Numerous cellular and molecular events have been described in development of gastric cancer. In this article, we overviewed roles of Helicobacter pylori (H pylori) infection on some of the important events in gastric carcinogenesis and discussed whether these cellular and molecular events are reversible after cure of the infection. There are several bacterial components affecting gastric epithelial kinetics and promotion of gastric carcinogenesis. The bacterium also increases risks of genetic instability and mutations due to NO and other reactive oxygen species. Epigenetic silencing of tumor suppressor genes such as RUNX3 may alter the frequency of phenotype change of gastric glands to those with intestinal metaplasia. Host factors such as increased expression of growth factors, cytokines and COX-2 have been also reported in non-cancerous tissue in H pylori-positive subjects. It is noteworthy that most of the above phenomena are reversed after the cure of the infection. However, some of them including overexpression of COX-2 continue to exist and may increase risks for carcinogenesis in metaplastic or dysplastic mucosa even after successful H pylori eradication. Thus, H pylori eradication may not completely abolish the risk for gastric carcinogenesis. Efficiency of the cure of the infection in suppressing gastric cancer depends on the timing and the target population, and warrant further investigation.

• Helicobacter
• Cancer
• Gastric acid
• p53
• In-flammation
• Gastric atrophy
• Intestinal metaplasia

• Animals
• Cell Transformation, Neoplastic/genetics
• Core Binding Factor Alpha 3 Subunit/genetics
• Core Binding Factor Alpha 3 Subunit/physiology
• Cyclooxygenase 2/physiology
• Cytokines/physiology
• Epigenesis, Genetic
• Gastric Mucosa/microbiology
• Gastric Mucosa/pathology
• Gene Expression Regulation, Neoplastic
• Genetic Predisposition to Disease
• Helicobacter Infections/physiopathology
• Helicobacter Infections/therapy
• Helicobacter pylori/physiology
• Humans
• Membrane Proteins/physiology
• Metaplasia/pathology
• Nitric Oxide/physiology
• Reactive Oxygen Species/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/pathology
• Stomach Neoplasms/prevention & control
• Tumor Suppressor Protein p53/physiology
• Virulence

AIM: To investigate the expression of NF-κBp65 protein and human telomerase reverse transcriptase (hTERT) and their correlation in gastric cancer and precancerous lesions.

METHODS: Forty-one patients with primary gastric cancer, 15 with dysplasia, 23 intestinal metaplasia and 10 with normal gastric mucosa were included in this study. Expression of NF-κBp65 protein, hTERT mRNA and protein were determined by immunohistochemistry and in situ hybridization.

RESULTS: The rate of p65 expression in normal gastric mucosa, intestinal metaplasia, dysplasia and carcinoma was 0%, 34.78%, 53.33% and 60.98%, respectively, while the rate of hTERT mRNA expression was 10.00%, 39.13%, 66.67% and 85.37% and the rate of hTERT protein expression was 0%, 30.43%, 60.00% and 78.05%, respectively. All the three parameters were significantly increased in dysplasia and carcinoma compared to normal mucosa, while the expression levels were also significantly higher in carcinoma than in intestinal metaplasia (P < 0.05). In gastric cancer tissues, nuclear staining rates of p65 and hTERT protein were both significantly associated with the degree of differentiation, lymph node metastasis, clinical stage and invasion depth (P < 0.05). However, hTERT mRNA expression was only significantly associated with clinical stage. There was a positive correlation between p65 and hTERT mRNA (r_s = 0.661 - 0.752, P < 0.01), and between hTERT protein and hTERT mRNA (r_s = 0.609-0.750, P < 0.01).

CONCLUSION: NF-κBp65 and hTERT expressions are upregulated at the early stage of gastric carcinogenesis. NF-κB activation may contribute to hTERT expression and thereby enhance telomerase activity, which represents an important step in carcinogenesis progress.

Wang W, Luo HS, Yu BP. Expression of NF-κB and human telomerase reverse transcriptase in gastric cancer and precancerous lesions.

• DNA-Binding Proteins
• Female
• Gastric Mucosa/pathology
• Gastric Mucosa/physiopathology
• Gene Expression Regulation, Neoplastic
• Humans
• In Situ Hybridization
• Male
• Middle Aged
• NF-kappa B/genetics
• Precancerous Conditions/pathology
• Precancerous Conditions/physiopathology
• RNA, Messenger/analysis
• Stomach Neoplasms/pathology
• Stomach Neoplasms/physiopathology
• Telomerase/genetics
• Transcription Factor RelA

To determine telomerase activity of exfoliated cells in tuberculous peritonitis and malignant ascites, and study the diagnostic value of telomerase activity in differentiating tuberculous peritonitis from malignant ascites.

TRAP-PCR-ELISA and TRAP-PCR-silver staining were employed to determine telomerase activity in 18 specimens of malignant ascites and 13 specimens of tuberculous peritonitis. Telomerase activities in tuberculous peritonitis and malignant ascites were analysed.

Telomerase activity in malignant ascites (0.387±0.023)was significantly higher than that in tuberculous peritonitis(0.023±0.004, P<0.01). The positive rate of telomerase activity in malignant ascites was significantly higher than that in tuberculous peritonitis, 88.9% (16/18) vs 7.7% (1/13), P<0.01. The sensitivity, specificity and accuracy of determination of telomerase activity in diagnosis of malignant ascites were 88.9%, 92.3%, and 90.3%, respectively.

Telomerase activity is positive in malignant ascites and may serve as a useful indicator for differentiating between tuberculous peritonitis and malignant ascites.

• N/A

AIM: To investigate the effects of allicin on both telomerase activity and apoptosis in gastric cancer SGC-7901 cells.

METHODS: The gastric cancer SGC-7901 adenocarcinoma cells were treated with allicin and the cell cycle, inhibitory rate, apoptosis, telomerase activity and morphologic changes were studied by MTT assay, flow cytometry (FCM), TRAP-PCR-ELISA assay, light microscope, electron microscope respectively. Results were compared with that of AZT (3’-Azido-3’-deoxythymidine).

RESULTS: SGC-7901 cells were suppressed after exposure to allicin of 0.016 mg/mL, 0.05 mg/mL, and 0.1 mg/mL for 48 h. Compared with the control, the difference was significant (P < 0.05). Allicin could induce apoptosis of the cells in a dose-dependent and non-linear manner and increase the proportion of cells in the G₂/M phase. Compared with the control, the difference was significant in terms of the percentage of cells in the G₂/M phase (P < 0.05). Allicin could inhibit telomerase activity in a time-dependent and dose-dependent pattern. After exposure to allicin at 0.016 mg/mL for 24 hours, SGC-7901 cells showed typical morphologic change.

CONCLUSION: Allicin can inhibit telomerase activity and induce apoptosis of gastric cancer SGC-7901 cells. Allicin may be more effective than AZT.

• Adenocarcinoma/enzymology
• Adenocarcinoma/pathology
• Adenocarcinoma/physiopathology
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Disulfides
• Dose-Response Relationship, Drug
• Stomach Neoplasms/enzymology
• Stomach Neoplasms/pathology
• Stomach Neoplasms/physiopathology
• Sulfinic Acids/administration & dosage
• Sulfinic Acids/pharmacology
• Telomerase/antagonists & inhibitors
• Time Factors
• Tumor Cells, Cultured

AIM: To investigate the expression of human telomerase reverse transcriptase gene (hTRT) in gastric cancer (GC) and its relevance with cell cycle regulators including P16INK4, cyclin and P53.

METHODS: In situ hybridization (ISH) for hTRT mRNA was performed in 53 cases of gastric cancer and adjacent cancerous tissues. Immunohistochemical staining (S-P method) for hTRT protein, P16INK4, cyclinD1 and P53 was performed in 53 cases of GC and adjacent cancerous tissues.

RESULTS: Of 53 cases of GC, the expression of hTRT mRNA and hTRT protein was significantly higher than the expression of hTRT mRNA and hTRT protein in adjacent canerous tissues (P < 0.01), the positive rates of hTRTmRNA and hTRT protein were 79.2% and 88.6%. There was a stastical difference of the expression of hTRT protein among well differentiated adenocarcinoma, poorly differentiated adenocarcinoma and mucoid carcinoma. And there was a highly significant positive correlation between the expression of hTRT mRNA and hTRT protein (r = 0.625, P < 0.01). However, the expression of hTRT mRNA and its protein in GC were not related with other clinicopathological parameters including gender, age, location and size of neoplasm, invasion depth, lymph node metastasis and clinical stage. There was a significant positive correlation between the expression of hTRT mRNA and cyclinD1 protein (r = 0.350, P < 0.01). There was a significant positive correlation between the expression of cyclinD1 protein and hTRT protein (r = 0.549, P < 0.01), so was between P53 and hTRT protein (r = 0.319, P < 0.05).

CONCLUSION: The expression of hTRT gene is correlated significantly to the specific defects of cell cycle on G1/S check point ; telomerase activity may depend on cell cycle in gastric cancer and it is available to clarify the molecular mechanism of telomerase activity regulation. The expression of hTRT mRNA and hTRT protein in GC is significantly different from the expression of hTRT mRNA and hTRT protein in adjacent cancerous tissue which indicates that these targets are correlated closely to the occurrence of GC and can provide important morphologic index for diagnosis of GC.

• Adult
• Aged
• Cell Cycle/physiology
• Cyclins/genetics
• DNA-Binding Proteins
• Female
• Gene Expression
• Genes, p16
• Genes, p53
• Humans
• Male
• Middle Aged
• Stomach Neoplasms/genetics
• Telomerase/genetics

AIM: To observe the expression of Human telomerase reverse transcriptase (hTERT) in gastric carcinomas and precancerosis lesions, to evaluate the immune state of such patients, and to then study the clinical significance of hTERT and immune state for the diagnosis, treatment and prognosis of gastric cancer.

METHODS: In situ hybridization was used to detect the expression of hTERT mRNA in 116 endoscopic of gastric mucosa. Analyzed tissue samples were as follows: 30 cases of chronic superficial gastritis (CSG), 44 of precancerosis lesions (including 27 of chronic atrophic gastritis, 8 of adenomatous polyp and 9 of gastric ulcer) and 42 of gastric cancer (GC). In addition, the T lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺) and natural killer cells (NK) in peripheral blood were determined by flow cytometric analysis (FCM) in 30 cases of CSG, 27 of precancerosis (chronic atrophic gastritis, CAG), and 42 of GC. The data were compared with those of normal control (NC).

RESULTS: The detected positive rate of hTERT varied as follows: 86% (36/42) in GC, 36% (16/44) in precancerosis lesions and 0% (0/30) in CSG. The expression of hTERT mRNA was not associated with patient gender, tumor location, macroscopic type, lymph node metastasis, or degree of differentiation. It was found that the CD3⁺, CD4⁺ of the CSG group were lower than that of NC (P < 0.05). Meanwhile, the T lymphocyte subsets (CD3⁺, CD4⁺, CD4⁺/CD8⁺ ratio) and NK cells of CAG were remarkably lower than that of NC and CSG groups (P < 0.05-0.01). Values of T cells and NK cells of the GC group were significantly abnormal when compared with the CAG group (P < 0.05-0.01). Furthermore, with tumor progression, the function of T cells was weakened gradually.

CONCLUSION: The expression of telomerase may be a crucial step in gastric carcinogenesis and increased hTERT mRNA may serve as a novel marker for diagnosis of GC. The immune state of patients with GC and precancerosis was somewhat depressed, which indicates the importance of cellular immunological assays in cancer patients.

• Adult
• DNA-Binding Proteins
• Gene Expression
• Humans
• Immunity, Cellular
• Killer Cells, Natural/immunology
• Middle Aged
• Precancerous Conditions/enzymology
• Precancerous Conditions/genetics
• Precancerous Conditions/immunology
• RNA, Messenger/genetics
• RNA, Neoplasm/genetics
• Stomach Neoplasms/enzymology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/immunology
• T-Lymphocyte Subsets/immunology
• Telomerase/genetics