Long noncoding RNA H19 is a critical oncogenic driver and contributes to epithelial-mesenchymal transition in papillary thyroid carcinoma.

BACKGROUND: Growing evidence has indicated that the long noncoding RNA H19 (lncRNA H19), frequently deregulated in almost all tumor types tested, acted as a pivotal contributor to both cancer initiation and progression. However, the role of lncRNA H19 in human papillary thyroid carcinoma (PTC) remains controversial. The aim of the study was to investigate the expression and potential function of lncRNA H19 in human PTC. PATIENTS AND METHODS: The lncRNA H19 level was determined by quantitative real-time (RT)-PCR analyses in 58 PTC tissue samples and their paired paracancerous tissue samples. RNA interference, RT-PCR analysis, and Western blot assay were used to determine the impact of lncRNA H19 on epithelial-mesenchymal transition (EMT) markers in human PTC cells. The migratory and invasive capacities of PTC cells were determined by wound-healing and transwell migration and invasion assays. RESULTS: lncRNA H19 expression was 2.417-fold higher in PTC tissues than their paired paracancerous tissue (95% CI: 1.898-2.935, P<0.0001). Higher level of lncRNA H19 was correlated to elevated expression of Vimentin, ZEB2, Twist, and Snail2. Inhibition of lncRNA H19 resulted in upregulation of E-cadherin and downregulation of Vimentin both at mRNA and protein levels. Conversely, enforced expression of the exogenous lncRNA H19 led to E-cadherin mRNA and protein downregulation and relative upregulation of Vimentin. Moreover, wound-healing and transwell migration and invasion assays showed that lncRNA H19 could promote the migratory and invasive abilities of PTC cells. CONCLUSION: The level of lncRNA H19 was significantly higher in PTC tissues than paired paracancerous tissue or normal tissues. Overexpression of lncRNA H19 was correlated with higher tumor burden of PTC. It also contributes to EMT process, as well as promotes migration and invasion of PTC cells.

Prognostic values of the inhibitor of DNA­binding family members in breast cancer.

The inhibitor of DNA­binding (ID) proteins are dominant­negative modulators of transcription factors with basic helix­loop­helix (bHLH) structures, which control a variety of genes in cell cycle regulation. An increasing volume of evidence has demonstrated that the deregulated expression of IDs in several types of malignancy, including breast carcinoma, has been proven to serve crucial regulatory functions in tumorigenesis and the development of breast cancer (BC). The present study evaluated the prognostic values of the ID family members by investigating a set of publicly accessible databases, including Oncomine, bc­GenExMiner, Kaplan­Meier plotter and the Human Protein Atlas. The results demonstrated that mRNA levels of distinct IDs exhibited diverse profiles between BC and normal counterparts. The mRNA expression level of ID2 was significantly higher in breast cancer than normal tissues, while the mRNA expression levels of ID1, ID3 and ID4 were significantly lower in breast cancer tissues than in normal tissues. Furthermore, higher mRNA expression levels of ID1 and ID4 were associated with subgroups with lower pathological grades and fewer lymph node metastases. Survival analysis revealed that elevated mRNA levels of ID1 and ID4 predicted an improved survival in all patients with BC. Increased ID1 mRNA levels were associated with higher relapse­free survival rates in all patients with BC, particularly in those with ER positive and Luminal A subtype tumors. Increased ID4 mRNA expression predicted longer survival times in all patients with BC, particularly in those with hormone receptor­positive tumors or those treated with endocrine therapy. These results indicated that IDs are essential prognostic indicators in BC. Future studies on the effect of IDs on the pathogenesis and development of BC are warranted.

FoxM1 is a promising candidate target in the treatment of breast cancer.

Forkhead box protein M1(FoxM1) is a member of forkhead superfamily transcription factors. Emerging evidences have progressively contributed to our understanding on a central role of FoxM1 in human cancers. However, perspectives on the function of FoxM1 in breast cancer (BC) remain conflicting, and mostly were from basic research. Here, we explored the expression profile and prognostic values of FoxM1 based on analysis of pooled clinical datasets derived from online accessible databases, including ONCOMINE, Breast Cancer Gene-Expression Miner v4.0, and Kaplan-Meier plotter. It was found that, FoxM1 mRNA expression was significantly higher in breast tumor versus normal control. FoxM1expression profile presented a distinct pattern in different molecular subtypes of BC patients. Higher expression of FoxM1 was correlated to low mRNA expression of estrogen receptor 1 (ESR1), erb-B2 receptor tyrosine kinase 2 (ERBB2), and was inversely associated with the expression of classical luminal regulators forkhead box protein A1 (FoxA1) and GATA binding protein 3 (GATA3). Elevated FoxM1 expression predicted shorter distance metastasis free survival (DMFS) in BC patients, particularly with estrogen receptor (ER) positive and Luminal A, Luminal B subtypes of BC. More interestingly, elevated FoxM1 expression predicted poor survival in breast cancer patients, especially in the ER (+), progesterone receptor (PR) (+) subgroups and BC patients received adjuvant chemotherapy only or treated with tamoxifen only. These results implied that FoxM1 is an essential prognostic factor and promising candidate target in the treatment of breast cancer.

Predictive Value of Preoperative Multidetector-Row Computed Tomography for Axillary Lymph Nodes Metastasis in Patients With Breast Cancer.

Introduction: Axillary lymph nodes (ALN) status is an essential component in tumor staging and treatment planning for patients with breast cancer. The aim of present study was to evaluate the predictive value of preoperative multidetector-row computed tomography (MDCT) for ALN metastasis in breast cancer patients. Methods: A total of 148 cases underwent preoperative MDCT examination and ALN surgery were eligible for the study. Logistic regression analysis of MDCT variates was used to estimate independent predictive factors for ALN metastasis. The prediction of ALN metastasis was determined with MDCT variates through receiver operating characteristic (ROC) analysis. Results: Among the 148 cases, 61 (41.2%) cases had ALN metastasis. The cortical thickness in metastatic ALN was significantly thicker than that in non-metastatic ALN (7.5 ± 5.0 mm vs. 2.6 ± 2.8 mm, P < 0.001). Multi-logistic regression analysis indicated that cortical thickness of >3 mm (OR: 12.32, 95% CI: 4.50-33.75, P < 0.001) and non-fatty hilum (OR: 5.38, 95% CI: 1.51-19.19, P = 0.009) were independent predictors for ALN metastasis. The sensitivity, specificity and AUC of MDCT for ALN metastasis prediction based on combined-variated analysis were 85.3%, 87.4%, and 0.893 (95% CI: 0.832-0.938, P < 0.001), respectively. Conclusions: Cortical thickness (>3 mm) and non-fatty hilum of MDCT were independent predictors for ALN metastasis. MDCT is a potent imaging tool for predicting ALN metastasis in breast cancer. Future prospective study on the value of contrast enhanced MDCT in preoperative ALN evaluation is warranted.

CCR10 activation stimulates the invasion and migration of breast cancer cells through the ERK1/2/MMP-7 signaling pathway.

CCR10, a member of the chemokine receptor subfamily, is overexpressed in several tumors and play a crucial role in cancer development and progression. However, the functions of CCR10 in breast cancer are unknown. Here, we detected the protein levels of CCR10 in breast cancer cells by western blotting, and examined CCR10 expression in breast cancer tissues via immunohistochemical assay. The results showed that CCR10 expression was elevated in breast cancer MCF7, BT-474 and MDA-MB-231 cells. Further, 63 of 89 cases (70.8%) had positive CCR10 staining, and the CCR10 level was closely related to capsular invasion, lymph node metastasis and tumor stage. Moreover, CCL27, the ligand of CCR10, dose-dependently stimulated the invasion and migration of breast cancer cells, and promoted MMP-7 expression and ERK1/2 activation. CCR10 knockdown in breast cancer cells through siRNA transfection attenuated CCL27-induced cell invasiveness, and suppressed MMP-7 expression and ERK1/2 activation. Additionally, blocking the ERK1/2 pathway inhibited the CCL27/CCR10-promoted cell invasion of breast cancer cells. Together, these data suggest that CCL27/CCR10 interaction induces the ERK1/2 pathway, which then increases MMP-7 expresion and subsequently promotes breast cancer cell invasion and migration. Thus, CCR10 may be a key regulator in breast cancer cell invasion and migration.

[Database Establishing and Data Mining of Pulmonary Diseases Based on Clinical Works by Modern Famous Veteran Doctors of Chinese Medicine].

OBJECTIVE: To explore syndrome and treatment laws for treating diseases of the pulmonary system by establishing database based on clinical works by modern famous veteran doctors of Chinese medicine (CM). METHODS: Clinical experience and literature of medical records in clinical works by modern famous veteran doctors of CM were taken as data source. Database was established by fields and program design. On these bases, data mining methods such as frequency analysis, cluster analysis, factor analysis, and correlation laws were performed in syndrome and treatment laws for treating diseases of the pulmonary system. RESULTS: Established were database capable of literature searching, information statistics, data mining of modern famous veteran doctors of CM. A total of 34,414 data were input, including medical records and notes 28,045 items (81.49%) and clinical experience 6,369 items (18.51%). In medical records and notes, there were 14,048 items (50.09%) in male and 9,466 items (33.75%) in female, and the ratio of male to female was 1.48:1. There were 4,531 items (16.16%) with no marked gender in medical records or notes. Data mining such as correlation analysis, cluster analysis, factor analysis, correlation laws in more fields could be realized. CONCLUSIONS: Medical records and notes were dominated in data collected in this paper. The prevalence of pulmonary diseases was obviously higher in males than in females. The trend of concentrated manifestations in related fields for pulmonary diseases could be surfed by this database. Diagnosis and treatment laws for treating diseases of the pulmonary system could be found by various adaptive data mining targeting different fields. Multi-variables of symptoms, syndromes, prescriptions, and herbal drugs could be data mined in large samples of clinical literatures.

[Transformation of inorganic nitrogen in slag-wetland during the start-up period].

Lab-scale subsurface flow slag-wetlands were constructed to study the removal efficiency and transformation processes of low-concentration inorganic N during the start-up period. As for ammonium-dominated wastewater, the removal rates of total nitrogen (TN), ammonium nitrogen (NH4(+)-N), nitrate nitrogen (NO3(-)-N) and nitrite nitrogen (NO2(-)-N) were 0.12 g x (m2 x d)(-1), 0.07 g x (m2 x d)(-1), 0.10 g x (m2 x d)(-1) and 0.04 g x (m2 x d)(-1), respectively. Nitrifying bacteria was not detected by fluorescence in situ hybridization (FISH) on the slag. NH3 volatilization is the main contribution for N removal resulting from high pH (> 10) and surface soil absorbed most of NH3. For nitrate-dominated wastewater, the removal rates of TN and NO3(-)-N were 0.23 g x (m2 x d)(-1) and 0.48 g x (m2 x d)(-1), and NO2(-)-N accumulated by 0.22 g x (m2 x d)(-1) during the process of denitrification. Removal efficiency of inorganic N for nitrate-dominated wastewater was higher than that for ammonium-dominated wastewater during the start-up period of slag-wetlands, so steel slag can be used as a substrate in constructed wetlands for extensive treatment of nitrate pollution.

hTERT extends proliferative lifespan and prevents oxidative stress-induced apoptosis in human lens epithelial cells.

PURPOSE: Telomerase is a specialized polymerase that catalyzes synthesis of telomeres in most eukaryotes. When introduced into somatic cells, it extends the proliferative lifespan and prevents replicative senescence. Whether it has similar functions in lens epithelial cells, especially in human lens epithelial cells (HLECs) remains to be determined. In this study, the human telomerase reverse transcriptase (hTERT) catalytic subunit was introduced into HLECs. A stable cell line expressing hTERT was established and the functions of hTERT were studied. METHODS: The telomeric repeat amplification protocol (TRAP) assay was used to analyze the telomerase activity. Western blot analysis was used to examine hTERT expression. Southern blot analysis was used to detect telomere length. HLECs isolated from intact lenses were cultured in DMEM and transfected with hTERT cDNA. The expression of the exogenous hTERT was examined with RT-PCR, Western blot analysis, and TRAP assay. The functions of hTERT were examined with various techniques. RESULTS: Among the human, bovine, and rabbit lenses examined, only the central epithelium from the 6-month rabbit lens displayed telomerase activity. In both transparent and cataractous human lenses, hTERT activity and expression were not detected. However, the template RNA was present in both types of human lenses. The telomeres in transparent lenses were approximately 1 kb longer than those in cataractous lenses. The primary cultures and later passages of HLECs also displayed no detectable telomerase activity. Introduction of hTERTcDNA into HLECs followed by G418 selection yielded a stable line of HLECs expressing hTERT. In this line, hTERT has supported normal growth after 48 population doublings (PDs) to date and also enhanced antiapoptotic activity against oxidative stress. CONCLUSIONS: Telomere lengths may be associated with cataractogenesis. hTERT introduced into HLECs prevents replicative senescence through telomere synthesis. Furthermore, hTERT displays functions beyond telomere synthesis in normal HLECs.

Gravity travelling waves for two superposed fluid layers, one being of infinite depth: a new type of bifurcation.

In this paper, we study the travelling gravity waves in a system of two layers of perfect fluids, the bottom one being infinitely deep, the upper one having a finite thickness h. We assume that the flow is potential and the dimensionless parameters are the ratio between densities rho = rho(2)/rho(1) and lambda = gh/c(2). We study special values of the parameters such that lambda(1 - rho) is near 1(-), where a bifurcation of a new type occurs. We formulate the problem as a spatial reversible dynamical system, where U = 0 corresponds to a uniform state (velocity c in a moving reference frame), and we consider the linearized operator around 0. We show that its spectrum contains the entire real axis (essential spectrum), with, in addition, a double eigenvalue in 0, a pair of simple imaginary eigenvalues +/-ilambda at a distance O(1) from 0, and for lambda(1 - rho) above 1, another pair of simple imaginary eigenvalues tending towards 0 as lambda(1 - rho) --> 1(+). When lambda(1 - rho)