1.The expression of heparanase and vascular endothelial growth factor-C in gastric carcinoma and its implication
Yuanshui SUN ; Zaiyuan YE ; Zhongsheng ZHAO
Chinese Journal of Digestion 2001;0(07):-
Objective To investigate the expression of heparanase and vascular endothelial growth factor-C (VEGF-C) protein in human gastric carcinoma, and to evaluate its clinical implications during the progress of gastric carcinoma. Methods The expression of heparanase and VEGF-C protein in 97 cases of gastric cancer, adjacent tissues and normal tissues in 20 subjects was determined by immuno- histochemistry. Results The positive rate of heparanase and VEGF-C protein in tumor tissues (61.9% and 66.0%) were significantly higher than those in adjacent tissues of cancer (7.2% and 5.0%) and normal tissues (8.3% and 5.0%, P 0.05) . The positive expression of VEGF-C protein in the tumor tissues was significantly related with serosal infiltration, lymphatic invasion, lymph node metastasis and TNM stage Ⅲ-Ⅳ (P0.05). The 1, 3 and 5-year survival rates of patients with expression of heparanase or VEGF-C protein were significantly less than that of patients without expression of heparanase or VEGF-C (P
2.Clinical evaluation of preoperative arterial infusion chemotherapy and surgical operation for colorectal carci-noma
Jianhua YUAN ; Zhongsheng ZHAO ; Gaoli DENG
Journal of Interventional Radiology 2001;0(05):-
0.05). Conclusions Peroperative transcatheter arterial infusion chemotherapy resulting in apoptosis of adenocarnoma, can raise the radical operation rate, and prolong survival rate for colprectal carcinoma patients.
3.Expression of cyclin E, P53 protein in human gastric carcinoma and its prognostic significance
Zhongsheng ZHAO ; Guoqing RU ; Jie MA ;
China Oncology 2001;0(03):-
Purpose:To study the expressions of cyclin E and P53 in gastric carcinoma in relation to biological behavior and prognosis.Methods:Cyclin E and P53 expressions at protein level were determined by immunohistochemistry technique in 128 patients with gastric carcinoma.Results:Of the 128 patients , cyclin E positive expression was in 57(44 5%),P53 positive expression was in 67(52.3%),P53 and cyclin E were both positive in 48(37.5%),respectively.Cyclin E and P53 expression level were correlated with tumor size , invasion depth, regional lymph node status, vessel invasion, and distant metastasis, Univariate analysis demonstrated better survival in patients with negative cyclin E and P53 expressions than those with positive expression. By COX multivariate analysis, cyclin E expression level was found to be of independent prognostic significance, however p53 expression level was not found to be of independent prognostic significance.Conclusions:Cyclin E expression within gastric carcinoma tissues is an indicator of tumor behavior and prognosis, p53 expression within gastric carcinoma tissue is only an indicator of tumor behavior. [
4.Experimental study on inguinal subcutaneous immunotherapy for allergic rhinitis in mice
Zhenan ZHAO ; Ji DAI ; Wanjun ZHAO ; Qingyun WANG ; Zhongsheng CAO
Chinese Journal of Immunology 2015;(6):785-789
Objective:To explore the feasibility of inguinal subcutaneous immunotherapy for allergic rhinitis ( AR ) in mice. Methods:36 female BALB/c mice were divided randomly into six groups( n=6 per group) including the control A,the model A, the treatment A groups,and the control B,the model B,the treatment B groups(inguinal subcutaneous immunotherapy for group A, cervical back subcutaneous immunotherapy for for group B). AR model was established with ovalbumin. At 25 to 55 days,ovalbumin im-munotherapy were performed in treatment groups,once two days,15 times totally. After intranasal rechallenge was performed at 56 to 62 days the AR symptom scores were documented. The eosinophils(EOS)in the nasal mucosa were measured by chromotropic acid 2R staining. Ovalbumin-specific IgE( OVA-sIgE) in the serum and expression of interferon-γ and interleukin-4 in the nasal lavage were measured by enzyme-linked immunosorbent assay meanwhile the ratio of interferon-γ and interleukin-4 was calc μlated. SPSS17. 0 software was used to analyze the data. Results:Before treatment ,the AR symptom scores of the model and treatment groups were more than 5. After treatment,the treatment A group were less than 5. The EOS count of the control A,model A,treatment A groups and the control B,model B, treatment B groups was 0. 78 ± 0. 31, 21. 60 ± 2. 90, 10. 43 ± 2. 56, 0. 83 ± 0. 46, 22. 44 ± 3. 39, 23. 40 ± 4. 24, respectively. The EOS count of the treatment A group was significantly lower than those in model A group ( P<0. 05 ) . There was no significant difference between treatment B and model B group ( P>0. 05 ) . OVA-sIgE expressed was negative in control groups and positive in other groups. The ratio of interferon-γ and interleukin-4 was 10. 75 ± 3. 38,10. 38 ± 3. 08,3. 02 ± 0. 69,2. 71 ± 0. 89,2. 52 ± 0. 30,5. 45±1. 41,respectively. The ratio in treatment A group was significantly higher than those in model A group(P<0. 05). There was no significant difference between treatment B and model B group ( P>0. 05 ) . Conclusion: Inguinal subcutaneous immunotherapy has a good effect on this disease. It spends short time ,has simple operation and good feasibility,which is a novel treatment method for AR in mice.
5.The changes of microRNA in nasal mucosa after the specific immunotherapy for allergic rhinitis in mice.
Zhen'an ZHAO ; Ji DAI ; Wanjun ZHAO ; Qingyun WANG ; Zhongsheng CAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2015;29(5):457-465
OBJECTIVE:
To explore the changes of microRNAs in nasal mucosa after the specific immunotherapy (SIT) for allergic rhinitis (AR) in mice.
METHOD:
Female BALB/c mice, 6-8 weeks of age, were randomly divided into control group, model group and treatment group. AR model were established by intraperitoneal injection and intranasal challenge of ovalbumin and SIT was performed by inguinal subcutaneous injections. AR symptom scores were documented. The eosinophils (EOS) in the nasal mucosa were measured. Ovalbumin-specific IgE (OVA-sIgE) in the serum and expression of interferon-γ and interleukin-4 in the nasal lavage were measured by enzyme-linked immunosorbent assay meanwhile the ratio of interferon-γ and interleukin-4 was calculated. The microRNAs in the nasal mucosa were preliminary screened by microRNA gene microarray. Comparing with model group, the Fold changes of microRNA of the treatment group were ≥ 2.0 and the P < 0.05. MicroRNA target genes were predicted with GeneSpring 12.5 software. We took the intersection between genes in the signal pathway which associated with immune response,inflammation and target genes. The MEV-4-6-0 and Cytoscape_v2. 8. 2. software was applied to perform the cluster analysis and target gene regulatory networks maps.
RESULT:
The model of AR in mice and its SIT were successful. Comparing with the model group, the Fold changes of 15 microRNAs, of which 9 microRNAs were up-regulated and 6 microRNAs were down-regulated, were ≥ 2.0 in treatment group (P < 0.05). Cluste analysis showed clearly that microRNAs in the treatment group and model group respectively aggregated in two branches. The 15 microRNAs had 5302 target genes, of which, 451 genes were related more with SIT by the intersection. One microRNA can regulate many target genes, and one gene can also be affected by many microRNAs. Their synergistic effects may be involved in the mechanism of SIT.
CONCLUSION
The expressions of microRNAs are changed in nasal mucosa after SIT for AR in mice and we can speculate that microRNAs are involved in the process of SIT for AR. Bioinformatics methods can diminish the scope of target genes of microRNAs, which will help us studying the effect of changed microRNA on its relative target genes after SIT, and make us better understanding the mechanism of the disease and its SIT.
Administration, Intranasal
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Animals
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Disease Models, Animal
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Enzyme-Linked Immunosorbent Assay
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Eosinophils
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immunology
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Female
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Immunoglobulin E
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blood
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Immunotherapy
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Interferon-gamma
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immunology
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Interleukin-4
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immunology
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Mice
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Mice, Inbred BALB C
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MicroRNAs
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metabolism
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Nasal Mucosa
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drug effects
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metabolism
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Ovalbumin
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Rhinitis, Allergic
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therapy
6.The expression and clinical significance of Twist, E-cadherin and N-cadherin in gallbladder carcinoma by tissue microarray
Chengwu ZHANG ; Zhongsheng ZHAO ; Dajian ZHAO ; Wenjuan XU ; Jie LIU
Chinese Journal of Digestion 2011;31(9):598-603
Objective To explore the expression and clinical significance of Twist. E-cadherin and N-cadherin in gallbladder carcinoma. Methods From 2000 to 2008, in Zhejiang Provincial People's Hospital, the expression of Twist, E-cadherin and N-cadherin protein were detected in 79 surgically removed gallbladder carcinoma tissue specimens in paraffin blocks and 20 normal gallbladder tissue specimens by tissue microarray technique and immunohistochemistry. Results Compared with normal gallbladder tissues, the expression of Twist and N-cadherin was up-regulated in gallbladder carcinoma tissues and the positive percentage was 68.3% and 49.4% respectively, while which both were 1/20 in normal gallbladder tissues. The percentage of high E-cadherin expression in gallbladder carcinoma tissues was only 27.8 %, which was significantly lower than that in normal gallbladder tissues (20/20;X2 =29.31, P<0. 05). The expression of Twist was correlated with T classification, lymph node metastasis, distant organ metastasis, hepatoduodenal ligament invasion, lymphatic invasion and UICC stage of gallbladder carcinoma (P<0.05). The expression of E-cadherin was correlated with T classification, distant organ metastasis, hepatoduodenal ligament invasion, differentiation degree and UICC stage of gallbladder carcinoma (P<0.05). The expression of N-cadherin was only correlated with lymphatic invasion of gallbladder carcinoma (P <0.05 ). There was significant negative correlation between Twist and E-cadherin expression (P<0. 01). All the 79 gallbladder carcinoma patients were followed up after the surgery, the mean follow-up time was 30.6±14.3months. The 3-year survival rates of patients with low or high Twist expressions were 66% and 7% respectively,there was significant difference between the two groups(P<0. 01). The 3-year survival rates of patients with low or high E-cadherin expressions were 25 % and 86 % respectively, the difference of two groups was significant(P<0.01). The 3-year survival rates of patients with low or high Ncadherin expressions were 39% and 41% respectively, there was no significant difference between the two groups(P>0.05). The multivariate analysis indicated that the Twist expression was one of independent prognostic factors of gallbladder carcinoma. Conclusion The abnormal expression of Twist and E-cadherin was correlated with the development and progression of gallbladder carcinoma,and Twist expression was one of the independent prognostic factors of gallbladder carcinoma.
7.UPA mRNA and MMP-9 mRNA expression and their correlation with invasion and metastasis and prognosis of gastric carcinoma
Zhongsheng ZHAO ; Genyou YAO ; Guoqing RU ; Jie MA ; Wenjuan XU
Chinese Journal of General Surgery 2000;0(12):-
Objective To investigate the mRNA expression of UPA and MMP-9 in gastric carcinoma and their correlation with histological type, growth-type, differentiation, vessel invasion, metastasis and prognosis. MethodsIn situ hybridization was used to detect the mRNA expression of UPA and MMP-9. ResultsIn situ hybridization revealed that among 105 cases, the positive rates of UPA mRNA and MMP-9 mRNA were both 58.1%. There was no significant relationship between UPA mRNA and histological type( r _ s = 0.123, P =0.210)and differentiation ( r _ s =0.102, P =0.298)of the tumor. However, there was a significant difference between growth-type( r _ s =0.344, P =0.001),tumor invasion depth( r _ s =0.296, P =0.002),vessel invasion( r _ s =0.198, P =0.042),lymph node( r _ s =0.332, P =0.001)and distant metastasis( r _ s =0.530, P =0.001);there was no significant relationship between MMP-9 mRNA staining and histological type( r _ s =0.143, P =0.145)and differentiation( r _ s =0.102, P =0.298)of the tumor. However, there was a statistically significant difference between growth-type( r _ s =0.267, P =0.006),tumor invasion depth ( r _ s =0.335, P =0.001)、vessel invasion( r _ s =0.209, P =0.032),lymph node( r _ s =0.343, P =0.001)and distant metastasis( r _ s =0.468, P =0.001);There was a positive relationship between UPA mRNA and MMP-9 mRNA expression( r _ s =0.237, P =0.015). The mean survival time in cases with positive UPA mRNA and MMP-9 mRNA expression were significantly shorter than that of cases with negative expression. ConclusionThe mRNA expression of UPA and MMP-9 can predict the invasion and metastasis of gastric carcinoma, They can be used as markers of prognosis of gastric carcinoma in clinical practice.
8.Cyclin E and epidermal growth factor receptor expression and its correlation with the prognosis of breast carcinoma
Genyou YAO ; Jun RUAN ; Zhongsheng ZHAO ; Yunqin HU
Chinese Journal of General Surgery 2001;0(08):-
Objective To study the expression of cyclin E and epidermal growth factor receptor (EGFR) in breast carcinoma and their correlation with metastasis,relapse and survival time. [WT5”HZ]Methods Cyclin E and EGFR expressions at protein level were determined by immunohistochemistry technique in 110 patients with breast carcinoma. Results Of the 110 patients,cyclin E and EGFR positive expression were both in 60 (54.55%),and there was a positive relationship between cyclin E and EGFR expression (r s=0.823,P =0.001);Cyclin E and EGFR expression level were correlated with clinical stage (? 2=12.86,P =0.005;? 2=14.21,P =0.004),tumor histological grading (? 2=8.86,P =0.005;? 2=4.90,P =0.04),lymph node metastasis (? 2=10.22,P =0.001;? 2=9.62,P =0.002),ER expression (? 2=29.8,P =0.001;? 2=32.08,P =0.001) and PR expression (? 2=19.56,P =0.001;? 2=26.92,P =0.001). The rate of local relapse and distant metastasis in cases with positive cyclin E and EGFR expression were significantly higher than that in cases with negative expression (? 2=7.33,P =0.01;? 2=7.88,P =0.005);The mean survival time and 5-year survival rate in cases with positive cyclin E and EGFR was significantly shorter than that in cases with negative expression. [WT5”HZ]ConclusionCyclin E and EGFR expression can predict the relapse and metastasis of breast carcinoma. They can be used as markers of prognosis of breast carcinoma in clinical practice.
9.Screening metastasis-associated genes of gastric carcinoma by gene-chip assay and primary detecting the expression of TLN1
Li ZHANG ; Zhongsheng ZHAO ; Jie MA ; Guoqing RU ; Laihua DONG
Chinese Journal of Pathophysiology 2000;0(07):-
AIM:To screen the gene expression profiles of normal gastric mucosa,primary gastric cancer and metastatic lymph nodes by gene expression microarray and the associated genes with lymph node metastasis by bioinformatics. METHODS:The differentially expressed genes of nontumorous gastric mucosa (group A),primary gastric cancer (group B) and metastatic lymph nodes (group C) were screened by gene expression microarray obtained from Affymetrix company. The results were further analyzed by bioinformatic software including Gene Expression Profiles Analysis of Cohort Experiment,Gene Ontology Enrichment Analysis and Pathway Significant Analysis. The expression of TLN1 in group A,B and C were confirmed by real-time reverse transcription PCR. RESULTS:278 genes were persistent up-regulated in group A,B,C,which participated mainly in immunologic responses,cell adhesion,phosphate transport,inorganic anion transport,cell chemotaxis,cell motility and signal transduction. While 387 genes were persistent down-regulated in group A,B,C,which were concerned with digestion,glucide metabolism,lipid metabolism,protein metabolism,one-carbon compound metabolism,nitrogen compound catabolism and cell adhesion. The pathway analysis suggested that integrin-mediated cell adhesion pathway were abnormally regulated. These genes including THBS1,TLN,CAPN3,ITGAX,SORBS1,CAPN6,CAPN9 were continuous up-regulated or down-regulated in integrin-mediated cell adhesion pathway. The expressions of TLN1 in group A,B,C were 0.0000342?0.0000711,0.1064?0.1251 and 0.2886?0.3529,respectively. The expression of TLN1 in metastatic lymph nodes was significantly higher than that in nontumorous gastric mucosa and primary gastric cancer (P
10.Pharmacokinetic study of palonosetron hydrochloride in healthy volunteers
Zhongling ZHU ; Zhongsheng TONG ; Duanyun SI ; Weilin DONG ; Zhao YAN
Chinese Journal of Clinical Oncology 2013;(20):1256-1260
Objective: To evaluate the pharmacokinetics of palonosetron hydrochloride in healthy volunteers. Methods: Thir-ty-one healthy volunteers were grouped into three palonosetron hydrochloride dosage regimens of 0.125, 0.25, and 0.5 mg. The plasma concentrations of palonosetron were determined by ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). DAS 2.1 software was applied to assess the plasma concentration-time data. Results:After intravenous injection of 0.125, 0.25, and 0.5 mg palonosetron to the subjects, the AUC0-168h values of palonosetron were (7.5±2.5), (15.2±4.0), and (34.8±9.7) μg· h·mL-1. The t1/2 values were (27.2±9.5), ( 27.2±6.5), and (31.4±5.6) h. Palonosetron exposure increased proportionally with the dose range of 0.125 mg to 0.5 mg. The correlation coefficient was 0.998. No grade 3 or grade 4 toxicity was observed during the study. Con-clusion:A rapid, sensitive, and selective UPLC-MS/MS method for palonosetron quantification in human plasma was developed and validated. All the participants indicated high tolerance throughout the study. Our data showed that palonosetron exhibits linear pharma-cokinetics over the the dose range of 0.125 mg to 0.5 mg.