Effects of different nitrogen application rates on soil water stable aggregates and N2O emission in winter wheat field.

Excessive nitrogen application would deteriorate soil structure and increase greenhouse gas emission. We set up six treatments, i.e., N0, N120, N180, N240, N300and N360(nitrogen application rates of 0, 120, 180, 240, 300 and 360 kg·hm-2, all straws returned into the field in situ) in the nitrogen fertilizer experimental site to investigate the effects of different nitrogen application rates on soil N2O emission, soil water-filled porosity (WFPS), soil temperature, nitrate and ammonium contents, composition and stability of water stable aggregates in winter wheat filed in 2018-2020. The results showed that there was a significant positive correlation between soil N2O emission and nitrogen application rate. There was no correlation between WFPS and nitrogen application rate. Soil temperature in the 0-10 cm layer decreased significantly with the increases of nitrogen application rates. There was a significant positive correlation between nitrate and ammonium contents and nitrogen application rate. With the increases of nitrogen application rates, the content of water stable aggregates with diameter >2 mm decreased, while that of water-stable aggregates with diameter <0.5 mm increased. The particle size of soil water-stable aggregates also decreased gradually. There was a significant negative correlation between nitrogen application rate with mean weight diameter (MWD) and geometric mean diameter, while no correlation with fractal dimension. The fitting equation between MWD and N2O emission flux was y=3928.3e-2.171x (R2=0.55, P<0.001), indicating that N2O emission increased markedly as MWD decreasing. The increases in nitrogen application rate reduced soil temperature in the 0-10 cm layer, increased nitrate and ammonium contents, decreased the average particle size of soil water stable aggregates, and the stability of soil aggregates, and increased soil N2O emission.

[Modified single-needle arthroscopic repair technique for the treatment of longitudinal meniscal tear].

OBJECTIVE: To compare therapeutic efficacy of modified single-needle arthroscopic repair technique and Fast-Fix technique in repairing longitudinal meniscus injuries. METHODS: From July 2016 to July 2017, patients with longitudinal meniscus injuries who underwent meniscal repair surgery were retrospectively analyzed. Ninety-one patients treated with modified single-needle technique and 77 patients were treated with Fast-Fix technique, the average age were (26.7±7.6) and (27.9±6.1) years old respectively, the average lengths of follow-up were (32.5±9.2) and (33.2±11.9) months, respectively. Operation cost, suture time, intraoperative failure rate and postoperative failure rate were used as clinical outcomes, MRI of knee joint was used as main diagnosis and evaluation basis; 2000 IKDC subjective score, Lysholm score and Tegner activity scale were compared between two groups preoperatively, 12 months after operation and at the latest follow-up. Intraoperative and postopertaive complications were observed. RESULTS: Compared with Fast-Fix group, patients in modified single-needle technique group had lower operation costs [(645.7±133.1 vs.(12 184.8±4 709.8), P<0.01)], and average time per suture was shorter[(4.5±2.1) vs.(5.9±2.7), P<0.001)];and there were no significant difference in intraoperative failure rate and postoperative failure rate between two groups. There were no statistical differences in subjective function score, Lysholm score, Tegner activity knee joint at 12 months after opertaion and the latest follow-up (P>0.05);These scores between two groups at the latest followup were significantly improved compared with those of before operation(P<0.000 1). CONCLUSION: Modified single-needle arthrscopicrepair technique could achieve the similar therapeutic efficacy as Fast-Fix technique, and it has advantageds of simple opertion and more economical. This study recommends clinical application of modified single-needle arthrscopic repair technique in treating meniscus injuries.

Acetyl-11-keto-ß-boswellic acid inhibits proliferation and induces apoptosis of gastric cancer cells through the phosphatase and tensin homolog /Akt/ cyclooxygenase-2 signaling pathway.

BACKGROUND: Gastric cancer is one of the most common malignant tumors of the digestive system worldwide, posing a serious danger to human health. Cyclooxygenase (COX)-2 plays an important role in the carcinogenesis and progression of gastric cancer. Acetyl-11-keto-ß-boswellic acid (AKBA) is a promising drug for cancer therapy, but its effects and mechanism of action on human gastric cancer remain unclear. AIM: To evaluate whether the phosphatase and tensin homolog (PTEN)/Akt/COX-2 signaling pathway is involved in the anti-tumor effect of AKBA in gastric cancer. METHODS: Human poorly differentiated BGC823 and moderately differentiated SGC7901 gastric cancer cells were routinely cultured in Roswell Park Memorial Institute 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. Gastric cancer cell proliferation was determined by methyl thiazolyl tetrazolium colorimetric assay. Apoptosis was measured by flow cytometry. Cell migration was assessed using the wound-healing assay. Expression of Bcl-2, Bax, proliferating cell nuclear antigen, PTEN, p-Akt, and COX-2 were detected by Western blot analysis. A xenograft nude mouse model of human gastric cancer was established to evaluate the anti-cancer effect of AKBA in vivo. RESULTS: AKBA significantly inhibited the proliferation of gastric cancer cells in a dose- and time-dependent manner, inhibited migration in a time-dependent manner, and induced apoptosis in a dose-dependent manner in vitro; it also inhibited tumor growth in vivo. AKBA up-regulated the expression of PTEN and Bax, and down-regulated the expression of proliferating cell nuclear antigen, Bcl-2, p-Akt, and COX-2 in a dose-dependent manner. The PTEN inhibitor bpv (Hopic) reversed the high expression of PTEN and low expression of p-Akt and COX-2 that were induced by AKBA. The Akt inhibitor MK2206 combined with AKBA down- regulated the expression of p-Akt and COX-2, and the combined effect was better than that of AKBA alone. CONCLUSION: AKBA inhibits the proliferation and migration and promotes the apoptosis of gastric cancer cells through the PTEN/Akt/COX-2 signaling pathway.

Cyclooxygenase-2 mediated synergistic effect of ursolic acid in combination with paclitaxel against human gastric carcinoma.

Ursolic acid (UA) induces apoptosis in gastric cancer cells by inhibiting cyclooxygenase-2 (COX-2). Paclitaxel (PTX) is an important chemotherapy agent used to treat solid tumors. We evaluated the in vitro antitumor activity of UA in combination with PTX against gastric cancer cells and investigated the mechanisms underlying the combined effects. A cytotoxicity test and flow cytometry were utilized to study the effects of UA and PTX on proliferation and apoptosis, respectively. To further elucidate the mechanism, Western blot analysis was used to assess changes in the expression of a series of related proteins, including COX-2, proliferating cell nuclear antigen (PCNA), Bcl-2, and Bax. UA and PTX dose- and time-dependently inhibited BGC-823 and SGC-7901 gastric cancer cell proliferation. Combined delivery of UA and PTX synergistically reduced cell proliferation and induced apoptosis in these cells by lowering COX-2, PCNA, and Bcl-2 expression and by increasing Bax expression. These results indicate that the synergistic inhibition of proliferation and induction of apoptosis by UA and PTX may be induced by reducing COX-2 expression in gastric cancer cells.

Pre-clinical characterization of PKC412, a multi-kinase inhibitor, against colorectal cancer cells.

The potential effect of PKC412, a small molecular multi-kinase inhibitor, in colorectal cancer (CRC) cells was evaluated here. We showed that PKC412 was cytotoxic and anti-proliferative against CRC cell lines (HT-29, HCT-116, HT-15 and DLD-1) and primary CRC cells. PKC412 provoked caspase-dependent apoptotic death, and induced G2-M arrest in the CRC cells. AKT activation was inhibited by PKC412 in CRC cells. Reversely, expression of constitutively-active AKT1 (CA-AKT1) decreased the PKC412's cytotoxicity against HT-29 cells. We propose that Bcl-2 could be a primary resistance factor of PKC412. ABT-737, a Bcl-2 inhibitor, or Bcl-2 siRNA knockdown, dramatically potentiated PKC412's lethality against CRC cells. Forced Bcl-2 over-expression, on the other hand, attenuated PKC412's cytotoxicity. Significantly, PKC412 oral administration suppressed AKT activation and inhibited HT-29 tumor growth in nude mice. Mice survival was also improved with PKC412 administration. These results indicate that PKC412 may have potential value for CRC treatment.

Helicobacter pylori infection, gastrin and cyclooxygenase-2 in gastric carcinogenesis.

Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori (H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.

Gastrin acting on the cholecystokinin2 receptor induces cyclooxygenase-2 expression through JAK2/STAT3/PI3K/Akt pathway in human gastric cancer cells.

Gastrin, cholecystokinin2 receptor (CCK2R), and cyclooxygenase-2 (COX-2) have been implicated in the carcinogenesis and progression of gastric cancer. Our study demonstrated that antagonist or siRNA against CCK2R blocked amidated gastrin (G17)-induced activation of STAT3 and Akt in gastric cancer cell lines. G17-increased COX-2 expression and cell proliferation were effectively blocked by CCK2R antagonist and inhibitors of JAK2 and PI3K. In addition, knockdown of STAT3 expression significantly attenuated G17-induced PI3K/Akt activation, COX-2 expression, and cell proliferation. These results suggest that CCK2R-mediated COX-2 up-regulation via JAK2/STAT3/PI3K/Akt pathway is involved in the proliferative effect of G17 on human gastric cancer cells.

Downregulation of miR-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. It has been demonstrated that COX-2 overexpression depends on different cellular pathways, involving both transcriptional and post-transcriptional regulation. MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators. Here, we characterize miR-101 expression and its role in the regulation of COX-2 expression, which in turn, will provide us with additional insights into the potential therapeutic benefits of exogenous miR-101 for treatment of gastric cancer. Our results showed that miR-101 levels in gastric cancer tissues were significantly lower than those in the matched normal tissue (P < 0.01). Furthermore, lower levels of miR-101 were associated with increased tumor invasion and lymph node metastasis (P < 0.05). We also found an inverse correlation between miR-101 and COX-2 expression in both gastric cancer specimens and cell lines. Significant decreases in COX-2 mRNA and COX-2 levels were observed in the pre-miR-101-infected gastric cancer cells. One possible mechanism of interaction is that miR-101 inhibited COX-2 expression by directly binding to the 3'-UTR of COX-2 mRNA. Overexpression of miR-101 in gastric cancer cell lines also inhibited cell proliferation and induced apoptosis in vitro, as well as inhibiting tumor growth in vivo. These results collectively indicate that miR-101 may function as a tumor suppressor in gastric cancer, with COX-2 as a direct target.

Effects of angiopoietin-1 on attachment and metastasis of human gastric cancer cell line BGC-823.

AIM: To evaluate the effects of angiopoietin-1 (Ang-1) on adhesion of gastric cancer cell line BGC-823 and expression of integrin beta1, CD44V6, urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-2 (MMP-2). METHODS: BGC-823 cells were transfected transiently with adenovirus-Ang-1 (Ad-Ang-1). Cells transfected transiently with adenovirus-green fluorescent protein (Ad-GFP) and untransfected cells were used as a negative and blank control group, respectively. The cell adhesion rate between cell and extracellular matrix (ECM) was determined by cell adhesion assay. To investigate whether Ang-1 could reinforce gastric carcinoma metastasis, we performed migration and invasion assays in BGC-823 cells. The mRNA and protein expression of integrin beta1, CD44V6, uPA and MMP-2 were detected by reverse transcription polymerase chain reaction and Western blotting, respectively. The expression of integrin beta1 and CD44V6 was measured by immunohistochemistry. RESULTS: BGC-823 cells were transfected successfully. The adhesion rate increased significantly in the Ad-Ang-1 group (P < 0.05). The Ad-Ang-1-transfected group had a significant increase in migration and invasion compared with that of the mock-transfected and Ad-GFP groups. The mRNA and protein expression of integrin beta1, CD44V6, uPA and MMP-2 in the Ad-Ang-1 group was higher than that in the Ad-GFP and blank control groups (P < 0.05). Compared with mock-transfected and Ad-GFP groups, integrin beta1 and CD44V6 expression intensity greatly increased (P < 0.05). CONCLUSION: Transfection of Ang-1 into human gastric cancer cell line BGC-823 can significantly increase expression of integrin beta1 and CD44V6, by which cell adhesion and metastasis to the ECM are promoted.

Inhibition of COX-2 and activation of peroxisome proliferator-activated receptor gamma synergistically inhibits proliferation and induces apoptosis of human pancreatic carcinoma cells.

Although inhibition of cyclooxygenase-2 (COX-2) or activation of peroxisome proliferators-activated receptor gamma (PPAR-gamma) leads to growth inhibition in malignancies, the synergistic anti-tumor effects of combination of COX-2 inhibitor (NS-398) and PPAR-gamma agonist (rosiglitazone) on the human pancreatic cancer cells remains unknown. Here, we evaluated the effects of NS-398 and/or rosiglitazone on the cell proliferation and apoptosis in a pancreatic cancer cell line, SW1990. NS-398 and rosiglitazone decreased cell proliferation in a dose- and time-dependent manner. Proliferating cell nuclear antigen (PCNA) labeling index significantly decreased in the cells treated with either NS-398 or rosiglitazone. Both NS-398 and rosiglitazone alone induced apoptotic cell death of SW1990. The combination of NS-398 and rosiglitazone exerted synergistic effects on proliferation inhibition, and apoptosis induction in SW1990 cells, with down-regulation of Bcl-2 and up-regulation of Bax expression. Our results indicate that simultaneous targeting of COX-2 and PPAR-gamma inhibits pancreatic cancer development more effectively than targeting each molecule alone.

Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro.

Gastrin and cyclooxygenase-2 (COX-2) play important roles in the carcinogenesis and progression of gastric cancer. However, it remains unknown whether the combination of cholecystokinin-2 (CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer. Here, we demonstrated that the combination of AG-041R (a CCK-2 receptor antagonist) plus NS-398 (a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition, apoptosis induction, down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells. These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.

[Application endoscopic mucosal resection to therapy early gastrointestinal cancer and precancerous lesion].

OBJECTIVE: To explore the clinical value of endoscopic mucosal resection (EMR) on early gastrointestinal cancer and precancerous lesion. METHODS: The EMR data of 42 lesions from 28 patients, collected from Apr. 2001 to Dec. 2005, were retrospectively analyzed. All the lesions were confirmed histologically before and after operation. RESULTS: Forty-two lesions were removed by the EMR from 28 patients. Lesion types observed under endoscopy were as follows: type I 9 lesions (type Isp 2 lesions, type Is 7 lesions), type II 33 lesions (type IIa 23 lesions, type IIa + IIc 4 lesions, type IIb 6 lesions). Thirty-eight EMRs were performed by using snare resection techniques and 4 EMRs by using suction cap-assisted techniques. The size of lesions changed from 0.6 cm x 0.6 cm to 3.0 cm x 3.5 cm. Complete resections were achieved in 36 of 40, among them, 2 lesions were divided into 2 pieces and 1 lesion was divided into 3 pieces. Post-EMR histopathologic evaluation revealed the following RESULTS: carcinoma in 4 lesions, high-grade dysplasia (HGD) in 11 lesions, middle-grade dysplasia (MGD) in 17 lesions, adenoma in 6 lesions, non-adenoma in 2 lesions. The pathology match rate between local biopsy and EMR was 60.0%. The detection rates of cancer, HGD and MGD by EMR were higher than that by routine biopsy. No serious complications were seen in this study. CONCLUSION: Endoscopic mucosal resection has significant impact on the endoscopic intervention treatment of early cancer and precancerous lesion in digestive tract.

Influences of Helicobacter pylori on cyclooxygenase-2 expression and prostaglandinE2 synthesis in rat gastric epithelial cells in vitro.

BACKGROUND AND AIM: It is known that cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasia and Helicobacter pylori (H. pylori) infection is causally linked to gastric cancer. The present study aimed to elucidate the effects of H. pylori on COX-2 expression and prostaglandinE(2) (PGE(2)) production in a gastric epithelial cell line derived from normal rat gastric mucosa (RGM1). METHOD: H. pylori water extracts were prepared from a supernatant of the H. pylori suspension in distilled water. RGM1 cells were cultured with H. pylori water extracts at the final concentration of 2.5, 5, 10 microg/mL for 24 h. For the time sequence study, RGM1 cells were cultured with 10 microg/mL H. pylori water extracts for 0, 6, 12, 24 and 48 h. COX-1 and COX-2 expression in the RGM1 cells was analyzed by western blotting. The levels of PGE(2) in the cultured media were measured by enzyme immunoassay. RESULTS: H. pylori did not affect COX-1 expression; whereas COX-2 expression increased by six-fold at 24 h after incubation of RGM1 cells with 10 microg/mL H. pylori water extracts. The increase in COX-2 expression was evident after 12 h of incubation; reached a peak at 24 h and declined at 48 h. H. pylori dose dependently increased COX-2 expression and PGE(2) synthesis in RGM1 cells. CONCLUSION: H. pylori induces COX-2 expression and increases PGE(2) synthesis in RGM1 cells in vitro. These results indicate that H. pylori-associated gastric carcinogenesis may depend on COX-2 expression.

[Effects of gastrin receptor antagonist and cyclooxygenase-2 inhibitor on proliferation and apoptosis of gastric cancer cell].

OBJECTIVE: To investigate the regulative roles of the gastrin receptor antagonist proglumide and the specific cyclooxygenase (COX)-2 inhibitor NS-398 on the proliferation and apoptosis of gastric cancer cells. METHODS: Human gastric cancer cells of the line MKN-45 were routinely cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. Subconfluent cell cultures were treated with proglumide at a final concentration of 5 mmol/L, NS-398 at a final concentration of 10.0 micromol/L, or proglumide in combination with NS-398 for 48 h. The growth and proliferation of MKN-45 cells were analyzed with MTT assay. Flow cytometric analysis was used to detect the apoptosis of the gastric cancer cells. RT-PCR and Western blotting were used to detect the expression of apoptosis-inhibited gene bcl-2 mRNA and protein. RESULTS: The apoptosis rates of the cells treated by proglumide, NS-398, and combination of two agents were 24.7% +/- 3.2%, 26.7% +/- 3.4%, and 36.1% +/- 4.6% respectively, all significantly higher than that in the control group (1.6% +/- 0.6%, all P < 0.01). The apoptosis rates of the MKN-45 cells treated with proglumide combined with NS-398 was significantly greater than those of the cells treated by the two agents alone (both P < 0.05). Treatment with proglumide and NS-398 significantly reduced the bcl-2 mRNA and protein expression in the MKN-45 cells (P < 0.05). CONCLUSION: Both proglumide and NS-398 inhibit the proliferation and induce the apoptosis of human gastric cells. This apoptosis may be mediated by down-regulation of the expression of apoptosis-inhibited gene bcl-2. Co-treatment with proglumide and NS-398 have synergistic anticancer role.

Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis.

OBJECTIVE: To investigate the expression of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in gastric carcinomas, and to correlate this expression with clinicopathological parameters and angiogenesis. METHODS: Ninety-six resected tumor specimens from patients with gastric carcinoma were obtained, and 30 corresponding paracancerous normal tissues were randomly selected as a control. Immunohistochemical staining was used for detecting the expression of COX-2 and MMP-9. Monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was calculated by counting of CD34-positive vascular endothelial cells. RESULTS: The positive expression rates of COX-2, MMP-9 and MVD in the cancerous tissue were 80.2%, 74.0%, and 32.5 +/- 8.3, respectively, which were significantly higher than those in the normal tissue (P < 0.01). COX-2, MMP-9 expression rates and MVD in the patients with stages III and IV were 91.4%, 84.5% and 34.9 +/- 8.7, respectively, which were significantly higher than those in the patients with stages I and II (P < 0.01). In addition, the Spearman rank correlation test showed that tumor MVD was closely associated with COX-2 (r = 0.311, P < 0.01) and MMP-9 (r = 0.349, P < 0.01) expressions. CONCLUSIONS: Overexpression of COX-2 and MMP-9 is related to tumor invasion and lymph node metastasis in the gastric carcinoma. These results provide evidence that COX-2 contribute to gastric cancer development by promoting MMP-9 expression and angiogenesis.

[Expression of glutathione S-transferase-pi and DNA topoisomerase II alpha and their implications in colorectal carcinoma].

OBJECTIVE: To investigate the expression of GST-pi and Topo II-alpha, and their relationships with clinicopathological parameters in colorectal carcinoma. METHODS: The expression of GST-pi and Topo II-alpha were detected by avidin-biotin-peroxide complex (ABC) method in tumor specimens, matched paratumor tissues from 60 cases with colorectal carcinoma and normal colonic tissues from 15 cases. RESULTS: The expression rates of GST-pi and Topo II-alpha were 90.0% and 86.7% respectively in tumor tissues, significantly higher than those in matched paratumor tissues and normal tissues (P< 0.01). The expressions of GST-pi and Topo II-alpha were associated with cellular differentiation, Dukes stage and lymph node metastasis (all P< 0.01), but not with tumor size and histological type (all P > 0.05). The expression level of GST-pi was significantly higher in poorly differentiated tumors than that in well differentiated tumors. The expression level of Topo II-alpha in well-differentiated tumors were stronger than that in poorly differentiated tumors. CONCLUSIONS: The detection of GST-pi and Topo II-alpha expressions may be helpful to judge the malignant behavior, metastasis and prognosis in human colorectal carcinoma.

[Relationship between cyclooxygenase- 2 expression and angiogenesis in patients with gastric cancer].

OBJECTIVE: To investigate COX-2 expression in patients with gastric cancer and its relationship with angiogenesis and clinicopathologic features of gastric cancer. METHODS: COX-2 expression and CD34-stained microvessel density (MVD) were detected by immunohistochemical methods in specimens from 96 patients with gastric cancer. The correlations among COX-2 expression, MVD and clinicopathologic features were analyzed. RESULTS: The COX-2 positive rate and MVD in gastric cancer were significantly higher than those in the normal gastric mucosa (80.2% vs. 13.3%; 32.5+/- 8.3 vs. 13.1+/- 2.4, all P< 0.01). The COX-2 positive rate and MVD in the patients with stage III and IV were significantly higher (91.4% and 34.9+/- 8.7 respectively, P< 0.01), than that in the patients with stage I and II. The COX-2 positive rate and MVD in the cases with lymph node metastasis were 87.9% and (35.0+/- 8.5) respectively, higher than those in the cases without lymph node metastasis (P< 0.05). The Spearman rank correlation test showed a significant correlation between COX-2 expression and tumor MVD (r=0.311, P< 0.01). CONCLUSIONS: COX-2 plays an important role in gastric cancer angiogenesis. COX-2 and angiogenesis induced by COX-2 contribute to tumor invasion and lymph node metastasis.

Efficacy of omeprazole and amoxicillin with either clarithromycin or metronidazole on eradication of Helicobacter pylori in Chinese peptic ulcer patients.

AIM: One-week triple therapy with proton pump inhibitors, clarithromycin and amoxicillin has recently been proposed as the first-line treatment for Helicobacter pylori (H. pylori) infection; however, data regarding the effects of this regimen in China are scarce. The aim of this prospective and randomized study was to compare the efficacy of clarithromycin and metronidazole when they were combined with omeprazole and amoxicillin on eradication of H. pylori and ulcer healing in Chinese peptic ulcer patients. METHODS: A total of 103 subjects with H. pylori-positive peptic ulcer were randomly divided into two groups, and accepted triple therapy with omeprazole 20 mg, amoxicillin 1000 mg and either clarithromycin 500 mg (OAC group, n = 58) or metronidazole 400 mg (OAM group, n = 45). All drugs were given twice daily for 7 d. Patients with active peptic ulcer were treated with omeprazole 20 mg daily for 2-4 wk after anti-H. pylori therapy. Six to eight weeks after omeprazole therapy, all patients underwent endoscopies and four biopsies (two from the antrum and two others from the corpus of stomach) were taken for rapid urease test and histological analysis (with modified Giemsa staining) to examine H. pylori. Successful eradication was defined as negative results from both examination methods. RESULTS: One hundred patients completed the entire course of therapy and returned for follow-up. The eradication rate of H. pylori for the per-protocol analysis was 89.3% (50/56) in OAC group and 84.1% (37/44) in OAM group. Based on the intention-to-treat analysis, the eradication rate of H. pylori was 86.2% (50/58) in OAC group and 82.2% (37/45) in OAM group. There were no significant differences in eradication rates between the two groups on either analysis. The active ulcer-healing rate was 96.7% (29/30) in OAC group and 100% (21/21) in OAM group (per-protocol analysis, P>0.05). Six patients in OAC group (10.3%) and five in OAM group (11.1%) reported adverse events (P>0.05). CONCLUSION: One-week triple therapy with omeprazole and amoxicillin in combination with either clarithromycin or metronidazole is effective for the eradication of H. pylori. The therapeutic regimen comprising metronidazole with low cost, good compliance and mild adverse events may offer a good choice for the treatment of peptic ulcers associated with H. pylori infection in China.

Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions.

AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1,000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03+/-3.37 microg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83+/-3.02 microg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.

Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis.

AIM: Cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasm. Helicobacter pylori (H pylori) infection is causally linked to gastric cancer. However, the expression of COX-2 in various stages of H pylori-associated gastric carcinogenesis pathway has not been elucidated. Therefore, the aim of this study was to clarify the role of H pylori induced COX-2 expression during carcinogenesis in the stomach. METHODS: Gastric biopsies from 138 subjects (30 cases of chronic superficial gastritis (CSG), 28 cases of gastric glandular atrophy (GA), 45 cases of gastric mucosal intestinal metaplasia (IM), 12 cases of moderate gastric epithelial dysplasia and 23 cases of gastric cancer) were enrolled. H pylori infection was assessed by a rapid urease test and histological examination (modified Giemsa staining). The expression of COX-1 and COX-2 in human gastric mucosa was detected by immunohistochemical staining. RESULTS: H pylori infection rate was 64.3% in GA and 69.5% in gastric cancer, which was significantly higher than that (36.7%) in CSG (P<0.05). The positive expression rates of COX-2 were 10.0%, 35.7%, 37.8%, 41.7% and 69.5% in CSG, GA, IM, dysplasia and gastric cancer, respectively. From CSG to GA, IM, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency, whereas COX-1 expression did not change significantly in the gastric mucosa. The level of COX-2 expression in IM and dysplasia was significantly higher in H pylori-positive than in H pylori-negative subjects (P<0.01). CONCLUSION: COX-2 expression induced by H pylori infection is a relatively early event during carcinogenesis in the stomach.