AIM:To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and signifi cance of their expression in gastric carcinoma and precancerous lesions.METHODS: Th...AIM:To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and signifi cance of their expression in gastric carcinoma and precancerous lesions.METHODS: The PV9000 immunohistochemical method was used to detect the expression of YAP and survivin in 98 cases of normal gastric mucosa, 58 intestinal metaplasia (IM), 32 dysplasia and 98 gastric carcinoma.RESULTS: The positive rates of YAP in dysplasia (37.5%) and gastric carcinoma (48.0%) were significantly higher than that in normal gastric mucosa (13.3%), P<0.01. The positive rates of survivin in IM (53.4%), dysplasia (59.4%) and gastric carcinoma (65.3%) were significantly higher than in normal gastric mucosa (11.2%), P<0.01. Survivin expression gradually increased from 41.7% in well differentiated adenocarcinoma through 58.3% in moderately differentiated adenocarcinoma to 75.6% in poorly differentiated adenocarcinoma, with significant Rank correlation, rk=0.279, P<0.01. The positive rate of survivin in gastric carcinoma of diffused type (74.6%) was significantly higher than that in intestinal type (51.3%), P<0.05. In gastric carcinoma with lymph node metastasis (76.9%), the positive rate of survivin was signifi cantly higher than that in the group without lymph node metastasis (41.2%), P<0.01. In 98 cases of gastric carcinoma, the expression of YAP and of survivin were positively correlated, rk=0.246, P<0.01.CONCLUSION: YAP may play an important role as a carcinogenic factor and may induce survivin expression. Detecting both markers together may help in early diagnosis of gastric carcinoma.展开更多
In the model rat with precancerous lesion of stomach induced by the combined method of insertion of a spring into the pylorus and high salt hot paste,effects of San Qi (三七 Radix Notoginseng) on gastric secretion and...In the model rat with precancerous lesion of stomach induced by the combined method of insertion of a spring into the pylorus and high salt hot paste,effects of San Qi (三七 Radix Notoginseng) on gastric secretion and protective factors of stomach were investigated.The results indicated that gastric secretion,gastric mucosal blood flow (GMBF) and aminohexose content lowered significantly,and malondialdehyde (MDA) increased significantly (P<0.01) in the model group as compared with the normal group;after treatment with San Qi Powder for 12 weeks,both gastric secresion and GMBF increased,and MDA content decreased as compared with the negative control group (P<0.01),with no significant increase of aminohexose content.It is suggested that San Qi (三七 Radix Notoginseng) may improve gastric secretion,and that increase of GMBF and antagonism against the lesion of oxygen free radicals are possibly one of its mechanisms.展开更多
AIM: To investigate the expression and significance of caudal-related homeobox transcription factor (Cdx2) in gastric carcinoma (GC) and precancerous lesions. METHODS: The expression of Cdx2 in GC, precancer- ou...AIM: To investigate the expression and significance of caudal-related homeobox transcription factor (Cdx2) in gastric carcinoma (GC) and precancerous lesions. METHODS: The expression of Cdx2 in GC, precancer- ous lesions and normal gastric mucosa were detected using immunohistochemical method. Hematoxylin and eosin staining, alcian blue/periodic acid-schiff and high iron diamine/alcian blue staining were used to classify intestinal metaplasia (IM) and GC. RESULTS: Cdx2 was not detected in normal gas- tric mucosa. Cdx2 expression was detected in 87.1% (101/116) of IM, 50% (36/72) of dysplasia and 48.2% (41/85) of GC. The Cdx2-expressing cells in IM were more prevalent than in dysplasia and carcinoma (P 〈 0.05). There was no relationship between Cdx2 ex- pression and the classification of IM or the degree of dysplasia. Expression of Cdx2 was significantly higher in intestinal-type carcinoma than in diffuse and mixed- type carcinoma (P 〈 0.05). Positive expression of Cdx2was mainly found in moderately to well differentiated GC. There was a negative association between nuclear Cdx2 expression and lymph node metastasis and tumor, nodes, metastasis stage of GC (P 〈 0.05). The patients with Cdx2-positive expression showed a higher survival rate than those with Cdx2-negative expression (P = 0.038). Multivariate analysis revealed that the expres- sion of Cdx2 and lymph node metastasis were indepen- dent prognostic indicators of GC (P 〈 0.05).展开更多
AIM: To investigate the microsatellite instability (MSI) in cancer and pre-cancerous lesions of the stomach and its mechanisms underlying the development of gastric cancer.METHODS: Thirty-six gastric cancer samples we...AIM: To investigate the microsatellite instability (MSI) in cancer and pre-cancerous lesions of the stomach and its mechanisms underlying the development of gastric cancer.METHODS: Thirty-six gastric cancer samples were obtained from patients undergoing surgery. Forty-one gastric mucosa samples with dysplasia and 51 with intestinal metaplasia (IM) were obtained from patients with chronic gastritis undergoing gastro-endoscopy. Genomic DNA was extracted from the samples. Silver staining single strand conformation polymorphis-polymerize chain reaction (SSCP-PCR) was used to screen MSI markers at 5 loci (Bat-25, Bat-26, D5S346, D17S250, and D2S123)in fresh tissues and formalin-fixed, paraffin-embedded samples and their corresponding normal gastric mucosa.RESULTS: The abnormal shifting of the single-strand DNA (MSI) was identified in 21 out of 36 (58.3%) gastric cancers.Seven cases showed high-level MSI (two or more loci altered) and 14 showed low-level MSI (one locus altered).Gastric cancer with MSI had a tendency to be located in the distal stomach. MSI was also detected in 11 out of 41(26.8%) dysplasia samples and in 9 of 51 (17.6%) IM samples respectively. Three cases of dysplasia and one case of IM showed high-level MSI. Eight cases of dysplasia and 8 cases of IM displayed low-level MSI. MIS in IM was found only in moderate or severe-grade IM. No association was detected between MSI and dysplasia grade.CONCLUSION: Accumulation of MSI in dysplasia and intestinal metaplasia of gastric mucosa may be an early molecular event during gastric carcinogenesis and may contribute to the acquisition of transformed cell phenotype and the development of gastric cancer.展开更多
Objective: To study the expressions of Bcl-2 and Bax proteins and explore the relationships between them and apoptosis in gastric carcinoma and precancerous lesions. Methods: TUNEL method was used to detect apoptosis ...Objective: To study the expressions of Bcl-2 and Bax proteins and explore the relationships between them and apoptosis in gastric carcinoma and precancerous lesions. Methods: TUNEL method was used to detect apoptosis and im- munohistochemical staining method was used to detect the expressions of Bcl-2 and Bax proteins in 70 cases of chronic gastritis, 49 cases of intestinal metaplasia, 64 cases of dysplasia and 81 cases of gastric carcinoma. Results: The positive incidences of Bcl-2 and Bax were the highest in severe dysplasia. In intestinal metaplasia and dysplasia, positive incidences of Bcl-2 and Bax were higher than those in chronic gastritis and gastric carcinoma. During the process of evolvement from chronic gastritis to intestinal metaplasia then to dysplasia, apoptosis indexes gradually rise up to mid-high dysplasia, which reached the highest point, then it began to fall down, when it reached the lowest point in gastric carcinoma. There were nega- tive correlations between the expressions of Bcl-2, Bax proteins and apoptosis. Conclusion: The expression of Bcl-2 may be an early behavior in the gastric carcinogenesis. Bax had antagonistic effect to Bcl-2. Detections of Bcl-2 and Bax may be beneficial to the early diagnosis of gastric tumor and precancerous lesions.展开更多
Fundic gland polyps are now commonly recognized during endoscopy. These polyps are benign, often multiple and usually detected in the gastric body and fundus. In the past, these polyps were sometimes associated with f...Fundic gland polyps are now commonly recognized during endoscopy. These polyps are benign, often multiple and usually detected in the gastric body and fundus. In the past, these polyps were sometimes associated with familial adenomatous polyposis. In recent years, it has become evident that increasing numbers of these polyps are being detected during endoscopic studies, particularly in patients treated with proton pump inhibitors for prolonged periods. In some, dysplastic changes in these polyps have also been reported. Recent studies have suggested that there may be no increase in risk of colon cancer with long-term proton pump inhibitor therapy. While temporarily reassuring, ongoing vigilance, particularly in those genetically predisposed to colon cancer, is still warranted.展开更多
AIM:To investigate the mutation in D-loop region of mitochondrial DNA in gastric cancer and its influence on the changes of reactive oxygen species (ROS) and cell cycle. METHODS: The D-loop region was amplified by PCR...AIM:To investigate the mutation in D-loop region of mitochondrial DNA in gastric cancer and its influence on the changes of reactive oxygen species (ROS) and cell cycle. METHODS: The D-loop region was amplified by PCR and sequenced.Reactive oxygen species and cell cycle were detected by flow cytometry in 20 specimens from gastric cancer and adjacent normal tissues.According to the sequence results,gastric cancer tissue was divided into mutation group and control group.Reactive oxygen species,apoptosis and proliferation in the two groups were compared. RESULTS:Among the 20 gastric cancer specimens, 18 mutations were identified in 7 patients,the mutation rate being 35%.There were four microsatellite instabilities in the mutations. No mutation was found in the adjacent tissues. Reactive oxygen species,apoptosis,and proliferation in the mutation group were all significantly higher than those in control group. CONCLUSION: Mutation in D-loop region plays a role in the genesis and development of gastric cancer.展开更多
AIM: To detect the variations of mitochondrial 12S rRNA in patients with gastric carcinoma, and to study their significance and the relationship between these variations and the genesis of gastric carcinoma.METHODS: P...AIM: To detect the variations of mitochondrial 12S rRNA in patients with gastric carcinoma, and to study their significance and the relationship between these variations and the genesis of gastric carcinoma.METHODS: PCR amplified mitochondrial 12S rRNA of 44 samples including 22 from gastric carcinoma tissues and 22 from adjacent normal tissues, was detected by direct DNA sequencing. Then laser capture microdissection technique (LCM) was used to separate the cancerous cells and dysplasia cells with specific mutations. Denaturing high performance liquid chromatography (DHPLC) plus allele-specific PCR (ASPCR), nest-PCR and polyacrylamide gel electrophoresis (PAGE)were used to further evaluate this mutant property and quantitative difference of mutant type between cancerous and dysplasia cells. Finally, RNAdraw biosoft was used to analyze the RNA secondary structure of mutant-type 12S rRNA.RESULTS: Compared with Mitomap database, some new variations were found, among which np652 G insertion and np716 T-G transversion were found only in cancerous tissues.There was a statistic difference in the frequency of 12S rRNA variation between intestinal type (12/17, 70.59%) and diffusive type (5/17, 29.41%) of gastric carcinoma (P<0.05).DHPLC analysis showed that 12S rRNA np652 G insertion and np716 T-G transversion were heteroplasmic mutations.The frequency of 12S rRNA variation in cancerous cells was higher than that in dysplasia cells (P<0.01). 12S rRNA np652 G insertion showed obviously negative effects on the stability of 12S rRNA secondary structure, while others such as T-G transversion did not.CONCLUSION: The mutations of mitochondrial 12S rRNA may be associated with the occurrence of intestinal-type gastric carcinoma. Most variations exist both in gastric carcinomas and in normal tissues, and they might not be the characteristics of tumors. However, np652 G insertion and np716 T-G transversion may possess some molecular significance in gastric carcinogenesis. During the process from normality to dysplasia, then to carcinoma, 12S rRNA tends to convert from homoplasmy (wild type) to heteroplasmy,then to homoplasmy (mutant type, np717 T-G).展开更多
AIM: To assess the possibility of non-invasive screening of atrophic chronic gastritis for preventing further development of gastric cancer.METHODS: One hundred and seventy-eight consecutive Helicobacter pylori ( H py...AIM: To assess the possibility of non-invasive screening of atrophic chronic gastritis for preventing further development of gastric cancer.METHODS: One hundred and seventy-eight consecutive Helicobacter pylori ( H pylori)-positive dyspeptic patients after detection of serum levels of pepsinogen-1 (PG-1) and gastrin-17 (G-17) by enzyme immunoassay were proposed for endoscopy and histology. The serologic and morphologic results were compared with estimating the sensitivity, specificity and prognostic values of the tests.RESULTS: There was statistically significant reverse dependence between the grade of stomach mucosal antral or corpus atrophy and the proper decreasing of serum G17 or PG1 levels. The serologic method was quite sensitive in the diagnosis of non-atrophic and severe antral and corpus gastritis. Also, it was characterized by the high positive and negative prognostic values.CONCLUSION: Detection of serum G-17 and PG1 levels can be offered as the screening tool for atrophic gastritis. The positive serologic results require further chromoendoscopy with mucosal biopsy, for revealing probable progressing of atrophic process with development of intestinal metaplasia, dysplasia or gastric cancer.展开更多
Objective: To explore the relationship between expressions of apoptosis-related protein Bax, Survivin and p53 and the molecular mechanisms of carcinogenesis and progression of gastric carcinoma. Methods: Tissue micr...Objective: To explore the relationship between expressions of apoptosis-related protein Bax, Survivin and p53 and the molecular mechanisms of carcinogenesis and progression of gastric carcinoma. Methods: Tissue microarray and immunohistochemistry were used in this study. Results: The positive rate of Bax protein in gastric cancer (17.7%, 17/96) was significantly lower than those in adjacent normal mucosa (51%), intestinal metaplasia (69.2%) and dysplasia (75%), P 〈 0.01. The positive rate of Survivin expression in gastric cancer (80.6%, 89/98) was significantly higher than that in adjacent normal mucosa (3.9%), P 〈 0.01. The positive rates of Survivin expression in tumors with different organ metastases (in lymph node metastasis 86.2%, liver 100% and ovarian 100%) were statistically higher than in tumors without metastasis (64.3%), P 〈 0.05. Bax expression was correlated with Survivin but not with rap53 that was closely related to Survivin expression (P 〈 0.05) in gastric cancer. Conclusion: The abnormal expressions of Bax, Survivin and rap53 were correlated with the tumorigenesis and progression of gastric carcinoma. P53 and Survivin genes may share the similar mechanism in regulating cell apoptosis, and because of the mutation, p53 gene may lower its down-regulation to Survivin expression.展开更多
Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are ...Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.展开更多
AIM: To validate gastric anti-ulcer properties of Rocket "Eruca sativa" on experimentally-induced gastric secretion and ulceration in albino rats. METHODS: Gastric acid secretion studies were undertaken using pylo...AIM: To validate gastric anti-ulcer properties of Rocket "Eruca sativa" on experimentally-induced gastric secretion and ulceration in albino rats. METHODS: Gastric acid secretion studies were undertaken using pylorus-ligated rats. Gastric lesions in the rats were induced by noxious chemicals including ethanol, strong alkalis, indomethacin and hypothermic restraint stress. The levels of gastric wall mucus (GWM), nonprotein sulfhydryls (NP-SH) and malondialdehyde (MDA) were also measured in the glandular stomach of rats following ethanol administration. The gastric tissue was also examined histologically. The extract was used in two doses (250 and 500 mg/kg body weight) in all experiments. RESULTS: In pylorus-ligated Shay rats, the ethanolic extract of Rocket "Eruca sativa L." (EER) significantly and dose-dependently reduced the basal gastric acid secretion, titratable acidity and ruminal ulceration. Rocket extract significantly attenuated gastric ulceration induced by necrotizing agents (80% ethanol, 0.2 mol/L NaOH, 25% NaCl), indomethacin and hypothermic restraint stress. The anti-ulcer effect was further confirmed histologically. On the other hand, the extract significantly replenished GWM and NP-SH levels, as well as the MDA level significantly reduced by extract pretreatment. CONCLUSION: Rocket extract possesses antisecretory, cytoprotective, and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect is possibly through prostaglandinmediated activity and/or through its anti-secretory and antioxidant properties.展开更多
AIM: To discuss the possible effect of PTEN gene mutations on occurrence and development of gastric cancer. METHODS: Fifty-three gastric cancer specimens were selected to probe PTEN gene mutations in genome of gastric...AIM: To discuss the possible effect of PTEN gene mutations on occurrence and development of gastric cancer. METHODS: Fifty-three gastric cancer specimens were selected to probe PTEN gene mutations in genome of gastric cancer and paracancerous tissues using PCR-SSCP-DNA sequencing method based on microdissection and to observe the protein expression by immunohistochemistry technique. RESULTS: PCR-SSCP-DNA sequencing indicated that 4 kinds of mutation sites were found in 5 of 53 gastric cancer specimens. One kind of mutation was found in exons. AA-TCC mutation was located at 40bp upstream of 3’ lateral exon 7 (115946 AA-TCC). Such mutations led to terminator formation in the 297th codon of the PTEN gene. The other 3 kinds of mutation were found in introns,including a G-C point mutation at 91 bp upstream of 5’ lateral exon 5(90896 G-C),a T-G point mutation at 24 bp upstream of 5’ lateral exon 5 (90963 T-G),and a single base A mutation at 7 bp upstream of 5’ lateral exon 5 (90980 A del). The PTEN protein expression in gastric cancer and paracancerous tissues detected using immunohistochemistry technique indicated that the total positive rate of PTEN protein expression was 66% in gastric cancer tissue,which was significantly lower than that (100%) in paracancerous tissues (P < 0.005). CONCLUSION: PTEN gene mutation and expression may play an important role in the occurrence and development of gastric cancer.展开更多
AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal m...AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed. Differences in histology of the primary and metastatic gastric cancer were assessed. MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer. RESULTS: Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177) and primary gastric cancer in 75.7% (134/177) of the patients. The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%). MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer, while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer. CONCLUSION: Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer. This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.展开更多
Objective:To find out the potential mechanisms of Si-Jun-Zi(SJZ)decoction in the treatment of gastric precancerous lesions(GPL).Methods:A network pharmacology approach was used to analyze the active compounds,drug tar...Objective:To find out the potential mechanisms of Si-Jun-Zi(SJZ)decoction in the treatment of gastric precancerous lesions(GPL).Methods:A network pharmacology approach was used to analyze the active compounds,drug targets and interacting pathways of SJZ decoction in treating GPL.The compounds and predicted targets of SJZ decoction were screened from TCMSP,and the disease targets were obtained from GeneCards.The therapeutic mechanisms of action of the SJZ decoction were analyzed by gene ontology(GO)enrichment,Kyoto encyclopedia of genes and genomes pathway enrichment analyses.Results:The results show that 111 compounds and 90 targets were obtained in this work.These targets were further mapped to 654 GO biological process terms and 21 remarkably pathways.Active compounds,targets,and pathways were used to construct a compound-target network,a target-pathways network,and an integrated GPL pathway.These results indicated that SJZ decoction may treat the dysfunctions of GPL mainly from intervening in the mucosal inflammation,cell apoptosis process,and cell proliferation.Conclusions:This work provided a novel approach to understand the pathogenesis of GPL and revealed the therapeutic mechanisms of SJZ decoction,which facilitate the modernization of herbal medicine for complex diseases in the future.展开更多
基金Supported by National Natural Science Foundation of China,No.30371607
文摘AIM:To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and signifi cance of their expression in gastric carcinoma and precancerous lesions.METHODS: The PV9000 immunohistochemical method was used to detect the expression of YAP and survivin in 98 cases of normal gastric mucosa, 58 intestinal metaplasia (IM), 32 dysplasia and 98 gastric carcinoma.RESULTS: The positive rates of YAP in dysplasia (37.5%) and gastric carcinoma (48.0%) were significantly higher than that in normal gastric mucosa (13.3%), P<0.01. The positive rates of survivin in IM (53.4%), dysplasia (59.4%) and gastric carcinoma (65.3%) were significantly higher than in normal gastric mucosa (11.2%), P<0.01. Survivin expression gradually increased from 41.7% in well differentiated adenocarcinoma through 58.3% in moderately differentiated adenocarcinoma to 75.6% in poorly differentiated adenocarcinoma, with significant Rank correlation, rk=0.279, P<0.01. The positive rate of survivin in gastric carcinoma of diffused type (74.6%) was significantly higher than that in intestinal type (51.3%), P<0.05. In gastric carcinoma with lymph node metastasis (76.9%), the positive rate of survivin was signifi cantly higher than that in the group without lymph node metastasis (41.2%), P<0.01. In 98 cases of gastric carcinoma, the expression of YAP and of survivin were positively correlated, rk=0.246, P<0.01.CONCLUSION: YAP may play an important role as a carcinogenic factor and may induce survivin expression. Detecting both markers together may help in early diagnosis of gastric carcinoma.
文摘In the model rat with precancerous lesion of stomach induced by the combined method of insertion of a spring into the pylorus and high salt hot paste,effects of San Qi (三七 Radix Notoginseng) on gastric secretion and protective factors of stomach were investigated.The results indicated that gastric secretion,gastric mucosal blood flow (GMBF) and aminohexose content lowered significantly,and malondialdehyde (MDA) increased significantly (P<0.01) in the model group as compared with the normal group;after treatment with San Qi Powder for 12 weeks,both gastric secresion and GMBF increased,and MDA content decreased as compared with the negative control group (P<0.01),with no significant increase of aminohexose content.It is suggested that San Qi (三七 Radix Notoginseng) may improve gastric secretion,and that increase of GMBF and antagonism against the lesion of oxygen free radicals are possibly one of its mechanisms.
基金Supported by The Natural Science Foundation of Anhui Province,No. 090413118
文摘AIM: To investigate the expression and significance of caudal-related homeobox transcription factor (Cdx2) in gastric carcinoma (GC) and precancerous lesions. METHODS: The expression of Cdx2 in GC, precancer- ous lesions and normal gastric mucosa were detected using immunohistochemical method. Hematoxylin and eosin staining, alcian blue/periodic acid-schiff and high iron diamine/alcian blue staining were used to classify intestinal metaplasia (IM) and GC. RESULTS: Cdx2 was not detected in normal gas- tric mucosa. Cdx2 expression was detected in 87.1% (101/116) of IM, 50% (36/72) of dysplasia and 48.2% (41/85) of GC. The Cdx2-expressing cells in IM were more prevalent than in dysplasia and carcinoma (P 〈 0.05). There was no relationship between Cdx2 ex- pression and the classification of IM or the degree of dysplasia. Expression of Cdx2 was significantly higher in intestinal-type carcinoma than in diffuse and mixed- type carcinoma (P 〈 0.05). Positive expression of Cdx2was mainly found in moderately to well differentiated GC. There was a negative association between nuclear Cdx2 expression and lymph node metastasis and tumor, nodes, metastasis stage of GC (P 〈 0.05). The patients with Cdx2-positive expression showed a higher survival rate than those with Cdx2-negative expression (P = 0.038). Multivariate analysis revealed that the expres- sion of Cdx2 and lymph node metastasis were indepen- dent prognostic indicators of GC (P 〈 0.05).
基金Supported by the Science and Technology Committee Foundation of Jiangsu Province, No. BS98028
文摘AIM: To investigate the microsatellite instability (MSI) in cancer and pre-cancerous lesions of the stomach and its mechanisms underlying the development of gastric cancer.METHODS: Thirty-six gastric cancer samples were obtained from patients undergoing surgery. Forty-one gastric mucosa samples with dysplasia and 51 with intestinal metaplasia (IM) were obtained from patients with chronic gastritis undergoing gastro-endoscopy. Genomic DNA was extracted from the samples. Silver staining single strand conformation polymorphis-polymerize chain reaction (SSCP-PCR) was used to screen MSI markers at 5 loci (Bat-25, Bat-26, D5S346, D17S250, and D2S123)in fresh tissues and formalin-fixed, paraffin-embedded samples and their corresponding normal gastric mucosa.RESULTS: The abnormal shifting of the single-strand DNA (MSI) was identified in 21 out of 36 (58.3%) gastric cancers.Seven cases showed high-level MSI (two or more loci altered) and 14 showed low-level MSI (one locus altered).Gastric cancer with MSI had a tendency to be located in the distal stomach. MSI was also detected in 11 out of 41(26.8%) dysplasia samples and in 9 of 51 (17.6%) IM samples respectively. Three cases of dysplasia and one case of IM showed high-level MSI. Eight cases of dysplasia and 8 cases of IM displayed low-level MSI. MIS in IM was found only in moderate or severe-grade IM. No association was detected between MSI and dysplasia grade.CONCLUSION: Accumulation of MSI in dysplasia and intestinal metaplasia of gastric mucosa may be an early molecular event during gastric carcinogenesis and may contribute to the acquisition of transformed cell phenotype and the development of gastric cancer.
文摘Objective: To study the expressions of Bcl-2 and Bax proteins and explore the relationships between them and apoptosis in gastric carcinoma and precancerous lesions. Methods: TUNEL method was used to detect apoptosis and im- munohistochemical staining method was used to detect the expressions of Bcl-2 and Bax proteins in 70 cases of chronic gastritis, 49 cases of intestinal metaplasia, 64 cases of dysplasia and 81 cases of gastric carcinoma. Results: The positive incidences of Bcl-2 and Bax were the highest in severe dysplasia. In intestinal metaplasia and dysplasia, positive incidences of Bcl-2 and Bax were higher than those in chronic gastritis and gastric carcinoma. During the process of evolvement from chronic gastritis to intestinal metaplasia then to dysplasia, apoptosis indexes gradually rise up to mid-high dysplasia, which reached the highest point, then it began to fall down, when it reached the lowest point in gastric carcinoma. There were nega- tive correlations between the expressions of Bcl-2, Bax proteins and apoptosis. Conclusion: The expression of Bcl-2 may be an early behavior in the gastric carcinogenesis. Bax had antagonistic effect to Bcl-2. Detections of Bcl-2 and Bax may be beneficial to the early diagnosis of gastric tumor and precancerous lesions.
文摘Fundic gland polyps are now commonly recognized during endoscopy. These polyps are benign, often multiple and usually detected in the gastric body and fundus. In the past, these polyps were sometimes associated with familial adenomatous polyposis. In recent years, it has become evident that increasing numbers of these polyps are being detected during endoscopic studies, particularly in patients treated with proton pump inhibitors for prolonged periods. In some, dysplastic changes in these polyps have also been reported. Recent studies have suggested that there may be no increase in risk of colon cancer with long-term proton pump inhibitor therapy. While temporarily reassuring, ongoing vigilance, particularly in those genetically predisposed to colon cancer, is still warranted.
文摘AIM:To investigate the mutation in D-loop region of mitochondrial DNA in gastric cancer and its influence on the changes of reactive oxygen species (ROS) and cell cycle. METHODS: The D-loop region was amplified by PCR and sequenced.Reactive oxygen species and cell cycle were detected by flow cytometry in 20 specimens from gastric cancer and adjacent normal tissues.According to the sequence results,gastric cancer tissue was divided into mutation group and control group.Reactive oxygen species,apoptosis and proliferation in the two groups were compared. RESULTS:Among the 20 gastric cancer specimens, 18 mutations were identified in 7 patients,the mutation rate being 35%.There were four microsatellite instabilities in the mutations. No mutation was found in the adjacent tissues. Reactive oxygen species,apoptosis,and proliferation in the mutation group were all significantly higher than those in control group. CONCLUSION: Mutation in D-loop region plays a role in the genesis and development of gastric cancer.
基金Supported by the National Natural Science Foundation of China,No.30371607
文摘AIM: To detect the variations of mitochondrial 12S rRNA in patients with gastric carcinoma, and to study their significance and the relationship between these variations and the genesis of gastric carcinoma.METHODS: PCR amplified mitochondrial 12S rRNA of 44 samples including 22 from gastric carcinoma tissues and 22 from adjacent normal tissues, was detected by direct DNA sequencing. Then laser capture microdissection technique (LCM) was used to separate the cancerous cells and dysplasia cells with specific mutations. Denaturing high performance liquid chromatography (DHPLC) plus allele-specific PCR (ASPCR), nest-PCR and polyacrylamide gel electrophoresis (PAGE)were used to further evaluate this mutant property and quantitative difference of mutant type between cancerous and dysplasia cells. Finally, RNAdraw biosoft was used to analyze the RNA secondary structure of mutant-type 12S rRNA.RESULTS: Compared with Mitomap database, some new variations were found, among which np652 G insertion and np716 T-G transversion were found only in cancerous tissues.There was a statistic difference in the frequency of 12S rRNA variation between intestinal type (12/17, 70.59%) and diffusive type (5/17, 29.41%) of gastric carcinoma (P<0.05).DHPLC analysis showed that 12S rRNA np652 G insertion and np716 T-G transversion were heteroplasmic mutations.The frequency of 12S rRNA variation in cancerous cells was higher than that in dysplasia cells (P<0.01). 12S rRNA np652 G insertion showed obviously negative effects on the stability of 12S rRNA secondary structure, while others such as T-G transversion did not.CONCLUSION: The mutations of mitochondrial 12S rRNA may be associated with the occurrence of intestinal-type gastric carcinoma. Most variations exist both in gastric carcinomas and in normal tissues, and they might not be the characteristics of tumors. However, np652 G insertion and np716 T-G transversion may possess some molecular significance in gastric carcinogenesis. During the process from normality to dysplasia, then to carcinoma, 12S rRNA tends to convert from homoplasmy (wild type) to heteroplasmy,then to homoplasmy (mutant type, np717 T-G).
文摘AIM: To assess the possibility of non-invasive screening of atrophic chronic gastritis for preventing further development of gastric cancer.METHODS: One hundred and seventy-eight consecutive Helicobacter pylori ( H pylori)-positive dyspeptic patients after detection of serum levels of pepsinogen-1 (PG-1) and gastrin-17 (G-17) by enzyme immunoassay were proposed for endoscopy and histology. The serologic and morphologic results were compared with estimating the sensitivity, specificity and prognostic values of the tests.RESULTS: There was statistically significant reverse dependence between the grade of stomach mucosal antral or corpus atrophy and the proper decreasing of serum G17 or PG1 levels. The serologic method was quite sensitive in the diagnosis of non-atrophic and severe antral and corpus gastritis. Also, it was characterized by the high positive and negative prognostic values.CONCLUSION: Detection of serum G-17 and PG1 levels can be offered as the screening tool for atrophic gastritis. The positive serologic results require further chromoendoscopy with mucosal biopsy, for revealing probable progressing of atrophic process with development of intestinal metaplasia, dysplasia or gastric cancer.
基金National Natural Sciences Foundation of China (No. 30600286)Specialized Research Fund for the Doctoral Program of Higher Education (No. 20040159021).
文摘Objective: To explore the relationship between expressions of apoptosis-related protein Bax, Survivin and p53 and the molecular mechanisms of carcinogenesis and progression of gastric carcinoma. Methods: Tissue microarray and immunohistochemistry were used in this study. Results: The positive rate of Bax protein in gastric cancer (17.7%, 17/96) was significantly lower than those in adjacent normal mucosa (51%), intestinal metaplasia (69.2%) and dysplasia (75%), P 〈 0.01. The positive rate of Survivin expression in gastric cancer (80.6%, 89/98) was significantly higher than that in adjacent normal mucosa (3.9%), P 〈 0.01. The positive rates of Survivin expression in tumors with different organ metastases (in lymph node metastasis 86.2%, liver 100% and ovarian 100%) were statistically higher than in tumors without metastasis (64.3%), P 〈 0.05. Bax expression was correlated with Survivin but not with rap53 that was closely related to Survivin expression (P 〈 0.05) in gastric cancer. Conclusion: The abnormal expressions of Bax, Survivin and rap53 were correlated with the tumorigenesis and progression of gastric carcinoma. P53 and Survivin genes may share the similar mechanism in regulating cell apoptosis, and because of the mutation, p53 gene may lower its down-regulation to Survivin expression.
文摘Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.
文摘AIM: To validate gastric anti-ulcer properties of Rocket "Eruca sativa" on experimentally-induced gastric secretion and ulceration in albino rats. METHODS: Gastric acid secretion studies were undertaken using pylorus-ligated rats. Gastric lesions in the rats were induced by noxious chemicals including ethanol, strong alkalis, indomethacin and hypothermic restraint stress. The levels of gastric wall mucus (GWM), nonprotein sulfhydryls (NP-SH) and malondialdehyde (MDA) were also measured in the glandular stomach of rats following ethanol administration. The gastric tissue was also examined histologically. The extract was used in two doses (250 and 500 mg/kg body weight) in all experiments. RESULTS: In pylorus-ligated Shay rats, the ethanolic extract of Rocket "Eruca sativa L." (EER) significantly and dose-dependently reduced the basal gastric acid secretion, titratable acidity and ruminal ulceration. Rocket extract significantly attenuated gastric ulceration induced by necrotizing agents (80% ethanol, 0.2 mol/L NaOH, 25% NaCl), indomethacin and hypothermic restraint stress. The anti-ulcer effect was further confirmed histologically. On the other hand, the extract significantly replenished GWM and NP-SH levels, as well as the MDA level significantly reduced by extract pretreatment. CONCLUSION: Rocket extract possesses antisecretory, cytoprotective, and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect is possibly through prostaglandinmediated activity and/or through its anti-secretory and antioxidant properties.
基金Zabei Medical Science and Technology Foundation of Shanghai,No.grant 200701
文摘AIM: To discuss the possible effect of PTEN gene mutations on occurrence and development of gastric cancer. METHODS: Fifty-three gastric cancer specimens were selected to probe PTEN gene mutations in genome of gastric cancer and paracancerous tissues using PCR-SSCP-DNA sequencing method based on microdissection and to observe the protein expression by immunohistochemistry technique. RESULTS: PCR-SSCP-DNA sequencing indicated that 4 kinds of mutation sites were found in 5 of 53 gastric cancer specimens. One kind of mutation was found in exons. AA-TCC mutation was located at 40bp upstream of 3’ lateral exon 7 (115946 AA-TCC). Such mutations led to terminator formation in the 297th codon of the PTEN gene. The other 3 kinds of mutation were found in introns,including a G-C point mutation at 91 bp upstream of 5’ lateral exon 5(90896 G-C),a T-G point mutation at 24 bp upstream of 5’ lateral exon 5 (90963 T-G),and a single base A mutation at 7 bp upstream of 5’ lateral exon 5 (90980 A del). The PTEN protein expression in gastric cancer and paracancerous tissues detected using immunohistochemistry technique indicated that the total positive rate of PTEN protein expression was 66% in gastric cancer tissue,which was significantly lower than that (100%) in paracancerous tissues (P < 0.005). CONCLUSION: PTEN gene mutation and expression may play an important role in the occurrence and development of gastric cancer.
文摘AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed. Differences in histology of the primary and metastatic gastric cancer were assessed. MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer. RESULTS: Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177) and primary gastric cancer in 75.7% (134/177) of the patients. The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%). MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer, while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer. CONCLUSION: Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer. This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.
文摘Objective:To find out the potential mechanisms of Si-Jun-Zi(SJZ)decoction in the treatment of gastric precancerous lesions(GPL).Methods:A network pharmacology approach was used to analyze the active compounds,drug targets and interacting pathways of SJZ decoction in treating GPL.The compounds and predicted targets of SJZ decoction were screened from TCMSP,and the disease targets were obtained from GeneCards.The therapeutic mechanisms of action of the SJZ decoction were analyzed by gene ontology(GO)enrichment,Kyoto encyclopedia of genes and genomes pathway enrichment analyses.Results:The results show that 111 compounds and 90 targets were obtained in this work.These targets were further mapped to 654 GO biological process terms and 21 remarkably pathways.Active compounds,targets,and pathways were used to construct a compound-target network,a target-pathways network,and an integrated GPL pathway.These results indicated that SJZ decoction may treat the dysfunctions of GPL mainly from intervening in the mucosal inflammation,cell apoptosis process,and cell proliferation.Conclusions:This work provided a novel approach to understand the pathogenesis of GPL and revealed the therapeutic mechanisms of SJZ decoction,which facilitate the modernization of herbal medicine for complex diseases in the future.