Published online Sep 28, 2014. doi: 10.3748/wjg.v20.i36.12860
Revised: March 12, 2014
Accepted: May 29, 2014
Published online: September 28, 2014
Processing time: 308 Days and 19.4 Hours
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.
Core tip:Helicobacter pylori (H. pylori) is one of the most common pathogens, infecting approximately half of the world’s population. It is well known that H. pylori infection has been associated with an elevated risk of developing gastric carcinoma. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and cyclooxygenase-2 in H. pylori-infected patients and their possible association with gastric cancer risk.
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Citation: Shao Y, Sun K, Xu W, Li XL, Shen H, Sun WH.
Helicobacter pylori infection, gastrin and cyclooxygenase-2 in gastric carcinogenesis. World J Gastroenterol 2014; 20(36): 12860-12873 - URL: https://www.wjgnet.com/1007-9327/full/v20/i36/12860.htm
- DOI: https://dx.doi.org/10.3748/wjg.v20.i36.12860
Helicobacter pylori (H. pylori) is one of the most common pathogens, infecting approximately half of the world’s population. It is well known that H. pylori infection has been associated with an elevated risk of developing gastric carcinoma[1-4]; and this bacterium has been classified as a class I biological carcinogen by the World Health Organization[5]. However, the exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients remains unclear.
Numerous studies suggested a positive association between hypergastrinemia (caused by H. pylori infection) and gastric cancer in humans and mice[6-11]. Hypergastrinemia and H. pylori infection synergistically promoted gastric carcinogenesis in transgenic mice that overexpress amidated gastrin (INS-GAS)[8-11]. The role of H. pylori infection and hypergastrinemia in the development of gastric carcinogenesis has been a matter of scientific debate.
Cyclooxygenase (COX) is a key enzyme that catalyses the formation of prostaglandins (PGs) and other eicosanoids from arachidonic acid. Two isoforms of COX have been identified: constitutively expressed COX-1 and mitogen-inducible COX-2[12,13]. Increased expression of COX-2 has been linked to gastric carcinogenesis[14-17]. Furthermore, enhanced COX-2 expression in human stomach has been linked to H. pylori infection[6,17-22]. However, the molecular mechanisms underlying the aberrant expression of COX-2 in gastric cancer patients infected with H. pylori remain unclear. 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.
Infection with H. pylori and the resulting chronic inflammation are a major step in the initiation and development of gastric cancer. Early epidemiological studies linking H. pylori infection with gastric cancer include a plethora of case-control[23] and prospective cohort studies[24], and the evidence is now available as pooled estimates from meta-analyses[25]. To clarify the association between gastric cancer and prior infection with H. pylori, three nested case-controlled studies were performed in 1991 and the results showed that the positive rate of H. pylori antibody was higher in the patients with gastric cancer than that in the control group[26-28]. A prospective study confirmed that gastric cancer developed in 2.9% of the H. pylori-infected group but none of the uninfected patients[29].
In a review of 5 meta-analyses concerning the association of H. pylori seropositivity with gastric cancer, Eslick[25] reported a pooled estimate of the relative risk ranging from 1.92-2.56 (mean 2.28), and confidence interval ranging from 1.35-3.55. Despite some differences in the number, type, and design of the included studies, the strength of association from each of the meta-analyses was consistent in size and precision, supporting the validity of the pooled estimate and conclusions regarding the association. Six meta-analyses of cohort studies, case-controlled and nested case-controlled studies revealed a positive odds ratio between H. pylori seropositivity and gastric cancer[23,24,30-33]. All these meta-analyses showed that H. pylori infection is associated with approximately a two-fold increased risk of developing gastric cancer.
In addition, a multicentre epidemiological study was designed to look at the relation between the prevalence of H. pylori infection and the incidence of gastric cancer in 17 populations from 13 countries, chosen to reflect the global range of gastric cancer incidence. The results indicated an approximately six-fold increased risk of gastric cancer in populations with 100% H. pylori infection compared with populations that have no infection[34]. The main carcinogenic effect of H. pylori is dependent on the presence of the cytotoxic associated gene A (cagA) and vacuolating cytotoxin A (vacA)[35,36]. A meta-analysis conducted by Huang et al[33] showed that the risk of gastric cancer was twice as high in people who were positive for antibodies against CagA in sera.
Nevertheless, a later meta-analysis conducted by Wang et al[37] showed a protective role for H. pylori infection in the prognosis of gastric cancer. Several studies have also examined the relationship between H. pylori infection and prognosis of patients with gastric cancer, providing evidence of a better prognosis in patients with H. pylori infection compared with patients without H. pylori infection[38-41]. The underlying mechanisms need to be further elucidated, which could provide new therapeutic approaches for gastric cancer.
In experimental research, gastric cancer was induced in Mongolian gerbils through H. pylori inoculation plus administration of low-dose chemical carcinogens, and H. pylori eradication suppressed the incidence of gastric cancer[42]. The animal experiment also suggested that eradication at an earlier period was effective in reducing gastric carcinogenesis compared with that at the middle or late period[43]. The strong association of H. pylori with gastric cancer has spurred a large number of randomized controlled trials to investigate the effects of H. pylori eradication on gastric carcinogenesis.
According to Correa’s model, gastric cancer develops in a multistep process from chronic active gastritis, gastric glandular atrophy, intestinal metaplasia, dysplasia (currently distinguished into low-grade and high-grade intraepithelial neoplasia), and finally to gastric cancer[44]. In studies of precancerous gastric lesions, H. pylori eradication generally reduced the rate of progression[45]. To clarify the effects of H. pylori eradication on prevention of gastric cancer development in patients with chronic gastritis, Uemura et al[46] conducted a nonrandomized H. pylori eradication trial in cases whose gastric cancer was removed by endoscopic resection, and suggested that H. pylori eradication might improve neutrophil infiltration and intestinal metaplasia in the gastric mucosa and inhibit the development of new carcinomas. A multi-centre, open-label, randomized controlled trial demonstrated that patients in whom H. pylori had been successfully eradicated following their initial gastric cancer resection had a highly significantly reduced risk of developing a second gastric cancer (hazard ratio 0.35 at 3 years of follow-up)[47].
However, a double-blind randomized study in China showed that gastric cancer still occurred after successful eradication of H. pylori and that H. pylori eradication did not lead to a significant decrease in the incidence of gastric cancer[48]. Sub-analysis of previous papers showed that the preventive effect of H. pylori eradication for gastric cancer incidence was limited to patients without atrophy and metaplasia[48,49]. Randomized prospective studies demonstrated that eradication significantly reduced the presence of premalignant lesions, providing additional evidence that H. pylori had an effect on early stages of gastric carcinogenesis[45,48]. It is speculated that eradication of H. pylori significantly decreases the risk of gastric cancer in infected individuals without premalignant lesions. In meta-analysis, the relative risk of gastric cancer following H. pylori eradication was calculated to be 0.65 overall (95%CI: 0.43-0.98)[50]. Taken together, these studies support an unequivocal role for H. pylori in the development of gastric cancer and indicate that anti-H. pylori therapy may be an effective means of gastric cancer prevention.
The role of H. pylori infection and hypergastrinemia in the development of gastric carcinogenesis has been a matter of scientific debate. A possible pathogenetic mechanism involves the persistent H. pylori colonization and inflammation of the gastric mucosa, particularly when the H. pylori strains express CagA which often results in the development of chronic atrophic gastritis and subsequently hypergastrinemia, through a reverse-feedback mechanism[51]. To clarify whether H. pylori CagA can induce gastrin expression, Zhou et al[52] constructed a eukaryotic expression vector pcDNA3.1/cagA and a luciferase reporter vector pGL/gastrin promoter, and then co-transfected them into gastric cancer cells, and suggested that CagA could activate the gastrin promoter and up-regulate gastrin mRNA expression in AGS and SGC-7901 cells. It has been widely reported that the number of G cells and the release of gastrin increase during H. pylori infection in human subjects and various animal models[53-55]. As H. pylori infection inhibits acid secretion[56], the observed hypergastrinemia might be in response to the hypochlorhydria. Indeed, direct inhibition of acid secretion by omeprazole is sufficient to stimulate gastrin gene expression in vivo[57]. Previous studies suggested that H. pylori colonizing the gastric antrum might create an alkaline pH sufficient to stimulate G cells through its production of urease and conversion of urea to ammonia[58]. However, this mechanism was subsequently disproven by studies showing that H. pylori products rather than the live organism can stimulate gastrin release from cultured G cells[59,60]. Furthermore, H. pylori-induced inflammatory cytokines stimulate antral G cells to release gastrin[61].
Several previous studies have shown that H. pylori can increase circulating gastrin levels in the blood[62-64]. H. pylori has been reported to induce G-cell hyperfunction in antral gastric tissue, which could contribute to the onset of hypergastrinemia[65]. Gibbons et al[66] showed that patients infected with H. pylori had increased gastrin mRNA levels, whereas Sumii et al[67] reported no change in gastrin mRNA expression. Buchan and coworkers reported that H. pylori increases basal levels of gastrin in primary G-cell cultures, but did not induce secretion, suggesting that H. pylori increased gastrin synthesis and possibly gene expression[68]. H. pylori also activates gastrin releasing peptide and regulates the gastrin modulator somatostatin to increase gastrin expression[53,69]. Taken together, it is unclear whether the hypergastrinemia that occurs in H. pylori-infected individuals is attributable to hypochlorhydria, suppression of somatostatin, chronic gastritis, gastric atrophy or the direct induction of gastrin gene expression by the bacterium itself.
Asymptomatic patients with H. pylori colonisation have been shown to have elevated serum gastrin concentrations relative to a control population, despite similar gastric acid output[62], while Levi et al[70] demonstrated that following H. pylori eradication, there was a reduction in fasting serum gastrin concentration. It has also been demonstrated that following eradication of H. pylori, there was an increase in somatostatin mRNA and a concomitant decrease in gastrin mRNA in patients with duodenal ulcers[71]. This was associated with increased numbers of D-cells in the gastric corpus[71], suggesting that the hypergastrinemia caused by H. pylori infection may result from a loss of somatostatin control over gastrin secretion.
Clinical and experimental evidence indicates that gastrin can potentiate the carcinogenic effects of H. pylori infection on the gastric mucosa[72]. Our prior studies suggested that the proliferation of MKN-45 cells, which were derived from a poorly differentiated gastric carcinoma and had been reported to express CCK2/gastrin receptor (CCK2R), decreased when treated with the CCK2R antagonists[73,74]. It also has been demonstrated that long-term treatment with CCK2R antagonist YF476 prevented the development of H. pylori-associated gastric cancer in INS-GAS mice[10,75]. Taken together, these results indicate that the gastrin signaling pathway provides a potential target for cancer chemoprevention.
On the other hand, aberrant DNA methylation in gastric biopsies from H. pylori-infected patients was found to be correlated with a greater gastric cancer risk[76,77]. Previous studies have reported that infection with H. pylori is associated with promoter methylation of various gastric cancer-associated genes[78,79] and eradication of the bacteria was able to reverse the process in patients with gastritis, but not in patients with intestinal metaplasia[80,81]. Recently, Niwa et al[82] demonstrated that treatment with the DNA demethylation agent 5-aza-2’-deoxycytidine decreases the incidence of gastric cancers in an animal model of H. pylori-promoted gastric cancer. This study also showed that induction of aberrant methylation is an important mechanism for gastric carcinogenesis by H. pylori infection.
It is well known that H. pylori infection causes inflammation, and COX-2 is involved in inflammatory responses[21]. However, in H. pylori associated gastritis, COX-2 protein mainly localizes to the lamina propria[18,19,83,84], with variable levels in the epithelium[18,84]; but in gastric cancer, COX-2 is most strongly expressed in the epithelium of malignant and dysplastic glands[18,85,86]. Romano et al[87] reported that H. pylori up-regulates COX-2 mRNA expression and stimulates the release of PGE2 in MKN 28 gastric mucosal cells in vitro; and this effect was independent of VacA, CagA, or urease-generated ammonia. However, other in vitro studies have demonstrated that H. pylori up-regulates COX-2 expression in human gastric cancer cells; and this effect is specifically related to VacA toxin[88,89].
Our previous study using rat gastric epithelial cells treated with H. pylori water extract (only containing bacterial proteins but not bacterial cells) led to an increase in COX-2 expression (Figure 1) and PGE2 levels (Figure 2) that peaked 24 h after treatment and declined at 48 h[90]. These results indicate that development of gastric carcinoma associated with H. pylori infection may depend on COX-2 expression. The expression of COX-2 results in the induction of the proinflammatory prostaglandin, PGE2[91,92]. PGs play an important role in the growth and stimulation of the inflammation-associated gastric carcinogenesis[93,94]. In addition, H. pylori-induced chronic gastritis is associated with overexpression of COX-2 and increased production of eicosanoids, especially PGE2[95]. Noteworthy, successful eradication of H. pylori infection leads to a significant reduction in COX-2 expression[96].
COX-2 is upregulated in the gastric mucosa of H. pylori-infected patients[19,21,83,84,97]. In vivo studies show that COX-2 is further upregulated in H. pylori-mediated gastric adenocarcinoma[18,85,98]. Overexpression of COX-2 has been observed not only in H. pylori-positive gastritis, but also in pre-cancerous lesions such as atrophic gastritis and intestinal metaplasia, and in gastric cancer, suggesting a role of COX-2 in early gastric carcinogenesis[19,21,98]. Recent studies showed that COX-2 expression significantly decreases following H. pylori eradication in patients with atrophic gastritis[22,99]. Several previous studies showed that the expression of COX-2 was even high in the early stage of gastric carcinogenesis (pre-cancerous lesions) and gradually increased with the aggravation of gastric mucosal lesions[100,101]. Our previous study also showed that COX-2 was expressed in human gastric cancer and its precursor lesions as detected by immunohistochemistry[21] (Figure 3). From chronic superficial gastritis to gastric glandular atrophy, intestinal metaplasia, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency[21] (Table 1). These results collectively suggest that COX-2 expression induced by H. pylori infection is a relatively early event during carcinogenesis in the stomach. In addition, COX-2 overexpression enhances the possibility of invasion and metastasis and correlates with poor prognosis in human gastric carcinoma[102-104] (Table 2).
Clinicopathological parameter | n | COX-2 expression | |||||
0 | 1 | 2 | 3 | Rate | P value | ||
Age (yr) | |||||||
< 60 | 35 | 7 | 9 | 9 | 10 | 80.0% | 0.5261 |
≥ 60 | 61 | 12 | 15 | 26 | 8 | 80.3% | 0.9692 |
Gender | |||||||
Male | 67 | 10 | 17 | 27 | 13 | 85.1% | 0.1561 |
Female | 29 | 9 | 7 | 8 | 5 | 69.0% | 0.0692 |
Tumor site | |||||||
Cardia | 30 | 9 | 7 | 9 | 5 | 70.0% | 0.4271 |
Corpus | 26 | 5 | 6 | 9 | 6 | 80.8% | 0.1912 |
Antrum | 40 | 5 | 11 | 17 | 7 | 87.5% | |
Stages | |||||||
I + II | 38 | 14 | 9 | 10 | 5 | 63.2% | 0.0041 |
III + IV | 58 | 5 | 15 | 25 | 13 | 91.4% | 0.0012 |
Histological type | |||||||
Tubular | 54 | 12 | 13 | 20 | 9 | 77.8% | 0.1071 |
Papillary | 30 | 6 | 9 | 9 | 6 | 80.0% | 0.6332 |
Mucinous | 6 | 1 | 2 | 3 | 0 | 83.3% | |
Signet ring cell | 6 | 0 | 0 | 3 | 3 | 100.0% | |
Histological grading | |||||||
Well and moderately | 65 | 11 | 17 | 26 | 11 | 83.1% | 0.7351 |
Poorly | 31 | 8 | 7 | 9 | 7 | 74.2% | 0.3072 |
Lymph node metastasis | |||||||
Present | 58 | 7 | 13 | 26 | 12 | 87.9% | 0.0181 |
Absent | 38 | 12 | 11 | 9 | 6 | 68.4% | 0.0192 |
Gastrin has been shown to mediate the induction of COX-2 in gastrointestinal cells[105,106], indicating that there is a direct mechanistic link between gastrin and inflammation (Figure 4). Chronic atrophic gastritis caused by H. pylori activates synthesis of growth factors, cytokines, and gastrin leading to elevated COX-2 expression[107]. Recent studies have demonstrated that hypergastrinemia induced by H. pylori infection is often associated with increased COX-2 expression in chronic atrophic gastritis and gastric cancer[6,96]. Some studies have shown that COX-2 is co-expressed with gastrin in gastric ulcers and gastric cancer[6,55]. On the other hand, an in vitro study indicates that gastrin stimulates COX-2 gene and protein expression in human gastric cancer cells[108]. Our recent study demonstrated that gastrin up-regulates COX-2 experssion in gastric cancer cell lines and this occurs through CCK-2R-mediated JAK2/STAT3 and subsequent PI3K/Akt activation[74] (Figure 5). Additionally, Subramaniam et al[109] reported that gastrin induced COX-2 expression in human gastric cancer cell line AGS stably expressing CCK2R. Gastrin not only increased the stability of COX-2 mRNA in a p38-dependent manner but also enhanced COX-2 gene transcription through the activator protein-1 (AP-1) transcription factor[109].
In another study using AGS gastric cancer cells, H. pylori promoted COX-2 transcription through TLR2/TRL9 that activated the MAPK pathways (ERK1/2, p38, JNK) and resulted in the activation of CRE and AP-1 in the COX-2 promoter[110]. In MKN-45 gastric cancer cells the p38MAPK/ATF-2 pathway was necessary for increased COX-2 expression after H. pylori infection[111]. Thus, H. pylori clearly induces COX-2, but the mechanism seems to be dependent on the H. pylori strain properties and the recipient cells.
In recent years dysregulated microRNAs (miRNAs) have also been found in gastric cancer, and they are linked to many processes, such as cell proliferation, apoptosis, and invasion[112]. Recently, we characterize miRNA-101 (miR-101) expression and its role in COX-2 expression regulation, and the results showed that miR-101 levels in gastric cancer tissues were significantly lower than those in the matched normal tissue[14]. 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 protein levels were observed in the pre-miR-101 infected gastric cancer cells. These results collectively indicate that miR-101 may function as a tumor suppressor in gastric cancer, with COX-2 as a direct target[14]. When miR-101 was overexpressed in gastric cancer cells lines, the mRNA level of COX-2 was decreased in BGC-823, SGC-7901, MKN-45, and AGS cells[14,113]. In addition, miR-101 is downregulated in gastric mucosa infected with H. pylori[114]. These results provide new insights into miR-101 involvement in the pathogenesis of H. pylori-associated gastric cancer, with COX-2 as a direct target.
A lower risk of gastric cancer has been associated with non-steroidal anti-inflammatory drugs (NSAIDs) in a dose-dependent manner[115]. There is also evidence from animal studies showing a reduced gastric cancer incidence under suppression of COX-2 using specific COX-2 inhibitors[116,117]. Considering the association between COX-2/PGE2 pathway and H. pylori-associated gastric carcinogenesis, NSAIDs have been proposed as candidates for chemoprevention of gastric cancer. COX-2 selective inhibitors such as etodolac and celecoxib may have chemopreventive effects[118,119] not only suppressing inflammation, but also causing regression of early-stage tumors[120,121]. Therefore, there is a possibility that COX-2 inhibitors could be useful drugs for regression of remaining precancerous lesion and prevention of gastric cancer occurrence after H. pylori eradication.
The chemopreventive effect of NSAIDs on the development of gastric cancer among H. pylori infected individuals has not been conclusively shown in human clinical trials[122,123]. In patients who underwent H. pylori eradication therapy, chronic use of celecoxib was associated with a higher regression rate of gastric precancerous intestinal metaplasia[122]. However, in patients who had received H. pylori eradication therapy, treatment with another selective COX-2 inhibitor, rofecoxib, for 2 years did not reduce intestinal metaplasia[123]. Considering that cancer chemoprevention by NSAIDs is modulated by both COX-2-dependent and -independent pathways[124], NSAIDs may have variable efficacy in their abilities to prevent gastric cancer.
H. pylori infection is considered a major risk factor for the development of gastric cancer. Hypergastrinemia associated with H. pylori infection induces COX-2 expression, which appears to be related to the carcinogenesis and progression of gastric cancer.
P- Reviewer: Ding SG, Tong Q S- Editor: Gou SX L- Editor: Wang TQ E- Editor: Ma S
1. | Wang F, Meng W, Wang B, Qiao L. Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett. 2014;345:196-202. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 375] [Cited by in F6Publishing: 517] [Article Influence: 51.7] [Reference Citation Analysis (1)] |
2. | Greenfield LK, Jones NL. Modulation of autophagy by Helicobacter pylori and its role in gastric carcinogenesis. Trends Microbiol. 2013;21:602-612. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 67] [Cited by in F6Publishing: 70] [Article Influence: 6.4] [Reference Citation Analysis (0)] |
3. | Long M, Luo J, Li Y, Zeng FY, Li M. Detection and evaluation of antibodies against neutrophil-activating protein of Helicobacter pylori in patients with gastric cancer. World J Gastroenterol. 2009;15:2381-2388. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 14] [Cited by in F6Publishing: 20] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
4. | Sepulveda AR. Helicobacter, Inflammation, and Gastric Cancer. Curr Pathobiol Rep. 2013;1:9-18. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 69] [Cited by in F6Publishing: 53] [Article Influence: 4.8] [Reference Citation Analysis (0)] |
5. | Infection with Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:177-240. [PubMed] [Cited in This Article: ] |
6. | Konturek PC, Hartwich A, Zuchowicz M, Labza H, Pierzchalski P, Karczewska E, Bielanski W, Hahn EG, Konturek SJ. Helicobacter pylori, gastrin and cyclooxygenases in gastric cancer. J Physiol Pharmacol. 2000;51:737-749. [PubMed] [Cited in This Article: ] |
7. | Miyaji M, Ogoshi K, Tajima T, Mitomi T. Association between serum gastrin levels, gastric acid secretion and age in early gastric cancer. Tumour Biol. 1997;18:311-320. [PubMed] [Cited in This Article: ] |
8. | Takaishi S, Tu S, Dubeykovskaya ZA, Whary MT, Muthupalani S, Rickman BH, Rogers AB, Lertkowit N, Varro A, Fox JG. Gastrin is an essential cofactor for helicobacter-associated gastric corpus carcinogenesis in C57BL/6 mice. Am J Pathol. 2009;175:365-375. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 43] [Cited by in F6Publishing: 48] [Article Influence: 3.2] [Reference Citation Analysis (0)] |
9. | Fox JG, Wang TC, Rogers AB, Poutahidis T, Ge Z, Taylor N, Dangler CA, Israel DA, Krishna U, Gaus K. Host and microbial constituents influence Helicobacter pylori-induced cancer in a murine model of hypergastrinemia. Gastroenterology. 2003;124:1879-1890. [PubMed] [Cited in This Article: ] |
10. | Takaishi S, Cui G, Frederick DM, Carlson JE, Houghton J, Varro A, Dockray GJ, Ge Z, Whary MT, Rogers AB. Synergistic inhibitory effects of gastrin and histamine receptor antagonists on Helicobacter-induced gastric cancer. Gastroenterology. 2005;128:1965-1983. [PubMed] [Cited in This Article: ] |
11. | Wang TC, Dangler CA, Chen D, Goldenring JR, Koh T, Raychowdhury R, Coffey RJ, Ito S, Varro A, Dockray GJ. Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer. Gastroenterology. 2000;118:36-47. [PubMed] [Cited in This Article: ] |
12. | Smith WL, Meade EA, DeWitt DL. Pharmacology of prostaglandin endoperoxide synthase isozymes-1 and -2. Ann N Y Acad Sci. 1994;714:136-142. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 133] [Cited by in F6Publishing: 139] [Article Influence: 4.6] [Reference Citation Analysis (0)] |
13. | Rodrigues NL, Doré M, Doucet MY. Expression of cyclooxygenase isoforms in ulcerated tissues of the nonglandular portion of the stomach in horses. Am J Vet Res. 2010;71:592-596. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 4] [Cited by in F6Publishing: 4] [Article Influence: 0.3] [Reference Citation Analysis (0)] |
14. | He XP, Shao Y, Li XL, Xu W, Chen GS, Sun HH, Xu HC, Xu X, Tang D, Zheng XF. Downregulation of miR-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth. FEBS J. 2012;279:4201-4212. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 74] [Cited by in F6Publishing: 78] [Article Influence: 6.5] [Reference Citation Analysis (0)] |
15. | Tseng YC, Tsai YH, Tseng MJ, Hsu KW, Yang MC, Huang KH, Li AF, Chi CW, Hsieh RH, Ku HH. Notch2-induced COX-2 expression enhancing gastric cancer progression. Mol Carcinog. 2012;51:939-951. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 35] [Cited by in F6Publishing: 46] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
16. | Forones NM, Kawamura KY, Segreto HR, Artigiani Neto R, Focchi GR, Oshima CT. Expression of COX-2 in stomach carcinogenesis. J Gastrointest Cancer. 2008;39:4-10. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 13] [Cited by in F6Publishing: 14] [Article Influence: 0.9] [Reference Citation Analysis (0)] |
17. | Yamac D, Ayyildiz T, Coşkun U, Akyürek N, Dursun A, Seckin S, Koybasioglu F. Cyclooxygenase-2 expression and its association with angiogenesis, Helicobacter pylori, and clinicopathologic characteristics of gastric carcinoma. Pathol Res Pract. 2008;204:527-536. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 21] [Cited by in F6Publishing: 27] [Article Influence: 1.7] [Reference Citation Analysis (0)] |
18. | Sung JJ, Leung WK, Go MY, To KF, Cheng AS, Ng EK, Chan FK. Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions. Am J Pathol. 2000;157:729-735. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 196] [Cited by in F6Publishing: 210] [Article Influence: 8.8] [Reference Citation Analysis (0)] |
19. | Tatsuguchi A, Sakamoto C, Wada K, Akamatsu T, Tsukui T, Miyake K, Futagami S, Kishida T, Fukuda Y, Yamanaka N. Localisation of cyclooxygenase 1 and cyclooxygenase 2 in Helicobacter pylori related gastritis and gastric ulcer tissues in humans. Gut. 2000;46:782-789. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 86] [Cited by in F6Publishing: 91] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
20. | Chan FK, To KF, Ng YP, Lee TL, Cheng AS, Leung WK, Sung JJ. Expression and cellular localization of COX-1 and -2 in Helicobacter pylori gastritis. Aliment Pharmacol Ther. 2001;15:187-193. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 28] [Cited by in F6Publishing: 32] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
21. | Sun WH, Yu Q, Shen H, Ou XL, Cao DZ, Yu T, Qian C, Zhu F, Sun YL, Fu XL. Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis. World J Gastroenterol. 2004;10:2809-2813. [PubMed] [Cited in This Article: ] |
22. | Liu D, He Q, Liu C. Correlations among Helicobacter pylori infection and the expression of cyclooxygenase-2 and vascular endothelial growth factor in gastric mucosa with intestinal metaplasia or dysplasia. J Gastroenterol Hepatol. 2010;25:795-799. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 18] [Cited by in F6Publishing: 19] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
23. | Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology. 1998;114:1169-1179. [PubMed] [Cited in This Article: ] |
24. | Danesh J. Helicobacter pylori infection and gastric cancer: systematic review of the epidemiological studies. Aliment Pharmacol Ther. 1999;13:851-856. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 146] [Cited by in F6Publishing: 152] [Article Influence: 6.1] [Reference Citation Analysis (0)] |
25. | Eslick GD. Helicobacter pylori infection causes gastric cancer? A review of the epidemiological, meta-analytic, and experimental evidence. World J Gastroenterol. 2006;12:2991-2999. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 58] [Cited by in F6Publishing: 52] [Article Influence: 2.9] [Reference Citation Analysis (0)] |
26. | Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey AR, Wald N, Sitas F. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ. 1991;302:1302-1305. [PubMed] [Cited in This Article: ] |
27. | Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325:1127-1131. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2805] [Cited by in F6Publishing: 2681] [Article Influence: 81.2] [Reference Citation Analysis (0)] |
28. | Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI, Blaser MJ. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991;325:1132-1136. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1302] [Cited by in F6Publishing: 1209] [Article Influence: 36.6] [Reference Citation Analysis (0)] |
29. | Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784-789. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3126] [Cited by in F6Publishing: 3061] [Article Influence: 133.1] [Reference Citation Analysis (0)] |
30. | Eslick GD, Lim LL, Byles JE, Xia HH, Talley NJ. Association of Helicobacter pylori infection with gastric carcinoma: a meta-analysis. Am J Gastroenterol. 1999;94:2373-2379. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 268] [Cited by in F6Publishing: 264] [Article Influence: 10.6] [Reference Citation Analysis (0)] |
31. | Xue FB, Xu YY, Wan Y, Pan BR, Ren J, Fan DM. Association of H. pylori infection with gastric carcinoma: a Meta analysis. World J Gastroenterol. 2001;7:801-804. [PubMed] [Cited in This Article: ] |
32. | Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut. 2001;49:347-353. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 704] [Cited by in F6Publishing: 719] [Article Influence: 31.3] [Reference Citation Analysis (1)] |
33. | Huang JQ, Zheng GF, Sumanac K, Irvine EJ, Hunt RH. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology. 2003;125:1636-1644. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 365] [Cited by in F6Publishing: 364] [Article Influence: 17.3] [Reference Citation Analysis (0)] |
34. | An international association between Helicobacter pylori infection and gastric cancer. The EUROGAST Study Group. Lancet. 1993;341:1359-1362. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 842] [Cited by in F6Publishing: 726] [Article Influence: 23.4] [Reference Citation Analysis (0)] |
35. | Guillemin K, Salama NR, Tompkins LS, Falkow S. Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proc Natl Acad Sci USA. 2002;99:15136-15141. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 166] [Cited by in F6Publishing: 173] [Article Influence: 7.9] [Reference Citation Analysis (0)] |
36. | Ferreira AC, Isomoto H, Moriyama M, Fujioka T, Machado JC, Yamaoka Y. Helicobacter and gastric malignancies. Helicobacter. 2008;13 Suppl 1:28-34. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 39] [Cited by in F6Publishing: 40] [Article Influence: 2.5] [Reference Citation Analysis (0)] |
37. | Wang F, Sun G, Zou Y, Zhong F, Ma T, Li X. Protective role of Helicobacter pylori infection in prognosis of gastric cancer: evidence from 2,454 patients with gastric cancer. PLoS One. 2013;8:e62440. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 20] [Cited by in F6Publishing: 22] [Article Influence: 2.0] [Reference Citation Analysis (0)] |
38. | Kang SY, Han JH, Ahn MS, Lee HW, Jeong SH, Park JS, Cho YK, Han SU, Kim YB, Kim JH. Helicobacter pylori infection as an independent prognostic factor for locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection. Int J Cancer. 2012;130:948-958. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 30] [Cited by in F6Publishing: 33] [Article Influence: 2.5] [Reference Citation Analysis (0)] |
39. | Marrelli D, Pedrazzani C, Berardi A, Corso G, Neri A, Garosi L, Vindigni C, Santucci A, Figura N, Roviello F. Negative Helicobacter pylori status is associated with poor prognosis in patients with gastric cancer. Cancer. 2009;115:2071-2080. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 71] [Cited by in F6Publishing: 74] [Article Influence: 4.9] [Reference Citation Analysis (0)] |
40. | Meimarakis G, Winter H, Assmann I, Kopp R, Lehn N, Kist M, Stolte M, Jauch KW, Hatz RA. Helicobacter pylori as a prognostic indicator after curative resection of gastric carcinoma: a prospective study. Lancet Oncol. 2006;7:211-222. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 73] [Cited by in F6Publishing: 78] [Article Influence: 4.3] [Reference Citation Analysis (0)] |
41. | Choi IK, Sung HJ, Lee JH, Kim JS, Seo JH. The relationship between Helicobacter pylori infection and the effects of chemotherapy in patients with advanced or metastatic gastric cancer. Cancer Chemother Pharmacol. 2012;70:555-558. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 15] [Cited by in F6Publishing: 16] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
42. | Shimizu N, Ikehara Y, Inada K, Nakanishi H, Tsukamoto T, Nozaki K, Kaminishi M, Kuramoto S, Sugiyama A, Katsuyama T. Eradication diminishes enhancing effects of Helicobacter pylori infection on glandular stomach carcinogenesis in Mongolian gerbils. Cancer Res. 2000;60:1512-1514. [PubMed] [Cited in This Article: ] |
43. | Nozaki K, Shimizu N, Ikehara Y, Inoue M, Tsukamoto T, Inada K, Tanaka H, Kumagai T, Kaminishi M, Tatematsu M. Effect of early eradication on Helicobacter pylori-related gastric carcinogenesis in Mongolian gerbils. Cancer Sci. 2003;94:235-239. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 102] [Cited by in F6Publishing: 89] [Article Influence: 4.2] [Reference Citation Analysis (0)] |
44. | Correa P. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992;52:6735-6740. [PubMed] [Cited in This Article: ] |
45. | Mera R, Fontham ET, Bravo LE, Bravo JC, Piazuelo MB, Camargo MC, Correa P. Long term follow up of patients treated for Helicobacter pylori infection. Gut. 2005;54:1536-1540. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 239] [Cited by in F6Publishing: 243] [Article Influence: 12.8] [Reference Citation Analysis (0)] |
46. | Uemura N, Mukai T, Okamoto S, Yamaguchi S, Mashiba H, Taniyama K, Sasaki N, Haruma K, Sumii K, Kajiyama G. Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer. Cancer Epidemiol Biomarkers Prev. 1997;6:639-642. [PubMed] [Cited in This Article: ] |
47. | Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008;372:392-397. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 876] [Cited by in F6Publishing: 879] [Article Influence: 54.9] [Reference Citation Analysis (0)] |
48. | Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291:187-194. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1015] [Cited by in F6Publishing: 995] [Article Influence: 49.8] [Reference Citation Analysis (0)] |
49. | Yanaoka K, Oka M, Ohata H, Yoshimura N, Deguchi H, Mukoubayashi C, Enomoto S, Inoue I, Iguchi M, Maekita T. Eradication of Helicobacter pylori prevents cancer development in subjects with mild gastric atrophy identified by serum pepsinogen levels. Int J Cancer. 2009;125:2697-2703. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 101] [Cited by in F6Publishing: 107] [Article Influence: 7.1] [Reference Citation Analysis (0)] |
50. | Fuccio L, Zagari RM, Eusebi LH, Laterza L, Cennamo V, Ceroni L, Grilli D, Bazzoli F. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 2009;151:121-128. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 246] [Cited by in F6Publishing: 235] [Article Influence: 15.7] [Reference Citation Analysis (0)] |
51. | Strofilas A, Lagoudianakis EE, Seretis C, Pappas A, Koronakis N, Keramidaris D, Koukoutsis I, Chrysikos I, Manouras I, Manouras A. Association of helicobacter pylori infection and colon cancer. J Clin Med Res. 2012;4:172-176. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 15] [Cited by in F6Publishing: 29] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
52. | Zhou J, Xie Y, Zhao Y, Wang S, Li Y. Human gastrin mRNA expression up-regulated by Helicobacter pylori CagA through MEK/ERK and JAK2-signaling pathways in gastric cancer cells. Gastric Cancer. 2011;14:322-331. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 14] [Cited by in F6Publishing: 15] [Article Influence: 1.2] [Reference Citation Analysis (0)] |
53. | Rieder G, Merchant JL, Haas R. Helicobacter pylori cag-type IV secretion system facilitates corpus colonization to induce precancerous conditions in Mongolian gerbils. Gastroenterology. 2005;128:1229-1242. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 139] [Cited by in F6Publishing: 145] [Article Influence: 7.6] [Reference Citation Analysis (0)] |
54. | Kudo T, Lu H, Wu JY, Ohno T, Wu MJ, Genta RM, Graham DY, Yamaoka Y. Pattern of transcription factor activation in Helicobacter pylori-infected Mongolian gerbils. Gastroenterology. 2007;132:1024-1038. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 31] [Cited by in F6Publishing: 33] [Article Influence: 1.9] [Reference Citation Analysis (0)] |
55. | Konturek SJ, Konturek PC, Plonka A, Duda A, Sito E, Zuchowicz M, Hahn EG. Implication of gastrin in cyclooxygenase-2 expression in Helicobacter pylori infected gastric ulceration. Prostaglandins Other Lipid Mediat. 2001;66:39-51. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 18] [Cited by in F6Publishing: 19] [Article Influence: 0.8] [Reference Citation Analysis (0)] |
56. | Waghray M, Zavros Y, Saqui-Salces M, El-Zaatari M, Alamelumangapuram CB, Todisco A, Eaton KA, Merchant JL. Interleukin-1beta promotes gastric atrophy through suppression of Sonic Hedgehog. Gastroenterology. 2010;138:562-72, 572.e1-2. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 78] [Cited by in F6Publishing: 86] [Article Influence: 6.1] [Reference Citation Analysis (0)] |
57. | Brand SJ, Stone D. Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria. J Clin Invest. 1988;82:1059-1066. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 131] [Cited by in F6Publishing: 139] [Article Influence: 3.9] [Reference Citation Analysis (0)] |
58. | Chittajallu RS, Neithercut WD, Macdonald AM, McColl KE. Effect of increasing Helicobacter pylori ammonia production by urea infusion on plasma gastrin concentrations. Gut. 1991;32:21-24. [PubMed] [Cited in This Article: ] |
59. | Beales I, Blaser MJ, Srinivasan S, Calam J, Pérez-Pérez GI, Yamada T, Scheiman J, Post L, Del Valle J. Effect of Helicobacter pylori products and recombinant cytokines on gastrin release from cultured canine G cells. Gastroenterology. 1997;113:465-471. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 75] [Cited by in F6Publishing: 78] [Article Influence: 2.9] [Reference Citation Analysis (0)] |
60. | Beales IL, Calam J. Helicobacter pylori increases gastrin release from cultured canine antral G-cells. Eur J Gastroenterol Hepatol. 2000;12:641-644. [PubMed] [Cited in This Article: ] |
61. | Lehmann FS, Golodner EH, Wang J, Chen MC, Avedian D, Calam J, Walsh JH, Dubinett S, Soll AH. Mononuclear cells and cytokines stimulate gastrin release from canine antral cells in primary culture. Am J Physiol. 1996;270:G783-G788. [PubMed] [Cited in This Article: ] |
62. | Smith JT, Pounder RE, Nwokolo CU, Lanzon-Miller S, Evans DG, Graham DY, Evans DJ. Inappropriate hypergastrinaemia in asymptomatic healthy subjects infected with Helicobacter pylori. Gut. 1990;31:522-525. [PubMed] [Cited in This Article: ] |
63. | Kai H, Ito M, Kitadai Y, Tanaka S, Haruma K, Chayama K. Chronic gastritis with expression of inducible nitric oxide synthase is associated with high expression of interleukin-6 and hypergastrinaemia. Aliment Pharmacol Ther. 2004;19:1309-1314. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 10] [Cited by in F6Publishing: 9] [Article Influence: 0.5] [Reference Citation Analysis (0)] |
64. | De Francesco V, Zullo A, Rinaldi V, Hassan C, Ballanti P, Winn S, Diana F, Morini S, Attili AF. Relationship between antral lymphocyte density and basal gastrin levels in patients with Helicobacter pylori infection. Dig Liver Dis. 2000;32:676-681. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 5] [Cited by in F6Publishing: 6] [Article Influence: 0.3] [Reference Citation Analysis (0)] |
65. | Sokic-Milutinovic A, Todorovic V, Milosavljevic T, Micev M, Drndarevic N, Mitrovic O. Gastrin and antral G cells in course of Helicobacter pylori eradication: six months follow up study. World J Gastroenterol. 2005;11:4140-4147. [PubMed] [Cited in This Article: ] |
66. | Gibbons AH, Legon S, Walker MM, Ghatei M, Calam J. The effect of gastrin-releasing peptide on gastrin and somatostatin messenger RNAs in humans infected with Helicobacter pylori. Gastroenterology. 1997;112:1940-1947. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 19] [Cited by in F6Publishing: 22] [Article Influence: 0.8] [Reference Citation Analysis (0)] |
67. | Sumii M, Sumii K, Tari A, Kawaguchi H, Yamamoto G, Takehara Y, Fukino Y, Kamiyasu T, Hamada M, Tsuda T. Expression of antral gastrin and somatostatin mRNA in Helicobacter pylori-infected subjects. Am J Gastroenterol. 1994;89:1515-1519. [PubMed] [Cited in This Article: ] |
68. | Richter-Dahlfors A, Heczko U, Meloche RM, Finlay BB, Buchan AM. Helicobacter pylori-infected human antral primary cell cultures: effect on gastrin cell function. Am J Physiol. 1998;275:G393-G401. [PubMed] [Cited in This Article: ] |
69. | Brzozowski T, Konturek PC, Mierzwa M, Drozdowicz D, Bielanski W, Kwiecien S, Konturek SJ, Stachura J, Pawlik WW, Hahn EG. Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression, apoptosis, and functional gastric mucosal impairment in Helicobacter pylori-infected Mongolian gerbils. Helicobacter. 2006;11:10-20. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 30] [Cited by in F6Publishing: 24] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
70. | Levi S, Beardshall K, Swift I, Foulkes W, Playford R, Ghosh P, Calam J. Antral Helicobacter pylori, hypergastrinaemia, and duodenal ulcers: effect of eradicating the organism. BMJ. 1989;299:1504-1505. [PubMed] [Cited in This Article: ] |
71. | Moss SF, Legon S, Bishop AE, Polak JM, Calam J. Effect of Helicobacter pylori on gastric somatostatin in duodenal ulcer disease. Lancet. 1992;340:930-932. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 204] [Cited by in F6Publishing: 184] [Article Influence: 5.8] [Reference Citation Analysis (0)] |
72. | Chao C, Hellmich MR. Gastrin, inflammation, and carcinogenesis. Curr Opin Endocrinol Diabetes Obes. 2010;17:33-39. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 40] [Cited by in F6Publishing: 42] [Article Influence: 3.0] [Reference Citation Analysis (0)] |
73. | Sun WH, Zhu F, Chen GS, Su H, Luo C, Zhao QS, Zhang Y, Shao Y, Sun J, Zhou SM. Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro. Cancer Lett. 2008;263:302-311. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 42] [Cited by in F6Publishing: 44] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
74. | Xu W, Chen GS, Shao Y, Li XL, Xu HC, Zhang H, Zhu GQ, Zhou YC, He XP, Sun WH. Gastrin acting on the cholecystokinin2 receptor induces cyclooxygenase-2 expression through JAK2/STAT3/PI3K/Akt pathway in human gastric cancer cells. Cancer Lett. 2013;332:11-18. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 30] [Cited by in F6Publishing: 33] [Article Influence: 3.0] [Reference Citation Analysis (0)] |
75. | Semple G, Ryder H, Rooker DP, Batt AR, Kendrick DA, Szelke M, Ohta M, Satoh M, Nishida A, Akuzawa S. (3R)-N-(1-(tert-butylcarbonylmethyl)-2,3-dihydro-2-oxo-5-(2-pyridyl)-1H-1,4-benzodiazepin-3-yl)-N’-(3-(methylamino)phenyl)urea (YF476): a potent and orally active gastrin/CCK-B antagonist. J Med Chem. 1997;40:331-341. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 5] [Cited by in F6Publishing: 5] [Article Influence: 0.2] [Reference Citation Analysis (0)] |
76. | Niwa T, Tsukamoto T, Toyoda T, Mori A, Tanaka H, Maekita T, Ichinose M, Tatematsu M, Ushijima T. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res. 2010;70:1430-1440. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 289] [Cited by in F6Publishing: 305] [Article Influence: 21.8] [Reference Citation Analysis (0)] |
77. | Nakajima T, Enomoto S, Yamashita S, Ando T, Nakanishi Y, Nakazawa K, Oda I, Gotoda T, Ushijima T. Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication. J Gastroenterol. 2010;45:37-44. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 91] [Cited by in F6Publishing: 98] [Article Influence: 7.0] [Reference Citation Analysis (0)] |
78. | Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, Arii K, Kaneda A, Tsukamoto T, Tatematsu M. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res. 2006;12:989-995. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 474] [Cited by in F6Publishing: 463] [Article Influence: 25.7] [Reference Citation Analysis (0)] |
79. | Yoshida T, Kato J, Maekita T, Yamashita S, Enomoto S, Ando T, Niwa T, Deguchi H, Ueda K, Inoue I. Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis. Gastric Cancer. 2013;16:488-497. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 22] [Cited by in F6Publishing: 27] [Article Influence: 2.5] [Reference Citation Analysis (0)] |
80. | Wen XZ, Akiyama Y, Pan KF, Liu ZJ, Lu ZM, Zhou J, Gu LK, Dong CX, Zhu BD, Ji JF. Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas. World J Gastroenterol. 2010;16:1201-1208. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 41] [Cited by in F6Publishing: 41] [Article Influence: 2.9] [Reference Citation Analysis (0)] |
81. | Guo XB, Guo L, Zhi QM, Ji J, Jiang JL, Zhang RJ, Zhang JN, Zhang J, Chen XH, Cai Q. Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa. J Gastroenterol Hepatol. 2011;26:1685-1690. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 12] [Cited by in F6Publishing: 14] [Article Influence: 1.1] [Reference Citation Analysis (0)] |
82. | Niwa T, Toyoda T, Tsukamoto T, Mori A, Tatematsu M, Ushijima T. Prevention of Helicobacter pylori-induced gastric cancers in gerbils by a DNA demethylating agent. Cancer Prev Res (Phila). 2013;6:263-270. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 50] [Cited by in F6Publishing: 55] [Article Influence: 5.0] [Reference Citation Analysis (0)] |
83. | Fu S, Ramanujam KS, Wong A, Fantry GT, Drachenberg CB, James SP, Meltzer SJ, Wilson KT. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology. 1999;116:1319-1329. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 294] [Cited by in F6Publishing: 308] [Article Influence: 12.3] [Reference Citation Analysis (0)] |
84. | Sawaoka H, Kawano S, Tsuji S, Tsuji M, Sun W, Gunawan ES, Hori M. Helicobacter pylori infection induces cyclooxygenase-2 expression in human gastric mucosa. Prostaglandins Leukot Essent Fatty Acids. 1998;59:313-316. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 68] [Cited by in F6Publishing: 71] [Article Influence: 2.7] [Reference Citation Analysis (0)] |
85. | Ristimäki A, Honkanen N, Jänkälä H, Sipponen P, Härkönen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res. 1997;57:1276-1280. [PubMed] [Cited in This Article: ] |
86. | Uefuji K, Ichikura T, Mochizuki H, Shinomiya N. Expression of cyclooxygenase-2 protein in gastric adenocarcinoma. J Surg Oncol. 1998;69:168-172. [PubMed] [DOI] [Cited in This Article: ] [Cited by in F6Publishing: 7] [Reference Citation Analysis (0)] |
87. | Romano M, Ricci V, Memoli A, Tuccillo C, Di Popolo A, Sommi P, Acquaviva AM, Del Vecchio Blanco C, Bruni CB, Zarrilli R. Helicobacter pylori up-regulates cyclooxygenase-2 mRNA expression and prostaglandin E2 synthesis in MKN 28 gastric mucosal cells in vitro. J Biol Chem. 1998;273:28560-28563. [PubMed] [Cited in This Article: ] |
88. | Hisatsune J, Yamasaki E, Nakayama M, Shirasaka D, Kurazono H, Katagata Y, Inoue H, Han J, Sap J, Yahiro K. Helicobacter pylori VacA enhances prostaglandin E2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein kinase/activating transcription factor 2 cascade in AZ-521 cells. Infect Immun. 2007;75:4472-4481. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 33] [Cited by in F6Publishing: 34] [Article Influence: 2.0] [Reference Citation Analysis (0)] |
89. | Caputo R, Tuccillo C, Manzo BA, Zarrilli R, Tortora G, Blanco Cdel V, Ricci V, Ciardiello F, Romano M. Helicobacter pylori VacA toxin up-regulates vascular endothelial growth factor expression in MKN 28 gastric cells through an epidermal growth factor receptor-, cyclooxygenase-2-dependent mechanism. Clin Cancer Res. 2003;9:2015-2021. [PubMed] [Cited in This Article: ] |
90. | Shen H, Sun WH, Xue QP, Wu J, Cheng YL, Ding GX, Fu HY, Tsuji S, Kawano S. Influences of Helicobacter pylori on cyclooxygenase-2 expression and prostaglandinE2 synthesis in rat gastric epithelial cells in vitro. J Gastroenterol Hepatol. 2006;21:754-758. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 14] [Cited by in F6Publishing: 14] [Article Influence: 0.8] [Reference Citation Analysis (0)] |
91. | Oshima H, Popivanova BK, Oguma K, Kong D, Ishikawa TO, Oshima M. Activation of epidermal growth factor receptor signaling by the prostaglandin E(2) receptor EP4 pathway during gastric tumorigenesis. Cancer Sci. 2011;102:713-719. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 52] [Cited by in F6Publishing: 49] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
92. | Wong BC, Zhang L, Ma JL, Pan KF, Li JY, Shen L, Liu WD, Feng GS, Zhang XD, Li J. Effects of selective COX-2 inhibitor and Helicobacter pylori eradication on precancerous gastric lesions. Gut. 2012;61:812-818. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 110] [Cited by in F6Publishing: 107] [Article Influence: 8.9] [Reference Citation Analysis (0)] |
93. | Wang D, Dubois RN. Prostaglandins and cancer. Gut. 2006;55:115-122. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 630] [Cited by in F6Publishing: 659] [Article Influence: 36.6] [Reference Citation Analysis (0)] |
94. | Oshima H, Hioki K, Popivanova BK, Oguma K, Van Rooijen N, Ishikawa TO, Oshima M. Prostaglandin E2 signaling and bacterial infection recruit tumor-promoting macrophages to mouse gastric tumors. Gastroenterology. 2011;140:596-607.e7. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 88] [Cited by in F6Publishing: 98] [Article Influence: 7.5] [Reference Citation Analysis (0)] |
95. | Konturek PC, Kania J, Kukharsky V, Raithel M, Ocker M, Rembiasz K, Hahn EG, Konturek SJ. Implication of peroxisome proliferator-activated receptor gamma and proinflammatory cytokines in gastric carcinogenesis: link to Helicobacter pylori-infection. J Pharmacol Sci. 2004;96:134-143. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 23] [Cited by in F6Publishing: 25] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
96. | Konturek PC, Rembiasz K, Konturek SJ, Stachura J, Bielanski W, Galuschka K, Karcz D, Hahn EG. Gene expression of ornithine decarboxylase, cyclooxygenase-2, and gastrin in atrophic gastric mucosa infected with Helicobacter pylori before and after eradication therapy. Dig Dis Sci. 2003;48:36-46. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 27] [Cited by in F6Publishing: 30] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
97. | McCarthy CJ, Crofford LJ, Greenson J, Scheiman JM. Cyclooxygenase-2 expression in gastric antral mucosa before and after eradication of Helicobacter pylori infection. Am J Gastroenterol. 1999;94:1218-1223. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 107] [Cited by in F6Publishing: 111] [Article Influence: 4.4] [Reference Citation Analysis (0)] |
98. | Nardone G, Rocco A, Vaira D, Staibano S, Budillon A, Tatangelo F, Sciulli MG, Perna F, Salvatore G, Di Benedetto M. Expression of COX-2, mPGE-synthase1, MDR-1 (P-gp), and Bcl-xL: a molecular pathway of H pylori-related gastric carcinogenesis. J Pathol. 2004;202:305-312. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 68] [Cited by in F6Publishing: 72] [Article Influence: 3.6] [Reference Citation Analysis (0)] |
99. | Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology. 2007;133:659-672. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 467] [Cited by in F6Publishing: 483] [Article Influence: 28.4] [Reference Citation Analysis (0)] |
100. | Saukkonen K, Nieminen O, van Rees B, Vilkki S, Härkönen M, Juhola M, Mecklin JP, Sipponen P, Ristimäki A. Expression of cyclooxygenase-2 in dysplasia of the stomach and in intestinal-type gastric adenocarcinoma. Clin Cancer Res. 2001;7:1923-1931. [PubMed] [Cited in This Article: ] |
101. | Uefuji K, Ichikura T, Mochizuki H. Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer. Clin Cancer Res. 2000;6:135-138. [PubMed] [Cited in This Article: ] |
102. | Shi H, Xu JM, Hu NZ, Xie HJ. Prognostic significance of expression of cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma. World J Gastroenterol. 2003;9:1421-1426. [PubMed] [Cited in This Article: ] |
103. | Murata H, Kawano S, Tsuji S, Tsuji M, Sawaoka H, Kimura Y, Shiozaki H, Hori M. Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenterol. 1999;94:451-455. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 179] [Cited by in F6Publishing: 201] [Article Influence: 8.0] [Reference Citation Analysis (0)] |
104. | Sun WH, Sun YL, Fang RN, Shao Y, Xu HC, Xue QP, Ding GX, Cheng YL. Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis. Jpn J Clin Oncol. 2005;35:707-713. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 48] [Cited by in F6Publishing: 54] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
105. | Abdalla SI, Lao-Sirieix P, Novelli MR, Lovat LB, Sanderson IR, Fitzgerald RC. Gastrin-induced cyclooxygenase-2 expression in Barrett’s carcinogenesis. Clin Cancer Res. 2004;10:4784-4792. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 63] [Cited by in F6Publishing: 72] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
106. | Guo YS, Cheng JZ, Jin GF, Gutkind JS, Hellmich MR, Townsend CM. Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways. Evidence for involvement of ERK5 kinase and transactivation of the epidermal growth factor receptor. J Biol Chem. 2002;277:48755-48763. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 77] [Cited by in F6Publishing: 84] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
107. | Konturek PC, Konturek SJ, Brzozowski T. Helicobacter pylori infection in gastric cancerogenesis. J Physiol Pharmacol. 2009;60:3-21. [PubMed] [Cited in This Article: ] |
108. | Konturek PC, Kania J, Kukharsky V, Ocker S, Hahn EG, Konturek SJ. Influence of gastrin on the expression of cyclooxygenase-2, hepatocyte growth factor and apoptosis-related proteins in gastric epithelial cells. J Physiol Pharmacol. 2003;54:17-32. [PubMed] [Cited in This Article: ] |
109. | Subramaniam D, Ramalingam S, May R, Dieckgraefe BK, Berg DE, Pothoulakis C, Houchen CW, Wang TC, Anant S. Gastrin-mediated interleukin-8 and cyclooxygenase-2 gene expression: differential transcriptional and posttranscriptional mechanisms. Gastroenterology. 2008;134:1070-1082. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 45] [Cited by in F6Publishing: 52] [Article Influence: 3.3] [Reference Citation Analysis (0)] |
110. | Chang YJ, Wu MS, Lin JT, Sheu BS, Muta T, Inoue H, Chen CC. Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-kappaB activation. Mol Pharmacol. 2004;66:1465-1477. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 113] [Cited by in F6Publishing: 123] [Article Influence: 6.2] [Reference Citation Analysis (0)] |
111. | Li Q, Liu N, Shen B, Zhou L, Wang Y, Wang Y, Sun J, Fan Z, Liu RH. Helicobacter pylori enhances cyclooxygenase 2 expression via p38MAPK/ATF-2 signaling pathway in MKN45 cells. Cancer Lett. 2009;278:97-103. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 19] [Cited by in F6Publishing: 24] [Article Influence: 1.6] [Reference Citation Analysis (0)] |
112. | Wu WK, Lee CW, Cho CH, Fan D, Wu K, Yu J, Sung JJ. MicroRNA dysregulation in gastric cancer: a new player enters the game. Oncogene. 2010;29:5761-5771. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 202] [Cited by in F6Publishing: 235] [Article Influence: 16.8] [Reference Citation Analysis (0)] |
113. | Wang HJ, Ruan HJ, He XJ, Ma YY, Jiang XT, Xia YJ, Ye ZY, Tao HQ. MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion. Eur J Cancer. 2010;46:2295-2303. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 189] [Cited by in F6Publishing: 208] [Article Influence: 14.9] [Reference Citation Analysis (0)] |
114. | Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, Nakao K, Hirayama T, Kohno S. MicroRNA signatures in Helicobacter pylori-infected gastric mucosa. Int J Cancer. 2011;128:361-370. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 136] [Cited by in F6Publishing: 152] [Article Influence: 10.9] [Reference Citation Analysis (0)] |
115. | Wang WH, Huang JQ, Zheng GF, Lam SK, Karlberg J, Wong BC. Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2003;95:1784-1791. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 191] [Cited by in F6Publishing: 209] [Article Influence: 10.5] [Reference Citation Analysis (0)] |
116. | Hu PJ, Yu J, Zeng ZR, Leung WK, Lin HL, Tang BD, Bai AH, Sung JJ. Chemoprevention of gastric cancer by celecoxib in rats. Gut. 2004;53:195-200. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 113] [Cited by in F6Publishing: 123] [Article Influence: 6.2] [Reference Citation Analysis (0)] |
117. | Saukkonen K, Tomasetto C, Narko K, Rio MC, Ristimäki A. Cyclooxygenase-2 expression and effect of celecoxib in gastric adenomas of trefoil factor 1-deficient mice. Cancer Res. 2003;63:3032-3036. [PubMed] [Cited in This Article: ] |
118. | Futagami S, Suzuki K, Hiratsuka T, Shindo T, Hamamoto T, Tatsuguchi A, Ueki N, Shinji Y, Kusunoki M, Wada K. Celecoxib inhibits Cdx2 expression and prevents gastric cancer in Helicobacter pylori-infected Mongolian gerbils. Digestion. 2006;74:187-198. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 15] [Cited by in F6Publishing: 17] [Article Influence: 1.0] [Reference Citation Analysis (0)] |
119. | Magari H, Shimizu Y, Inada K, Enomoto S, Tomeki T, Yanaoka K, Tamai H, Arii K, Nakata H, Oka M. Inhibitory effect of etodolac, a selective cyclooxygenase-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils. Biochem Biophys Res Commun. 2005;334:606-612. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 24] [Cited by in F6Publishing: 22] [Article Influence: 1.2] [Reference Citation Analysis (0)] |
120. | Chiu CH, McEntee MF, Whelan J. Sulindac causes rapid regression of preexisting tumors in Min/+ mice independent of prostaglandin biosynthesis. Cancer Res. 1997;57:4267-4273. [PubMed] [Cited in This Article: ] |
121. | Reddy BS, Maruyama H, Kelloff G. Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal antiinflammatory drug, during different stages of rat colon tumor development. Cancer Res. 1987;47:5340-5346. [PubMed] [Cited in This Article: ] |
122. | Yang HB, Cheng HC, Sheu BS, Hung KH, Liou MF, Wu JJ. Chronic celecoxib users more often show regression of gastric intestinal metaplasia after Helicobacter pylori eradication. Aliment Pharmacol Ther. 2007;25:455-461. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 31] [Cited by in F6Publishing: 25] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
123. | Leung WK, Ng EK, Chan FK, Chan WY, Chan KF, Auyeung AC, Lam CC, Lau JY, Sung JJ. Effects of long-term rofecoxib on gastric intestinal metaplasia: results of a randomized controlled trial. Clin Cancer Res. 2006;12:4766-4772. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 38] [Cited by in F6Publishing: 44] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
124. | Grösch S, Maier TJ, Schiffmann S, Geisslinger G. Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst. 2006;98:736-747. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 362] [Cited by in F6Publishing: 348] [Article Influence: 19.3] [Reference Citation Analysis (0)] |