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Diagnosis Of Chronic Atrophic Gastritis From Serum Sample And Study Of The Expression Of ING1 In Gastric Mucosa

Posted on:2005-06-16Degree:MasterType:Thesis
Country:ChinaCandidate:H T LiFull Text:PDF
GTID:2144360122495948Subject:Internal Medicine
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Backgroud: The prevalence of chronic atrophic gastritis (CAG) is high in the aged people in China. CAG is often acompanied with intestinal metaplasia (IM) and dysplasia (DYS), which is considered to be one of the most important pre-cancerous states of the stomach and is regarded to be a predisposing factor for gastric cancer especially associated with Helicobacter pylori (H.pylori) infection. The severity of CAG is considered to be a key risk factor of gastric cancer and the risk is especially high if the atrophy occurs in both antrum and corpus. At present the commonly used means for diagnosis of CAG is gastroscopy with biopsy, which is an efficient and reliable means but is an invasive procedure. Moreovers it needs well-trained and experienced staff to operate and is relatively expensive, inconvenient for patients and generally is not recommended for children or for old patients with severe cardiopulmonary diseases. Hence establishing an efficient and convenient serologic method to identify people who have this precancerous condition, CAG, has a crucial importance for CAG mass screening and prevention of gastric cancer. Serum levels of gastrin-17 (G-17) and pepsinogen (PG) have been described as biomarkers for atrophy of gastric antral and corpus mucosa, respectively. Atrophic changes of the gastric mucosa can beevaluated by blood test such as low serum pepsinogen I (PGI), G-17, and low ratio of serum pepsinogen I to pepsinogen II (PGI/PGII). However, because of potential ethnic, environmental, and disease differences, the use of these biomarkers requires local validation. There was no data available on serologic PG and G-17 in patients with CAG in China. So we want to establish appropriate cut-off values of these serum markers for diagnosing CAG for the Chinese and verify its accuracy with endoscopy and biopsies. The majority of gastric cancers arise through a multistep process. It might be detected at early stage by using tumor markers. Inhibitor of growth-1 (ING1) is a new candidate tumour suppressor gene, of which the reduction is an important event in some human cancers. ING1 is suggested involved in the negative regulation of cell proliferation and in the control of cellular senescence, anchorage dependence, and apoptosis. These cellular functions depend largely on the activity of p53. Furthermore, activation of transcription of p21, a key mechanism of p53-mediated growth control, depends on the expression of ING1.Aim: 1. Using serum iG-17, PGI/PGII as biomarkers, additionally with measurement of H.pylori antibody IgG (Hp IgG), to establish a non-invasive pregastroscopy screening test for CAG for the Chinese. 2. To characterize the expression of ING1 in human gastric mucosa and gastric cell lines, and to investigate its relationship with the expression of MG7, p53, p21, and serum PGI, PGI/PGII and H.pylori infection. To explore the contribution of ING1 in the carcinogenesis and development of gastric cancer and determine whether ING1 could be a novel tumor-screening marker and a new target for gastric cancer early diagnosing and gene therapy.Methods: 1. The study recruited 120 selected patients (mean age 62.8+0.7 years and M/F ratio was 63/57) who underwent gastroscopy for dyspeptic symptoms at the endoscopy center ofXIJING hospital from Feb.2002 to May.2003. At least four biopsy specimens were taken from antrum and corpus for histological diagnosis. Based on histological results, the patients were divided into 5 groups: normal, non-atrophic, mild, moderate and severe CAG group, respectively. Blood samples for ELISA assays of serum PGI, PGII, Hp IgG and basal G-17 (bG-17) were drawn after an overnight fast. The sample for serum postprandial G-17 (pG-17) assay was taken 20min after a protein rich drink. Cut-off points of PGI, PGII and increased G-17 (iG-17) were calculated using receiving operator characteristics (ROC) curves. 2. Immunohistochemistry and Western blot were used to detect the expression of ING1, as well as MG7 antigen, p53 and p21, on the biopsy samples obta...
Keywords/Search Tags:Chronic atrophic gastritis, Gastrin-17, Pepsinogen, Helicobacter pylori, ING1
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