MicroRNA-572 targets CDH1 to promote metastasis of Wilms' tumor.

INTRODUCTION: Wilms' tumor (WT) is the most common childhood tumor, and recent studies have demonstrated that abnormal expression of microRNA (miRNA) plays an important role in the progression of WT. However, the effect of miR-572 on cell metastasis and epithelial-mesenchymal transition (EMT) in WT is unclear. PATIENTS AND METHODS: The alternation of miR-572 and cadherin 1 (CDH1) expression was assessed by quantitative Real-time polymerase chain reaction (qRT-PCR). Transwell assay was performed to explore the effects of miR-572 and CDH1 on the metastasis of WT cells. The EMT markers and CDH1 expressions were detected by Western blot. The relationship between miR-572 and CDH1 was verified by dual-luciferase reporter assay. RESULTS: Upregulation of miR-572 was identified in WT tissues. Increased miR-572 promoted cell metastasis and EMT progress in WT. Moreover, miR-572 directly targeted CDH1 and negatively regulated CDH1 expression in WT tissues. The knockdown of CDH1 showed a promoting effect on cell metastasis and EMT, while overexpression of CDH1 significantly weakened the effect of miR-572. CONCLUSIONS: MiR-572 targeted CDH1 to promote cell metastasis in WT by suppressing EMT.

[Clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma].

Objective: To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma (FDCS). Methods: We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real-time PCR and EBER in situ hybridization was performed on 4 cases. Results: Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low-grade FDCS and 3 cases of high-grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2-40, EGFR and CXCL13, but negative for S-100, CD68, HMB45, SMA, Desmin, CD117, Dog-1, CD34, CD30, EMA and CK.Five cases were positive for PD-L1 and the its expression in high-grade FDCS were higher than that in low-grade FDCS.Two cases of low-grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren't detected in all of 7 cases. The result of EBER in-situ hybridization showed that only the nasopharynx FDCS was positive.The follow-up information of 5 patients were available (7~43 months), 4 patients died and 1 still alive with rectum metastasis. Conclusions: FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first-line antibodies including CD21, CD23, CD35 and second-line antibodies including D2-40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD-L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.

[Significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma of the larynx].

Objective: To study the significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma (BSCC) of the larynx. Methods: Twenty-nine cases of laryngeal BSCC from Beijing Tongren Hospital from January 2005 to December 2011 were reviewed. HPV typing by polymerase chain reaction-reverse dot blot (PCR-RDB) and p53, Ki-67, p16, p21 and cyclin D1 expression by immunohistochemistry were performed. The relationship between these indicators, various pathologic parameters (TNM, tumor size, tumor site and lymph node metastasis) and HPV status was analyzed. Results: There were 27 male and 2 female patients. The median age was 62 years. Lymph node metastasis and supraglottic tumor location were slightly higher than that of "usual" SCC, but not statistically significant (P>0.05). HPV DNA was detected in 27.6% (8/29) of the laryngeal BSCC, and all were HPV16. The expression of HPV was not related to age, alcohol consumption, tumor stage and tumor size. p53 was expressed in 31.0%(9/29) of laryngeal BSCC, and these cases were more likely supraglottic and had lymph node metastases (P<0.05). p16 staining was seen in 24.1% (7/29) of laryngeal BSCC, and these cases showed slightly higher rate of lymph node metastasis compared to p16 negative cases. The expression rates of p21 and cyclinD1 were 27.6% (8/29) and 69.0%(20/29), respectively, which were not related to age, tumor size, stage, lymph node metastasis, smoking and drinking. There were only 3 p16+ /HPV+ cases, which showed higher p21 and Ki-67 index compared to the HPV negative group (P<0.05). Conclusion: Some laryngeal BSCC expresses HPV DNA, possibly indicating an association with HPV; but p16 expression is not a reliable indicator for HPV infection.

Enhanced glycolysis in the process of renal fibrosis aggravated the development of chronic kidney disease.

OBJECTIVE: To explore the effect of glycometabolism on renal fibrosis and its underlying mechanism. MATERIALS AND METHODS: For in vivo experiments, unilateral ureteral obstruction (UUO) mouse model was constructed to induce renal interstitial fibrosis. Fibrosis and proliferation indicators in renal tissues were detected to observe the fibroblast phenotype changes during the process of renal fibrosis. Moreover, mRNA and protein levels of key enzymes in glycometabolism were also detected. For in vitro experiments, plasmid transfection was performed to overexpress pyruvate kinase M2 (PKM2) to explore the relationship between PKM2 and renal interstitial fibrosis. Energy metabolism monitoring was performed to detect changes in aerobic glycolysis and oxidative phosphorylation during the process of TGF-ß1-induced fibroblast phenotype changes. RESULTS: Fibroblast phenotype was changed. Both fibrosis and proliferation indicators were upregulated during renal fibrosis. Meanwhile, elevated expressions of key enzymes in glycometabolism and metabolic reprogramming of fibroblasts were observed. Overexpressed PKM2 activated fibroblasts and induced renal interstitial fibrosis, accompanied by increased glycometabolism level. CONCLUSIONS: Metabolic reprogramming promoted renal interstitial fibrosis, which leads to alteration of cell energy metabolism model.

Cardiovascular disease in rheumatoid arthritis: medications and risk factors in China.

This study aims to assess the risk factors of cardiovascular disease (CVD) and to determine the association of traditional and biologic disease-modifying anti-rheumatic drugs (DMARDs) with risk for CVD in Chinese rheumatoid arthritis (RA) patients. A cross-sectional cohort of 2013 RA patients from 21 hospitals around China was established. Medical history of CVD was documented. The patients' social background, clinical manifestations, comorbidities, and medications were also collected. Of the 2013 patients, 256 had CVD with an incidence of 12.7%. Compared with non-CVD controls, RA patients with CVD had a significantly advanced age, long-standing median disease duration, more often male and more deformity joints. Patients with CVD also had higher rates of smoking, rheumatoid nodules, interstitial lung disease, and anemia. The prevalence of comorbidities, including hypothyroidism, diabetes mellitus (DM), hypertension, and hyperlipidemia, was also significant higher in the CVD group. In contrast, patients treated with methotrexate, hydroxychloroquine (HCQ), and TNF blockers had lower incidence of CVD. The multivariate analysis showed that the use of HCQ was a protective factor of CVD, while hypertension, hyperlipidemia, and interstitial lung disease were independent risk factors of CVD. Our study shows that the independent risk factors of CVD include hypertension, hyperlipidemia, and interstitial lung disease. HCQ reduces the risk of CVD in patients with RA.

Overexpression of TNF-alpha and TNFRII in invasive micropapillary carcinoma of the breast: clinicopathological correlations.

AIMS: Angiogenesis is essential for tumour growth and metastasis and tumour necrosis factor (TNF)-alpha is a potent angiogenic factor. Invasive micropapillary carcinoma of the breast (IMPC), a rare subtype of breast cancer, possesses a lymphotropic nature with a high incidence of lymph node metastasis and poor prognosis. The aim was to evaluate the role of TNF-alpha and its receptor TNFRII in the vascular development and metastasis of IMPC. METHODS AND RESULTS: One hundred cases of IMPC and 97 cases of invasive ductal carcinoma, not otherwise specified (IDC) were studied in parallel by immunohistochemistry for TNF-alpha and TNFRII, and microvessel density (MVD) of the tumours was measured. The results showed that the expression of TNF-alpha and TNFRII and the MVD were higher in IMPC than in IDC (P < 0.05). In IMPC, MVD was significantly increased in those with lymph node metastasis compared with those without nodal metastasis (P = 0.001). TNF-alpha expression showed a significant positive correlation with the rate of proliferation, histological grade, lymph node metastasis and MVD (P < 0.05), whereas expression of TNFRII was correlated with TNF-alpha expression and the proliferation of tumour cells in IMPC (P < 0.05). CONCLUSIONS: Expression of TNF-alpha and TNFRII might play an important role in the angiogenesis, tumour cell proliferation and metastasis of IMPC. These markers could represent new targets for therapeutic intervention, i.e. blocking of TNF-alpha and its signal transduction could be a promising tool for treatment.

[Preparative GC separation and identification of methyl 2-methyl-3-furyl disulfide flavour].

On 4% FFAP + 1% H3PO4 Chromosorb W/AW-DMCS (80 mesh-100 mesh)column, the optimized separation of methyl 2-methyl-3-furyl disulfide flavour was obtained. By using automatic preparative attachment model App-5 to GC-9A, the content of methyl 2-methyl-3-furyl disulfide flavour was raised from about 77% to 99.5%. The product was identified by IR, MS and 1HNMR.