Clinical pathological features analysis of 694 gastric cancer cases / 中华消化杂志

Objective To explore the clinical pathological features of gastric cancer and to provide a basis for research and treatment of gastric cancer.Methods From 2001 to 2004,a total of 694 cases of gastric cancer with radical gastrectomy were collected.Gender,age,tumor location,tumor size,World Health Organization (WHO) histological type and grade,Lauren type,blood/lymphatic vessel invasion,lymph node metastasis,depth of tumor invasion (pT) and pathological TNM staging (pTNM) were retrospectively analyzed.Results Among 694 gastric cancer cases,male to female ratio was 3.96∶ 1; a total of 644 cases (92.8％) were aged from 41 to 70,and cases aged from 51 to 70 had a high incidence of gastric cancer.The predilection site for gastric cancer was cardia (33.43％),antrum (28.96％) and the body (21.76％) accordingly.The common WHO histological types were tubular adenocarcinoma (70.32 ％) and signet ring cell carcinoma (24.50 ％).The common histological grades were Ⅱ,Ⅲ and Ⅰ.The intestinal type was most common in Lauren classification,accounting for 58.93 ％; followed by the diffuse type,accounting for 22.33 ％.Blood/lymphatic vessel invasion was detected in 438 cases (63.11％),lymphnode metastasis in 504 cases (72.62％).A total of 319 cases (45.97％) were pT3 stage,241 cases (34.73％) were on pTNM Ⅲ stage.Conclusions In recent years,cardia and antrum are the predilection sites of gastric cancer.Tubular adenocarcinoma and signet ring cell carcinoma are common which indicate that the mechanism of gastric cancer pathogenesis is varied.

Identification and evaluation of differentiation related genes in gastric cancer by gene expression profiling / 中华检验医学杂志

Objective To identify biomarkers associated with the differentiated phenotype based on gene expression profiling of gastric cancer. Methods Two bioinformatic methods, BAGEL and k-TSP, were used to identify featured genes associated with differentiation in gastric cancer samples based on the Oligo gene chip data, and ROC curves were used to verify the classification sensitivity and specificity of the identified genes. Finally, a total of 30 gastric cancer samples with different differentiation levels were collected for laboratory validation using real-time PCR analyses. Results A total of 121 differentially expressed genes were identified using the BAGEL algorithm, the criterion were FC ＞ 2. 0 and P ＜ 0. 001.Then, the k-TSP algorithm for feature selection based on this differential expression data were used, and 3 groups of featured genes which had potential to classify poor and well differentiation gastric cancer samples were identified, including MYLIP and TMPRSS3, ZNF266 and TM4SF1, SNAI2 and CNFN. To define the featured gene groups that had the highest classification capability, ROC curves to calculate the classification sensitivity and specificity of each gene group were used. The results showed that the combination of SNAI2and CNFN as a classifier had the highest classification sensitivity and specificity. Real-time PCR results showed that 18 of 22 poor differentiation samples were found with high expression of SNAI2 and low expression of CNFN (82%); 6 of 8 well differentiation samples were of low expression of SNAI2 and high expression of CNFN (75%). Conclusion The results indicate that SNAI2 and CNFN are constantly expressed in poor or well differentiation gastric cancer samples, and the expression pattern of these two genes is opposite. These results indicate that SNAI2 and CNFN have the potential for the identification of the differentiation level of gastric cancer.

CD44s expression study in colorectal cancer tissues / 中华普通外科杂志

Objective To investigate the relationship between standard CD44(CD44s)expression and tumor stage and prognosis in colorectal cancer.Methods CD44s expression was detected by immunohistochemistry in tumor tissues and normal mucosa specimens from 74 cases of primary colorectal cancer.Results Of 74 cases,the expression of CD44s in colorectal cancer tissue and normal mucosa specimens was documented in 42% and 16%,respectively.The expression of CD44s in primary tumors significantly increased in stage Ⅲ and Ⅳ than in stage Ⅰ and Ⅱ(39% vs.6%,x~2=8.46,P＜0.01).A statistically significant correlation was observed between the overall survival and CD44s expression(x~2=17.82,P＜0.01).Furthermore,a poor prognosis of CD44s-positive tumors was observed in patients with stage Ⅲ and Ⅳ colorectal cancer(x~2=16.23,P＜0.01),but not in patients with stage Ⅰ and Ⅱ colorectal cancer(x~2=1.34,P＞0.05).Multivariate analysis indicated that TNM stage and CD44s expression were independent predictors of overall survival in colorectal cancer.Conclusion CD44s overexpression is involved in the progress of colorectal cancer and predicting the prognosis.

Identification of a gene associated with astragalus and angelica's renal protective effects by silver staining mRNA differential display / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To identify genes associated with the chronic progression of renal disease and a stragalus and angelica (A&A)'s renal protective effects.</p><p><b>METHODS</b>The technique of silver staining mRNA differential display (DD) was used to investigate changes of gene expression in normal, sclerotic and A&A treated sclerotic kidneys. We isolated genes differentially expressed during the progression of renal disease which could be normalized by A&A.</p><p><b>RESULTS</b>Several genes related to A&A's protective effects were isolated and one of them was confirmed by Northern blot.</p><p><b>CONCLUSION</b>Silver staining mRNA differential display is a simple and effective technique for isolating differentially expressed genes. The isolated new gene may be related to the progression of chronic renal disease and contribute to A&A's protective effects.</p>

Tumor Susceptibility and Digestic System Tumor Susceptible Gene / 基础医学与临床

The carcinogenesis and development is a progress of multi-gene alterations in the human gastric cancer (HGC)．In order to determine the relation between the aberration of these genes and gastric cancer，we chose c-met (7q31)、hMLH1 (3p21)、E-cadherin (16q22.1) and HLA loci DQA1、DR2、DR3、DR4、DR7、DR9 and detected their changes in 32 tumor specimens of intestinal type HGC and 4 cell lines of gastric cancer by performing analysis of SSP/PCR、PCR/SSCP and MSI technigues．Our data show that none point mutation was detected in c-met gene．We examined two microsatellites loci D3S1298 and D3S1561 in hMLH1 gene and detected that 6 cases retain MSI (Microsatellite Instability) and 2 cases of LOH (Loss of Heterozygosity) at D3S1298 and 2 cases of MSI at D3S1561．We also examined E-cadherin gene at two microsatellites loci D16S3083 and D16S3095 close to the gene and detected that 5 cases retain MSI and 1 case of LOH at D16S3083 and no change at D16S3095．The point mutation incidence of HLA-DR4 loci is 9/20 (45%)，higher than the other loci in HLA-Ⅱ．High frequent deletion，expression deregulation and methylation of mts1/p16 gene were detected in cell lines and solid tumors from human gastric cancer patients． 　　Our data showed that the point mutation of c-met gene is not the main pattern of alteration in intestinal type HGC that is consistent with the previous results．E-cadherin and hMLH1 are related to intestinal type HGC but whether they are susceptibility gene still need further study．The point mutation of the HLA-Ⅱ loci DR4 is closely related to intestinal type HGC．Methylation of mts1/p16 gene 5 CpG island might be plays an important role in the carcinogenesis in HGC．

Advances in research on relation of ubiquitin-proteasome pathway to malignancy / 中国癌症杂志

Ubiquitin-proteasome pathway is an important mechanism regulating many processes of cellular biology,and also a potential target for abnormal regulation associated with malignancy. This pathway may up-regulate or down-regulate the expression of some tumor-inhibitory genes, transcriptional factors and cyclins,and alter the generation of MHC-I-restricting antigen peptides through the activity of specific proteasome, and consequently,participates in the genesis and progression of malignancy.

Introduction of Rb, p53, p16 and H-ras Antisense UNA Suppresses Tumorigenicity in Human Gastric Cancer Cell Lines / 中国肿瘤生物治疗杂志

Our previous investigation have demonstrated that multiple genes alterations, such as deletion of Rb, p53 and p16 gene, point mutation of H-ras gene were detected in cell line and solid tumor of human gastric cancer. We have transfect-ed the independent construct containing Rb, p53, p16 and expression of H-ras antisense RNA respectively into human gastric cancer cell line, and we have analyzed the biological properties of several independent transfectant cell lines, which express exogenous Rb, p53, p16 and H-ras antisense RNA respectively. The cell growth ability was inhibited by introduction of p53 and H-ras antisense RNA, and tumorigenicity also suppressed significantly by p53, p16 and H-ras antisense RNA. These results indicated that alterations of p53, p16 and H-ras gene were involved in human gastric car-cinogenesis.

Suppression of Growth and Tumorigcnicity in Human Gastric Cancer Cells by the Introduction of Exogenous p53 Gene / 中国肿瘤生物治疗杂志

The p53 gene is one of the most common targets for genetic abnormalities in human tumors. Restoring wild - type p53 gene (wt-p53) into cancer cells which have p53 deletion is a strategy in cancer gene therapy. In order to explore the feasibility of this hypothesis, we selected a gastric cancer cell line BGC823 which was confirmed having deletion of chromosome 17pl3 and decreased expression level of p53 mRNA . We transfected construct pC53SN3 containing wt - p53 into BGC823 cell line with lipofectin mediated gene transferration, and G418 resistant colonies were characterized by using analysis of PCR, Southern blot hybridization, Northern blot hybridization and Western blot hybridization. These data showed that exogenous wt-p53 had successfully transferred into BGC823 cells and obtained high expression. The cell growth rates in regular medium and soft agar were inhibited from 30 to 40 percent in the BGC823 cells transfected with wt - p53. The tumorigenicity in nude mice showed that one of four mice failed to form tumor and three of them delayed to form tumor from 7 to 14 days comparing with monk and parent BGC823 cells. These results suggested that exogenous wt -p53 could suppress the growth ability and tumorigenicity of human gastric cancer cells. The method of using lipofectin mediated wt-p53 gene transfection may have a potentially therapeutic effect on human gastric cancer.

A study on the activation of oncogene and inactivation of suppressor gene in human gastric cancer / 第三军医大学学报

The changes of several oncogenes and suppressor genes in the specimens of cancerous and juxtacancerous tissues of 42 cases of gastric cancer were studied with Southern blot hybridization and PCR-RELP method.The probes used were c-Ha-ras,K-ras,N-ras,N-myc,c-myc,hst,EGFR,c-erbB-2,p53 and Rb.Amplification,rearrangement,and deletion of c-Ha-ras were detected in 8/33 (25.8%) cases of gastric cancer (amplification or rearrangement of hst and c-erbB-2 in 11/42 (26.6%) and 12/42 (29.2%) cases respectively (amplification of EGFR in 21.4% of cas-esideletion or rearrangement of p53 and Rb in S/30 (30%) and 2/15 (13%) cases respectively) and amplification or rearrangement of N-ras (0/33),K-ras (1/26),N-myc (1/26),and c-myc (1/ 35) was only rarely encounted.The point mutation in codon 248 and 249 of p53 in gastric cancer was analyzed.2 cases of the 42 harbored point mutation in codon 248 of p53.These findings suggest that e-Ha-ras,hst,c-erbB-2,EGFR and p53 may be the hot point genes in the occurrence and development of gastric cancer.

A study on the amplification, rearrangement and deletion of ras-oncogenes in gastric cancerous and juxtacancerous tissues / 第三军医大学学报

The amplification,rearrangement and deletion of c-Ha-ras,K-ras and N-ras were studied in 33 cases of gastric cancerous and juxtacancerous tissues.It was found that the amplification rearangement,and deletion of c-Ha-ras were shown in 25.8% (8/33) of cases and the ampli-cation of K-ras in 3.8% (1/26).No such changes was found for N-ras.