Down-regulated expression of LINC00518 prevents epithelial cell growth and metastasis in breast cancer through the inhibition of CDX2 methylation and the Wnt signaling pathway.

Breast cancer (BC)-related mortality is associated with the potential metastatic properties of the primary breast tumors. The following study was conducted with the main focus on the effect of LINC00518 on the growth and metastasis of BC epithelial cells via the Wnt signaling pathway through regulation of the methylation of CDX2 gene. Initially, differentially expressed long intergenic non-protein coding RNAs (lincRNAs) related to BC were screened out in the Cancer Genome Atlas (TCGA) database, after which we detected the LINC00518 expression and localization in BC tissues and cells. Then the CDX2 positive expression and methylation level were identified. The targeting relationship of LINC00518 and CDX2, and binding methyltransferase in the promoter region were examined. BC epithelial cell proliferation, colony formation ability, invasion, migration and apoptosis were further evaluated. The lincRNA expression data related to BC downloaded from the TCGA database revealed that there was a high expression of LINC00518 in BC, and a negative correlation between LINC00518 and CDX2. In addition, LINC00518 promotes CDX2 methylation by recruiting DNA methyltransferase through activating the Wnt signaling pathway. The down-regulation of LINC00518 inhibited proliferation, invasion, migration, and EMT of BC epithelial cells while enhancing apoptosis. The inhibitory effects of LINC00518 down-regulation was reversed by CDX2 down-regulation. In conclusion, our findings revealed that down-regulation of LINC00518 might have the ability to suppress BC progression by up-regulating CDX2 expression through the reduction of methylation and blockade of the Wnt signaling pathway, resulting in the inhibition of proliferation and promotion of apoptosis of BC epithelial cells.

Characteristics of vascular remodeling in pregnant hypertensive rats induced by L-NAME / 医用生物力学

Objective To elucidate the characteristics of vascular remodeling in pregnant hypertensive rats. Methods Pregnant rats were induced by L-nitro-arginine methylester (L-NAME) to build hypertension models and normal pregnant rats were used as control. Using a programmable sphygmomanometer, the blood pressure was recorded with the tail-cuff method to ensure the hypertension model was successfully replicated. The changes of mean shear stress in left common carotid artery were determined after the blood viscosity, the average blood flow and the inner diameter were measured. To analyze the degree of arterial remodeling, the protein expression levels of Collagen I (Col I) and III (Col III) were detected by Western blotting and the media thickness, the inner diameter, the opening angel were determined in both thoracic aorta and carotid artery. Results The mean shear stress of common carotid artery in pregnant hypertensive rats was reduced by (28.52 ± 3.08)% with the blood viscosity increasing and the average blood flow decreasing in pregnant hypertensive rats. Compared with control groups, the ratio of media thickness and inner diameter was significantly increased in thoracic aorta and carotid artery, while the opening angel decreased in carotid artery while increased in thoracic aorta. With the expression of COL I decreasing and COL III increasing, the ratio of Col I and Col III went an apparent decline. Conclusions The mean shear stress is descending, and the remodeling of thoracic aorta and carotid artery are found in pregnant hypertensive rats. These results may provide new experimental references for further illustrating the pathogenesis of pregnant hypertension.

Characteristics of vascular remodeling in pregnant hypertensive rats induced by L-NAME / 医用生物力学

Objective To elucidate the characteristics of vascular remodeling in pregnant hypertensive rats.Methods Pregnant rats were induced by L-nitro-arginine methylester (L-NAME) to build hypertension models and normal pregnant rats were used as control.Using a programmable sphygmomanometer,the blood pressure was recorded with the tail-cuff method to ensure the hypertension model was successfully replicated.The changes of mean shear stress were determined after the blood viscosity,the average blood flow and the inner diameter in left common carotid artery were measured.To analyze the degree of arterial remodeling,the protein expression levels of collagen Ⅰ (Col Ⅰ) and Ⅲ (Col Ⅲ) were detected by Western blotting,and the media thickness,the inner diameter,the opening angel both in thoracic aorta and carotid artery were determined.Results The mean shear stress of common carotid artery was reduced by (28.52 ± 3.08) ％ with the blood viscosity increasing and the average blood flow decreasing in pregnant hypertensive rats.Compared with control groups,the ratio of media thickness and inner diameter significantly increased in thoracic aorta and carotid artery,while the opening angel decreased in carotid artery and increased in thoracic aorta.With the expression of Col Ⅰ decreasing and Col Ⅲ increasing,the ratio of Col Ⅰ and Col Ⅲ went an apparent decline.Conclusions The mean shear stress is descending in pregnant hypertensive rat,with the remodeling of thoracic aorta and carotid artery.These results may provide new experimental references for further illustrating pathogenesis of pregnant hypertension.

Characteristics of vascular remodeling in pregnant hypertensive rats induced by L-NAME / 医用生物力学

Objective To elucidate the characteristics of vascular remodeling in pregnant hypertensive rats.Methods Pregnant rats were induced by L-nitro-arginine methylester (L-NAME) to build hypertension models and normal pregnant rats were used as control.Using a programmable sphygmomanometer,the blood pressure was recorded with the tail-cuff method to ensure the hypertension model was successfully replicated.The changes of mean shear stress were determined after the blood viscosity,the average blood flow and the inner diameter in left common carotid artery were measured.To analyze the degree of arterial remodeling,the protein expression levels of collagen Ⅰ (Col Ⅰ) and Ⅲ (Col Ⅲ) were detected by Western blotting,and the media thickness,the inner diameter,the opening angel both in thoracic aorta and carotid artery were determined.Results The mean shear stress of common carotid artery was reduced by (28.52 ± 3.08) ％ with the blood viscosity increasing and the average blood flow decreasing in pregnant hypertensive rats.Compared with control groups,the ratio of media thickness and inner diameter significantly increased in thoracic aorta and carotid artery,while the opening angel decreased in carotid artery and increased in thoracic aorta.With the expression of Col Ⅰ decreasing and Col Ⅲ increasing,the ratio of Col Ⅰ and Col Ⅲ went an apparent decline.Conclusions The mean shear stress is descending in pregnant hypertensive rat,with the remodeling of thoracic aorta and carotid artery.These results may provide new experimental references for further illustrating pathogenesis of pregnant hypertension.

Clinicopathological characteristics and prognosis of mucinous breast carcinoma.

PURPOSE: The clinical features and prognosis of mucinous breast carcinoma (MBC) are unclear because of its rarity. The aim was to describe the clinicopathological features and prognosis of patients with MBC in comparison with nonmucinous breast carcinoma (NMBC). Furthermore, we described the biological behavior of pure mucinous breast carcinoma (PMBC) by comparing clinicopathological features and prognosis with mixed mucinous breast carcinoma (MMBC). METHODS: We reviewed the records of 5,872 consecutive patients diagnosed with breast carcinoma who were resected surgically from March 2003 to October 2010. Among them, 117 patients with MBC were compared to 5,575 patients with NMBC. Furthermore, 88 patients with PMBC were compared to 29 patients with MMBC. RESULTS: There were statistical differences in age, pN stage, ER level, and PR level between the patients with MBC and NMBC. There were statistical differences in pT stage and pN stage between the patients with PMBC and MMBC. The overall five-year survival of patients with MBC was 88.1 % as compared with 81.9 % for patients with NMBC. The overall five-year survival of patients with PMBC was 91.3 % as compared with 80.4 % for patients with MMBC. The overall five-year survival of patients with PMBC was 91.3 % as compared with 81.9 % for patients with NMBC. CONCLUSIONS: PMBC tended to have a better prognosis in comparison with other types of breast carcinoma.

Expression of tissue levels of matrix metalloproteinases and their inhibitors in breast cancer.

BACKGROUND: We examined mRNA expression for MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 in human breast cancer tissues, and the association between their expression and clinicopathological variables. PATIENTS AND METHODS: Breast tissue samples from 120 patients with breast cancer were available for this study. To determine mRNA expression for MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out on tumor and normal tissues, respectively. RESULTS: Mean MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the breast cancer was significantly higher than in the normal tissue. In terms of tumor size and lymph node metastasis of breast cancer, the differences in MMP-2, MMP-7, MMP-9, and MT1-MMP mRNA expression levels were significant. CONCLUSION: The association between the increased expression of MMP-2, MMP-7, MMP-9, and MTI-MMP and clinicopathological parameters reflects a role in predicting the aggressive behavior of breast cancer.

Long CAG repeat sequence and protein expression of androgen receptor considered as prognostic indicators in male breast carcinoma.

BACKGROUND: The androgen receptor (AR) expression and the CAG repeat length within the AR gene appear to be involved in the carcinogenesis of male breast carcinoma (MBC). Although phenotypic differences have been observed between MBC and normal control group in AR gene, there is lack of correlation analysis between AR expression and CAG repeat length in MBC. The purpose of the study was to investigate the prognostic value of CAG repeat lengths and AR protein expression. METHODS: 81 tumor tissues were used for immunostaining for AR expression and CAG repeat length determination and 80 normal controls were analyzed with CAG repeat length in AR gene. The CAG repeat length and AR expression were analyzed in relation to clinicopathological factors and prognostic indicators. RESULTS: AR gene in many MBCs has long CAG repeat sequence compared with that in control group (P = 0.001) and controls are more likely to exhibit short CAG repeat sequence than MBCs. There was statistically significant difference in long CAG repeat sequence between AR status for MBC patients (P = 0.004). The presence of long CAG repeat sequence and AR-positive expression were associated with shorter survival of MBC patients (CAG repeat: P = 0.050 for 5y-OS; P = 0.035 for 5y-DFS AR status: P = 0.048 for 5y-OS; P = 0.029 for 5y-DFS, respectively). CONCLUSION: The CAG repeat length within the AR gene might be one useful molecular biomarker to identify males at increased risk of breast cancer development. The presence of long CAG repeat sequence and AR protein expression were in relation to survival of MBC patients. The CAG repeat length and AR expression were two independent prognostic indicators in MBC patients.

The differences in CXCR4 protein expression are significant for the five molecular subtypes of breast cancer.

The aim was to investigate the expression of the CXCR4 protein in five molecular subtypes of breast cancer. The authors randomly selected the breast cancer paraffin-embedded specimens of the Affiliated Third Hospital of Harbin Medical University between 2007 and 2009. Details are as follows: basal-like subtype-ER (-), PR (-), C-erbB-2 (-), CK5/6 (+), n = 36; normal breast subtype-ER (-), PR (-), C-erbB-2 (-), CK5/6(-), n = 40; luminal A subtype-ER/PR (+), C-erbB-2 (-), n = 38; luminal B subtype-ER/PR (+), C-erbB-2 (+), n = 60; C-erbB-2 (+) subtype-ER (-), PR (-), C-erbB-2 (+), n = 58. Using the immunohistochemistry method, the authors detected the expression of the CXCR4 protein in the five subtypes. The CXCR4 protein expression in the basal-like subtype was the highest, and that in the luminal A subtype was the lowest. In terms of five molecular subtypes of breast cancer, the differences in CXCR4 protein expression were significant (p < .001). In terms of C-erbB-2 expression, tumor stage, and lymph node metastasis of breast cancer, the differences in CXCR4 protein expression were significant (p < .01).

A variant in microRNA-196a2 is associated with susceptibility to hepatocellular carcinoma in Chinese patients with cirrhosis.

AIMS: Cirrhosis is an important risk factor for hepatocellular carcinoma (HCC) in China, while little is known of the genetic susceptibility to hepatocarcinogenesis. Traditional approaches to identification of novel genetic predisposition genes have focused on protein encoding genes. There is evidence to suggest that microRNAs (miRNA) may play an important role in tumorigenesis. Recent studies have implicated that the rs11614913 SNP in miR-196a2 may be associated with susceptibility to lung cancer, congenital heart disease, breast cancer, as well as reduced survival in non-small cell lung cancer. This study aims to assess whether this functional polymorphism can influence susceptibility to and the progression of cirrhosis-related HCC. METHODS: 532 patients with hepatic cirrhosis (310 patients with HCC and 222 patients without HCC) were enrolled. DNA was extracted from blood specimens, and miR-196a2 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, tumour tissues of liver (n=59) were obtained from the studied HCC patients for measurement of miR-196a expression levels. RESULTS: The frequency of the CC genotype among HCC patients was higher than that in the control group, implying that the cirrhotic patients with the CC genotype or C allele containing genotypes (CT and CC) may have a higher risk of HCC. However, in a subsequent analysis of the association between this polymorphism and clinicopathological characteristics, there was an association between rs11614913 genotype and tumour size (p=0.046), but not with tumour number, grade, stage, invasiveness or Child-Pugh grade. In a genotype-phenotype correlation analysis using 59 tumour tissues of liver, rs11614913 CC or carrying at least one C allele was associated with significantly increased mature miR-196a expression (p=0.006 or =0.002). CONCLUSIONS: Our results suggest, for the first time, that miR-196a2 polymorphism may contribute to cirrhosis-related HCC susceptibility in Chinese patients through influencing mature miR-196a expression.

[Effect of lateral lymph nodes dissection and autonomic nerve preservation in anterior resection for rectal cancer: 124 cases review].

OBJECTIVE: To investigate the clinical effect of lateral lymph nodes dissection and autonomic nerve preservation in anterior resection for rectal cancer. METHODS: One hundred and twenty-four patients with rectal cancer underwent anterior resection with lateral lymph nodes resection and autonomic nerve preservation. The patients were followed-up through post-operational questionnaire about the function of defecation, urination and sex after the operation. And post-operative survival was analyzed retrospectively. RESULTS: Urinary catheters were removed in 112 cases (90.3%) in 3 days post operation, the mean time of indwelling catheter was (58.3 +/- 2.1) h. Nineteen patients experienced fecal incontinence, 12 cases of them recovered through release-training and one recovered spontaneously. Of the 98 questionnaire respondents, 61 cases (62.3%) could erect normally, and 56 cases (57.1%) had normal sexual function. The max-micturition-desire urine volume was (401.2 +/- 23.1) ml and the residual urine volume was (28.2 +/- 2.2) ml. Five year survival rate of all the patients was 61.2%. CONCLUSIONS: Lateral lymph nodes dissection and autonomic nerve preservation in anterior resection for rectal cancer can decrease the post-operative dysfunction of defecation, urination and sex life and does not affect the survival.

[Extended radical resection with nerve-preservation for rectal cancer].

OBJECTIVE: To investigate the clinical value of extended radical resection with nerve- preservation for rectal cancer. METHOD: Ninety-eight patients with rectal cancer received extended radical resection with nerve- preservation in our hospital. The questionnaire were used to collect the data of the patients urination and sexual function. The survival was analyzed retrospectively. RESULTS: 62.3% (61/98) of the patients could erect normally and 57.1% (56/98) of the patients had normal sexual function. The average time of catheterization in 57 patients was 60 hours, the residual urine volume (RUV) was 28 ml and the max-micturition-desire urine volume was 400 ml. The 5-year survival rate of those who underwent extended radical resection with nerve-preservation was 61.2%. CONCLUSION: Extended radical resection with nerve-preservation,which could decrease the incidences of post-operative urination and sexual dysfunction, and have not affect the survival, was the most optimal operation for rectal cancer.