1.Inhibition of gastric cancer cells growth in vitro by sulindac.
Dong-Hong YU ; Lei ZHOU ; Ping WANG ; Qi-Zhi WANG ; Ze-Nong CHENG
Chinese Journal of Oncology 2006;28(7):498-502
OBJECTIVETo investigate the effect of sulindac on proliferation and apoptosis of human gastric cancer BGC-823 cells and its antineoplastic mechanisms.
METHODSHuman gastric cancer BGC-823 cells were incubated with sulindac at various concentrations and for different times. Morphological changes of BGC-823 cells were observed under an inversion microscope. MTT colorimetric assay was used to examine the effect of sulindac on the proliferation of BGC-823 cells. Flow cytometry was used to determine the cell cycle distribution and apoptosis. Transmission electron microscopy was performed to examine cell apoptosis morphology. Immunohistochemical staining was used to detect the expressions of COX-2, bcl-2 and ki-67 in the cells.
RESULTSsulindac induced morphologic alterations in BGC-823 cells, inhibited cell proliferation, increased the proportion of cells in G0/G1 phase and decreased the proportion of cells in S phase, induced apoptosis of BGC-823 cells, and decreased expressions of COX-2, bcl-2, ki-67 in the cells. All the effects were in a time- and dose-dependent manner (P < 0.05). Some characteristic morphologic features of apoptosis were revealed by transmission electron microscopy.
CONCLUSIONsulindac may inhibit the growth of gastric cancer BGC-823 cells in vitro and the anti-tumor mechanism may be related to changes in cell cycle distribution, induction of apoptosis and inhibition of expression of COX-2, bcl-2, and ki-67.
Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 ; metabolism ; Dose-Response Relationship, Drug ; Humans ; Ki-67 Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Sulindac ; administration & dosage ; pharmacology
2.Expression of Gal-3 and CD82/KAI1 proteins in non-small cell lung cancer and their clinical significance.
Shi-wu WU ; Lan YU ; Lei ZHOU ; Ze-nong CHENG ; Yi-sheng TAO
Chinese Journal of Oncology 2013;35(2):124-128
OBJECTIVETo study the expression of galectin 3 (Gal-3) and CD82/KAI1 proteins in non-small cell lung cancer (NSCLC) and the correlation between their expression and clinical significance.
METHODSThe expression of Gal-3 and CD82/KAI1 proteins was detected by immunohistochemistry in 160 specimens of NSCLC and 20 specimens of normal lung tissue.
RESULTSThe positive rates of Gal-3 and CD82/KAI1 proteins in the NSCLC were 63.8% and 37.5%, respectively, the positive rates of Gal-3 and CD82/KAI1 proteins in the normal lung tissue were 25.0% and 95.0%, respectively, and there was a significant difference between the two groups (P < 0.01). The expression of Gal-3 and CD82/KAI1 proteins was significantly correlated with the grade of tumor, lymph node metastasis, and pathological-TNM stages (all P < 0.05). Spearman analysis showed that there was a negative correlation between expressions of Gal-3 and CD82/KAI1 in NSCLC (r = -0.732, P < 0.01). Overexpression of Gal-3 and low expression of CD82/KAI1 were related to poor prognosis: the survival rate was significantly lower in the positive Gal-3 group (survival time: 23.0 ± 17.5 months) than that in the negative group (survival time: 71.6 ± 21.6 months) (P < 0.01). The survival rates of the CD82/KAI1-positive group (survival time: 72.5 ± 19.5 months) and CD82/KAI1-negative group (survival time: 21.6 ± 16.1 months) were significantly different (P < 0.01). Multivariate analysis indicated that pTNM stage and positive expression of Gal-3 and CD82/KAI1 are independent prognostic factors of NSCLC (P < 0.01).
CONCLUSIONSThe expression of Gal-3 and CD82/KAI1 may be related to the initiation, development and metastasis of NSCLC. Combined detection of Gal-3 and CD82/KAI1 has an important role in predicting the progression and prognosis of NSCLC.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Female ; Galectin 3 ; metabolism ; Humans ; Kangai-1 Protein ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate
3.Comparative proteomic analysis of human gallbladder carcinoma.
Yi TAN ; Hai-ping MENG ; Fu-qiang WANG ; Ze-nong CHENG ; Qiong WU ; Hao-rong WU
Chinese Journal of Oncology 2010;32(1):29-32
OBJECTIVETo find out potential molecular targets for gallbladder carcinoma diagnosis and treatment by analyzing and comparing the proteins expressed in human gallbladder carcinoma tissue and benign gallbladder tissue.
METHODSProteomic analysis of 6 human gallbladder carcinoma tissues and 6 benign gallbladder tissues was carried out. Total proteins of the carcinoma tissue and benign gallbladder tissue were separated by two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were analyzed and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Immunohistochemistry was used to examine the expression of PEBP1 protein in an independent series of samples.
RESULTSProtein extracts of individual samples in each type of tissues were separated on two-dimensional gels. There were forty six differentially expressed proteins in the gallbladder carcinom tissues. Seventeen proteins were successfully identified by MS, in which nine proteins were overexpressed in tumors while the other eight proteins were underexpressed. The increased level of PEBP1 protein in gallbladder carcinoma was further confirmed by immunohistochemical analysis.
CONCLUSIONSeventeen differentially expressed proteins were successfully characterized by comparative proteomic analysis. Those results may provide scientific foundation for screening the molecular biomarkers which can be used in diagnosis and treatment of gallbladder carcinoma, as well as to improve its prognosis and provide a new clue for carcinogenesis research of gallbladder carcinoma.
Adenocarcinoma ; diagnosis ; metabolism ; pathology ; Adult ; Aged ; Biomarkers, Tumor ; analysis ; Electrophoresis, Gel, Two-Dimensional ; Gallbladder Neoplasms ; diagnosis ; metabolism ; pathology ; Gallstones ; diagnosis ; metabolism ; pathology ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Middle Aged ; Phosphatidylethanolamine Binding Protein ; metabolism ; Proteomics ; methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
4.Relation between helicobacter pylori L-form infection and tumor angiogenesis in human esophageal carcinoma.
Dong-hong YU ; Ze-nong CHENG ; Ji-hui JIA ; Su-lan TANG ; Yan WU ; Qi-zhi WANG ; Yi TIAN ; Ping WANG
Chinese Journal of Oncology 2003;25(1):51-54
OBJECTIVETo investigate the correlation between helicobacter pylori L-form (Hp-L) infection in human esophageal carcinoma (EC) and tumor angiogenesis, and study the effect of Hp-L on the malignant biological behaviors of EC.
METHODSHp-L was examined in 98 patients with EC and 30 controls by Gram stain, electronmicroscopic technique and immunohistochemical stain (ABC method). VEGF, p53 protein and microvessel density (MVD) were examined by immunohistochemical stain (SP method) with their relationship with the clinicopathologic factors analyzed.
RESULTSThe positive rate of Hp-L was 60.2% in EC group. Two types of Hp-L were detected in the tissue of EC by electronmicroscopic technique, which lay in the outer or inner carcinoma cells. The positive rates of Hp-L, MVD, VEGF and p53 in the cancer group were significantly higher than those in control group (P < 0.005-0.001). The positive rates of MVD, VEGF and p53 in the Hp-L positive group of EC were significantly higher than those in Hp-L negative group (P < 0.005-0.001). The positive rate of Hp-L was correlated with MVD (r = 0.46, P < 0.01) and the expression of VEGF and p53 (r = 0.31, P < 0.01). The positive rate of Hp-L in the EC group was correlated with vessel invasion, depth of invasion, metastasis to the para-esophageal and distant lymph nodes except tumor size.
CONCLUSIONHp-L infection in EC is closely related with tumor angiogenesis and may be an important promoting factor in esophageal carcinoma growth, invasion and metastasis.
Adult ; Aged ; Esophageal Neoplasms ; complications ; Female ; Helicobacter Infections ; complications ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; complications
5.Epstein-Barr virus infection and p16(INK4a) overexpression in gastric adenocarcinoma.
Ping WANG ; Qing ZHANG ; Jin-Feng YANG ; Ze-Nong CHENG ; Ke ZHANG ; Dong-Hong YU
Chinese Journal of Experimental and Clinical Virology 2008;22(4):244-246
OBJECTIVETo study Epstein-Barr virus infection and p16 protein abnormal expresson in carcinogenesis and progression of gastric adenocarcinomas (GAC).
METHODSImmunohistochemical staining SP method was used to detect the expression of LMP-1 and p16 in 97 cases of GAC.
RESULTSEBV LMP-1 and p16 protein were detected in 30.9% (30/97) and in 63.91% (62/97) cases of gastric adenocarcinomas respectively. There was no significant difference between EBV-positive and EBV-negative gastric carcinomas in sex, histologic type, depth of tumor invision, lymph node metastasis and clinical stages (P > 0.05); overexpression of p16 was associated with lymph node metastasis and clinical stages; no correlation was found between the expression of EBV LMP-1 and p16 protein.
CONCLUSION1. EBV play a role in carcinogensis of GAC. 2. P16 gene abnormality is frequently involved in GAC and might be one of the important prognostic factors. 3. EBV infection and p16 alteration are two independent roles in GAC carcinogenesis.
Adenocarcinoma ; genetics ; metabolism ; pathology ; virology ; Adult ; Aged ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; metabolism ; Epstein-Barr Virus Infections ; genetics ; metabolism ; pathology ; virology ; Female ; Gene Expression Regulation, Neoplastic ; Herpesvirus 4, Human ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; virology ; Viral Matrix Proteins ; genetics ; metabolism
6.Expressions of Slug, ZEB1 and KISS-1 in gastric adenocarcinoma and their clinical significance.
Lei ZHOU ; Yong-Lian HU ; Shi-Wu WU ; Lan YU ; Ze-Nong CHENG ; Bo ZHU
Journal of Southern Medical University 2016;36(4):532-537
OBJECTIVETo identify potential markers for predicting invasion, metastasis, and prognosis of gastric adenocarcinoma (GAC).
METHODSThe expressions of Slug, ZEB1 and KISS-1 were detected immunohistochemically in 261 GAC tissues and 80 normal gastric tissues.
RESULTSThe positivity rates of Slug, ZEB1, and KISS-1 in gastric tissues were 2.5%, 1.3%, and 87.5%, respectively, significantly different from the rates of 62.1%, 28.4%, and 41.1% in GAC tissues (P<0.05). The expression level of Slug was significantly correlated with the depth of invasion, lymph node metastasis, and pTNM stages; the positivity rates of both ZEB1 and KISS-1 were significantly correlated with the tumor grade, depth of invasion, lymph node metastasis and pTNM stages. Slug expression was positively correlated with ZEB1 expression, and KISS-1 expression was inversely correlated with Slug and ZEB1 expressions. Kaplan-Meier analysis showed that the overall survival time of patients with positive expressions of Slug and ZEB1 was significantly shorter than that of the negative patients, and the survival time of patients positive for KISS-1 was significantly longer than the negative patients. COX multivariate analysis showed that positive Slug, ZEB1 and KISS-1 protein expressions and pTNM stages were independent prognostic factors of GAC (P<0.05).
CONCLUSIONThe abnormal expressions of Slug, ZEB1 and KISS-1 may contribute to the tumorigenesis of GAC and are related with lymph node metastasis, pTNM stages, and prognosis of GAC. The combined detection of Slug, ZEB1, and KISS-1 expression has an important value in predicting the progression and prognosis of GAC.
Adenocarcinoma ; metabolism ; pathology ; Disease Progression ; Homeodomain Proteins ; metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Kisspeptins ; metabolism ; Lymphatic Metastasis ; Neoplasm Grading ; Prognosis ; Proportional Hazards Models ; Snail Family Transcription Factors ; Stomach Neoplasms ; metabolism ; pathology ; Transcription Factors ; metabolism ; Zinc Finger E-box-Binding Homeobox 1
7.Expression of secreted frizzled related protein 1, β-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significances.
Yu-rong OU ; Juan LIU ; Shan GAO ; Gui-ying JING ; Ze-nong CHENG ; Xiu-qin DONG
Journal of Zhejiang University. Medical sciences 2014;43(4):397-405
OBJECTIVETo investigate the expression of secreted frizzled-related protein 1 (SFRP1), β-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significance.
METHODSThe expression of SFRP1, β-catenin and E-cadherin mRNA and protein in tumor and pericancerous tissue samples from 60 cases of colorectal cancer was assayed by reverse-transcription PCR and immunohistochemistry, respectively. The correlation of their expression with clinicopathological factors of colorectal cancer was analyzed.
RESULTSIn 52/60 cases the relative mRNA expression of SFRP1 in cancer tissue and pericancerous tissue was 0.4837±0.1532 and 0.7170 ±0.1830; for β-catenin was 0.9293± 0.3705 and 0.6469±0.3166; and for E-cadherin was 0.5556±0.2535 and 0.9422±0.2372 (P<0.01), respectively. SFRP1 mRNA expression was associated with lymphatic metastasis (P<0.05). The positive rate of SFRP1 in colorectal cancer was 31.67% (19/60), and was significantly lower than that in pericancerous colorectal mucosa (75.00%, 45/60). No relationship between SFRP1 protein expression and clinical pathology was found. Abnormal expression rates of β-catenin and E-cadherin in colorectal cancer were 75.00% (45/60) and 58.33% (35/60), respectively, which were significantly higher than that in pericancerous colorectal mucosa (1.67% and 6.67%), respectively. Abnormal β-catenin and E-cadherin expression was associated with tumor differentiation, lymphatic metastasis and Duke's staging. SFRP1 protein expression was negatively correlated with β-catenin and E-cadherin expression (r=-0.517, -0.442, Ps<0.01).
CONCLUSIONDown-regulation of SFRP1 in colorectal cancer may cause abnormal Wnt signaling and induce abnormal β-catenin and E-cadherin expression, indicating that SFRP1 might be involved in the development and progression of colorectal cancer, and could be a novel therapeutic target for colorectal cancer.
Adult ; Aged ; Aged, 80 and over ; Cadherins ; metabolism ; Colorectal Neoplasms ; metabolism ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Lymphatic Metastasis ; Male ; Membrane Proteins ; metabolism ; Middle Aged ; beta Catenin ; metabolism