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ABSTRACT: AIM: To evaluate the role of mitochondrial microsatellite instability (mtMSI) in gastric carcinogenesis.
METHODS: MtMSI was measured with PCR-single strand conformation polymorphism (PCR-SSCP) in 68 cases of advanced gastric cancer, 40 cases of chronic gastritis, 30 cases of intestinal metaplasia and 20 cases of dysplasia.
RESULTS: MtMSI was observed in 12.5% (5 of 40) of chronic gastritis, 20.0% (6 of 30) of intestinal metaplasia, 25.0% (5 of 20) of dysplasia and 38.2% (26 of 68) of gastric cancer. These findings showed a sequential accumulation of mtMSI in the histological progression from chronic gastritis to gastric cancer. An association of mtMSI with intestinal histological type and distal location was found (P=0.001 and P=0.002), whereas no significant correlation was found between mtMSI and age at diagnosis, sex, tumor size, depth of invasion, lymph node spread and clinical stages (P>0.05).
CONCLUSION: MtMSI may play an early and important role in the gastric carcinogenesis pathway, especially in the intestinal type and distal gastric cancer.
World Journal of Gastroenterology. 01/2004;
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ABSTRACT: AIM: To study the nuclear microsatellite instability (nMSI) at BAT26 and mitochondrial microsatellite instability (mtMSI) in the occurrence and development of hepatocellular carcinoma and the relationship between nMSI and mtMSI.
METHODS: nMSI was observed with PCR and mtMSI with PCR-SSCP in 52 cases of hepatocellular carcinoma.
RESULTS: mtMSI was detected in 11 out of the 52 cases of hepatocellular carcinoma (21.2%). Among the 11 cases of hepatocellular carcinoma with mtMSI, 7 occurred in one locus and 4 in 2 loci. The frequency of mtMSI in the 52 cases of hepatocellular carcinoma showed no correlation to sex, age, infection of hepatitis B, liver cirrhosis as well as positive AFP of the patients (P>0.05). In addition, nMSI was detected in 3 out of 52 cases of hepatocellular carcinoma (5.8%) and there was no correlation of the incidence of mtMSI to that of nMSI (P>0.05).
CONCLUSION: mtMSI may be involved in the coccurrence and development of hepatocellular carcinoma and it is independent of nMSI.
World Journal of Gastroenterology. 01/2004;
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ABSTRACT: AIM: The pathophysiology underlying gastrointestinal complications of long-standing diabetes is poorly understood. Recent evidence suggests an important role of intestitial cells of cajal in controlling gastrointestinal motility. The aim of this study was to clarify the changes of ultrastructural characteristics of interstitial cells of cajal in stomach of diabetic gastro-electric dysrhythmic rats.
METHODS: Rats were randomly divided into diabetic group and control group, the model of diabetic rats was established by peritoneally injection of streptozotocin. Electrogastrograms were recorded and intestitial cells of cajal in antrum were observed by electrictelescopy after diabetic model rat was established for 3 mo.
RESULTS: In the rats of diabetic group, the gastro-electric dysrhythmia was increased compared with control group, the abnormal rhythm index and the cofficient of variation of slow wave frequency were significantly higher than those of normal rats. The number of the gap junctions of interstitial cells of cajal in antrum of diabetic rats was significantly decreased, and the remaining structures were damaged. The organelles were also damaged, and vacuoles were formed.
CONCLUSION: It is possible that changes in ultrastructural characteristics of interstitial cells of cajal in stomach are one of the mechanisms underlying gastro-electric dysrhythm in diabetic rats.
World Journal of Gastroenterology. 01/2004;
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ABSTRACT: AIM: To investigate the effects of gastric pacing on gastric emptying and plasma motilin level in a canine model of gastric motility disorders and the correlation between gastric emptying and plasma motilin level.
METHODS: Ten healthy Mongrel dogs were divided into: experimental group of six dogs and control group of four dogs. A model of gastric motility disorders was established in the experimental group undergone truncal vagotomy combined with injection of glucagon. Gastric half-emptying time (GEt(1/2)) was monitored with single photon emission computerized tomography (SPECT), and the half-solid test meal was labeled with an isotope-(99m)Tc sulfur colloid. Plasma motilin concentration was measured with radioimmunoassay (RIA) kit. Surface gastric pacing at 1.1-1.2 times the intrinsic slow-wave frequency and a superimposed series of high frequency pulses (10-30 Hz) was performed for 45 min daily for a month in conscious dogs.
RESULTS: After surgery, GEt(1/2) in dogs undergone truncal vagotomy was increased significantly from 56.35+/-2.99 min to 79.42+/-1.91 min (P<0.001), but surface gastric pacing markedly accelerated gastric emptying and significantly decreased GEt(1/2) to 64.94+/-1.75 min (P<0.001) in animals undergone vagotomy. There was a significant increase of plasma level of motilin at the phase of IMCIII (interdigestive myoelectrical complex, IMCIII) in the dogs undergone bilateral truncal vagotomy (baseline vs vagotomy, 184.29+/-9.81 pg/ml vs 242.09+/-17.22 pg/ml; P<0.01). But plasma motilin concentration (212.55+/-11.20 pg/ml; P<0.02) was decreased significantly after a long-term treatment with gastric pacing. Before gastric pacing, GEt(1/2) and plasma motilin concentration of the dogs undergone vagotomy showed a positive correlation (r=0.867, P<0.01), but after a long-term gastric pacing, GEt(1/2) and motilin level showed a negative correlation (r=-0.733, P<0.04).
CONCLUSION: Surface gastric pacing with optimal pacing parameters can improve gastric emptying parameters and significantly accelerate gastric emptying and can resume or alter motor function in a canine model of motility disorders. Gastric emptying is correlated well with plasma motilin level before and after pacing, which suggests that motilin can modulate the mechanism of gastric pacing by altering gastric motility.
World Journal of Gastroenterology. 01/2004;
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ABSTRACT: AIM: To study the effect of NF-kappaB, survivin, Bcl-2 and Caspase3 on tumor necrosis factors related apoptosis inducing ligand (TRAIL) induced apoptosis of gastric cancer cells.
METHODS: Gastric cancer cells of SGC-7901, MKN28, MKN45 and AGS lines were cultured in PRMI-1640 medium and the apoptosis rates of the cells of 4 lines were observed after treatment of tumor necrosis factors related apoptosis inducing ligand (TRAIL) with a flow cytometer. The expression of NF-kappaB, survivin, Bcl-2 and Caspase3 in gastric cancer cells of 4 lines was analyzed with Western blot.
RESULTS: After the gastric cancer cells were exposed to TRAIL 300 ng/ml for 24 hours, the apoptosis rate was 36.05%, 20.27%, 16.50% and 11.80% in MKN28, MKN45, AGS and SGC-7901cells respectively. Western blot revealed that the expressions of NF-kappaB and survivin were lower in MKN28 cells than in MKN45, AGS and SGC-7901 cells. In contrast, the expression of Caspase3 was higher in MKN28 cells than in MKN45, AGS and SGC-7901 cells.
CONCLUSION: There is a selectivity of TRAIL potency to induce apoptosis in gastric cancer cells of different cell lines. The anticancer potency of TRAIL is associated with the decreased expression of NF-kappaB and survivin and increased expression of Caspase3 of gastric cancer cells.
World Journal of Gastroenterology. 01/2004;
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ABSTRACT: AIM: To investigate the effect of Helicobacter pylori (H pylori) infection on the expressions of Bcl-2 family members in gastric adenocarcinoma.
METHODS: Gastric adenocarcinoma and resection margin tissues of 95 patients were studied. Semi-quantitative RT-PCR was used to measure Bid, Bax and Bcl-2 mRNA expressions.
RESULTS: Expressions of Bid and Bax in gastric adenocarcinoma tissues without H pylori infection, with cagA- H pylori infection and cagA+ H pylori infection increased significantly in turn (Bid, 0.304, 0.422 and 0.855 respectively, P<0.05; Bax, 0.309, 0.650 and 0.979 respectively, P<0.05). Bcl-2 mRNA levels increased significantly in gastric adenocarcinoma tissues with cagA- H pylori infection and cagA+ H pylori infection, compared with those without H pylori infection (0.696 and 0.849 vs 0.411, P<0.05). Expressions of Bid, Bax and Bcl-2 in resection margin tissues without H pylori infection, with cagA- H pylori infection and cagA+ H pylori infection increased significantly in turn (Bid, 0.377, 0.686 and 0.939 respectively, P<0.05; Bax, 0.353, 0.645 and 1.001 respectively, P<0.05; Bcl-2, 0.371, 0.487 and 0.619 respectively, P<0.05). In H pylori negative specimens, expressions of Bid and Bax correlated negatively with that of Bcl-2 respectively in adenocarcinoma tissues (Bid vs Bcl-2, r=-0.409, P<0.05; Bax vs Bcl-2, r=-0.451, P<0.05). In H pylori positive specimens, expressions of Bid and Bax did not correlate with that of Bcl-2 in adenocarcinoma tissues (Bid vs Bcl-2, r=0.187, P>0.05; Bax vs Bcl-2, r=0.201, P>0.05), but correlated positively with that of Bcl-2 respectively in resection margin tissues (Bid vs Bcl-2, r=0.331, P<0.05; Bax vs Bcl-2, r=0.295, P<0.05).
CONCLUSION: H pylori may enhance Bid, Bax and Bcl-2 mRNA levels and cause deregulation of these apoptosis-associated genes expressions, which may play a role during development of gastric adenocarcinoma induced by H pylori.
World Journal of Gastroenterology. 01/2004;
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ABSTRACT: AIM: To explore the correlation of magnifying endoscopic patterns and histopathology, Helicobacter pylori (H pylori) infection of the gastric mucosa.
METHODS: Gastric mucosal patterns in 140 patients with chronic gastritis were studied using Olympus GIF-Q240Z magnifying endoscope. Histopathological examination, rapid urease test and Warrthin-Starry staining were taken with biopsy samples from the magnified sites of stomach. The magnifying endoscopic patterns were compared with histopathological results and H pylori detection.
RESULTS: The pit patterns of gastric mucosa were classified as types A (round spot), B (short rod), C (branched), D (reticular) and E (villus). The detection rate of chronic atrophic gastritis (CAG) by magnifying endoscopy was 94.3% (33/35), which was significantly higher than that by routine endoscopy (22.9%, 8/35) (P<0.01). The pit patterns of 31 cases of intestinal metaplasia (IM) appeared as type E in 18 cases (58.1%), type D in 8 cases (25.8%) and type C in 5 cases (16.1%). Fourteen out of 18 patients (77.8%) with complete type (type I) of IM appeared as type E of pit patterns, whereas only 4 of 13 (30.8%) patients with incomplete type (types II and III) of IM appeared as type E (P<0.05). Collecting venules in the anterior of lower part of gastric corpus were subgrouped into types R (regular), I (irregular) and D (disappeared). H pylori infection was found in 12.2%(9/74), 60%(9/15) and 84.3%(43/51) cases in these types respectively. H pylori infection rate in type R was significantly lower than that in other two types (P<0.01).
CONCLUSION: Magnifying endoscopy may have an obvious value in diagnosing chronic atrophic gastritis, intestinal metaplasia and H pylori infection.
World Journal of Gastroenterology. 01/2003;
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ABSTRACT: AIM: To appraise the correlation of mutation and methylation of hMSH1 with microsatellite instability (MSI) in gastric cancers.
METHODS: Mutation of hMLH1 was detected by Two-dimensional electrophoresis (Two-D) and DNA sequencing; Methylation of hMLH1 promoter was measured with methylation-specific PCR; MSI was analyzed by PCR-based methods.
RESULTS: Sixty-eight cases of sporadic gastric carcinoma were studied for mutation and methylation of hMLH1 promoter and MSI. Three mutations were found, two of them were caused by a single bp substitution and one was caused by a 2 bp substitution, which displayed similar Two-D band pattern. Methylation of hMLH1 promoter was detected in 11(16.2 %) gastric cancer. By using five MSI markers, MSI in at least one locus was detected in 17/68(25 %) of the tumors analyzed. Three hMLH1 mutations were all detected in MSI-H (>=2 loci, n=8), but no mutation was found in MSI-L (only one locus, n=9) or MSS (tumor lacking MSI or stable, n=51). Methylation frequency of hMLH1 in MSI-H (87.5 %, 7/8) was significantly higher than that in MSI-L (11.1 %, 1/9) or MSS (5.9 %, 3/51) (P<0.01-0.001), but no difference was found between MSI-L and MSS (P>0.05).
CONCLUSION: Both mutation and methylation of hMLH1 are involved in the MSI pathway but not related to the LOH pathway in gastric carcinogenesis.
World Journal of Gastroenterology. 01/2003;
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ABSTRACT: AIM: The E-cadherin-catenin complex is important for cell-cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. We evaluated the expression pattern of E-cadherin and beta-catenin in gastric carcinoma and dysplasia and analyzed their relationship with tumor clinicopathological features and patient survival.
METHODS: Immunohistochemical staining of E-cadherin and beta-catenin was performed from paraffin specimens of 163 gastric carcinomas, 44 gastric mucosal dysplasia, and 25 intestinal metaplasia, 28 atrophic gastritis and 12 healthy controls.
RESULTS: Normal membrane staining was observed in intestinal metaplasia, atrophic gastritis and control biopsy specimens for E-cadherin and beta- catenin. 36 % and 16 % of gastric dysplasia were stained abnormally for E-cadherin and beta- catenin respectively. Abnormal expression of E-cadherin and beta- catenin was demonstrated in 46 % and 44 % of gastric carcinoma respectively. Abnormal expression of E-cadherin and beta- catenin occurred more significantly in Borrmann III/IV than in Borrmann I/II type (P<0.005, respectively). A significantly higher proportion of signet-ring,mucinous and tubular adenocarcinomas were abnormally expressed for E-cadherin and beta- catenin as compared with papillary adenocarcinomas (chi(2)=8.47,P<0.005, and chi(2)=7.05, P<0.01, respectively). Morever, abnormal E-cadherin and beta- catenin staining occurred more frequently in diffuse than in intestinal type of tumor (chi(2)=18.18 and 17.79, P<0.005, respectively). There was a significant correlation between abnormal beta- catenin expression and positive lymph node metastasis. A survival advantage was noted in tumors retaining normal membranous expression of beta-catenin, independent of type, grade, or stage of the disease (P<0.0005).
CONCLUSION: Abnormal expression of the E-cadherin- catenin complex occurs frequently in gatric carcinoma, closely related to its histogenesis. Abnormal expression of the E-cadherin- catenin complex in gastric dysplasia may be an early event in the tumorigenesis. The close correlation with poor survival suggests that abnormal beta-catenin may be a useful prognostic marker.
World Journal of Gastroenterology. 01/2002;
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ABSTRACT: AIM: To evaluate the role of APC mutation in gastric carcinogenesis and to correlate APC mutation with microsatellite instability (MSI) in gastric carcinomas.
METHODS: APC mutation was measured with multiplex PCR, denaturing gradient gel electrophoresis and DNA sequencing; and MSI was analyzed by PCR-based methods.
RESULTS: Sixty-eight cases of sporadic gastric carcinoma were studied for APC mutation at exon 15 and MSI. APC mutations were detected in 15(22.1 %) gastric cancers. Frequence of APC mutation (33.3 %) in intestinal type of gastric cancer was significantly higher than that in diffuse type (13.1 %, P<0.05). On the contrary, no association was observed between APC mutation and tumor size, differentiation, depth of invasion, metastasis or clinical stages. Using five microsatellite markers, MSI in at least one locus was detected in 17 of 68 (25 %) of the tumors analyzed. APC mutations were all detected in MSI-L (only one locus, n=9) or MSS(tumor lacking MSI or stable, n=51), but no mutation was found in MSI-H (> or =2 loci, n=8).
CONCLUSION: APC mutation is involved in carcinogenesis of intestinal type of gastric cancer and is independent of MSI phenotype but related to the LOH pathway in gastric cancer.
World Journal of Gastroenterology. 01/2002;
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ABSTRACT: AIM: To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas.
METHODS: Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-betaRII and BAX genes were analyzed by PCR-based methods.
RESULTS: Sixty-eight cases of sporadic gastric carcinoma were studied for MSI using five microsatellite markers. MSI in at least one locus was detected in 17 (25%) of 68 tumors analyzed. Frameshift mutations of hMSH6, TGF-betaRII and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (> or = 2 loci, n = 8), but none was found in those showing low MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and low MSI, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters. No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P<0.01). This tendency was also observed in APC and MCC genes, although there was no statistical significance.
CONCLUSION: The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either low MSI or MSS, multiple deletions may represent the LOH pathway. Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer.
World Journal of Gastroenterology. 01/2001;
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ABSTRACT: AIM:To study hepatocarcinogenesis of hepatitis C virus (HCV).
METHODS: Expression of HCV antigens (CP10, NS3 and NS5) and several cancer-associated gene products (ras p21, c-myc, c-erbB-2, mutated p53 and p16 protein) in the tissues of hepatocellular carcinoma (HCC, n = 46) and its surrounding liver tissue were studied by the ABC(avidin-biotin complex) immunohistochemical method. The effect of HCV infection on expression of those gene products in HCC was analyzed by comparing HCV antigen positive group with HCV antigen negative group.
RESULTS:Positive immunostaining with one, two or three HCV antigens was found in 20 (43.5%) cases,with either of two or three HCV antigens in 16 (34.8%) cases, and with three HCV antigens in 9 (19.6%) cases.Deletion rate of p16 protein expression in HCC with positive HCV antigen (80%, 16/20)was significantly higher than that in HCC with negative HCV antigen. Whereas no significant difference of the other gene product expression was observed between the two groups.
CONCLUSION:HCV appears related to about one third of cases of HCC in Chongqing, the southwest of China, and it may be involved in hepatocarcinogenesis by inhibi ting the function of p16 gene, which acts as a negative regulator of cell cycle.
World Journal of Gastroenterology. 01/1999;
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ABSTRACT: AIM:To study the expression of proapoptotic gene Bax in human gastric carcinoma and its significance.
METHODS:Using immunohistochemistry methods, the Bax protein expression in 57 specimens of gastric carcinoma and its relationship with clinical status and pathomorphological parameters were observed.
RESULTS:Thirty- three (57.9%) cases were positive for Bax protein staining which was mainly located in the cytoplasm of tumor cells. The rate of Bax protein expression was not correlated with the tumor size, lymph node metastasis, depth of invasion, clinical stages of tumors and age and sex of patients (P >0.05), but strongly associated with the morphological type and differentiation degree of tumors. It was significantly higher in intestinal type and well or moderately differentiated gastric carcinoma than in diffuse type and poorly differentiated gastric carcinoma (P < 0.05 and P <0.01).
CONCLUSION:The proapoptotic gene Bax is differently expressed in most of gastric carcinoma and may take part in the modulation of apoptosis in gastric carcinoma. The expression of Bax might be associated with the occurrence of intestinal type gastric carcinoma and the differentiation of gastric carcinoma.
World Journal of Gastroenterology. 01/1999;
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World Journal of Gastroenterology. 01/1999;
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ABSTRACT: AIM:To further study the role of bcl-2 protein expression in gastric carcinogenesis and tumor progression.
METHODS:Using immunohistochemical staining, the bcl-2 protein expression in 50 cases of gastric carcinoma and its relation to clinical status and pathomorphological parameters were observed.
RESULTS:Forty-one (82%) cases were positive for bcl-2 protein staining which was located in the cytoplasm and nuclear membrane of tumor cells. The rate of bcl-2 protein expression was not correlated with the patient, sex, tumor size, lymph node status or clinical stages (P > 0.05). It was strongly associated with intestinal-type tumors and poorly differentiated tumors (P < 0.05 andP <0.01).
CONCLUSION:Aberrant bcl-2 protein expression appears to be specifically associated with development of intestinal-type gastric carcinoma, bcl-2 protein expression might play an important role in the early development/promotion and phenotypic differentiation of gastric carcinomas, but not in tumor progression.
World Journal of Gastroenterology. 01/1998;
