胃内细菌过度生长与残胃癌变

胃液pH是胃内含菌量的可靠指标。溃疡病行胃切除术后其残胃内细菌过度生长,尤其是厌氧菌和大便菌群,可催化亚硝基反应和分解这流入胃的胆酸,使胃内N-亚硝基化合物和次级游离胆酸等致癌物的浓度增高,促成残胃癌变。

加味柴芍六君方对胃癌前病变胃黏膜组织中的抑癌及促凋亡相关基因表达的影响

目的:观察加味柴芍六君方对胃癌前病变胃粘膜组织中的抑癌及促凋亡相关基因Syk、Survivin、突变型p53等表达的影响。方法:应用免疫组化S-P检测方法对120例胃癌前病变大鼠模型分组进行胃黏膜组织中的抑癌及促凋亡相关基因检测。结果:中药组在提升Syk的表达、下调Survivin、突变型p53表达显著(P<0.01);胃复春组对Syk表达相关性不显著(P>0.05),而对Survivin、突变型p53表达加大(P<0.05)。结论:加味柴芍六君方能提升Syk、下调Survivin、突变型p53表达,对防治胃癌前变有明显效果。

外周血检测CD44v6在胃癌患者中的意义

目的:探讨测定胃癌患者外周血淋巴细胞(PBL)CD44变异体6(CD44v6)含量的意义。方法:应用流式细胞术(FCM)对79例胃癌患者手术前外周血淋巴细胞CD44v6含量进行检测。结果:胃癌患者术前PBLCD44v6在淋巴结阳性患者中含量(13.83±4.96)%,明显高于淋巴结阴性者的(10.20±2.90)%(P<0.01);Ⅲ+Ⅳ期胃癌患者PBLCD44v6含量(14.50±4.87)%,明显高于Ⅰ+Ⅱ期者的(10.07±2.90)%(P<0.01);而病理胃低分化腺癌患者PBLCD44v6含量(13.15±4.93)%,与高、中分化腺癌者的(11.21±3.85)%比较无显著差异(P>0.05);浸润深度达浆膜层胃癌患者PBLCD44v6含量(12.87±5.00)%,与未达浆膜层者(11.04±3.14)%比较无显著差异(P>0.05)。结论:术前外周血PBLCD44v6的含量测定可作为判断胃癌疾病进展和预测胃癌转移潜能的辅助生物学指标。

Significance and relationship between Yes-associated protein and survivin expression in gastric carcinoma and precancerous lesions

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.

Effects of San Qi on Gastric Secretion and Protective Factors of Gastric Mucosa in the Rat with Precancerous Lesion of Stomach

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.

Expression and significance of homeodomain protein Cdx2 in gastric carcinoma and precancerous lesions

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）.

Microsatellite instability in gastric cancer and pre-cancerous lesions

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.

The expressions of Bcl-2 and Bax in gastric carcinoma and precancerous lesions

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.

Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis

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.

Mutation in D-loop region of mitochondrial DNA in gastric cancer and its significance

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.

Mutations of mitochondrial 12S rRNA in gastric carcinoma and their significance

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).

Possibility of non-invasive diagnosis of gastric mucosal precancerous changes

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.

CTA显示胃周动脉及其变异在胃癌术前评价中的应用价值

目的探讨CT血管造影(CT angiography,CTA)显示胃周动脉及其变异在胃癌术前评估中的应用价值。资料与方法对连续67例经胃镜活检证实或高度怀疑胃癌的患者,采用多层螺旋CT在患者服用产气粉和水(500～1000 ml)充分扩张胃后经静脉用压力注射器以3～4 ml/s的流率团注碘对比剂100 ml(碘必乐或碘普罗胺370),采用Bolus-Tracking追踪触发技术行三期增强扫描。在CT工作站采用容积再现(VR)和最大密度投影(MIP)重组CTA以显示胃周血管影像,重点分析变异动脉对手术方案的抉择与实施的影响,并与手术发现比较。结果 67例胃左动脉(LGA)均被显示,胃右动脉(RGA)的显示率为52.24%(35/67)。CTA显示12例胃周动脉变异。其中61例实施手术治疗,CTA获得的血管解剖信息与手术所见取得较好的一致性。结论 CTA能显示胃周主要动脉及其解剖变异,特别是与胃癌原发灶解剖密切相关并对手术实施有影响的血管,附加的CTA可以提高胃癌CT检查的成本效益比。

Significance and expression of Bax, Survivin and p53 in gastric carcinoma and precancerous lesions using tissue microarray

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.

Genomic and genetic alterations influence the progression of gastric cancer

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.

Rocket “Eruca sativa”:A salad herb with potential gastric anti-ulcer activity

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.

PCR-SSCP-DNA sequencing method in detecting PTEN gene mutation and its signifi cance in human gastric cancer

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.

Changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer

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.

A network pharmacology approach to investigate the mechanisms of Si-Jun-Zi decoction in the treatment of gastric precancerous lesions

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.