The status of genetic instability was determined with seven microsatellite markers from 40 patients with primary gastric adenocarcinoma. For those cases with microsatellite instability, alterations ...of hMSH2 were further investigated by direct sequencing of reverse transcription-polymerase chain reaction products. Twelve (30%) of 40 patients were found to have microsatellite instability. Among them, one patient (
1
6
, 16.7%) was early gastric cancer and 11 (
11
34
, 32.4%) were advanced gastric cancer. There were seven patients with diffuse type (
7
18
, 38.7%), while five (
5
22
, 22.7%) were intestinal type tumors. The entire coding region of the hMSH2 gene in these 12 affected individuals was amplified and sequenced. Only a 41-year-old female patient with diffuse type advanced gastric cancer showed a GCT to TCT missense mutation at codon 207 with predicted protein change from alanine to serine. Our results indicate that genetic instability plays an important role in gastric tumorigenesis and alterations of the hMSH2 gene are related to only a small portion of sporadic gastric adenocarcinoma with microsatellite instability.
The association between Helicobacter pylori infection and gastric cancer remains controversial. A community-based serosurvey was carried out in Taiwan to investigate the association. Serum IgG ...antibodies against Helicobacter pylori were examined in 728 subjects randomly selected from three townships with different gastric cancer mortality rates. The overall seropositivity of Helicobacter pylori was 54.7% (398/728) with no gender difference (males: 54.5%; females: 54.8%). The seroprevalence of Helicobacter pylori progressively increased with age in all three study townships. The age-specific seropositivity of Helicobacter pylori correlated well with age-adjusted gastric cancer mortality in the three townships. The difference in seropositivity was more profound in younger age groups. The ecological study in Taiwan suggests an association between Helicobacter pylori infection and gastric cancer. Helicobacter pylori infection in early childhood may be a key issue; in addition, a long induction time appears to be required for gastric carcinogenesis.
The increasing emergence of Helicobacter pylori strains resistant to antibiotics may cause unsuccessful treatment. An alternative agent or mixture with anti-H. pylori effect is urgently required to ...reduce H. pylori infection. We explored the preventive and therapeutic potential of a combination of catechins and sialic acid on H. pylori-infected human gastric cells in vitro and in mice in vivo. We evaluated the anti-H. pylori activity of catechins and/or sialic acid using the agar dilution and checkerboard methods. The effect of catechins and/or sialic acid on H. pylori infection-induced oxidative stress and apoptosis/autophagy in cell culture was explored using an ultrasensitive chemiluminescence analyzer, immunocytochemistry, and Western blotting. Specific pathogen-free BALB/c mice were divided into uninfected control, infected control, pretreated, and post-treated groups. The effects of catechins/sialic acid were determined by histology and immunocytochemistry. The combination of catechins and sialic acid showed synergistic or additive anti-H. pylori activity and significantly reduced inducible nitric oxide synthase expression and Bax/Bcl-2-mediated apoptosis but enhanced Beclin-1-mediated autophagy. All mice infected with H. pylori displayed gastritis and accumulation of 3-nitrotyrosine and 4-hydroxynonenal. Pretreatment with catechins/sialic acid completely prevented H. pylori infection and resulted in normal histology. Post-treatment with catechins/sialic acid decreased the bacterial load and gastritis score and eradicated up to 60% of H. pylori infections in a dose-dependent manner. This is the first demonstration to our knowledge of a nonprobiotic, nonantibiotic treatment that is 100% effective in preventing and has promising possibilities for treating H. pylori infection. Further studies are needed to confirm this result in humans. PUBLICATION ABSTRACT
The increasing emergence of Helicobacter pylori strains resistant to antibiotics may cause unsuccessful treatment. An alternative agent or mixture with anti-H. pylori effect is urgently required to ...reduce H. pylori infection. We explored the preventive and therapeutic potential of a combination of catechins and sialic acid on H. pylori-infected human gastric cells in vitro and in mice in vivo. We evaluated the anti-H. pylori activity of catechins and/or sialic acid using the agar dilution and checkerboard methods. The effect of catechins and/or sialic acid on H. pylori infection-induced oxidative stress and apoptosis/autophagy in cell culture was explored using an ultrasensitive chemiluminescence analyzer, immunocytochemistry, and Western blotting. Specific pathogen-free BALB/c mice were divided into uninfected control, infected control, pretreated, and post-treated groups. The effects of catechins/sialic acid were determined by histology and immunocytochemistry. The combination of catechins and sialic acid showed synergistic or additive anti-H. pylori activity and significantly reduced inducible nitric oxide synthase expression and Bax/Bcl-2–mediated apoptosis but enhanced Beclin-1–mediated autophagy. All mice infected with H. pylori displayed gastritis and accumulation of 3-nitrotyrosine and 4-hydroxynonenal. Pretreatment with catechins/sialic acid completely prevented H. pylori infection and resulted in normal histology. Post-treatment with catechins/sialic acid decreased the bacterial load and gastritis score and eradicated up to 60% of H. pylori infections in a dose-dependent manner. This is the first demonstration to our knowledge of a nonprobiotic, nonantibiotic treatment that is 100% effective in preventing and has promising possibilities for treating H. pylori infection. Further studies are needed to confirm this result in humans.
To study the clinicopathologic features of hepatitis C viremic patients negative for hepatitis C antibodies (anti-HCV) by current second-generation assay, we categorized 139 consecutive ...histologically verified patients with chronic non-A, non-B hepatitis into three groups: 121 (87%) were positive for second-generation anti-HCV (group A); 10 (7%) were negative for second-generation anti-HCV but positive for HCV RNA (group B); and 8 (6%) were negative for both antibodies and viremia (group C). Six (60%) of group B patients could be, further detected by a new third-generation assay, but none of group C patients was third-generation anti-HCV-positive. The demographic features, mean peak serum alanine aminotransferase levels, HCV genotype distribution, and histologic changes were comparable among the three groups. The study indicates that most patients with chronic hepatitis C in Taiwan could be identified by current second-generation assay, and viremic but antibody seronegative patients were clinicopathologically similar to the seropositives. Most patients of the latter group could be diagnosed by a third-generation assay, indicating the usefulness of this assay.
To elucidate the clinicopathological course and the role of hepatitis C virus in posttransfusion and sporadic chronic non-A, non-B hepatitis in Taiwan, we retrospectively studied 85 histologically ...confirmed patients with long-term follow up. Antibodies against hepatitis C virus (anti-HCV) by a second-generation assay were positive in 81% of the patients: 88% in the posttransfusion group and 76% in the sporadic group. Clinical manifestations were generally mild, and were noted in only half of the patients. During follow up, 33% (28 of 85 patients) had episodes of acute exacerbation of chronic liver disease and 24% (20 of 85) had normalized liver tests. Patients with normalized liver tests were usually anti-HCV negative (55% vs. 8%, p < 0.001). In 34 patients who had had blood transfusions, initial liver biopsies revealed chronic active hepatitis in 41%, active cirrhosis in 6%, and inactive cirrhosis in 9%. Follow-up biopsies in eight patients in this group showed histological progression in three after an average of 40.6 months. In the 51 sporadically infected patients, initial work-up revealed chronic active hepatitis in 37%, active cirrhosis in 4%, and inactive cirrhosis in 14%. Among the nine who underwent repeated biopsies, only one (11%) had progression. Patients above age 40 displayed more severe histologic activity than those below 40 (p < 0.005). Three patients, all with cirrhosis, died of hepatocellular carcinoma 7 to 12 years after follow up. Further genotyping study of hepatitis C virus in 28 patients showed that type II virus was most predominant in Taiwan and histologic severity was similar among patients infected with different genotypes.
A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second-generation immunoassay. To study the impact of this screening on ...post-transfusion hepatitis in Taiwan, a prospective study on post-transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow-up period for more than 6 months post-transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that the current anti-HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.
To investigate whether there are any differences between the clinicopathologic characteristics of early gastric cancer (EGC) patients in Eastern and Western countries, 208 Taiwanese patients with EGC ...were reviewed between 1964 and 1992. The incidence of cancer has increased slightly over the 29-year period. Men were diagnosed with EGC frequently than women, and their mean age was 56 years. Epigastralgia (58.2%) was the most common symptom, whereas 5.8% of cancers were incidentally detected by endoscopy. Physical signs and laboratory tests were of limited value in making the diagnosis. Endoscopy was a better diagnostic aid than radiology. Tumours were frequently located in the lower third (53.2%) and middle third (43.3%) of the stomach. Cancers of the elevated type (17.8%) were less frequent than the depressed type (82.2%). Type IIc (31.2%) was the most common macroscopic type. The frequency of mucosal carcinoma (51.0%) was similar to submucosal carcinoma (49.0%). Mucosal carcinoma had less lymph node metastases (3.1%) than submucosal carcinoma (12.2%; P < 0.05), with an overall frequency of metastases of 7.5% (14/186). The 5-year survival rate was 90.8%. The clinicopathologic characteristics of EGC in Taiwan were similar to those of Western countries and other Eastern countries. Improvement of diagnostic examinations and endoscopic surveillance of asymptomatic subjects may lead to early diagnosis and thus ensure a more favourable outcome.
Using an enzyme-linked immunosorbant assay for antibody against hepatitis C virus (anti-HCV), serial serum samples from 26 non-A, non-B (NANB) posttransfusion hepatitis (PTH) patients were studied in ...a prospective study in Taiwan. Sixteen (61.5%) of the 26 patients were positive for anti-HCV antibodies. Two of the 16 patients were positive for anti-HCV before transfusion. The remaining 10 patients were negative for anti-HCV antibodies. The rate of anti-HCV seroconversion is, therefore, 58.5%. Of the 14 patients with anti-HCV seroconversion, three were hepatitis B surface antigen (HBsAg) carriers. The time of seroconversion for anti-HCV ranges from 2 to 24 weeks after the first elevation of ALT (mean: of 8.7 weeks,) or 6-32 weeks from the date of transfusion (mean: 13 weeks). Twelve (85.7%) of the 14 anti-HCV seroconverted patients had persistent abnormal ALT 6 months after the onset of hepatitis in contrast to 30% of chronicity in the anti-HCV-negative patients. The results suggest that HCV is the major causative agent in NANB PTH in Taiwan, and patients positive for anti-HCV have a higher risk of chronicity.
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