, and their confidence intervals. RESULTS: Uniform membranous alpha catenin staining localised to the intercellular borders was observed in 46% of the tumours; 55% of all tumours had either heterogeneous or negative alpha catenin expression, and staining intensity was either negative or weak in 42% of the tumours. The cancer related and recurrence-free survival rates were lower among patients with a weak alpha catenin intensity in tumour epithelium (p < 0.001), a low fraction of positive tumour cells (p < 0.001), and an additional cytoplasmic accumulation of alpha catenin (p < 0.001). In multivariate analysis, the intensity of alpha catenin expression in tumour epithelium predicted cancer related survival independently; alpha catenin localisation in tumour epithelium was an independent prognostic factor of recurrence-free survival in the group as a whole and in the T1-3N0M0 tumour subgroup. CONCLUSIONS: A low proportion of positive carcinoma cells, additional cytoplasmic accumulation of alpha catenin, and reduced expression intensity in tumour epithelium predict a poor survival rate. The results suggest that alpha catenin has prognostic significance in colorectal cancer.     

E-cadherin/catenin complex in benign and malignant melanocytic lesions

E-cadherin is a calcium-dependent cell-cell adhesion molecule expressed by melanocytes and responsible for their adhesion to keratinocytes in vitro. In this study, the expression of E-cadherin and its associated cytoplasmic proteins alpha-, beta-, and gamma-catenin was evaluated in melanocytic lesions by immunohistochemistry. E-cadherin expression was evaluated in 70 malignant melanomas and the catenins in 35 of these specimens. Twenty benign melanocytic naevi were also evaluated for E-cadherin and catenin expression. In normal epidermis, E-cadherin/catenin immunostaining was localized at the intercellular borders. In melanomas, a differential loss of E-cadherin expression was observed. Membranous E-cadherin staining was absent in dermal nests of melanomas in their radial growth phase and in Clark level II and III lesions, whereas it was present in a high proportion of melanomas in their vertical growth phase, in Clark level IV and V lesions and in metastasizing melanomas. In contrast, superficial compartments of naevi showed membranous E-cadherin immunoreactivity and junctional naevus cell nests displayed heterogeneous or diffuse cytoplasmic staining. Cytoplasmic alpha- and beta-catenin, but not gamma-catenin staining were detected in all benign and malignant lesions. These findings indicate that qualitative changes in the expression and cellular localization of E-cadherin and of alpha-, beta-, and gamma-catenin occur in melanocytic lesions and may reflect different stages in their progression.     

Morphological plasticity that occurs in the neurohypophysis following activation of the magnocellular neurosecretory system can be mimicked in vitro by beta-adrenergic stimulation

The osmotic stress to rats of replacing drinking water with 2% NaCl for four days (salt loading) led to dramatic ultrastructural morphological changes in the neural lobe of the pituitary, including a decrease in the ratio of glial to neurosecretory terminal coverage of the pericapillary basal lamina. The decrease in the proportion of the basal lamina covered by pituicytes, the specialized astrocytic glial cells of the neural lobe, was due to a decrease in the number of pituicyte processes reaching the pericapillary spaces. The concomitant increase in the proportion of neuronal coverage was due to the combination of an increase in the length of individual nerve terminals and a change in the number of terminals. Similar structural changes to those seen in vivo were produced by incubation of the isolated neural lobe with the beta-adrenergic agonist isoprenaline. A decrease in the ratio of glial to neuronal coverage of the basal lamina was achieved within 1 h and could be blocked by inclusion of the beta-adrenergic antagonist propranolol. It is proposed that the morphological plasticity is explained by the active movement of pituicyte cytoplasm.