Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many epidemiological studies have shown a strong association between chronic Helicobacter pylori infection and the subsequent development of gastric carcinoma in humans. To confirm this link more clearly, it is necessary to use this bacterium in experimental studies to develop gastric carcinoma in suitable experimental animals. Persistent H. pylori infection has recently been achieved in the Mongolian gerbil model, with results demonstrating that the sequential histopathological changes in the gastric mucosa closely mimic the gastric mucosal changes caused by H. pylori infection in humans. These studies have demonstrated that H. pylori infection enhances gastric carcinogenesis in combination with known carcinogens, such as N-methyl-N-nitroso-urea and N-methyl-N-nitro-N'-nitrosoguanidine and have also demonstrated that H. pylori infection alone can result in the development of gastric carcinoma. These important results provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H. pylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.
 ...
PMID:Helicobacter pylori infection and gastric carcinoma in animal models. 1075 21

Helicobacter pylori infection has been associated with gastric carcinogenesis. Gastric epithelial cells proliferative rate is accelerated in H. pylori infected adult patients. Our study was performed to evaluate proliferative cell activity in gastric epithelium in the course of H. pylori infection in the early stage of its natural history. Gastric antral biopsy specimens were obtained from thirteen H. pylori positive and seven negative children. To assess replication rates we used nucleolar organiser regions staining with colloidal silver nitrate technique (AgNOR). The number of AgNORs per nucleus, area of single AgNOR, and the quotient of these two parameters (AgNOR content) were analysed. The mean area of AgNOR was lower in H. pylori positive than in negative children. Conversely, both the mean number of AgNOR per nucleus and AgNOR content were higher in infected than non infected subjects. These results show accelerated proliferation of gastric antral epithelial cells in the course of H. pylori infection in children. Such alteration of cell replication occurring in an initial phase of natural history of long lasting infection provides an explanation for the association between acquisition of H. pylori infection in the first years of life and the development of gastric cancer.
 ...
PMID:Proliferative activity of gastric epithelial cells in Helicobacter pylori infected children. 1083 74

Helicobacter pylori infection has been considered as a risk factor for gastric carcinoma. Strong evidence exists that reactive oxygen species (ROS) play an important role in carcinogenesis, and in vivo investigations have shown increased synthesis of ROS in the gastric mucosa of H.pylori-infected patients. In the present study the direct effects of H.pylori on ROS and DNA synthesis, induction of apoptosis and DNA repair were investigated in the gastric epithelial cell lines AGS and HM02. Incubation of gastric cells with H.pylori extract induced the synthesis of ROS, diminished the levels of reduced glutathione (GSH), induced DNA fragmentation and increased DNA synthesis in gastric cells. Poly(ADP-ribose) formation was increased in gastric cells exposed to H.pylori extract. FACS analysis of gastric cells exposed to H.pylori extract did not reveal any change in the percentage of cells in the G(2)/M phase of the cell cycle. The radical scavengers MnTBAP (a cell permeable superoxide dismutase mimic), ebselen (a GSH peroxidase mimic) and high doses of catalase completely blocked H.pylori extract-induced elevation in DNA synthesis. Our results indicate that H.pylori extract directly induces the synthesis of ROS in gastric epithelial cells and causes DNA damage.
Carcinogenesis 2000 Jun
PMID:Helicobacter pylori causes DNA damage in gastric epithelial cells. 1083 97

Gastric carcinogenesis is strongly associated with Helicobacter pylori infection, but the underlying genetic mechanisms are largely unknown. The aim of this study was to correlate chromosomal aberrations in gastric cancer to H. pylori status and its different strains, as well as to histological type and other clinico-pathological variables. DNA from 46 gastric cancers (male/female 35/11, age 27-85 years) was extracted from formaldehyde-fixed, paraffin-embedded material and tested for chromosomal gains and losses by comparative genomic hybridization (CGH). Chromosomal aberrations with frequencies of 20% or higher were considered to be non-random changes associated with gastric cancer. The mean number of chromosomal events per tumour was 9.7 (range 0-27), with a mean of 3.2 gains (range 0-16) and 6.5 losses (range 0-15). Gains were most frequently found at chromosomes 8q and 13q (24% and 26%, respectively). Losses were predominantly found on chromosome arms 2q, 9p, 12q, 14q, 15q, 16p, 16q, 17p, 17q, 19p, 19q, and 22q (22%, 30%, 43%, 22%, 33%, 50%, 28%, 50%, 39%, 33%, 39%, and 37%, respectively). Common regions of overlap narrowed down to 2q11-14, 8q23, 9p21, 12q24, 13q21-22, 14q24 and 15q11-15. The mean number of gains was higher in tumours with metastases than in localized tumours (4.1 vs. 1.9, p=0.04). Tumours with a loss at 17p showed a higher number of losses than tumours without a 17p loss (9. 5 vs. 4.7 on average, p<0.001). Neither H. pylori status (+, n=25; -, n=21) nor H. pylori strain was correlated to the total number of events or to any specific chromosomal aberration, nor were there differences between intestinal (n=30) and diffuse (n=15) cancers or any other clinico-pathological variable tested. In conclusion, a complex of chromosomal aberrations is involved in gastric cancer, but their pattern does not depend on H. pylori status or strain, nor on the histological type of the tumour. The exact biological meaning of these aberrations in carcinogenesis needs further clarification.
 ...
PMID:Helicobacter pylori-related and -non-related gastric cancers do not differ with respect to chromosomal aberrations. 1105 12

Risk factors for gastric cancer are receiving renewed attention in light of the recent positive association of Helicobacter pylori infection with gastric cancer. The effect of H.pylori on the balance between oxidants and antioxidants in the stomach is not well known. In this study, we investigated if exposure of gastric cells to H. pylori increases oxidant-associated gastric epithelial cell injury. A human gastric epithelial cell line (AGS) was grown on 96-well clusters, then exposed overnight to either live H.pylori (four cagA(+) and four cagA(-)) or broth culture supernatant from an isogenic H.pylori cagA(+) strain with and without vacA activity. Incubation of AGS cells with cagA(+) and cagA(-) H.pylori strains before exposure to reactive oxygen species (ROS) reduced cell viability on average to 73.7% and 39.5% of controls, respectively. The percent viability of cells exposed to ROS after incubation with control broth, vacA(-) broth and vacA(+) broth was 97.7%, 70.5% and 63.5%, respectively. Experiments were then performed to evaluate the effects of H.pylori exposure on the activities of ROS-scavenging enzymes [catalase, glutathione peroxidase and superoxide dismutase (SOD)] and formation of 8-hydroxy-2-deoxyguanosine (8-OH-dG) adducts in AGS cells. Overnight exposure to cagA(-) strains reduced catalase activity by 42%; in contrast, exposure to cagA(+) H.pylori strains increased catalase activity by 51%. Glutathione peroxidase activity increased with exposure to both cagA(-) and cagA(+) strains by 95% and 240%, respectively. Total SOD activity increased 156% after exposure to cagA(+) strains and was marginally increased (52%) with exposure to cagA(-) strains. CuZn-SOD protein levels, assayed by enzyme-linked immunosorbent assay, were not significantly altered by exposure to H.pylori strains; however, Mn-SOD concentrations were significantly increased (P: < 0.02) after exposure to both cagA(-) and cagA(+) H.pylori strains. Exposure of AGS cells to cagA(+) and cagA(-) H.pylori was associated with, on average, 44.5 and 99.0 8-OH-dG/10(6) dG, respectively. The increase in catalase, glutathione peroxidase and SOD activity is associated with fewer 8-OH-dG DNA adducts and reduced susceptibility of AGS cells to lethal injury from ROS after exposure to cagA(+) H.pylori strains when compared with exposure to cagA(-) H.pylori strains. Alteration in the activity of ROS-scavenging enzymes by the presence of H. pylori may in part be responsible for the increased risk of gastric cancer in persons infected with H.pylori.
Carcinogenesis 2000 Nov
PMID:Influence of Helicobacter pylori on reactive oxygen-induced gastric epithelial cell injury. 1106 73

To determine whether cure of Helicobacter pylori infection influences the expression of COX-2 and nitrotyrosine in the distal stomach of humans, biopsy specimens were examined immunohistochemically. H. pylori infection was determined using a rapid urease test, culture and histology. Positive staining of COX-2/nitrotyrosine in the epithelium was expressed as the percentage of stained cells to the total epithelial cells. There was a significant increase in COX-2/nitrotyrosine staining in H. pylori -positive subjects compared with H. pylori -negative subjects. Cure of the infection resulted in a significant decrease in both COX-2/nitrotyrosine staining in all patients (52.1+/-12.1% vs 15. 4+/-7.2%, P<0.001; and 57.3+/-13.6% vs 36.1+/-18.0%, P<0.01, respectively). However, immunoreactivity of COX-2/nitrotyrosine was observed in all cases with intestinal metaplasia even after the cure of H. pylori infection.Thus, cure of H. pylori infection may decrease the risk of gastric carcinogenesis due to COX-2 and NO-related compounds in gastric mucosa but not in those patients with intestinal metaplasia.
 ...
PMID:Expression of cyclooxygenase-2 and nitrotyrosine in human gastric mucosa before and after Helicobacter pylori eradication. 1109 Feb 59

Helicobacter pylori infection is associated with an increased cell proliferation activity, however the exact mechanisms have not been elucidated. Our aim was to study the effect of Helicobacter pylori infection on normal gastric epithelia, gastritis, intestinal metaplasia and carcinoma by the expression of proliferating cell nuclear antigen and nucleolus organizer regions. Antral biopsies were taken from 121 patients (61 women, 60 men; mean age 58.5 y.). Sections were scored for normal epithelia (n = 15), gastritis without intestinal metaplasia (n = 74), gastritis with intestinal metaplasia (n = 24) and gastric carcinoma (n = 8). 52 patients had H. pylori positive gastritis, and success of eradication therapy was controlled in 34 cases. To characterize cell proliferation immunohistochemistry (PCNA) and histochemistry methods (AgNOR) were used. Results of PCNA and AgNOR significantly correlated except of that in the intestinal metaplasia group. PCNA LI and AgNOR counts were not significant higher in H. pylori positive compared to the H. pylori negative gastritis. Presence of H. pylori caused higher proliferation rate in intestinal metaplasia group measured by PCNA. In the group of intestinal metaplasia the proliferation activity decreased to the activity of the normal epithelia after the successful eradication, but remained high if eradication therapy was failed. Our results suggest, that H. pylori infection plays only as a co-factor in gastric carcinogenesis. Results were controversial in the intestinal metaplasia group, that can be explained by the heterogeneity of the bacteria.
 ...
PMID:[Effect of Helicobacter pylori infection and eradication on proliferative kinetics of the gastric mucosa]. 1118 75

Low gastric juice total vitamin C concentration in the presence of Helicobacter pylori infection probably plays a role in gastric carcinogenesis. Vitamin C plays a role in the neutralization of various pathogenic factors connected with H. pylori infection, including the destruction of free radicals, which damage tissues and cell DNA, and inhibition of the formation of N-nitroso compounds, which have a strong carcinogenic activity. The aim of the study was to determine whether tobacco smoking had any effect on gastric juice vitamin C concentration in healthy subjects and in patients infected with H. pylori. Eighty-six patients with dyspeptic symptoms undergoing routine endoscopy entered the study after giving informed consent. In all patients plasma and gastric juice total vitamin C levels were measured by a spectrophotometric method. They were entered into four groups: group I (controls) - H. pylori-negative non-smokers (n = 17), group II - H. pylori-negative smokers (n = 16), group III - non-smokers with H. pylori infection (n = 21), and group IV - H. pylori-infected smokers (n = 32). In the control group (I) the mean gastric juice total vitamin C concentration was 17.1 microg/ml (range 5.3-40.0 microg/ml), which was significantly higher (P < 0.05) than in group II (12.6 microg/ml, range 5.1-21.0 microg/ml), group III (5.8 microg/ml range 2.1-13.7 microg/ml) and group IV (3.9 microg/ml, range 1.1-10.6 microg/ml) (P < 0.001). Statistically significant differences also were noted between groups II and III (P < 0.01) and groups II and IV (P < 0.001) and between groups III and IV (P < 0.05). These results demonstrate that the concentration of vitamin C in gastric juice is significantly lower in smokers than in non-smokers. This was observed in healthy subjects as well as H. pylori-infected patients. This phenomenon may be one of the mechanisms whereby smoking contributes to the production of gastric lesions, impairs healing of peptic ulcers and also increases the recurrence rate of peptic ulcers in cases with H. pylori infection.
 ...
PMID:Tobacco smoking and vitamin C concentration in gastric juice in healthy subjects and patients with Helicobacter pylori infection. 1120 81

Helicobacter pylori infection causes chronic gastritis (nonatrophic gastritis), which progresses to atrophic gastritis and intestinal metaplasia over a period of decades. Atrophy may result from inflammation and apoptosis caused by H. pylori infection. H. pylori is an important risk factor for peptic ulcer disease. Duodenitis in the gastric metaplasia of the duodenum, hypergastrinemia, and impaired proximal duodenal mucosal bicarbonate secretion are considered causal factors for duodenal ulcer disease. Low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) develops in response to H. pylori infection. Studies of Mongolian gerbil model demonstrated that H. pylori had an initiator or promoter effect on gastric carcinogenesis.
 ...
PMID:[Causal relationship between Helicobacter pylori infection and upper gastroduodenal diseases]. 1121 92

We assessed the possible association between CagA+ Helicobacter pylori infection and gastric carcinogenesis in gastric cancer patients. Gastric biopsy specimens were obtained from 64 patients with gastric cancer and were histologically classified into intestinal and diffuse types. H. pylori infection was determined by cultivation, flaA-PCR and serum antibody against CagA. p53, BAX and transforming growth factor-beta-RII (TGFbeta-RII) gene mutations were analyzed by PCR-SSCP and direct sequencing. Intestinal and diffuse types of cancer were detected in 45 and 19 patients, respectively. H. pylori infection was found in 55 (85.9%) of 64 patients. There was no significant difference in H. pylori positivity between intestinal and diffuse types. However, the CagA antibody was positive in 15 (78.9%) of 19 patients with the diffuse type and in 22 (48.9%) of 45 patients with the intestinal type (p = 0.030). Among the 55 H. pylori-positive cases, 11 (29.7%) of the 37 patients in the CagA+ group were found to have p53 alterations, compared with 2 (11.1%) in the 18 CagA- group (p = 0.182). Moreover, among the 64 gastric cancer patients, p53 alterations were more frequently found in the CagA+ group (29.7%) than in the H. pylori-positive CagA- and H. pylori-negative groups (7.4%; p = 0.033). BAX gene mutations were found in 19 (29.7%) of 64 patients and there was no relationship among CagA seropositivity, cancer stages and histopathological phenotypes. In contrast, the TGFbeta-RII gene mutation was only detected in one CagA- patient. The results suggest that CagA+ H. pylori infection may have an important role in the development of gastric cancer patients with p53 mutations
 ...
PMID:Association between CagA+ Helicobacter pylori infection and p53, bax and transforming growth factor-beta-RII gene mutations in gastric cancer patients. 1125 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>