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Qu H.,Weifang Peoples Hospital | Yang X.,Affiliated to Binzhou Medical College
Cell Biochemistry and Biophysics | Year: 2014

Accumulated evidences indicate metformin is associated with reduced risk of hepatocellular carcinoma (HCC) in diabetic patients, which inspired researchers to explore its therapeutic potentials in HCC. Since Hepatic stellate cells (HSCs) are believed to be the key contributors to tumor microenvironment in HCC and promotes tumor development, here, we explored the effect of metformin on tumor angiogenesis induced by interplay of HCC and HSCs. Our results showed that conditional medium from co-culture of HCC/HSCs induced VEGF secretions and stimulated human umbilical vein endothelial cells (HUVEC) tube formation. However, 25 µM metformin could inhibit this angiogenesis effect. Furthermore, knockdown AMPK of HSCs, not HCC, could abolish inhibition caused by metformin. Our finding suggested that metformin could inhibit HCC angiogenesis through targeting on HSCs through AMPK pathway. © 2014, Springer Science+Business Media New York. Source

Yang X.,Affiliated to Binzhou Medical College | Wang X.,Affiliated to Binzhou Medical College | Shen H.,Linyi Peoples Hospital | Deng R.,Lunan Pharmaceutical Group Corporation | Xue K.,Linyi Peoples Hospital
Cell Biochemistry and Biophysics | Year: 2015

Circulating miR-21 is upregulated in breast cancer. However, correlation of miR-21 expression with clinic pathologic characteristics remains questionable. In this study, we investigate whether combination of circulation miR-21 with circulating tumor cells (CTCs) marker (EpCAM, MUS1, HER2) could improve diagnostic specificity of metastatic breast cancer. Total 223 breast cancer patients were included. 89 % patients were associated with upregulation of miR-21 compared with health control. 20 % patients were detected for CTCs marker positive. For higher specificity purpose, triple marker positive samples were selected as true CTCs positive, which only occupied 59.5 % of total metastatic breast cancer patients. Specificity of detection of CTCs was 96.7 %. Furthermore, 59.5 % metastatic breast cancer patients were shown both abnormal miR-21 and true CTCs positive according to distribution of true CTCs positive and abnormal miR-21; Combination of miR-21 and CTCs was increased specificity of metastatic detection to 100 %. Our findings suggested that combination of miR-21 with CTCs marker could be used for better diagnosis of metastatic breast cancer in the future. © 2015, Springer Science+Business Media New York. Source

Wang D.,Shandong Academy of Sciences | Shi J.,Affiliated to Binzhou Medical College | Liang S.,Binzhou Medical University | Lu S.,Shandong Academy of Sciences | And 6 more authors.
Clinical and Translational Oncology | Year: 2013

Objective To assess the predictability of dose-volume histogram (DVH) parameters for radiation pneumonitis (RP) using receiver operating characteristic (ROC) curve. Methods One hundred and thirty-five cases of locally advanced non-small cell lung cancer patients treated with three-dimensional radiotherapy and chemotherapy were analyzed retrospectively. The end point of follow-up was C2 grade RP defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. The ROC curve was used to explore the predictive sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) for potential DVH parameters associated with RP. Results Relative volumes of total lungs receiving ≥5 Gy (V5), ≥10 Gy (V10), ≥13 Gy (V 13), ≥20 Gy (V20), and mean lung dose (MLD), were all correlated to the development of RP (p < 0.05), among which V5 and V20 were the most important factors (p = 0.045 and 0.037; OR = 3.166 and 3.030). However, collinearity was found between V5 and V 20 (Spearman's rho 0.771, p < 0.01). The area under the ROC curve was 0.643 and 0.648 for using V5 and V20 as predictors. If predictive cut-off values were established as follows: V5 = 0.8 and V20 = 0.3, the parameters could provide predictive SEN, SPE, PPV and NPV were 0.387 and 0.581, 0.882 and 0.701, 0.444 and 0.321, and 0.855 and 0.873, respectively. Conclusions V5 and V20 could act as predictors for RP; however, single DVH metrics did not appear to have high predictive power for RP. © Federación de Sociedades Españolas de Oncología (FESEO) 2012. Source

Shi J.,Affiliated to Binzhou Medical College | Yu G.,Affiliated to Binzhou Medical College
Journal of Cancer Research and Therapeutics | Year: 2014

Background: Breast cancer is one of the most frequently diagnosed cancers in women. Though death from this disease is mainly caused by the metastases of the aggressive cancer cells, few studies have expounded the aggressive behavior of breast cancer. Materials and Methods: We downloaded the gene expression profiles of GSE40057, including four aggressive and six less-aggressive breast cancer cell lines, from Gene Expression Omnibus and identified the differentially expressed genes (DEGs) between the aggressive and less-aggressive samples. An integrated gene regulatory network was built including DEGs, microRNAs (miRNAs), and transcription factors. Then, motifs and modules of the network were identified. Modules were further analyzed at a functional level using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to study the aggressive behavior of breast cancer. Results: A total of 764 DEGs were found and two modules were filtered from the integrated gene regulatory network. Totally two motifs and modules for DEGs were identified. Significant GO terms associated with cell proliferation and hormone stimulus of the modules were found and the target genes identified were CAV1, CD44, and TGFβR2. The KEGG pathway analysis discovered that CAV1 and FN1 were significantly enriched in focal adhesion, extracellular matrix (ECM)-receptor interaction, and pathways in cancer. Conclusion: Aggressive behavior of breast cancer was proved to be related to cell proliferation and hormone stimulus. Genes such as CAV1, CD44, TGFβR2, and FN1 might be potential targets to diagnose the aggressive behavior of breast cancer cells. Source

Wang H.,Affiliated to Binzhou Medical College | Yang X.,Affiliated to Binzhou Medical College
International Journal of Clinical and Experimental Pathology | Year: 2015

Recently, there is growing evidence that tight junction proteins are often abnormally regulated in human tumors. The function of tight junction proteins in the maintenance of normal epithelial physiology has been well discussed, but their role in the tumorigenesis of gastric cancer is less well defined. To explore the expression distinction of the tight junction proteins claudin-1, -3, and -4 expression in the gastric cancer, the expression of claudin-1, -3, and -4 in 92 gastric cancer tissues and the non-neoplastic tissues adjacent to the tumors were examined by immunohistochemistry. Compared with adjacent non-neoplastic tissues, the expression of claudin-1 was down regulated. However, the expression of claudin-3 and claudin-4 were up-regulated in gastric cancer tissue. In addition, the expression of claudin-3 is correlated with claudin-4 expression in gastric cancer. Our present study reveals that claudin- 1, -3, and -4 protein expression altered between human gastric cancers and adjacent non-neoplastic tissues. Source

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