Novel nomogram model for predicting 6-week mortality in liver cirrhosis patients with acute upper gastrointestinal bleeding.

OBJECTIVE: To develop and validate a nomogram for predicting 6-week mortality in patients with liver cirrhosis and acute upper gastrointestinal bleeding (UGIB) and to compare it with other commonly used scoring systems. METHODS: This retrospective study included cirrhotic patients with acute UGIB hospitalized between January 2013 and December 2020. Random sampling was used to divide patients into the training (n = 676) and validation cohorts (n = 291) at a 7:3 ratio. Multivariate logistic stepwise regression was used to establish a model for predicting 6-week mortality. Multiple indicators were used to validate the nomogram, including the area under the receiver operating characteristic curve (AUROC), calibration curve, and decision curve analysis (DCA). RESULTS: In the training cohort, total bilirubin (TBIL) (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.22-2.50), hemoglobin (Hb) (OR 0.97, 95% CI 0.95-0.99), C-reactive protein (OR 2.79, 95% CI 1.30-6.07), prothrombin time (OR 1.17, 95% CI 1.05-1.30), and hepatic encephalopathy (stage I-II: OR 4.15, 95% CI 1.73-9.61; stage III-IV: OR 19.6, 95% CI 5.33-76.8) were identified as independent factors of 6-week mortality. The AUROC of the UGIB-LC score was 0.873 (95% CI 0.820-0.927), which was higher than that of the Child-Pugh score (0.781), model for end-stage liver disease score (0.766), and neutrophil-to-lymphocyte ratio (0.716). CONCLUSION: The UGIB-LC score is useful for predicting 6-week mortality in patients with liver cirrhosis and acute UGIB, which is superior to the other three scoring systems.

Endoscopic treatment for pancreatic diseases: Needle-knife-guided cannulation via the minor papilla.

AIM: To determine the efficacy and safety of meticulous cannulation by needle-knife. METHODS: Three needle-knife procedures were used to facilitate cannulation in cases when standard cannulation techniques failed. A total of 104 cannulations via the minor papilla attempted in 74 patients at our center between January 2008 and June 2014 were retrospectively reviewed. RESULTS: Standard methods were successful in 79 cannulations. Of the 25 cannulations that could not be performed by standard methods, 19 were performed by needle-knife, while 17 (89.5%) were successful. Needle-knife use improved the success rate of cannulation [76.0%, 79/104 vs 92.3%, (79 + 17)/104; P = 0.001]. When the 6 cases not appropriate for needle-knife cannulation were excluded, the success rate was improved further (80.6%, 79/98 vs 98.0%, 96/98; P = 0.000). There were no significant differences in the rates of post-endoscopic retrograde cholangiopancreatography adverse events between the group using standard methods alone and the group using needle-knife after failure of standard methods (4.7% vs 10.5%, P = 0.301). CONCLUSION: The needle-knife procedure may be an alternative method for improving the success rate of cannulation via the minor papilla, particularly when standard cannulation has failed.

Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma.

X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1), a XIAP-binding protein, is a tumor suppressor gene. XAF1 was silent or expressed lowly in most human malignant tumors. However, the role of XAF1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the effect of XAF1 on tumor growth and angiogenesis in hepatocellular cancer cells. Our results showed that XAF1 expression was lower in HCC cell lines SMMC-7721, Hep G2 and BEL-7404 and liver cancer tissues than that in paired non-cancer liver tissues. Adenovirus-mediated XAF1 expression (Ad5/F35-XAF1) significantly inhibited cell proliferation and induced apoptosis in HCC cells in dose- and time- dependent manners. Infection of Ad5/F35-XAF1 induced cleavage of caspase -3, -8, -9 and PARP in HCC cells. Furthermore, Ad5/F35-XAF1 treatment significantly suppressed tumor growth in a xenograft model of liver cancer cells. Western Blot and immunohistochemistry staining showed that Ad5/F35-XAF1 treatment suppressed expression of vascular endothelial growth factor (VEGF), which is associated with tumor angiogenesis, in cancer cells and xenograft tumor tissues. Moreover, Ad5/F35-XAF1 treatment prolonged the survival of tumor-bearing mice. Our results demonstrate that XAF1 inhibits tumor growth by inducing apoptosis and inhibiting tumor angiogenesis. XAF1 may be a promising target for liver cancer treatment.

Rapid high-performance liquid chromatography method for determination of tryptophan in gastric juice.

OBJECTIVE: To develop a rapid, high-performance liquid chromatography (HPLC) method for the determination of tryptophan in gastric juice to help the differentiation between gastric cancer and benign gastric disease. METHODS: HPLC was performed on a restricted access material Shiseido Capcell Pak MF SCX SG80 column. Phosphate buffered solution (90mmol/L, pH 3.5)-acetonitrile (ACN; 80/20, V/V) was chosen as the mobile phase. Separation was done at room temperature using a constant flow rate of 1.0mL/min. Fluorescence emission signal intensity at 330nm excited by 288nm ultra violet light was detected and measured. RESULTS: Thirty-eight gastric juice samples from patients with gastric cancer and 48 gastric juice samples of patients with benign gastric disease were tested. A linear relationship in the range of 0.20-100mg/L was obtained between the concentration of tryptophan and its fluorescence emission signal intensity at 330nm. The limit of detection was 0.05mg/L. The recovery rate was 77.4-90.6%. CONCLUSIONS: An HPLC method based on strong cation-exchange restricted access columns for determination of concentration of tryptophan in gastric juice was developed. The method has excellent precision and stability. It is compatible with the analysis of gastric juice and has the potential to be used for gastric cancer screening.

The XAF1 tumor suppressor induces autophagic cell death via upregulation of Beclin-1 and inhibition of Akt pathway.

Autophagy is designated as type II programmed cell death and may confer a tumor-suppressive function. Our previous studies have shown that XIAP-associated factor 1 (XAF1) induced apoptosis and inhibited tumor growth in gastric cancer cells. In this study, we investigated the effect of XAF1 on the induction of autophagy in gastric cancer cells. We found that adenovirus vector-mediated XAF1 (adeno-XAF1) expression markedly induced autophagy, upregulated the level of Beclin-1 and inhibited phospho-Akt and phospho-p70S6K in gastric cancer cells. The downregulation of Beclin 1 or 3-methyladenine treatment suppressed adeno-XAF1-induced autophagy, but significantly enhanced adeno-XAF1-induced apoptosis. A pan-caspase inhibitor prevented adeno-XAF1-induced apoptosis, but significantly increased adeno-XAF1-induced autophagy. Furthermore, adeno-XAF1 induced autophagy in xenograft tumor and inhibited tumor growth. Our results document that adeno-XAF1 induces autophagy through upregulation of Beclin 1 expression and inhibition of Akt/p70S6K pathway, and reveal a new mechanism of XAF1 tumor suppression.

[Comparative study of laparoscopic-assisted radical gastrectomy versus open radical gastrectomy for early gastric cancer].

OBJECTIVE: To evaluate laparoscopic radical gastrectomy for early gastric cancer. METHODS: A total of 204 patients with early gastric cancer undergoing laparoscopic-assisted radical gastrectomy or open radical gastrectomy between October 2004 and December 2009 were retrospectively reviewed and analyzed. Patients were divided into laparoscopic group(LAP, n=78) and open group (OPEN, n=126). Operative time, blood loss, time to passage of flatus, postoperative hospital stay, complications and pathologic findings were compared between the two groups. RESULTS: Compared to the OPEN group, operative time in the LAP group was significantly shorter[(202.9±45.6) min vs.(219.8±45.2) min, P<0.05], blood loss was less[(144.5±146.5) ml vs. (245.0±146.4) ml, P<0.05], time to passage of flatus was shorter[(3.1±1.1) d vs.(4.5±1.6) d, P<0.05], postoperative hospital stay was shorter[(10.8±1.2) d vs. (12.4±3.8) d, P<0.05]. However, the two groups were comparable with regard to postoperative complication rate(10.3% vs. 12.7%, P>0.05), proximal resection margin[(4.0±1.9) cm vs. (4.2±1.7) cm, P>0.05], distal resection margin [(3.6±1.7) cm vs. (3.5±1.8) cm, P>0.05], number of harvested lymph node(13.1±6.5 vs. 14.5±8.2, P>0.05). The median follow up was 22(2-64) months. There were no tumor recurrences or metastases in the LAP group. In the OPEN group, only 1 patient died from peritoneal metastasis. Total hospital costs between the two groups were similar(P>0.05). CONCLUSION: Laparoscopic radical gastrectomy is a safe, feasible, effective, and less invasive surgery for early gastric cancer.

Endoscopic features predictive of gastric cancer in superficial lesions with biopsy-proven high grade intraepithelial neoplasia.

AIM: To investigate the macroscopic and clinico-pathologic features of gastric cancer in patients with biopsy-suggested high grade intraepithelial neoplasia. METHODS: Patients with biopsy-confirmed gastric high grade intraepithelial neoplasia were reviewed from January 2001 to March 2008. Pathologic sections were re-evaluated by two senior pathologists. Patients with an en-bloc resection of the lesion within two months after the diagnosis of high grade intraepithelial neoplasia were enrolled in the study. Clinical manifestations, endoscopic features, biopsy and surgical pathology of all patients were collected and analyzed. The data acquired were subjected to univariate and multivariate analysis. RESULTS: Seventy-two superficial gastric lesions with a pathologic diagnosis of high grade intraepithelial neoplasia based on biopsy specimens were enrolled. True high grade intraepithelial neoplasia was finally proved in 16 lesions and gastric cancer in the rest 56 lesions, most of which (96.4%) were differentiated carcinomas. The result of univariate analysis indicated that the size and the presence of marked ulcer plaque or scar in a superficial lesion were independently associated with gastric cancer (P<0.05), when high grade intraepithelial neoplasia was diagnosed by biopsy pathology. The results of multivariate analysis revealed the size greater than 1.5 cm [odds ratio (OR) 18.400, P<0.001] and the presence of 5-odd mm ulcer plaque or scar (OR 10.000, P=0.044) were associated with gastric cancer. Accordingly, the sensitivity, specificity and negative predictive value of multivariate analysis for predicting "true high grade intraepithelial neoplasia" was 87.5%, 89.3% and 96.2%, respectively. CONCLUSION: Macroscopic findings are of value in differentiation between high grade intraepithelial neoplasia and superficial gastric cancer. This may simplify patient work-up and save costs for patients and healthcare system.

Stat3 is involved in angiotensin II-induced expression of MMP2 in gastric cancer cells.

The expression of matrix metalloproteinase-2 (MMP2) has been linked with tumor invasion, angiogenesis, and metastasis. It has been reported that angiotensin II (Ang II) can induce MMP2 expression in gastric cancer cells. However, the molecular basis for Ang II regulates MMP2 expression in gastric cancer cells remains unclear. The aim of our study is to explore whether angiotensin II could induce MMP2 expression mediated through the Stat signaling pathway and its potential mechanism. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-binding assays was employed to determine the DNA-STAT binding activity. MMP2 and VEGF expression was analyzed with real-time PCR and Western blots. To examine the role of Stat3 in angiotensin II-induced MMP2 expression, A JAK-specific inhibitor and AG490 were used. Angiotensin II activated STAT-DNA binding activity in dose-dependent manners in gastric cancer cells. AG490 markedly inhibited angiotensin II-induced Stat3 activation and the expression of MMP2 and VEGF in gastric cancer cells. These results indicate that Stat3 may at least in part mediate angiotensin II-induced MMP2 mRNA expression in human gastric cancer cells. The activation of the JAK/Stat3 signaling pathway plays an important role in the progression of gastric cancer and that blockade of JAK/Stat3 signals may provide a novel therapeutic strategy for gastric cancer.

Suppression of gastric cancer growth by baculovirus vector-mediated transfer of normal epithelial cell specific-1 gene.

AIM: To study the inhibitory effect of baculovirus-mediated normal epithelial cell specific-1 (NES1) gene therapy on gastric cancer (GC) in vitro and in vivo. METHODS: We first constructed recombinant baculovirus vectors and then transfected them into gastric cancer cells (SGC-7901). Efficiency of the baculovirus for gene transfer into SGC-7901 cells and cell growth curves were detected by fluorescence microscopy, Western blot and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro, respectively. The therapeutic effect of this gene therapy on GC was confirmed in xenografted nude mice. Tumor growth was determined by tumor volume, and expression of NES1 in tumor was analyzed by immunohistochemistry. RESULTS: Baculovirus vectors were successfully transfected into SGC-7901 cells. SGC-7901 cells transfected with the NES1 gene inhibited cell growth. In the Bac-NES1 treated group, tumor growth was significantly reduced with a high level of NES1 expression CONCLUSION: Baculovirus-mediated NES1 gene can be used in gene therapy for GC.

Successful endoscopic sclerotherapy for bleeding gastric varices with combined cyanoacrylate and aethoxysklerol.

Two patients with liver cirrhosis and portal hypertension related to hepatitis infection were admitted to Shanghai Ruijin Hospital due to recurrent melena and hematemesis. Isolated gastric varices were observed in the gastric fundus during the retroflexion of gastroscope. We carried out endoscopic sclerotherapy successfully for bleeding gastric varices with combined cyanoacrylate and aethoxysklerol, which disappeared dramatically several months after two courses of sclerotherapy for each patient. No complication and clinical signs of gastrointestinal re-bleeding were observed during the 6-mo endoscopic follow-up. CT portal angiography (CTPA) has been widely used in the assessment of variceal treatment and improves the results of endoscopic injection therapy.

Angiotensin II type 1 receptor antagonist suppress angiogenesis and growth of gastric cancer xenografts.

Angiotensin II (Ang II) has been reported to promote tumor progression, tumor growth and angiogenesis in many cancers. We previously observed that angiotensin II type 1 receptors (AT1R) were upregulated in human gastric cancer and may be involved in the progression of gastric cancer. We studied the effects of AT1R antagonist on angiogenesis and growth in gastric cancer xenografts to observe the mechanism action of AT1R in the gastric cancer. The results showed that the growth of gastric cancer cells was significantly suppressed by treatment with AT1R antagonist. In vivo, TCV-116, at doses of both 2 and 5 mg/kg/day, significantly suppressed tumor growth in mice (47.3 and 70.2%). Microvessel density was significantly decreased by TCV-116 (3.4 +/- 0.9 and 2.8 +/- 0.5 per field) compared with the control group (12.9 +/- 1.1 per field), and VEGF expression was significantly suppressed by AT1R antagonist. These results demonstrate that AT1R plays an important role in the progression of gastric cancer. Suppression tumor angiogenesis could be one of the mechanisms by which AT1R antagonist suppresses the growth of gastric cancer. These findings also provide a theoretical basis for the future clinical application of AT1R antagonist against gastric cancer.

Angiotensin II type 1 receptor expression in human gastric cancer and induces MMP2 and MMP9 expression in MKN-28 cells.

Angiotensin II (Ang II), a main effector peptide in the renin-angiotensin system, acts as a growth-promoting and angiogenic factor via angiotensin II receptor1 (AT1R). In this study, we investigated the expression of angiotensin II type1 receptor (AT1R) in gastric cancer and the effects of Ang II on the expression of MMP2 and MMP9 in the human gastric cancer cell line MKN-28 cells. The expression of the Ang II type I receptor was examined by western and immunocytochemistry in gastric cancer cell lines and detected by real-time PCR and immunohistochemistry in normal and gastric cancer tissues. The expression of MMP2 and MMP9 were detected by real-time PCR and western after treatment with Ang II and/or AT1R antagonist. AT1R were expressed in all human gastric cancer lines and the expression of AT1R was significantly higher in cancer tissues than that in normal gastric tissues (P < 0.01). Furthermore, Ang II promoted the expression of MMP2 and MMP9 in MKN-28 cells, and the stimulatory effects of Ang II could be blocked by AT1R antagonist. These results suggest that AT1R is involved in the progression of gastric cancer and may promote the angiogenesis of gastric cancer cell line (MKN-28), and these effects may be associated with the upregulation of MMP2 and MMP9.

Upregulated expression of S100A6 in human gastric cancer.

OBJECTIVE: The expression of S100A6 (calcyclin), a member of the S100 calcium binding protein family, is elevated in a number of malignant tumors, but there have been few reports about its expression in gastric cancer. The aim of this study was to investigate its expression regulations in human gastric cancer and noncancerous mucosa, and the response to chemotherapeutic drugs in the gastric cancer cell line. MATERIALS AND METHODS: In one matched gastric cancer sample pair, the serial analysis of gene expression (SAGE) experiment was conducted to compare the gene expression profiles between cancerous and adjacent tissues. To detect the expression regulations among more cancerous tissues, microarrays were carried out and real-time RT-PCR was conducted to validate the results. At the protein level, Western blot and tissue microarray (TMA) examination were further used to verify S100A6 expression. The regulation detection of S100A6 with flurouracil and doxorubicin at the mRNA and protein level was performed in the SGC7901 cell line. RESULTS: With the SAGE strategy, five times more S100A6 tags were identified in cancer tissues than in normal tissues. With the cDNA microarray, S100A6 was found to be significantly upregulated in 21 of 42 (50%) nonselective gastric cancers. In 10 other paired samples, the upregulation of S100A6 was consolidated with RT-PCR and Western blot analysis as well. A total of 14 endoscopy-sectioned gastric noncancerous lesions and corresponding normal gastric mucosa were also applied to profile the gene expression; both cDNA microarray and RT-PCR demonstrated no significant alterations of S100A6 at the mRNA level. TMA examination showed that 34 of 52 (65.4%) cancer samples were positively stained, while only 17 of 80 (21.3%) noncancerous lesions were positively detected and all nine normal mucosae were detected to be negative. An in vitro experiment showed that in the gastric cell line SGC-7901, S100A6 mRNA was detected to be upregulated from 24 to 72 h after treatment with 5 mg/L 5-flurouracil or 0.3 mg/L doxorubicin, and there were two wave upregulations of the S100A6 protein. CONCLUSION: The observed regulated expression of S100A6 suggests that it is associated with gastric cancer tumorigenesis and quantitation of S100A6 is a promising tool for diagnosis of gastric cancer.

XAF1 mediates apoptosis through an extracellular signal-regulated kinase pathway in colon cancer.

BACKGROUND: XIAP-associated factor 1 (XAF1) negatively regulates the function of the X-linked inhibitor of apoptosis protein (XIAP), a member of the IAP family that exerts antiapoptotic effects. The extracellular signal-regulated kinase (ERK) pathway is thought to increase cell proliferation and to protect cells from apoptosis. The aim of the study was to investigate the correlation between the ERK1/2 signaling pathway and XAF1 in colon cancer. METHODS: Four human colon cancer cell lines, HCT1116 and Lovo (wildtype p53), DLD1 and SW1116 (mutant p53), were used. Lovo stable transfectants with XAF1 sense and antisense were established. The effects of dominant-negative MEK1 (DN-MEK1) and MEK-specific inhibitor U0126 on the ERK signaling pathway and expression of XAF1 and XIAP proteins were determined. The transcription activity of core XAF1 promoter was assessed by dual luciferase reporter assay. Cell proliferation was measured by MTT assay. Apoptosis was determined by Hoechst 33258 staining. RESULTS: U0126 increased the expression of XAF1 in a time- and dose-dependent manner. A similar result was obtained in cells transfected with DN-MEK1 treatment. Conversely, the expression of XIAP was down-regulated. Activity of the putative promoter of the XAF1 gene was significantly increased by U0126 treatment and DN-MEK1 transient transfection. rhEGF-stimulated phosphorylation of ERK appeared to have little or no effect on XAF1 expression. Overexpression of XAF1 was more sensitive to U0126-induced apoptosis, whereas down-regulation of XAF1 by antisense reversed U0126-induced inhibition of cell proliferation. CONCLUSIONS: XAF1 expression was up-regulated by inhibition of the ERK1/2 pathway through transcriptional regulation, which required de novo protein synthesis. The results suggest that XAF1 mediates apoptosis induced by the ERK1/2 pathway in colon cancer.

[Value of enteroscopy in localization diagnosis of small intestinal hemorrhage].

OBJECTIVES: To study the value of enteroscopy in determining bleeding lesion of small intestine. METHODS: Clinical data of ten cases with small intestinal bleeding diagnosed by enteroscopy were analyzed retrospectively from June 2003 to June 2004. RESULTS: Bleeding sites disclosed by enteroscopy were consistent with those confirmed by operation in 10 patients,but qualitative diagnosis was not consistent in 2 patients. CONCLUSIONS: Enteroscopy is a safe,reliable and valuable modality for diagnosing bleeding lesion of small intestine.

Synergistic effects of matrine and 5-fluorouracil on tumor growth of the implanted gastric cancer in nude mice.

OBJECTIVE: To investigate the inhibitive effects of matrine and 5-fluorouracil (5-FU) on the growth of human gastric adenocarcinoma cell line SGC-7901 when transplanted into nude mice and to investigate the bone marrow toxicity of these compounds. METHODS: 50 mg/kg and 100 mg/kg matrine with 50 mg/kg 5-FU, and 50 mg/kg matrine only, 50 mg/kg 5-FU only were intraperitoneally injected to observe their inhibitive effects by calculating the relative tumor volume (RTV) and tumor inhibition rates (IR%) as shown by the number of nucleated cells and bone marrow cell colony culture. RESULTS: The tumor inhibitive effect of the combined 100 mg/kg matrine and 50 mg/kg 5-FU group was stronger than that of the combined 50 mg/kg matrine and 50 mg/kg 5-FU groups (P < 0.05), and were also much stronger than that of the control group (50 mg/kg matrine only, 50 mg/kg 5-FU only, P < 0.01). As for the bone marrow inhibition effect, there was no significant statistical difference between the combination group and 5-FU alone group. In the cultured bone marrow cell colony, exuberant growth was seen in the combination group, but not in the control group. CONCLUSIONS: The inhibitive effect of combined matrine and 5-FU on the growth of transplanted human gastric cancer in nude mice is superior to that of matrine or 5-FU alone. Combined matrine and 5-FU can increase the inhibitive effect on proliferative hemopoietic bone marrow cells in nude mice and does not affect the resting bone marrow stem cells.

Inhibitory effect of human telomerase antisense oligodeoxyribonucleotides on the growth of gastric cancer cell lines in variant tumor pathological subtype.

AIM: To investigate the inhibitory effect of specialized human telomerase antisense oligodeoxyribonucleotides on the growth of well (MKN-28), moderately (SGC-7901) and poorly (MKN-45) differentiated gastric cancer cell lines under specific conditions and its inhibition mechanism, and to observe the correlation between the growth inhibition ratio and the tumor pathologic subtype of gastric cancer cells. METHODS: Telomerase activity in three gastric cancer cell lines of variant tumor pathologic subtype was determined by modified TRAP assay before and after the specialized human telomerase antisense oligodeoxyribonucleotides were dealt with under specific conditions. Effect of antisense oligomer under specific conditions of the growth and viability of gastric cancer cell lines was explored by using trypan blue dye exclusion assay, and cell apoptosis was detected by cell morphology observation, flow cytometry and TUNEL assay. RESULTS: Telomerase activity was detected in well, moderately and poorly differentiated gastric cancer cell lines (the quantification expression of telomerase activity was 43.7TPG, 56.5TPG, 76.7TPG, respectively). Telomerase activity was controlled to 30.2TPG, 36.3TPG and 35.2TPG for MKN-28, SGC-7901 and MKN-45 cell lines respectively after treatment with human telomerase antisense oligomers at the concentration of 5 mumol/L, and was entirely inhibited at 10 mumol/L, against the template region of telomerase RNA component, whereas no inhibition effect was detected in missense oligomers (P<0.05). After treatment with antisense oligomers at different concentrations under specific conditions for 96 h, significant growth inhibition effects were found in MKN-45 and SGC-7901 gastric cancer cell lines (the inhibition ratio was 40.89% and 71.28%), but not in MKN-28 cell lines (15.86%). The ratio of inactive SGC-7901 cells increased according to the prolongation of treatment from 48 to 96 h. Missense oligomers could not lead to the same effect (P<0.05). Apoptosis of SGC-7901 and MKN-45 cells was detected not only by morphology and TUNEL assay but also by flow cytometry. The apoptotic rate reached 33.56% for SGC-7901 cells and 44.75% for MKN-45 cells. CONCLUSION: The viability and proliferation of gastric cancer cells can be inhibited by antisense telomerase oligomers. The growth inhibition of gastric cancer cells is correlated with concentration, time and sequence specialty of antisense oligomers. The inhibition mechanism of antisense human telomerase oligomers depends not only on the sequence specialty but also on the biological characteristics of gastric cancer cell lines.

Comparison of Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients.

AIM: To compare Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients in different age groups and from different biopsy sites. METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of gastric ulcer and chronic gastritis patients. Giemsa staining, improved Toluidine-blue staining and H pylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used for the histological diagnosis of activity of H pylori infection, mucosal inflammation, glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System. RESULTS: Total rate of H pylori infection, mucosal inflammation, activity of H pylori infection, glandular atrophy and intestinal metaplasia in 3 839 gastric ulcer patients (78.5%, 97.4%, 82.1%, 61.1% and 64.2%, respectively) were significantly higher than those in 4 102 chronic gastritis patients (55.0%, 90.3%, 56.2%, 36.8%, and 37.0%, respectively, P<0.05). The rate of H pylori colonization of chronic gastritis in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 33.3%, 41.7%, 53.6%, 57.3%, 50.7%, 43.5%, respectively; in corpus, it was 32.6%, 41.9%, 53.8%, 60.2%, 58.0%, 54.8%, respectively; in angulus, it was 32.4%, 42.1%, 51.6%, 54.5%, 49.7%, 43.5%, respectively. The rate of H pylori colonization of gastric ulcer in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 60.5%, 79.9%, 80.9%, 66.8%, 59.6%, 45.6%, respectively; in corpus, it was 59.7%, 79.6%, 83.6%, 80.1%, 70.6%, 59.1%, respectively; in angulus, it was 61.3%, 77.8%, 75.3%, 68.8%, 59.7%, 45.8%, respectively. The rate of H pylori colonization at antrum was similar to corpus and angulus in patients, below 50 years, with chronic gastritis and in patients, below 40 years, with gastric ulcer. In the other age- groups, the rate of H pylori colonization was highest in corpus, lower in antrum and lowest in angulus (all P<0.05). The rates of glandular atrophy and intestinal metaplasia were higher and earlier in H pylori-positive patients than those without H pylori infection (both P<0.01). In comparison of gastric ulcer patients with chronic gastritis patients, the rate of glandular atrophy and intestinal metaplasia was higher in H pylori-positive patients with gastric ulcer than in H pylori-positive patients with chronic gastritis (both P<0.01); the rate of glandular atrophy and intestinal metaplasia were also higher in H pylori-negative patients with gastric ulcer than in H pylori-negative patients with chronic gastritis (both P<0.01). Both glandular atrophy and intestinal metaplasia were much more commonly identified in the angulus than in the antrum, lowest in corpus (all P<0.01). CONCLUSION: Rate of H pylori infection, glandular atrophy and intestinal metaplasia in gastric ulcer were higher than in chronic gastritis in all-different age -groups. Distribution of H pylori colonization is pangastric in the younger patients. It is highest in corpus, lower in antrum and lowest in angulus in the older age groups. Progression of glandular atrophy and intestinal metaplasia seem to have a key role in the distribution of H pylori colonization. H pylori appears to be the most important risk factor for the development of glandular atrophy and intestinal metaplasia, but it is not the only risk.

Helicobacter pylori infection, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer and early gastric cancer.

AIM: To evaluate the histological features of gastric mucosa, including Helicobacter pylori infection in patients with early gastric cancer and endoscopically found superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer. METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of all the patients. Giemsa staining, improved toluidine-blue staining, and H pylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used for the histological diagnosis of gastric mucosa inflammation, gastric glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System. RESULTS: The overall prevalence of H pylori infection in superficial gastritis was 28.7%, in erosive gastritis 57.7%, in gastric erosion 63.3%, in gastric ulcer 80.8%, in early gastric cancer 52.4%. There was significant difference (P<0.05), except for the difference between early gastric cancer and erosive gastritis. H pylori infection rate in antrum, corpus, angulus of patients with superficial gastritis was 25.9%, 26.2%, 25.2%, respectively; in patients with erosive gastritis 46.9%, 53.5%, 49.0%, respectively; in patients with gastric erosion 52.4%, 61.5%, 52.4%, respectively; in patients with gastric ulcer 52.4%, 61.5%, 52.4%, respectively; in patients with early gastric cancer 35.0%, 50.7%, 34.6%, respectively. No significant difference was found among the different site biopsies in superficial gastritis, but in the other diseases the detected rates were higher in corpus biopsy (P<0.05). The grades of mononuclear cell infiltration and polymorphonuclear cell infiltration, in early gastric cancer patients, were significantly higher than that in superficial gastritis patients, lower than that in gastric erosion and gastric ulcer patients (P<0.01); however, there was no significant difference compared with erosive gastritis. The grades of mucosa glandular atrophy and intestinal metaplasia were significantly highest in early gastric cancer, lower in gastric ulcer, the next were erosive gastritis, gastric erosion, the lowest in superficial gastritis (P<0.01). Furthermore, 53.3% and 51.4% showed glandular atrophy and intestinal metaplasia in angular biopsy specimens, respectively; but only 40.3% and 39.9% were identified in antral biopsy, and 14.1% and 13.6% in corpus biopsy; therefore, the angulus was more reliable for the diagnosis of glandular atrophy and intestinal metaplasia compared with antrum and corpus (P<0.01). The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pylori-positivity was 50.7%, 34.1%; of erosive gastritis 76.1%, 63.0%; of gastric erosion 84.8%, 87.8%; of gastric ulcer 80.6%, 90.9%; and of early gastric cancer 85.5%, 85.3%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pylori-negativity was 9.9%, 6.9%; of erosive gastritis 42.5%, 42.1%; of gastric erosion 51.1%, 61.9%; of gastric ulcer 29.8%, 25.5%; and of early gastric cancer 84.0%, 86.0%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis, erosive gastritis, gastric erosion, and gastric ulcer patients with H pylori positivity was significantly higher than those with H pylori negativity (P<0.01); however, there was no significant difference in patients with early gastric cancer with or without H pylori infection. CONCLUSION: The progression of the gastric pre-cancerous lesions, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis and gastric ulcer was strongly related to H pylori infection. In depth studies are needed to evaluate whether eradication of H pylori infection will really diminish the risk of gastric cancer.

Activation of STAT3 signaling in human stomach adenocarcinoma drug-resistant cell line and its relationship with expression of vascular endothelial growth factor.

AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STAT3 protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3-DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drug-resistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.