BACKGROUND:A regimen of epirubicin,cisplatin,and infused fluorouracil(ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma.We assessed whether the addition of a pe...BACKGROUND:A regimen of epirubicin,cisplatin,and infused fluorouracil(ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma.We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer.METHODS:We randomly assigned patients with resectable adenocarcinoma of the stomach,esophagogastric junction,or lower esophagus to either perioperative chemotherapy and surgery(250 patients) or surgery alone(253 patients) .Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin(50 mg per square meter of body-surface area) and cisplatin(60 mg per square meter) on day 1,and a continuous intravenous infusion of fluorouracil(200 mg per square meter per day) for 21 days.The primary end point was overall survival.RESULTS:ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer.Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group(46 percent and 45 percent,respectively) ,as were the numbers of deaths within 30 days after surgery.The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group.With a median follow-up of four years,149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died.As compared with the surgery group,the perioperative-chemotherapy group had a higher likelihood of overall survival(hazard ratio for death,0.75;95 percent confidence interval,0.60 to 0.93;P = 0.009;five-year survival rate,36 percent vs.23 percent) and of progression-free survival(hazard ratio for progression,0.66;95 percent confidence interval,0.53 to 0.81;P < 0.001) .CONCLUSIONS:In patients with operable gastric or lower esophageal adenocarcinomas,a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival.展开更多
AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture,...AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost completely inhibited by preventing the degradation of IkBalpha. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner. CONCLUSION: These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.展开更多
AIM: To evaluate the potential role of Nimesulide, a selective COX-2 inhibitor, in proliferation and apoptosis of gastric adenocarcinoma cells SGC7901.METHODS: Cell counts and MYT assay were used to quantify the influ...AIM: To evaluate the potential role of Nimesulide, a selective COX-2 inhibitor, in proliferation and apoptosis of gastric adenocarcinoma cells SGC7901.METHODS: Cell counts and MYT assay were used to quantify the influence of Nimesulide in the proliferation of SGC7901cells. Transmission electron microscopy and flow cytometry were used to observe the induction of Nimesulide the apoptosis of SGC7901 cells and influence in the distribution of cell cycle. The expression of P27kipl protein was observed by immunocytochemical staining.RESULTS: SGC-7901 Cells treated with Nimesulide at various concentrations exhibited a profound dose- and timedependent reduction in the proliferation rate over the 72 h test period. The highest survival rate of the cells was 78.7 %,but the lowest being 22.7 %. Nimesulide induced apoptosis of the cells in a dose-dependent and non-linear manner and increased the proportion of cells in the G0/G1 phase and decreased the proportion in the S and G2/M phase of the cell cycle. Meanwhile, Nimesulide could up-regulate the expression of P27kipl protein.CONCLUSION: The induction of apoptosis and cell cycle arrest are both anti-proliferative responses that likely contribute to the antineoplastic action of nimesulide on SGC7901 cells. The up-regulation of P27kipl gene may contribute to the accumulation of these cells in the G0/G1 phase following treatment with Nimesulide. Selective COX-2 inhibitor may be a new channel of the chemoprevention and chemotherapy for gastric carcinoma.展开更多
AIM: Several epidemiological studies have demonstrated a dose association between Helicobacter pylori (H Pylon) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with n...AIM: Several epidemiological studies have demonstrated a dose association between Helicobacter pylori (H Pylon) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences,leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H pyloriinfection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due tooxidative DNA damage.METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-κB(NFκB),MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2),inhibitor of apoptosis protein (IAP) and myeloid cellleukemia-1 (Mcl-1)] by Western-blot assay.RFSULTS: The concentrations of 8-OHdG, iNOS, NFx3, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFxB, Mcl-1 and lAP were detected in patients infected with H pyloricompared with patients who were not infected with HpylorL Furthermore,8-OHdG, iNOS, NFκB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage1 and 2 patients.CONCLUSION: Chronic Hpylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the rihypothesis that oxygen-free radical-mediated damage due to Hpyloriplays a pivotal rol展开更多
AIM： To investigate the expression of fragile histidine triad （FHIT） protein, and the possible relationship between FHIT expression and dinicopathological indices in gastric carcinoma. METHODS： FHIT protein expres...AIM： To investigate the expression of fragile histidine triad （FHIT） protein, and the possible relationship between FHIT expression and dinicopathological indices in gastric carcinoma. METHODS： FHIT protein expression was examined in 76 cases of gastric carcinoma, 58 cases of intraepithelial neoplasia, and 76 cases of corresponding normal mucosae by immunohistochemical method to analyze its relationship to histological grade, clinical stage, metastatic status and prognosis. RESULTS： The FHIT protein expression was positive in 28/76 （36.8%） cases of adenocarcinoma tissue, 22/58 （37.9%） cases of adjacent dysplastic tissue and 76/76 （100%） cases of distal normal gastric mucosa. There was a significant difference in the expression of FHIT protein between cancer or adjacent intraepithelial neoplasia and normal gastric mucosa （P = 0.000）. FHIT protein expression was found in 64.3% （18/28） of grades Ⅰ and Ⅲ cancers, and 20.8% （10/48） of grade Ⅲcancers （P = 0.000）, in 56.3% （18/32） of stages Ⅰ and Ⅱ cancers and 22.7% （10/44） of stages Ⅲ and IV cancers （P = 0.004）, and in 63.6% （14/22） of cancers without metastasis but only 25.9% （14/54） of those with metastasis （P = 0.003）. The significant difference in the expression of FHIT was found between histological grade, clinical stage and metastatic status of cancer. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of FHIT （71 mo） and those without （33 mo, log rank = 20.78, P = 0.000）. CONCLUSION： FHIT protein is an important tumor suppressor protein. Loss of FHIT protein expression may be associated with carcinogenesis, invasion, metastasis and prognosis of gastric adenocarcinoma. 2005 The WJG Press and Elsevier Inc. All rights reserved展开更多
AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell...AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/waf1) of SGC-7901 cells which were treated with various c9, t11-CLA concentrations (25, 50, 100 and 200 micromol.L(-1))of c 9, t 11-CLA for 24 and 48h, with a negative control (0.1% ethane). RESULTS: The cell growth and DNA synthesis of SGC-7901 cells were inhibited by c9, t11-CLA.SGC-7901 cells. Eight day after treatment with various concentrations of c9, t11-CLA mentioned above, the inhibition rates were 5.92%, 20.15%, 75.61% and 82.44%, respectively and inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 micromol.L, 24h) showed significantly less (3)H-TdR incorporation than that in the negative controls (P【0.05 and P【0.01). Immunocytochemical staining demonstrated that SGC-7901 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA (the expression rates were 7.2-3.0%, 24h and 9.1-0.9% at 48h, respectively), Cyclin A (11.0-2.3%, 24h and 8.5-0.5%,48h), B(1) (4.8-1.8% at 24h and 5.5-0.6% at 48h)and D(1) (3.6-1.4% at 24h and 3.7%-0 at 48h) as compared with those in the negative controls(the expressions of PCNA, Cyclin A, B(1) and D(1) were 6.5% at 24h and 9.0% at 48h, 4.2% at 24h and 5.1% at 48h, 9.5% at 24h and 6.0% at 48h,respectively)(P【0.01), whereas the expressions of P16(ink4a) and P21(cip/waf1), cyclin-dependent kinases inhibitors(CDKI), were increased. CONCLUSION: The cell growth and proliferation of SGC-7901 cell is inhibited by c9, t11-CLA via blocking the cell cycle, with reduced expressions of cyclin A,B(1) and D(1) and enhanced expressions of CDKI(P16(ink4a) and p21(cip/waf1)).展开更多
AIM: To study the expression of cyclooxygenase-2 (COX-2)gene in gastric cancer and the relationship between COX-2expression and clinicopathologic features of gastric cancer.METHODS: With reference to the expression of...AIM: To study the expression of cyclooxygenase-2 (COX-2)gene in gastric cancer and the relationship between COX-2expression and clinicopathologic features of gastric cancer.METHODS: With reference to the expression of β-actin gene,COX-2 mRNA level was examined in cancerous tissues andadjacent noncancerous mucosa from 33 patients bysemiquantitative reverse transcription- polymerase chainreaction (RT-PCR). Quantitation of relative band Adj volumecounts was performed using molecular Analyst for windowssoftware. The COX-2 index was determined from the band Adjvolume counts ratio of COX-2 to constitutively expressed actin.RESULTS: The COX-2 index in gastric carcinoma wassignificantly higher than that in normal mucosa (0.5966±0.2659vs 0.2979+0.171, u=5.4309, P＜0.01). Significantly higherexpression of COX-2 mRNA was also observed in patientswith lymph node involvement than that in those without(0.6775±0.2486 vs 0.4105±0.2182, t=2.9341, P＜0.01).Furthermore, the staging in the UICC TNM classificationsignificantly correlated with COX-2 overexpression (F＝3.656,P＜0.05), the COX-2 index in stage Ⅲ and IV was significantlyhigher than those in stage Ⅰ and Ⅱ(q=3.2728 and q=3.4906, P＜0.05). The COX-2 index showed no correlationwith patient's age, sex, blood group, tumor location, grosstyping, depth of invasion, differentiation, and the greatesttumor dimension (P＞0.05).CONCLUSION: Expression of COX-2 mRNA in gastriccarcinoma was significantly higher, which may enhancelymphatic metastasis in patients with gastric carcinoma. Thestaging in the UICC TNM classification was significantlycorrelated with COX-2 over-expression. COX-2 may contributeto progression of tumor in human gastric adenocarcinoma.展开更多
AIM: To investigate the possible association of G→A single nucleotide polymorphism (SNP) at the -1082 position of interleukin (IL)-10 promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gast...AIM: To investigate the possible association of G→A single nucleotide polymorphism (SNP) at the -1082 position of interleukin (IL)-10 promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of a high incidence region of North China.METHODS: IL-10-G1082A promoter SNP was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 355 cancer patients (203ESCC and 152 GCA) and 443 healthy controls.RESULTS: Smoking significantly increased the risk of ESCC and GCA development (the age and sex adjusted OR = 1.42and 2.64, 95%CI = 1.11-1.81 and 1.46-4.76, respectively).Similarly, family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age and sex adjusted OR = 1.44 and 3.10,95%CI = 1.18-1.75 and 1.94-4.97, respectively). The A/A, A/G and G/G genotype frequencies of IL-10-G1082A were 60.3%, 37.0% and 2.7% in healthy controls, 57.6%,39.9% and 2.5% in ESCC and 61.2%, 36.8% and 2.0% in GCA patients, respectively. The frequencies of A and G alleles were 78.8% and 21.2% in healthy controls, 77.6%and 22.4% in ESCC patients and 79.6%, 20.4% in GCA patients. The distribution of genotype and allelotype in ESCC and GCA patients was not significantly different from that in healthy controls (P＞0.05). Compared to the A/A genotype, the combination of A/G and G/G genotypes did not show a significant effect on the risk of developing ESCC and GCA; the adjusted odds ratio was 0.92 (95%CI = 0.76-1.11) in ESCC and 0.95 (95% CI = 0.61-1.46)in GCA, respectively. When stratified for smoking status and family history of UGIC, the combination of A/G and G/G genotypes also did not show any significant influence on the risk of ESCC and GCA development compared to A/A genotypes.CONCLUSION: IL-10-G1082A polymorphism might not be used as a stratification marker to predicate the risk of ESCC and GCA development in North China.展开更多
AIM: To evaluate the expression of cyclooxygenase (COX2) and the relationship with tumor angiogenesis and advancement in gastric adenocarcinoma.METHODS: Immunohistochemical stain was used for detecting the expression ...AIM: To evaluate the expression of cyclooxygenase (COX2) and the relationship with tumor angiogenesis and advancement in gastric adenocarcinoma.METHODS: Immunohistochemical stain was used for detecting the expression of COX-2 in 45 resected specimens of gastric adenocarcinoma; the monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was detected by counting of CD34-positive vascular endothelial cells. Paracancerous tissues were examined as control.RESULTS: Immunohistological staining with COX-2-specific polyclonal antibody showed cytoplasmic staining in the cancer cells, some atypical hyperplasia and intestinal metaplasia,as well as angiogenic vasculature present within the tumors and prexisting vasculature adjacent to cancer lesions. The rate of expression of COX-2 and MVD index in gastric cancers were significantly increased, compared with those in the paracancerous tissues (77.78 vs 33.33 %, 58.13±19.99 vs 24.02±10.28, P＜0.01, P＜0.05, respectively). In 36 gastric carcinoma specimens with lymph node metastasis, the rate of COX-2 expression and MVD were higher than those in the specimens without metostasis (86.11 vs 44.44 %,58.60±18.24 vs 43.54±15.05, P＜0.05, P＜0.05, respectively).The rate of COX-2 expression and MVD in the specimens with invasive serosa were significantly higher than those in the specimens without invasion to serosa (87.88 vs 50.0 %,57.01±18.79 vs42.35±14.65, P＜0.05, P＜0.05). Moreover,MVD in COX-2-positive specimens was higher than that in COX-2-negative specimens (61.29±14.31 vs 45.38±12.42,P＜0.05). COX-2 expression was positively correlated with MVD (r=0.63, P＜0.05).CONCLUSION: COX-2 expression might correlate with the occurance and advancement of gastric carcinoma and is involved in tumor angiogenesis in gastric carcinoma. It is likely that COX-2 by inducing angiogenesis can be one of mechanisms which promotes invasion and metastasis of gastric carcinoma. It may become a new therapeutic target for anti-an展开更多
AIM：To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics.METHODS： Methylation-specific PCR （MSP） assay was per...AIM：To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics.METHODS： Methylation-specific PCR （MSP） assay was performed in 13 nonneoplastic gastric adenocarcinorna, 30 intestinal-type gastric adenocarcinorna and 35 diffuse-type gastric adenocarcinorna samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher＇s exact test to assess associations between rnethylation status and clinico-pathological characteristics.RESULTS： Hypermethylation frequencies of CDH1, FHIT, MTAPand PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hyperrnethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hyperrnethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender.CONCLUSION： Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.展开更多
文摘BACKGROUND:A regimen of epirubicin,cisplatin,and infused fluorouracil(ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma.We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer.METHODS:We randomly assigned patients with resectable adenocarcinoma of the stomach,esophagogastric junction,or lower esophagus to either perioperative chemotherapy and surgery(250 patients) or surgery alone(253 patients) .Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin(50 mg per square meter of body-surface area) and cisplatin(60 mg per square meter) on day 1,and a continuous intravenous infusion of fluorouracil(200 mg per square meter per day) for 21 days.The primary end point was overall survival.RESULTS:ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer.Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group(46 percent and 45 percent,respectively) ,as were the numbers of deaths within 30 days after surgery.The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group.With a median follow-up of four years,149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died.As compared with the surgery group,the perioperative-chemotherapy group had a higher likelihood of overall survival(hazard ratio for death,0.75;95 percent confidence interval,0.60 to 0.93;P = 0.009;five-year survival rate,36 percent vs.23 percent) and of progression-free survival(hazard ratio for progression,0.66;95 percent confidence interval,0.53 to 0.81;P < 0.001) .CONCLUSIONS:In patients with operable gastric or lower esophageal adenocarcinomas,a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival.
基金National Natural Science Foundation of China,No.39770300,30070873the Overseas Chinese Affairs Office of the State Council Foundation,No.98-33
文摘AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost completely inhibited by preventing the degradation of IkBalpha. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner. CONCLUSION: These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.
文摘AIM: To evaluate the potential role of Nimesulide, a selective COX-2 inhibitor, in proliferation and apoptosis of gastric adenocarcinoma cells SGC7901.METHODS: Cell counts and MYT assay were used to quantify the influence of Nimesulide in the proliferation of SGC7901cells. Transmission electron microscopy and flow cytometry were used to observe the induction of Nimesulide the apoptosis of SGC7901 cells and influence in the distribution of cell cycle. The expression of P27kipl protein was observed by immunocytochemical staining.RESULTS: SGC-7901 Cells treated with Nimesulide at various concentrations exhibited a profound dose- and timedependent reduction in the proliferation rate over the 72 h test period. The highest survival rate of the cells was 78.7 %,but the lowest being 22.7 %. Nimesulide induced apoptosis of the cells in a dose-dependent and non-linear manner and increased the proportion of cells in the G0/G1 phase and decreased the proportion in the S and G2/M phase of the cell cycle. Meanwhile, Nimesulide could up-regulate the expression of P27kipl protein.CONCLUSION: The induction of apoptosis and cell cycle arrest are both anti-proliferative responses that likely contribute to the antineoplastic action of nimesulide on SGC7901 cells. The up-regulation of P27kipl gene may contribute to the accumulation of these cells in the G0/G1 phase following treatment with Nimesulide. Selective COX-2 inhibitor may be a new channel of the chemoprevention and chemotherapy for gastric carcinoma.
文摘AIM: Several epidemiological studies have demonstrated a dose association between Helicobacter pylori (H Pylon) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences,leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H pyloriinfection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due tooxidative DNA damage.METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-κB(NFκB),MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2),inhibitor of apoptosis protein (IAP) and myeloid cellleukemia-1 (Mcl-1)] by Western-blot assay.RFSULTS: The concentrations of 8-OHdG, iNOS, NFx3, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFxB, Mcl-1 and lAP were detected in patients infected with H pyloricompared with patients who were not infected with HpylorL Furthermore,8-OHdG, iNOS, NFκB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage1 and 2 patients.CONCLUSION: Chronic Hpylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the rihypothesis that oxygen-free radical-mediated damage due to Hpyloriplays a pivotal rol
文摘AIM： To investigate the expression of fragile histidine triad （FHIT） protein, and the possible relationship between FHIT expression and dinicopathological indices in gastric carcinoma. METHODS： FHIT protein expression was examined in 76 cases of gastric carcinoma, 58 cases of intraepithelial neoplasia, and 76 cases of corresponding normal mucosae by immunohistochemical method to analyze its relationship to histological grade, clinical stage, metastatic status and prognosis. RESULTS： The FHIT protein expression was positive in 28/76 （36.8%） cases of adenocarcinoma tissue, 22/58 （37.9%） cases of adjacent dysplastic tissue and 76/76 （100%） cases of distal normal gastric mucosa. There was a significant difference in the expression of FHIT protein between cancer or adjacent intraepithelial neoplasia and normal gastric mucosa （P = 0.000）. FHIT protein expression was found in 64.3% （18/28） of grades Ⅰ and Ⅲ cancers, and 20.8% （10/48） of grade Ⅲcancers （P = 0.000）, in 56.3% （18/32） of stages Ⅰ and Ⅱ cancers and 22.7% （10/44） of stages Ⅲ and IV cancers （P = 0.004）, and in 63.6% （14/22） of cancers without metastasis but only 25.9% （14/54） of those with metastasis （P = 0.003）. The significant difference in the expression of FHIT was found between histological grade, clinical stage and metastatic status of cancer. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of FHIT （71 mo） and those without （33 mo, log rank = 20.78, P = 0.000）. CONCLUSION： FHIT protein is an important tumor suppressor protein. Loss of FHIT protein expression may be associated with carcinogenesis, invasion, metastasis and prognosis of gastric adenocarcinoma. 2005 The WJG Press and Elsevier Inc. All rights reserved
基金the National Natural Science Foundation of China,No.39870661
文摘AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/waf1) of SGC-7901 cells which were treated with various c9, t11-CLA concentrations (25, 50, 100 and 200 micromol.L(-1))of c 9, t 11-CLA for 24 and 48h, with a negative control (0.1% ethane). RESULTS: The cell growth and DNA synthesis of SGC-7901 cells were inhibited by c9, t11-CLA.SGC-7901 cells. Eight day after treatment with various concentrations of c9, t11-CLA mentioned above, the inhibition rates were 5.92%, 20.15%, 75.61% and 82.44%, respectively and inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 micromol.L, 24h) showed significantly less (3)H-TdR incorporation than that in the negative controls (P【0.05 and P【0.01). Immunocytochemical staining demonstrated that SGC-7901 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA (the expression rates were 7.2-3.0%, 24h and 9.1-0.9% at 48h, respectively), Cyclin A (11.0-2.3%, 24h and 8.5-0.5%,48h), B(1) (4.8-1.8% at 24h and 5.5-0.6% at 48h)and D(1) (3.6-1.4% at 24h and 3.7%-0 at 48h) as compared with those in the negative controls(the expressions of PCNA, Cyclin A, B(1) and D(1) were 6.5% at 24h and 9.0% at 48h, 4.2% at 24h and 5.1% at 48h, 9.5% at 24h and 6.0% at 48h,respectively)(P【0.01), whereas the expressions of P16(ink4a) and P21(cip/waf1), cyclin-dependent kinases inhibitors(CDKI), were increased. CONCLUSION: The cell growth and proliferation of SGC-7901 cell is inhibited by c9, t11-CLA via blocking the cell cycle, with reduced expressions of cyclin A,B(1) and D(1) and enhanced expressions of CDKI(P16(ink4a) and p21(cip/waf1)).
文摘AIM: To study the expression of cyclooxygenase-2 (COX-2)gene in gastric cancer and the relationship between COX-2expression and clinicopathologic features of gastric cancer.METHODS: With reference to the expression of β-actin gene,COX-2 mRNA level was examined in cancerous tissues andadjacent noncancerous mucosa from 33 patients bysemiquantitative reverse transcription- polymerase chainreaction (RT-PCR). Quantitation of relative band Adj volumecounts was performed using molecular Analyst for windowssoftware. The COX-2 index was determined from the band Adjvolume counts ratio of COX-2 to constitutively expressed actin.RESULTS: The COX-2 index in gastric carcinoma wassignificantly higher than that in normal mucosa (0.5966±0.2659vs 0.2979+0.171, u=5.4309, P＜0.01). Significantly higherexpression of COX-2 mRNA was also observed in patientswith lymph node involvement than that in those without(0.6775±0.2486 vs 0.4105±0.2182, t=2.9341, P＜0.01).Furthermore, the staging in the UICC TNM classificationsignificantly correlated with COX-2 overexpression (F＝3.656,P＜0.05), the COX-2 index in stage Ⅲ and IV was significantlyhigher than those in stage Ⅰ and Ⅱ(q=3.2728 and q=3.4906, P＜0.05). The COX-2 index showed no correlationwith patient's age, sex, blood group, tumor location, grosstyping, depth of invasion, differentiation, and the greatesttumor dimension (P＞0.05).CONCLUSION: Expression of COX-2 mRNA in gastriccarcinoma was significantly higher, which may enhancelymphatic metastasis in patients with gastric carcinoma. Thestaging in the UICC TNM classification was significantlycorrelated with COX-2 over-expression. COX-2 may contributeto progression of tumor in human gastric adenocarcinoma.
基金Supported by the National Natural Science Foundation of China,No. 30371591
文摘AIM: To investigate the possible association of G→A single nucleotide polymorphism (SNP) at the -1082 position of interleukin (IL)-10 promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of a high incidence region of North China.METHODS: IL-10-G1082A promoter SNP was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 355 cancer patients (203ESCC and 152 GCA) and 443 healthy controls.RESULTS: Smoking significantly increased the risk of ESCC and GCA development (the age and sex adjusted OR = 1.42and 2.64, 95%CI = 1.11-1.81 and 1.46-4.76, respectively).Similarly, family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age and sex adjusted OR = 1.44 and 3.10,95%CI = 1.18-1.75 and 1.94-4.97, respectively). The A/A, A/G and G/G genotype frequencies of IL-10-G1082A were 60.3%, 37.0% and 2.7% in healthy controls, 57.6%,39.9% and 2.5% in ESCC and 61.2%, 36.8% and 2.0% in GCA patients, respectively. The frequencies of A and G alleles were 78.8% and 21.2% in healthy controls, 77.6%and 22.4% in ESCC patients and 79.6%, 20.4% in GCA patients. The distribution of genotype and allelotype in ESCC and GCA patients was not significantly different from that in healthy controls (P＞0.05). Compared to the A/A genotype, the combination of A/G and G/G genotypes did not show a significant effect on the risk of developing ESCC and GCA; the adjusted odds ratio was 0.92 (95%CI = 0.76-1.11) in ESCC and 0.95 (95% CI = 0.61-1.46)in GCA, respectively. When stratified for smoking status and family history of UGIC, the combination of A/G and G/G genotypes also did not show any significant influence on the risk of ESCC and GCA development compared to A/A genotypes.CONCLUSION: IL-10-G1082A polymorphism might not be used as a stratification marker to predicate the risk of ESCC and GCA development in North China.
文摘AIM: To evaluate the expression of cyclooxygenase (COX2) and the relationship with tumor angiogenesis and advancement in gastric adenocarcinoma.METHODS: Immunohistochemical stain was used for detecting the expression of COX-2 in 45 resected specimens of gastric adenocarcinoma; the monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was detected by counting of CD34-positive vascular endothelial cells. Paracancerous tissues were examined as control.RESULTS: Immunohistological staining with COX-2-specific polyclonal antibody showed cytoplasmic staining in the cancer cells, some atypical hyperplasia and intestinal metaplasia,as well as angiogenic vasculature present within the tumors and prexisting vasculature adjacent to cancer lesions. The rate of expression of COX-2 and MVD index in gastric cancers were significantly increased, compared with those in the paracancerous tissues (77.78 vs 33.33 %, 58.13±19.99 vs 24.02±10.28, P＜0.01, P＜0.05, respectively). In 36 gastric carcinoma specimens with lymph node metastasis, the rate of COX-2 expression and MVD were higher than those in the specimens without metostasis (86.11 vs 44.44 %,58.60±18.24 vs 43.54±15.05, P＜0.05, P＜0.05, respectively).The rate of COX-2 expression and MVD in the specimens with invasive serosa were significantly higher than those in the specimens without invasion to serosa (87.88 vs 50.0 %,57.01±18.79 vs42.35±14.65, P＜0.05, P＜0.05). Moreover,MVD in COX-2-positive specimens was higher than that in COX-2-negative specimens (61.29±14.31 vs 45.38±12.42,P＜0.05). COX-2 expression was positively correlated with MVD (r=0.63, P＜0.05).CONCLUSION: COX-2 expression might correlate with the occurance and advancement of gastric carcinoma and is involved in tumor angiogenesis in gastric carcinoma. It is likely that COX-2 by inducing angiogenesis can be one of mechanisms which promotes invasion and metastasis of gastric carcinoma. It may become a new therapeutic target for anti-an
基金Supported by Fundao de Amparo à Pesquisa do Estado de So Paulo, Coordenao de Aperfeioamento de Pessoal de Nível Superior and Conselho Nacional de Desenvolvimento Científico e Tecnológico
文摘AIM：To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics.METHODS： Methylation-specific PCR （MSP） assay was performed in 13 nonneoplastic gastric adenocarcinorna, 30 intestinal-type gastric adenocarcinorna and 35 diffuse-type gastric adenocarcinorna samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher＇s exact test to assess associations between rnethylation status and clinico-pathological characteristics.RESULTS： Hypermethylation frequencies of CDH1, FHIT, MTAPand PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hyperrnethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hyperrnethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender.CONCLUSION： Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.
