Gastric cancer is the second leading cause of cancer mortality worldwide,and in Asian countries like Japan,Korea and China,it remains the top killing cancer.As most cases of gastric cancer are in the advanced stage of the disease when they are first diagnosed,patients receiving conventional therapies including surgery,chemotherapy and radiotherapy have poor prognosis.An emerging modality called tumor molecular targeted therapy provides promise and insight to combat this malignancy.This article discusses the molecular basis of gastric cancer targeted therapy from the perspectives of screening and application of target molecules,modulation of tumor microenvironment and antitumor immunotherapy.

Colorectal cancer is a malignancy with poor prognosis and high mortality and is caused by multiple factors. Colonoscopy,flexible sigmoidoscopy,guaiac-based fecal occult blood test,immunochemical fecal occult blood test,fecal DNA test,CT colonoscopy and serum carcinoembryonic antigen test are the methods frequently used for screening of colorectal cancer,but they all have certain limitations. Elevation of methylation of SEPT9 is associated with the pathogenesis of colorectal cancer,and detection of the level of methylation of SEPT9 in peripheral blood can be used for screening of colorectal cancer in susceptible population. This article reviewed the application of peripheral blood SEPT9 DNA methylation assay for screening of colorectal cancer.

Objective To investigate the significance of expression of peroxisome proliferator activated receptor ?(PPAR?) and retinoid X receptor ?(RXR?) in chronic gastritis, gastric mucosal dysplasia and gastric carcinoma and to identify the correlation between PPAR? and RXR?. Methods Avidin biotin peroxidase complex immunohistochemical methods were adopted to examine the expression of PPAR? and RXR? in 53 patients with gastric carcinoma, and 18 with gastric mucosal dysplasia, 31 with chronic non atrophic gastritis and 30 with chronic atrophic gastritis were served as controls. Results The positive rates of PPAR? and RXR? were 41.5% and 54.7% in gastric carcinoma respectively, 27.8% and 38.9% in gastric mucosal dysplasia, 10.0% and 20.0% in chronic atrophic gastritis, 6.5% and 16.1% in chronic non atrophic gastritis. From chronic non atrophic gastritis, chronic atrophic gastritis to gastric carcinoma, expressions of PPAR? and RXR? showed an ascending tendency. Compared with those in chronic gastritis, expressions of PPAR? and RXR? in gastric mucosal dysplasia and gastric carcinoma were significantly enhanced ( P0.05). There was a significant correlation between expressions of PPAR? and RXR? in gastric carcinoma ( r =0.54). Conclusion PPAR? and RXR? protein overexpression is a relatively early event in gastric carcinogenesis, and it may play both an independent and synergetic role in progression of gastric carcionma.

Objective To compare the effect of seven commonly used nonsteroidal anti inflammatory drugs (NSAIDs) on proliferation, apoptosis, and neoplasmagenesis of gastric cancer cells in vivo. Methods Gastric cancer cell lines were treated with NSAIDs (aspirin 0-400 ?mol/L, indomethacin 0-25 ?mol/L, and ibuprofen, naproxen, sulindac, nimesulide, celecoxib 0-200 ?mol/L, respectively). Proliferation of the cells was detected by using MTT assay. Apoptosis of cells was measured by using fluorescence activated cell sorter (FACS). Nude mice bearing gastric cancer xenografts were administrated with NSAIDs (indomethacin 3 mg/kg, sulindac 8 mg/kg, nimesulide 6 mg/kg, celecoxib 15 mg/kg) for 30 days, and then the weight of implanted tumors was measured. Results There was a dose dependent inhibition of cell proliferation by majority of NSAIDs used, celecoxib the most, except for ibuprofen and naproxen. In nude mice, NSAIDs also showed a suppressive effect on tumor growth with inhibitory rate of celecoxib as (93.8?0.97)%, nimesulide (93.1?1.78)%, indomethacin (89.9?5.61)% and sulindac (89.3 ? 2.07)%. Once incubated with celecoxib and indomethacin, the gastric cancer cells went to apoptosis with an increase in percentage of apoptotic cells up to 30.4% and 23.9%, respectively. Conclusions Many NSAIDs, celecoxib in particular, appeared to be suppressive to gastric cancer cells with exception for ibuprofen and naproxen. Induction of apoptosis might be one of the mechanisms that NSAIDs inhibit gastric cancer.

The aims of this study were to compare the inhibitory effect of nimesulide and indomethacin on gastric cancer cells, to investigate the effect of nimesulide on SGC7901 and 7901-AS, and to evaluate its probable mechanism. After incubated with nimesulide (0～200?mol/L) or indomethacin (0～25?mol/L), the proliferation of gastric cancer cells was measured by MTT assay. The cell cycle of SGC7901, 7901-P, 7901-AS was respectively observed after being incubated with nimesulide and vehicle control, by using fluorescence activated cell sorter (FACS). Ultramicrostructure of gastric cancer cells (SGC7901,7901-AS,SGC7901+nimesulide) was observed by electronmicroscopy. The results showed that by MTT assay nimesulide, as indomethacin, had dose-dependent inhibitory effects on proliferation of gastric cancer cells. Compared to the inhibitory effect of nimesulide on SGC7901, it was less on 7901-AS (P

Objective To construct a fusion gene vaccine of gastric cancer MG7-Ag mimotope and heat shock protein 70, and to investigate the humoral and cellular immune response in mice induced by the vaccine. Methods The coding sequence of MG7 mimotope was incorporated with HSP70 gene at the 3' terminus by PCR amplification. Then the PCR product was cloned into pcDNA3.1(+) vector to construct the eukaryotic expression vector. The pcDNA3.1/MG7+hsp70 was sequenced to ensure the proper encoding. C57BL/6 mice were immunized with the fusion gene vaccine, and pcDNA3.1/hsp70 and empty pcDNA3.1 were used as controls. The serum was collected at the 3rd week after each immunization. Cellular ELISA was performed to evaluate the induced humoral immunity. The splenocytes were first separated at the 9th week for the assay of antigen specific CTL lysis activity by 51Cr release. Results A fragment about 2.0 kb was obtained by PCR amplification. Sequence analysis revealed that the sequence of mimotope was connected successfully to 3' terminus of hsp70 and the fusion gene was cloned into the pcDNA3.1(+) successfully. Cellular ELISA results suggested that the serum level of MG7-Ag antibody appeared in the vaccinated mice at 9th week, while no MG7-Ag antibody was detected in the controls. The results of the specific lysis rate of splenocytes showed no statistical difference between fusion gene vaccine group and control groups. Conclusion The fusion gene vaccine was constructed successfully and the specific humoral immune response was induced by the fusion gene vaccine.

Objective To investigate the retardation effect of voltage gated potassium channel Kv1 5 on growth of gastric cancer cells SGC7901. Methods By using restriction enzymes of Hind Ⅲ and Kpn I, cDNA encoding Kv1 5 was reversely constructed into eukaryotic expression vector pcDNA3 1. SGC7901 cells were transfected with the recombinants using LipofectAMINE2000. Stable clones of transfectants were obtained after selection by G418 The growth of cells was monitored by cell growth curve and cell colony formation. The effect of Kv1 5 protein on cell cycle was examined by flow cytometry. Expression of Cyclin D1 protein was detected by Western blot. Results The antisense was found to effectively inhibit the expression of Kv1 5 protein in the transfectants. The growth and colony formation of transfectants were significantly reduced as compared with controls. The cell cycle review showed retardation of transfectants with Kv1 5 antisense in the G 1 phase. Expression of Cyclin D1 protein was decreased in Kv1 5 antisense transfectants. Conclusion The antisense of Kv1 5 has effect of retardation on growth of gastric cancer cells SGC7901

Objective To detect the expression of cyclooxygenase(COX) in human gastric cancer cell lines and its subcellular location of the isoforms. Methods Immunohistochemistry、RTPCR combined with laser scanning cofocal microscopy (LSCM) were used to investigate expression and distribution of COX. Results Positive staining of COX2 and COX1 protein was seen in human gastric cancer cell line MKN45、SGC7901 and AGS. However, the COX2 staining was absent and COX1 staining was weak in MGC803; though their mRNA in all the four cell lines. When compared to COX1,COX2 showed a stronger signal at both protein and mRNA levels of the gastric cancer cell lines, which was confirmed by double labeling and LSCM. The quantitative analysis of fluorescein intensity indicated the pixel intensity peak of COX2 reached 50～70, while COX1 only 10. LSCM also showed that COX2 was both cytoplasmic and nuclear envelope staining but COX1 only in cytoplasm. Conclusions In human gastric cancer, there is stronger expression of COX2 than COX1, and different distribution of the two isoforms implies their distinct roles in cell function.

Objective To investigate the gene polymorphism of tumor necrosis factor (TNF) in patients with inflammatory bowel disease (IBD) among the Han nation and its role in the pathogenesis of IBD. Methods Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to analyze the gene polymorphism of TNF? and TNF? in 131 cases of IBD. Results The genotype frequency and allelic frequency of TNF?-308 in ulcerative colitis (UC) patients (15.5% and 8.7% ) were significantly higher than those in control subjects (4.1% and 2.0% respectively, P

To express a gene of heat shock protein 70(HSP70) in E.coli , HSP70 gene was amplified by PCR. The PCR products were cloned into pUCm T vector and were sequenced; The HSP70 gene was subcloned into vector pET 21a(+) and expressed in E.coli. SDS PAGE and Western blot were employed to identify the expression of the HSP70 gene. Results showed that a fragment about 1 96kb was amplified by PCR. Sequence analysis revealed that the sequence of HSP70 was correct. The HSP70 gene was cloned into pET 21a(+) identified by enzyme digestion and PCR. SDS PAGE and Western blot showed that a M 72 000 protein was expressed and could be recognized by anti HSP70 antibody. Therefore,HSP70 gene has been successfully expressed in E.coli .