Publications (10)

  • Ping Li · Dan Sun · Xiaoting Li · [...] · Yan Xin
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: To investigate the correlation between Nodal and YAP1 expression and the clinicopathological characteristics of gastric adenocarcinoma (GAC). Methods: Quantitative real-time RT-PCR, Western blot, and immunohistochemistry were performed to measure Nodal and YAP1 mRNA and protein in 20 fresh frozen samples and 220 paraffin-embedded GAC tissues with their paired non-tumor mucosa (PNTM). The prognostic values of Nodal and YAP1 were evaluated in 161 GAC patients using univariate and multivariate analyses. Results: Both mRNA and protein expression of Nodal and YAP1 were significantly increased in GAC compared to PNTM (P < 0.05). Immunohistochemistry showed that Nodal was more highly expressed in 56.4 % GAC samples compared to PNTM; additionally, Nodal expression correlated with depth of tumor invasion, lymph node metastasis, and distant metastasis (all P < 0.05). There was no association between Nodal and YAP1 in GAC (P = 0.171). Kaplan-Meier analysis showed that the outcome of Nodal-high patients was significantly worse than those with low Nodal expression (χ (2) = 30.452, P < 0.001). Cox multivariate regression showed that high Nodal expression was an independent risk factor affecting the prognosis of GAC patients (P = 0.000, RR = 2.976). Furthermore, patients with tumors in which both Nodal and YAP1 were expressed at high levels had the worst prognosis. Conclusions: Elevated Nodal expression is a marker of poor prognosis in gastric cancer. Patient outcome is further worsened if Nodal and YAP1 are both expressed in the same tumor. The datas we present here suggest that the inhibition of Nodal signaling may represent a new therapeutic strategy for the treatment of gastric adenocarcinoma.
    Article · Jun 2016 · Journal of Cancer Research and Clinical Oncology
  • Xiaobin Hu · Yan Xin · Yuping Xiao · Jing Zhao
    [Show abstract] [Hide abstract] ABSTRACT: YAP1 is overexpressed in numerous cancers, but its molecular mechanism in the carcinogenesis and clinic significance in tumor diagnosis and prognosis remains to be determined. We attempted to analyze the clinicopathologic significance of YAP1 expression and the correlation of the YAP1 levels with the progression, metastasis and prognosis of patients with gastric carcinoma. By immunohistochemistry, we determined YAP1 expression in 214 of primary gastric carcinoma (GC), 167 of matched normal gastric mucosa, 40 of chronic atrophic gastritis, 11 of dysplasia and 73 of intestinal metaplasia. The positive rate of YAP1 in gastric carcinoma was significantly higher than that in normal gastric mucosa, chronic atrophic gastritis and intestinal metaplasia. In the gastric cancers with lymph node metastasis, the positive rate of YAP1 was much higher than that in the group without lymph node metastasis. Moreover, gastric cancer patients with YAP1 overexpression demonstrated poorer prognosis than those with YAP1 negative staining. Finally, multivariate analysis of 191 patients with gastric carcinoma indicated that YAP1 overexpression, the invasion depth and lymph node metastasis were high hazard factors for gastric carcinoma. Our results demonstrated that YAP1 overexpression is correlated to the progression, lymph node metastasis and poor prognosis of gastric carcinoma, suggesting that overexpression of YAP1 might be an adjuvant factor for predicting lymph node metastasis, and a useful biomarker for the diagnosis and prediction of prognosis in patients with gastric cancers.
    Article · Mar 2014 · Pathology & Oncology Research
  • Hongju Wu · Yan Xin · Yuping Xiao · Jing Zhao
    [Show abstract] [Hide abstract] ABSTRACT: Low-dose metronomic (LDM) chemotherapy represents a new strategy to treat solid tumors by stronger antiangiogenic activity and less side-effects, especially in combination with other antiangiogenic agents. The aim of the study is to investigate the antiangiogenic effect of docetaxel alone and combined with (-)-epigallocatechin-3-gallate (EGCG) in preclinical settings of gastric cancer. BGC-823 human gastric cancer xenograft model was used, and tumor growth, side-effects of mice were closely monitored. Expression of vascular endothelial growth factor and CD31 were observed by immunohistochemistry, and microvessel density of the tumor tissues was assessed by CD31 immunohistochemical analysis. Our results indicated that LDM docetaxel inhibited angiogenesis and growth of gastric cancer with less toxicity, and the effects were further enhanced by the concurrent administration of EGCG. Our study, for the first time, rationally demonstrated that LDM docetaxel treatment used alone or combined with EGCG is effective and safe in preclinical settings of gastric cancer. Our data suggest that LDM docetaxel used alone or combined with EGCG may be an innovative and promising therapeutic strategy in the experimental treatment of human gastric cancer.
    Article · Jan 2012 · Cancer Biotherapy & Radiopharmaceuticals
  • Jing Zhao · Xiaoxiao Zhang · Yan Xin
    [Show abstract] [Hide abstract] ABSTRACT: Recent publications demonstrated that abnormal expression of Ezrin and c-Met proteins were related to carcinogenesis, metastasis and prognosis of various sorts of tumors. In this study we detected the expressions of Ezrin and c-Met proteins in normal gastric mucosa, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma and analyzed the correlations with metastasis and prognosis of gastric carcinomas. The results demonstrated that both Ezrin and c-Met overexpression were related to the occurrence and progression of gastric carcinoma. Our findings also demonstrated that combined detection of these two tumor-specific biomarkers in gastric carcinomas can provide additional efficacy in predicting the patients' outcomes.
    Article · Sep 2011 · Histology and histopathology
  • Jing Zhao · Xiaoxiao Zhang · Yan Xin
    [Show abstract] [Hide abstract] ABSTRACT: Recent publications demonstrated that abnormal expression of Ezrin and c-Met proteins were related to carcinogenesis, metastasis and prognosis of various sorts of tumors. In this study we detected the expressions of Ezrin and c-Met proteins in normal gastric mucosa, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma and analyzed the correlations with metastasis and prognosis of gastric carcinomas. The results demonstrated that both Ezrin and c-Met overexpression were related to the occurrence and progression of gastric carcinoma. Our findings also demonstrated that combined detection of these two tumor-specific biomarkers in gastric carcinomas can provide additional efficacy in predicting the patients' outcomes.
    Article · Sep 2011 · Histology and histopathology
  • Hongju Wu · Yan Xin · Jing Zhao · [...] · Shasha Wang
    [Show abstract] [Hide abstract] ABSTRACT: Low-dose metronomic (LDM) chemotherapy represents a new strategy to treat solid tumors by stronger antiangiogenic activity and less side effects. The aim of the study is to rationally develop a docetaxel metronomic regimen in preclinical settings of gastric cancer. In vitro cell proliferation, apoptosis, and thrombospondin-1/vascular endothelial growth factor (TSP-1/VEGF) expression analyses were performed on human umbilical vein endothelial cells (HUVECs) and gastric cancer (BGC-823) cells exposed for 144 h to metronomic concentrations of docetaxel. BGC-823 human gastric cancer xenograft model was used, and tumor growth and side effects were closely monitored. Quantitative real-time PCR was used to determine TSP-1/VEGF mRNA levels in tumor samples. Expression of VEGF and CD31 was observed by immunohistochemistry. Our results indicated that LDM docetaxel preferentially inhibited HUVEC cell proliferation and induced HUVEC apoptosis. Docetaxel significantly increased TSP-1 expression and secretion in HUVEC cells whereas the expression and secretion of VEGF significantly decreased in BGC-823 cells. LDM docetaxel significantly inhibited BGC-823 tumor growth in the absence of toxicity, which was accompanied by decreases in microvessel density (MVD) and VEGF and increases in TSP-1 gene expression in tumor tissues. In vitro results show the antiangiogenic properties of LDM docetaxel. In vivo, LDM docetaxel treatment is effective against gastric tumor and microvessel growth without toxic effect on nude mice.
    Article · Feb 2011 · Cancer Chemotherapy and Pharmacology
  • Jian-Guo Zhang · Jing Zhao · Yan Xin
    [Show abstract] [Hide abstract] ABSTRACT: To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis. The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal metaplasia (IM) and 25 dysplasia (DYS). The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were significantly higher in GC with lymph node metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relationship between CR-1 and p-STAT3 expressions in GC (r(k) = 0.189, P = 0.002). The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.
    Article · Feb 2010 · World Journal of Gastroenterology
  • XiaoBin Hu · Jing Zhao · Lin Yang · Yan Xin
    [Show abstract] [Hide abstract] ABSTRACT: Objective We investigated the relationship between the expression of Caspase-3, cell proliferation and apoptosis in gastric cancer and their precancerous lesions, to explore the tumorigenesis of the stomach mucosa. Methods Caspase-3 expression in 13 normal gastric mucosa, 6 chronic atrophic gastritis (CAG), 31 intestinal metaplasia (IM), 114 dysplasia (DYS) and 20 gastric carcinomas were investigated immunohistochemically. Cell proliferation was evaluated with anti-Ki-67 immunostaining and apoptosis was evaluated using DNA fragmentation in situ by TdT-mediated dUTP biotin nick end labeling (TUNEL) method. Results Caspase-3 mild-moderately positive expression was observed in most of normal superficial epithelia, its positively polar distribution in normal mucosa, CAG, IM, DYS and gastric carcinomas changed as seen in TUNEL, and so did the positive rate. Caspase-3 protein expression showed significantly positive correlation with the number of apoptotic cells labeled with TUNEL (correlation coefficient r = 0.94; P < 0.01). Ki-67 expression showed a negative but not significant correlation trend with Caspase-3 (correlation coefficient r = −0.23; P > 0.05). Conclusion Caspase-3 protein expression was up-regulated from CAG to IM and mild-moderate atypical dysplasia, but down-regulated in severe dysplasia and gastric carcinoma, indicating that inactivity or reduced expression of Caspase-3 is closely correlated with carcinogenesis of the stomach mucosa.
    Article · Nov 2009 · The Chinese-German Journal of Clinical Oncology
  • Chun-Li Da · Yan Xin · Jing Zhao · Xiang-Dong Luo
    [Show abstract] [Hide abstract] ABSTRACT: To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and significance of their expression in gastric carcinoma and precancerous lesions. The PV9000 immunohistochemical method was used to detect the expression of YAP and survivin in 98 cases of normal gastric mucosa, 58 intestinal metaplasia (IM), 32 dysplasia and 98 gastric carcinoma. The positive rates of YAP in dysplasia (37.5%) and gastric carcinoma (48.0%) were significantly higher than that in normal gastric mucosa (13.3%), P < 0.01. The positive rates of survivin in IM (53.4%), dysplasia (59.4%) and gastric carcinoma (65.3%) were significantly higher than in normal gastric mucosa (11.2%), P < 0.01. Survivin expression gradually increased from 41.7% in well differentiated adenocarcinoma through 58.3% in moderately differentiated adenocarcinoma to 75.6% in poorly differentiated adenocarcinoma, with significant Rank correlation, r(k) = 0.279, P < 0.01. The positive rate of survivin in gastric carcinoma of diffused type (74.6%) was significantly higher than that in intestinal type (51.3%), P < 0.05. In gastric carcinoma with lymph node metastasis (76.9%), the positive rate of survivin was significantly higher than that in the group without lymph node metastasis (41.2%), P < 0.01. In 98 cases of gastric carcinoma, the expression of YAP and of survivin were positively correlated, r(k) = 0.246, P < 0.01. YAP may play an important role as a carcinogenic factor and may induce survivin expression. Detecting both markers together may help in early diagnosis of gastric carcinoma.
    Article · Sep 2009 · World Journal of Gastroenterology
  • Jing Zhao · Xiang-Dong Luo · Chun-Li Da · Yan Xin
    [Show abstract] [Hide abstract] ABSTRACT: To explore the relation between B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) expression and the clinicopathological features of gastric carcinoma (GC). Immunohistochemistry was used to detect the expression of Bmi-1 and ki-67. Double-labeling staining was used to display the distribution of Bcl-2(+)/ki-67(-) cells in 162 cases of GC and its matched normal mucosa and precancerous lesion. The positive rate of Bmi-1 expression in GC (52.5%) was significantly higher than that in normal gastric mucosa (21.6%, chi(2) = 33.088, P < 0.05). The Bmi-1 expression in GC was closely related with the Lauren's and Borrmann's classification and clinical stage (chi(2) = 4.400, 6.122 and 11.190, respectively, P < 0.05). The expression of ki-67 was related to the Borrmann's classification (chi(2) = 13.380, P < 0.05). Bcl-2 expression was correlated with the Lauren's classification (chi(2) = 4.725, P < 0.05), and the Bmi-1 expression both in GC (r(k) = 0.157, P < 0.05) and in intestinal metaplasia (r(k) = 0.270, P < 0.05). Abnormal Bmi-1 expression in GC may be involved in cell proliferation, apoptosis and cancerization. This marker can objectively indicate the clinicopathological characteristics of GC.
    Article · May 2009 · World Journal of Gastroenterology