Clinical significance of preoperative regional intra-arterial infusion chemotherapy for advanced gastric cancer

AIM: Preoperative intra-arterial infusion chemotherapy could increase the radical resection rate of advanced gastric cancer, but its effect on the long-term survival has not been assessed. This study was designed to evaluate the clinical significance of preoperative intra-arterial infusion chemotherapy for advanced gastric cancer. METHODS: Clinicopathological data of 91 patients who underwent curative resection for advanced gastric cancer were collected. Among them, 37 patients undertaken preoperative intra-arterial infusion chemotherapy were used as the interventional chemotherapy group, and the remaining 54 patients as the control group. Eleven factors including clinicopathological variables, treatment procedures and molecular biological makers that might contribute to the long-term survival rate were analyzed using Cox multivariate regression analysis.RESULTS: The 5-year survival rate was 52.5% and 39.8%,respectively, for the interventional group and the control group (P<0.05). Cox multivariate regression analysis revealed that the TNM stage (P<0.001), preoperative intraarterial infusion chemotherapy (P=0.029) and growth pattern (P=0.042) were the independent factors for the long-term survival of patients with advanced gastric cancer. CONCLUSION: Preoperative intra-arterial infusion chemotherapy plays an important role in improving the prognosis of advanced gastric cancer.

Cell cycle arrest and apoptotic cell death in cultured human gastric carcinoma cells mediated by arsenic trioxide

AIM: To investigate the effect of arsenic trioxide on human gastric cancer cell line MKN45 with respect to both cytotoxicity and induction of apoptosis in vitro. METHODS: MKN45 cells were treated with arsenic trioxide (As2O3) at the concentration of 1, 5, and 10 μmol/L, respectively, for three successive days. Cell growth and proliferation were observed by cell counting and trypan blue exclusion. Cytotoxicity of As2O3 was determined by MTT assay. Morphologic changes were studied with light microscopy. Flow cytometry was used to assay cell DNA distribution and apoptotic cells were confirmed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and DNA electrophoresis. RESULTS: The growth of MKN45 cells was significantly inhibited by As2O3 which was confirmed by colony-forming assay. After 7 d of culture with various concentrations of As2O3, colony-forming capacity of MKN45 cells decreased with As2O3 increment in comparison with that of control group. The inhibitory rate of colony-formation was 38.5%, 99.1%, and 99.5% when the concentration of As2O3 was 1, 5, and 10 μmol/L in culture medium, respectively. The cell number of a single colony in drug treatment groups was less than that of control group. The cell-killing rate of As2O3 to MKN45 cells was both dose- and time-dependent with an IC50 of (11.05±0.25) μmol/L After incubation in 10 μmol/L As2O3 for 24 h, the cell-killing rate was 27.1%, and it was close to 50% after 48 h. The results showed that As2O3 induced time- and dose-dependent apoptosis in MKN45 cells, blocked at G2/M phase. The apoptotic peak (sub-G1 phase) appeared and cell apoptotic rate in MKN45 cells was 18.3-32.5% after treatment by 10 umol/L As2O3 for 48 h. The percentage of G2/M cell of the experimental groups was 2.0-5.0 times than that of the control group. Gel electrophoresis of DNA from cells treated with each concentration of As2O3 for 48 h revealed a 'ladder' pattern, indicating preferential DNA degradation at the internucleosomal, linker DNA sections. TUNEL also demonstrated strand breaks in DNA of MKN45 cells treated with As2O3, while control cells showed negative labeling. CONCLUSION: As2O3 can induce apoptosis of human gastric carcinoma cells MKN45, which is the basis of its effectiveness. It shows great potential in the treatment of gastric carcinoma.

Association of tumor necrosis factor genetic polymorphism with chronic atrophic gastritis and gastric adenocarcinoma in Chinese Han population

AIM:To investigate the association of TNF polymorphisms with chronic atrophic gastritis (CAG) and gastric adenocarcin-oma in Chinese Han patients.METHODS:The TNFa-e 5 microsatellites and 3 RFLP sites were typed using PCR technique,followed by high-voltage denaturing PAGE with silver staining and restriction enzyme digestion respectively in specimens from 53 patients with CAG and 56 patients with agstric daenocarcinoma and 164 healthy controls.The PCR products were cloned and sequenced.RESULTS:The frequency of TNF-β Ncol*1/2 genotype was higher in patients with chronic atrophic gastritis than in healthy controls,but no significant difference was observed(60.38% vs 46.34%,p=0.076).The frequency of TNa10 allele was significantly higher in patients with chronic atrophic gastritis than in healthy controls(19.81% vs 11.89%,p=0.04).However,it did not relate to age,gender,atrophic degree or intestinal metaplasin in patients with chronic atrophic gastritis,The frequency of TNF-β Ncol*1/2 and d2/d6 genotypes were significantly higher in patients with gastric adenocarcinoma than in healthy indiveduals(p>0.05).However,TNF-β Ncol*1/2 and d2/d6 genotypes did not relate to age,gender,grade of differentiation and clinicopathologic state in patients with gastric adenocarcinoma.The frequency of TNFa6b5c1 hapolotype homoaygote was significantly lower in patients with gastric adenocarcinoma than in healthy controls (1.79% vs 15.85%,p=0.006).CONCLUSION:TNFa10 allele may be a risk factor for chronic atrophic gastritis ,TNF-β Ncol*1/2 and d2/d6 genotypes are associated with the suscepotibility to gastric adenocarcinoma,whereas TNFa6b5c1 haplotype homozygote may contribute to the resistance against gastric adenocarcinoma.