Key Laboratory of Gastroenterology of Zhejiang Province

Hangzhou, China

Key Laboratory of Gastroenterology of Zhejiang Province

Hangzhou, China

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Ru G.-Q.,Wenzhou Medical College | Ru G.-Q.,Zhejiang Provincial Peoples Hospital | Wang H.-J.,Key Laboratory of Gastroenterology of Zhejiang Province | Xu W.-J.,Zhejiang Provincial Peoples Hospital | Zhao Z.-S.,Zhejiang Provincial Peoples Hospital
Pathology and Oncology Research | Year: 2011

Tumor invasion and metastasis are the most common causes of death in gastric carcinoma. Twist, a transcription factor of the basic helix-loop-helix class, reportedly regulates cancer metastasis and induces epithelial-mesenchymal transition (EMT). We evaluated the expression of Twist and its effect on cell migration in gastric carcinoma (GC). Twist expression was detected by real-time quantitative RT-PCR in gastric tumor tissue, metastatic lymph nodes and normal gastric tissue from 47 gastric carcinoma patients who had undergone gastrectomies with radical lymph node dissections without preoperative treatment. Twist expression was also analyzed immunohistochemically in 436 gastric cancer cases. GC tumor tissue and metastatic lymph nodes was upregulated compared with normal gastric mucosa (P<0.05). Twist protein expression differed significantly among gastric tumor tissue, matched normal gastric mucosa, and lymph nodes (P<0.05) In stages I, II, and III, 5-year survival rates of patients with high Twist expression were significantly lower than in patients with low expression (P<0.05). In stage IV, Twist expression did not correlate with 5-year survival rates (P=0.07). Further multivariate analysis suggested that depth of invasion, lymph-node and distant metastases, TNM stage, and upregulation of TWIST were independent prognostic indicators for GC. Twist expression in gastric cancer is associated significantly with lymph-node and distant metastases, and poor prognosis. Twist may be a useful marker for the development, progression and metastasis of GC. © Arányi Lajos Foundation 2010.


Wang Y.-Y.,Zhejiang Provincial Peoples Hospital | Li L.,Key Laboratory of Gastroenterology of Zhejiang Province | Zhao Z.-S.,Zhejiang Provincial Peoples Hospital | Wang Y.-X.,Zhejiang Provincial Peoples Hospital | And 2 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2013

Background: L1 cell adhesion molecule (L1CAM) and epithelial cell adhesion molecule (EPCAM) have been implicated in the development and progression of gastric cancer. The present study investigated the clinical significance of L1CAM and EPCAM in the development, progression and prognosis of gastric cancer. Methods. Expression of L1CAM and EPCAM were examined immunochemically in 601 clinicopathologically characterized gastric cancer cases. Results: L1CAM protein was detected in 23.9% of human non-tumor mucosa samples. All samples expressed L1CAM protein at low levels. High expression of L1CAM protein was detected in 163 (27.1%) tumors. Expression of L1CAM correlated with age, tumor location, size of tumors, Lauren's classification, depth of invasion, lymph node and distant metastases, regional lymph node stage, Tumor-Node-Metastasis (TNM) stage and prognosis. EPCAM protein was detected in 45.7% of human non-tumor mucosa samples. All samples expressed EPCAM protein at low levels. High expression of EPCAM protein was detected in 247 (41.1%) tumors. Expression of EPCAM correlated with age, tumor location, size of tumors, Lauren's classification, depth of invasion, lymph node and distant metastases, regional lymph node stage, TNM stage and prognosis. Cumulative 5-year survival rates of patients with high expression of both L1CAM and EPCAM were significantly lower than in patients with low expression of both. Conclusions: Expression of L1CAM and EPCAM in gastric cancer was significantly associated with lymph node and distant metastasis, and poor prognosis. L1CAM and EPCAM proteins could be useful markers to predict tumor progression and prognosis. © 2013 Wang et al.; licensee BioMed Central Ltd.


Wang Y.-Y.,Zhejiang Provincial Peoples Hospital | Li L.,Key Laboratory of Gastroenterology of Zhejiang Province | Ye Z.-Y.,Zhejiang Provincial Peoples Hospital | Zhao Z.-S.,Zhejiang Provincial Peoples Hospital | Yan Z.-L.,Zhejiang Provincial Peoples Hospital
World Journal of Surgical Oncology | Year: 2015

Background: This study aims to investigate the effect of miR-10b overexpression on cancer cell proliferation, migration, invasion, and Hoxd10 expression. Methods: The effect of miR-10b on proliferation, migration, and invasion of MKN-28, BGC-823, and SGC-7901 cells and the expression of Hoxd10 protein in SGC-7901 and BGC-823 cells were detected following transfection of miR-10b inhibitor or Negative Control B. Expression of Hoxd10 protein in 436 paraffin-embedded cancer tissues was also investigated. Results: miR-10b was significantly upregulated in AGS, MKN-28, BGC-823, HCG-27, SGC-7901, and MKN-45 cell lines, miR-10b inhibitor significantly inhibited proliferation and migration of MKN-45, BGC-823 and SGC-7901 cells 48h after transfection, while Hoxd10 protein in these cells lines had increased 72h after transfection. Hoxd10 was highly expressed in gastric cancer and correlated with size of tumor, Lauren classification, depth of invasion, lymph node and distant metastasis, Tumor-Node-Metastasis (TNM) stage, and prognosis. Conclusions: miR-10b promotes migration and invasion through Hoxd10 in human gastric cancer cell lines and may play an important role in tumorigenesis, progression, and prognosis. © 2015 Wang et al.


Wang Y.-Y.,Zhejiang Provincial Peoples Hospital | Li L.,Zhejiang Provincial Peoples Hospital | Zhao Z.-S.,Zhejiang Provincial Peoples Hospital | Wang H.-J.,Key Laboratory of Gastroenterology of Zhejiang Province
World Journal of Surgical Oncology | Year: 2013

Background: We examined preoperative kinesin II-associated protein (KAP1), TIMP metallopeptidase inhibitor 1 (TIMP1) and stanniocalcin 2 (STC2) expression levels in patients with gastric cancers to assess their clinical application for diagnosing and monitoring diseases.Methods: Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of KAP1, TIMP1, STC2, talin 2 (TLN2), sushi-repeat-containing protein, X-linked 2 (SRPX2) and secreted protein, acidic, cysteine-rich (SPARC) in the patients' peripheral blood karyocytes. The data were analyzed with receiver operating characteristics (ROC) curves.Results: A total of 112 patients with gastric cancer, 42 patients with recurrence and 107 healthy volunteers were recruited. There were significant correlations between KAP1, TIMP1 and STC2 levels, and TNM tumor stages and distant metastases. The area under the ROC curves (AUC) of KAP1 was 0.803 ± 0.040 (P = 0.0001), the AUC of TIMP1 was 0.767 ± 0.043 (P = 0.0001) and the AUC of STC2 was 0.769 ± 0.045 (P = 0.0001), thus differentiating preoperative gastric cancer patients from healthy volunteers by ROC curve analysis. The AUC of STC2 was 0.739 ± 0.070 (P = 0.004) and the AUC of KAP1 was 0.418 ± 0.088 (P = 0.319), thus differentiating recurrence of gastric cancer from healthy volunteers by ROC curve analysis. High TIMP1 and STC2 expression levels were suspected to be poor prognostic factors of disease recurrence in patients with gastric cancer.Conclusions: KAP1, TIMP1 and STC2 expression levels may be potential biomarkers for the screening, diagnosis, prognosis and surveillance of gastric cancer. © 2013 wang et al.; licensee BioMed Central Ltd.


Wang Y.-Y.,Zhejiang Provincial Peoples Hospital | Ye Z.-Y.,Zhejiang Provincial Peoples Hospital | Zhao Z.-S.,Zhejiang Provincial Peoples Hospital | Li L.,Key Laboratory of Gastroenterology of Zhejiang Province | And 4 more authors.
Human Pathology | Year: 2013

We have investigated microRNA (miRNA) expression profiles of gastric cancer and the clinicopathologic significance of miR-10b expression in gastric carcinoma. miRCURY LNA Arrays (v.16.0; Exiqon, Vedbaek, Denmark) were used to screen miRNAs in 17 gastric cancers. Reverse transcriptase polymerase chain reaction was performed to determine the expression of miR-10b in 56 gastric tumors. Expression of miR-10b in 436 paraffin-embedded cancer tissues was also investigated. In gastric cancer, 49 miRNAs were overexpressed by 2.0-fold or greater, and 39 miRNAs were down-regulated by 1.5-fold or greater, whereas miR-10b was up-regulated by 2.98-fold. miR-10b was highly expressed in gastric cancer and correlated with size of tumor, Lauren classification, depth of invasion, lymph node and distant metastasis, TNM stage, and prognosis. In stages I, II, and III, the 5-year survival rate of patients with high levels of miR-10b expression was significantly lower than that in patients with low levels of expression. In stage IV, the expression level of miR-10b did not correlate with the 5-year survival rate. miR-10b may play an important role in progression and prognosis of gastric cancer. © 2013 Elsevier Inc.


Zhao Z.-S.,Zhejiang Provincial Peoples Hospital | Li L.,Zhejiang Provincial Peoples Hospital | Wang H.-J.,Key Laboratory of Gastroenterology of Zhejiang Province | Wang Y.-Y.,Zhejiang Provincial Peoples Hospital
Journal of Surgical Oncology | Year: 2011

Background: We examined CEACAM6, ITGB1, and cyr61 concentrations from patients with gastric cancers (GCs) to assess their clinical application for diagnosing and monitoring diseases. Methods: Real-time reverse transcription-polymerase chain reaction was used to detect the expressions of CEA, CEACAM6, ITGB1, IGF1R, CK20, cyr61, and S100A4 in peripheral blood karyocyte from 82 patients with GC, 24 patients with recurrence, and 37 healthy volunteers. Receiver operating characteristics (ROC) curves were constructed. Results: There were significant association between these CEACAM6, ITGB1, and cyr61 and TNM Stages and distant metastasis. The AUC of CEACAM6 was 0.884±0.044 (P = 0.0001), the AUC of cyr61 was 0.833±0.047 (P = 0.0001), and the AUC of ITGB1 was 0.838±0.042 (P = 0.0001) by differentiating preoperative GC patients from healthy volunteers from ROC curve analysis. The AUC of CEACAM6 was 0.761±0.066 (P = 0.001), the AUC of CYR61 was 0.762±0.063 (P = 0.001), and the AUC of ITGB1 was 0.824±0.051 (P = 0.0001), by differentiating recurrence of GC from healthy volunteers from ROC curve analysis. Conclusion: The method of detecting the expression of CEACAM6, ITGB1, and CYR61 in peripheral blood of GC patients was more sensitive than CEA, IGF1R, CK20, and S100A4 for the early diagnosis of metastasis and recurrence. © 2011 Wiley-Liss, Inc.


Wang H.-J.,Key Laboratory of Gastroenterology of Zhejiang Province | Ruan H.-J.,Zhejiang Provincial Peoples Hospital | He X.-J.,Key Laboratory of Gastroenterology of Zhejiang Province | Ma Y.-Y.,Key Laboratory of Gastroenterology of Zhejiang Province | And 4 more authors.
European Journal of Cancer | Year: 2010

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles by repressing translation or cleaving RNA transcripts. Dysregulated expression of miRNAs is associated with several diseases, including cancer. In this study, we report that the expression of microRNA-101 (miR-101) is down-regulated in gastric cancer tissues and cells, and ectopic expression of miR-101 significantly inhibits cellular proliferation, migration and invasion of gastric cancer cells by targeting EZH2, Cox-2, Mcl-1 and Fos. Our animal study also indicates that miR-101 could potentially suppress tumour growth in vivo. Collectively, these results suggest that miR-101 may function as a tumour suppressor in gastric cancer, as it has an inhibitory role not only in cellular proliferation, migration and invasion in vitro, but also in tumour growth in vivo. © 2010 Elsevier Ltd. All rights reserved.


Ma Y.-Y.,Key Laboratory of Gastroenterology of Zhejiang Province | Tao H.-Q.,Key Laboratory of Gastroenterology of Zhejiang Province
Cancer Biotherapy and Radiopharmaceuticals | Year: 2012

Recent advancements in cancer research have led to major breakthroughs; however, the impact on overall cancer-related death rate remains unacceptable. Thus, further insights into tumor markers and subsequent development of targeted therapies are urgently needed. For decades the urokinase plasminogen activator (uPA) system has been thought to drive tumor progression by mediating directed extracellular proteolysis on the surface of migrating or invading cells. Intervention with this proteolysis by targeting of uPA receptor (uPAR) has been proposed to represent a novel approach for inhibiting tumor progression. Recent data have provided new insights into the role of uPAR in gastric cancer progression. In addition to mediating proteolysis, this receptor also appears to mediate cell signaling, proliferation, and survival, and these observations have revealed novel ways to target uPAR. In this review, we discuss uPAR expression in gastric cancer, the relationship between uPAR and Helicobacter pylori, and recent insights into uPAR-signaling mechanisms. The role of uPAR as a cancer target in gastric cancer is also summarized. © Copyright 2012, Mary Ann Liebert, Inc.


Ma Y.-Y.,Key Laboratory of Gastroenterology of Zhejiang Province | Tao H.-Q.,Key Laboratory of Gastroenterology of Zhejiang Province
Cancer Science | Year: 2012

Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein-coding proto-oncogenes and tumor-suppressor genes. Microribonucleic acids (miR) are a recently-described class of genes encoding small non-coding RNA molecules, which primarily act by downregulating the translation of target mRNA. It has become apparent that miR are also key factors in cancer, playing both oncogenic and tumor-suppressing roles in gastric cancer. Recent studies have shown that a substantial number of miR show differential expression in gastric cancer tissues, and they are turning out to be just like any other regulatory gene. In this connection, miR dysregulation are reported to be associated with incidence, early diagnosis and prognosis of gastric cancer. Therefore, investigation of the biological aspects of miR dysregulation might help us better understand the pathogenesis of gastric cancer and promote the development of miR-directed therapeutics against this deadly disease. The aim of the present review was to describe the mechanisms of several known miR, summarize recent studies on oncogenic miR (e.g. miR-21, miR-106a and miR-17), tumor suppressor miR (e.g. miR-101, miR-181, miR-449, miR-486, let-7a) and controversial roles of miR (e.g. miR-107, miR-126) for gastric cancer. In addition, their potential clinical applications and prospects in gastric cancer, such as biomarkers and clinical therapy tools, are also briefly discussed. © 2011 Japanese Cancer Association.


Xia Y.-J.,Key Laboratory of Gastroenterology of Zhejiang Province | Ma Y.-Y.,Key Laboratory of Gastroenterology of Zhejiang Province | He X.-J.,Key Laboratory of Gastroenterology of Zhejiang Province | Wang H.-J.,Key Laboratory of Gastroenterology of Zhejiang Province | And 2 more authors.
Human Pathology | Year: 2011

Gastric cancer is one of the leading causes of death in Asian countries, especially in China. Because of the lack of suitable biomarkers for early detection, most patients are diagnosed at late stages, and the 5-year survival rate is low. In this study, we used proteomic analysis to identify specific disease-associated proteins as potential clinical biomarkers in gastric cancer. Protein spots were determined and identified by 2-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time of flight mass spectrometry in 12 paired specimens. Twenty distinct proteins displaying a difference in expression of at least 1.8-fold between the tumor and compared adjacent normal mucosa were detected by 2-dimensional polyacrylamide gel electrophoresis, and one of the spots was selenium-binding protein 1 identified by matrix-assisted laser desorption ionization time of flight mass spectrometry. Selenium-binding protein 1 was significantly decreased or even absent in gastric cancer tissue compared with the adjacent normal mucosa in 44 paired specimens detected by reverse transcriptase-polymerase chain reaction and in 28 paired specimens detected by Western blot. Immunohistochemical staining result of 126 cases showed that the selenium-binding protein 1 level was correlated with differentiation, TNM stage, and lymph node metastasis (P <.05). The 3-year survival rate of patients with high expression of selenium-binding protein 1 was significantly higher than that of patients with low expression. Our results provided the first evidence of selenium-binding protein 1 as a potentially novel biomarker for prognosis of gastric cancer. © 2011 Elsevier Inc.

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