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Purpose: To explore the mechanisms underlying clear-cell renal cell carcinoma (ccRCC) metastasis using transcriptional profiling and bioinformatics analysis of ccRCC samples, and to elucidate the role of FOXO3a in ccRCC metastasis.Experimental Design: Gene expression profiling was performed using four primary metastatic and five primary nonmetastatic ccRCC samples. The mRNA and protein levels of FOXO3a in ccRCC samples were investigated by real-time reverse transcription PCR and immunohistochemistry, respectively. The association between metastasis-free survival of patients with ccRCC and FOXO3a mRNA levels was analyzed. Biologic functions of FOXO3a in renal cancer cell lines were investigated. The influence of FOXO3a on tumor metastasis was also studied in vivo orthotopic xenograft tumor model. Finally, the mechanism by which FOXO3a attenuation could increase invasion and migration of tumor cells was explored.Results: Bioinformatics analysis of the profiling data identified FOXO3a as a key factor in ccRCC metastasis. FOXO3a expression was decreased in primary metastatic ccRCC samples. Patients with low FOXO3a mRNA levels had poor metastasis-free survival (P = 0.003). Knocking down FOXO3a induced tumor cell invasion and migration in the nonmetastatic ccRCC cells. Induced FOXO3a overexpression in SN12-PM6 cells could inhibit tumor metastasis in vivo. Downregulation of FOXO3a increased SNAIL1 expression, thereby activating the epithelial–mesenchymal transition (EMT) of RCC cell lines.Conclusions: The loss of FOXO3a induced EMT of tumor cells by upregulating SNAIL1, which promoted tumor cells metastasis in vitro and in vivo. Thus, FOXO3a could be considered as an independent prognostic factor in ccRCC metastasis and could be a marker of occult metastases. Clin Cancer Res; 20(7); 1779–90. ©2014 AACR.

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PDF file - 143KB, Pathway analysis based on KEGG, Biocarta, and Reatome database.

PDF file - 136KB, Analysis of expression profiling data for filtering central genes.

PDF file - 2206KB, Scratch wound migration assays in the 786-O and SN12-PM6 cells.

In recent years, carbon emissions have gradually evolved from an environment issue into a political and economic one. Carbon tariff has brought about new trade barriers of developed countries, and in order to enhance the industrial competitiveness of developed countries, it will produce unfavorable impact on developing countries. Concentrated on the manufacturing industry, which is the most intensive high-carbon industry in China’s export structure, this article studies the relationship between carbon tariff policy and industry structure of export trade and builds up a relation between climate change and international trade. First, by means of establishing a partial equilibrium model, it applies geometric analysis and mathematical analysis to compute the impact on China’s manufacturing export trade and the consequences of the introduction of the US carbon tariff to China’s manufacturing industry that has already imposed a domestic shipping carbon tax. Furthermore, with the application of the GTAP model, i...

In recent years, the trading contact between China and South Korea has become more and more close. In the 21st anniversary of the establishment of diplomatic relations between China and South Korea 2013, China has become South Korea’s largest export market and largest import market. At the same time, South Korea has become China’s fourth largest exporter and second largest importer of foreign trade, which contributes to the rapid development of manufactured products intra-industry trade between China and South Korea. This paper summarizes the development status of industrial manufactured products intra-industry trade between China and South Korea since 1992, and uses empirical analysis, then drawing a conclusion that the direct investment from South Korea to China, total merchandise trade between China and South Korea, and the economic development level of China have great influences on the level of intra-industry trade between China and South Korea, but the degree of the influence is different for different types of manufactured goods. Finally, this article proposes policy recommendations to promote the further development of manufactured products intra-industry trade between China and South Korea.

Purpose: To explore the mechanisms underlying clear-cell renal cell carcinoma (ccRCC) metastasis using transcriptional profiling and bioinformatics analysis of ccRCC samples, and to elucidate the role of FOXO3a in ccRCC metastasis. Experimental Design: Gene expression profiling was performed using four primary metastatic and five primary nonmetastatic ccRCC samples. The mRNA and protein levels of FOXO3a in ccRCC samples were investigated by real-time reverse transcription PCR and immunohistochemistry, respectively. The association between metastasis-free survival of patients with ccRCC and FOXO3a mRNA levels was analyzed. Biologic functions of FOXO3a in renal cancer cell lines were investigated. The influence of FOXO3a on tumor metastasis was also studied in vivo orthotopic xenograft tumor model. Finally, the mechanism by which FOXO3a attenuation could increase invasion and migration of tumor cells was explored. Results: Bioinformatics analysis of the profiling data identified FOXO3a as a key factor in ccRCC metastasis. FOXO3a expression was decreased in primary metastatic ccRCC samples. Patients with low FOXO3a mRNA levels had poor metastasis-free survival (P = 0.003). Knocking down FOXO3a induced tumor cell invasion and migration in the nonmetastatic ccRCC cells. Induced FOXO3a overexpression in SN12-PM6 cells could inhibit tumor metastasis in vivo. Downregulation of FOXO3a increased SNAIL1 expression, thereby activating the epithelial–mesenchymal transition (EMT) of RCC cell lines. Conclusions: The loss of FOXO3a induced EMT of tumor cells by upregulating SNAIL1, which promoted tumor cells metastasis in vitro and in vivo. Thus, FOXO3a could be considered as an independent prognostic factor in ccRCC metastasis and could be a marker of occult metastases. Clin Cancer Res; 20(7); 1779–90. ©2014 AACR.

// Qing Bo Huang 1,* , Xin Ma 1,* , Hong Zhao Li 1 , Qing Ai 1 , Shang Wen Liu 2 , Yu Zhang 1 , Yu Gao 1 , Yang Fan 1 , Dong Ni 3 , Bao Jun Wang 1 and Xu Zhang 1 1 Department of Urology/State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/PLA Medical School, Beijing, China 2 Department of Urology, Chinese PLA 303 Hospital, Nanning, China. 3 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. Correspondence: Xu Zhang, email: // Keywords : Kidney neoplasms, Neoplasm metastasis, Cell communication, Signal transduction, Angiogenesis Received : January 2, 2014 Accepted : March 14, 2014 Published : March 14, 2014 Abstract The Notch ligand Delta-like 4 (DLL4) plays an important role in tumor angiogenesis, which is required for tumor invasion and metastasis. Here we showed that DLL4 was elevated in endothelium and Notch signaling was activated in renal cell carcinoma (RCC). Exogenous DLL4 induced RCC cell migration and invasion by activating intercellular Notch signaling. Importantly, the DLL4/Notch/Hey1/MMP9 cascades connecting the endothelium to the cancer cells in metastasis were identified. Knockdown of Hey1 decreased expression of MMP9 and attenuated tumor invasion. The clinical investigation on 120 cases of RCC specimens indicated that expressions of Hey1 and MMP9 correlated with DLL4 density. Moreover, univariate and multivariate analyses showed that tumor hematogenous metastasis not only was depended on microvessel density but was also associated with tumor size and DLL4 density. During 4-year surveillance, high-level of DLL4 density was associated with a higher probability of developing metastasis and being sensitive to target therapies. Our data suggest that RCC progression is caused in part by activated DLL4/Notch signaling, interaction of endothelium and cells, which can be therapeutically targeted.

Fund Program: Liaoning province social science fund project (L14AJY001): Liaoning province fund project of finance scientific research (14D008); Basic scientific research fund project of central university (3132015052) Abstract Agreement on Trade Related Aspects of Intellectual Property Rights(TRIPs) is the first to use the name of international laws to require the WTO members to supply the effective procedures of the intellectual property rights. This throws great challenges towards its protection, technology exploration, technology transfer, etc., and it is of great meaning to China’s technology strategy. Index Terms intellectual property rights(IPR), technology innovation, strategy

Background Endothelial DLL4 plays an important role in controlling of tumor angiogenesis, which is required for tumor invasive growth and metastasis. However, the regulation of DLL4 in clear cell renal cell carcinoma (ccRCC) has not yet been systematically elucidated. Methodology We performed bioinformatical analysis to explore miRNAs targeting DLL4. miR-30a was selected as a representative to validate its functional association in endothelial cell. Then, the expressions of DLL4 and mature miR-30a from 90 cases of ccRCC and 28 cases of nonmatched adjacent non-tumor tissues were measured by quantitative real-time PCR. Finally, the expression of miR-30a was correlated with DLL4 expression, tumor features (metastatic condition and microvessel density), and patient metastasis-free survival. The univariate and multivariate analyses were performed to select the risk factors associated with hematogenous metastasis, respectively. Principal Findings miR-30a negatively regulated DLL4 and inhibited the proliferation and migration of endothelial cells. DLL4 was up-regulated in ccRCC and further increased in hematogenous metastatic cases, while miR-30a was down-regulated in tumor tissues and further decreased in hematogenous metastatic ccRCC (student t test, all p

To explore the role of NOTCH1/HES1/PTEN signaling pathway in invasive TCCB (bladder transitional cell carcinoma).The expressions of NOTCH1, HES1 and PTEN were detected in 36 cases of invasive TCCB tissues and 10 cases of normal bladder samples by real-time q-polymerase chain reaction (q-PCR) and Western blot. Then NOTCH1-ORF plasmid and its blank vector pCMV6-Entry were transfected into T24 cell respectively. And the expressions of three above-mentioned target genes were measured by real-time q-PCR and Western blot. Furthermore, cell proliferation, cell apoptosis and cell cycle were analyzed respectively by MTS assay and flow cytometry.Compared with normal bladder samples, the higher levels of both mRNA and protein of NOTCH1 and HES1 were detected in invasive TCCB tissues while there was a lower expression of PTEN (P0.05). The mRNA expression levels of NOTCH1 and HES1 were 4.22 and 3.75 folds respectively higher than those of normal tissues. In NOTCH1-overexpressed T24 cell, the expression of HES1 was 5.43 folds higher than that of the blank vector control group while the expression of PTEN declined to 41.76% (P0.01). MTS assay showed that the NOTCH1-ORF transfection obviously promoted cell proliferation in T24 cell (P0.01).NOTCH1 gene may function as an oncogene by regulating HES1/PTEN in invasive TCCB and its aberrant activation promotes cell proliferation.