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Beijing, China

Wang D.-J.,Chinese PLA General Hospital | Zhi X.-Y.,Capital Medical University | Zhang S.-C.,Capital Medical University | Jiang M.,Beijing University of Chinese Medicine | And 5 more authors.
Oncology Reports | Year: 2012

Gremlin is a member of the bone morphogenetic protein (BMP) antagonist family and its antagonistic effect is likely through direct binding to BMP proteins. As an antagonist of BMP, Gremlin plays a role in regulating organogenesis, body patterning and tissue differentiation. Recent studies have shown a deregulation of Gremlin in several types of human cancers. However, the role of Gremlin in human malignant mesothelioma (MM) is still unknown. In this study, we investigated the expression of Gremlin in human MM. We found that Gremlin mRNA and protein were both overexpressed in the majority of primary MM tissue samples that we examined. We also observed high level expression of the Gremlin gene in 4 of the 6 MM cell lines. Consistently, we found that the Gremlin promoter activity was significantly elevated in those MM cell lines expressing the Gremlin gene. On the other hand, no activity of the Gremlin promoter was detected in the two MM cell lines lacking Gremlin expression. Moreover, to examine the functional significance of the Gremlin overexpression in MM, we used shRNA to knock down Gremlin expression in MM cell lines expressing Gremlin and found that inhibition of Gremlin expression significantly suppressed proliferation of those MM cells. Taken together, our results suggest that the BMP antagonist Gremlin is overexpressed in MM and that aberrant activation of Gremlin may play a critical role in the tumorigenesis of human MM. Source


Niu R.,Hospice Hospital | Jing H.,Clinical Laboratory | Chen Z.,Tsinghua University | Xu J.,ACCB Biotech Ltd. | And 2 more authors.
Asia-Pacific Journal of Clinical Oncology | Year: 2012

Aim: For several decades urinary arylsulfatase (ARS) activity has been reported to be elevated in many cancers. It has been shown that urinary ARS activity may serve as a marker of tumor progression and therapy surveillance. This study was designed to evaluate the clinical application of detection of urinary ARS activity. Methods: We used a modified precipitation method to separate ARS from urine samples. This method was easy to use and applicable for a high throughput assay. We tested and analyzed the morning urinary ARS activity in 300 normal controls, 97 patients with benign tumors and 119 with malignant colorectal tumor. Results: Compared to normal male and female controls, morning urinary ARS activity was significantly higher in malignant colorectal tumor patients. Moreover, morning urinary ARS activity had a relatively high efficacy in distinguishing patients with malignant colorectal tumors from those with benign colorectal tumors. The area under the curve in the receiver operator characteristics curve analysis was 0.89 (95% CI, 0.83-0.95) and 0.87 (95% CI, 0.79-0.94) in male and female colorectal patients, respectively. Conclusion: These data suggest the potential application of morning urinary ARS activity to conventional clinical use. © 2012 Wiley Publishing Asia Pty Ltd. Source


Li J.,Tsinghua University | Mo M.-L.,Tsinghua University | Chen Z.,Tsinghua University | Yang J.,Tsinghua University | And 9 more authors.
Cancer Science | Year: 2011

The HSulf-1 gene encodes an extracellular 6-O-endosulfatase and regulates the sulfation status of heparan sulfate proteoglycans (HSPG). We have demonstrated that promoter hypermethylation is correlated with the HSulf-1 silencing in gastric cancer. To investigate the functional importance of HSulf-1 silencing in gastric cancer, we restored HSulf-1 expression in the gastric cancer cell line MKN28, which lacks endogenous HSulf-1. Following restoration of expression, HSulf-1 inhibited cell proliferation, motility, and invasion in vitro, as well as significantly suppressing the MKN28 xenograft model (P < 0.05). No noticeable changes in proliferation and motility were observed following restoration of HSulf-1 in another gastric cancer cell line, namely AGS cells. Interestingly, in MKN28 cells, which have been reported to be dependent on extracellular Wnt signaling, we found that HSulf-1 inhibited the transcriptional activity of the Wnt/β-catenin pathway and downregulated its targeted genes. Conversely, in AGS cells, in the constitutive Wnt/β-catenin pathway is active, HSulf-1 had no effect on the activity of the Wnt/β-catenin pathway. Furthermore, transfection of Wnt3a cDNA or β-catenin shRNA resulted in rescue or enhancement, respectively, of the effects of HSulf-1 in MKN28 cells. Furthermore, HSPG epitope analysis confirmed that HSulf-1 affected the structure of heparan sulfate on the cell surface. Together, the results of the present study suggest that extracellular HSulf-1 may function as a negative regulator of proliferation and invasion in gastric cancer by suppressing Wnt/β-catenin signaling at the cell surface. © 2011 Japanese Cancer Association. Source


Mo M.-L.,Tsinghua University | Li M.-R.,Zhejiang Sci-Tech University | Chen Z.,Tsinghua University | Liu X.-W.,ACCB Biotech Ltd. | And 3 more authors.
Oncology Letters | Year: 2013

Similarly to the Wnt protein palmitoyltransferase, porcupine (PPN) is essential to the activation of the Wnt/β-catenin signaling pathway. However, little is known about the role of PPN activity in human gastric cancer, one of the most common causes of cancer-related mortality. Real-time quantitative PCR was used to detect the expression levels of PPN in paired gastric cancer tissues. Cell proliferation, migration and invasion assays were performed following treatment using a newly developed small molecule PPN inhibitor (inhibitors of Wnt production, IWP-2) in the gastric cancer MKN28 cell line. Expression of downstream target genes and transcriptional activity of the Wnt/β-catenin signaling pathway were examined following IWP-2 treatment in MKN28. We identified that PPN was overexpressed in human gastric cancer tissue samples and cell lines. Following treatment of the gastric cancer cell line MKN28 with IWP-2, we detected that IWP-2 decreased MKN28 cell proliferation, migration and invasion, and elevated caspase 3/7 activity. Further analysis demonstrated that IWP-2 downregulated the transcriptional activity of the Wnt/β-catenin signaling pathway and downregulated the expression levels of downstream Wnt/β-catenin target genes in MKN28 cells. As current Wnt pathway-targeting strategies used for anticancer therapy have mainly focused on. Source


Gu Y.-F.,Capital Medical University | Zhang H.,Capital Medical University | Su D.,Capital Medical University | Mo M.-L.,Tsinghua University | And 3 more authors.
Chinese Medical Journal | Year: 2013

Background Aberrantly expressed microRNAs are a hallmark of cancer, and microRNA expression profiling is associated with tumor progression and response to chemotherapy, suggesting their potential application as prognostic and predictive biomarkers. The role of microRNAs in lung cancer remains elusive. It has been recently reported that epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) tyrosine kinase can regulate expression of specific microRNAs including miR-30b, miR-30c, miR-221, miR-222, miR-103 and miR-203, and induce tumorigenesis and gefitinib resistance in lung cancers. We intend to study the role of miR-30b and miR-30c expression in predicting response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Methods We have therefore retrospectively examined expression of miR-30b miR-30c in 41 formalin fixed paraffin embedded tissue samples from NSCLC patients when TKIs were used as first line therapy. Results We found a significant correlation between expression of miR-30b and miR-30c. Furthermore, miR-30b and miR-30c expression correlated with short-term response. Kaplan-Meier analysis further revealed that the expression of miR-30b and miR-30c predicted progression free survival and the overall survival rate in the examined cohort. Conclusion Our study identified miR-30b and miR-30c as useful prognostic predictors in NSCLC patients who underwent first line treatment with TKIs. Source

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