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Antonia R Sepulveda

Publications and source records attributed to Antonia R Sepulveda.

At least 19 recordsLinked to original sources
PubMed2007

Why do African Americans get more colon cancer than Native Africans?

The incidence of colorectal cancer (CRC) is dramatically higher in African Americans (AAs) than in Native Africans (NAs) (60:100,000 vs. <1:100,000) and slightly higher than in Caucasian Americans (CAs). To explore whether the difference could be explained by interactions between diet and colonic bacterial flora, we compared randomly selected samples of healthy 50- to 65-y-old AAs (n = 17) with NAs (n = 18) and CAs (n = 17). Diet was measured by 3-d recall, and colonic metabolism by breath hydrogen and methane responses to oral lactulose. Fecal samples were cultured for 7-alpha dehydroxylating bacteria and Lactobacillus plantarum. Colonoscopic mucosal biopsies were taken to measure proliferation rates. In comparison with NAs, AAs consumed more (P < 0.01) protein (94 +/- 9.3 vs. 58 +/- 4.1 g/d) and fat (114 +/- 11.2 vs. 38 +/- 3.0 g/d), meat, saturated fat, and cholesterol. However, they also consumed more (P < 0.05) calcium, vitamin A, and vitamin C, and fiber intake was the same. Breath hydrogen was higher (P < 0.0001) and methane lower in AAs, and fecal colony counts of 7-alpha dehydroxylating bacteria were higher and of Lactobacilli were lower. Colonic crypt cell proliferation rates were dramatically higher in AAs (21.8 +/- 1.1% vs. 3.2 +/- 0.8% labeling, P < 0.0001). In conclusion, the higher CRC risk and mucosal proliferation rates in AAs than in NAs were associated with higher dietary intakes of animal products and higher colonic populations of potentially toxic hydrogen and secondary bile-salt-producing bacteria. This supports our hypothesis that CRC risk is determined by interactions between the external (dietary) and internal (bacterial) environments.

Africa↗
PubMed2006

HER-2/neu overexpression is an independent prognostic factor in colorectal cancer.

BACKGROUND AND AIMS: The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth, as it is extensively homologous and is related to the epidermal growth factor receptor. This phenomenon has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease and poor prognoses, and also constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationships between the expression of HER-2/neu and the clinicopathological characteristics of colorectal cancer, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for colorectal cancer patients. PATIENTS AND METHODS: HER-2/neu overexpression and gene amplification were examined via semiquantitative standardized immunohistochemical staining and fluorescence in situ hybridization (FISH) in 137 colorectal cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. RESULTS: Sixty-five (47.4%) out of 137 patients were determined by immunohistochemistry to have overexpressed HER-2/neu protein. HER-2/neu gene amplification was detected in two patients by FISH. Tumors with HER-2/neu overexpression showed higher postoperative recurrence rate (39.3% vs 14.6%, p=0.013). Tumors with HER-2/neu overexpression were associated with poor 3-year (70.8% vs 83.7%) and 5-year survival rates (55.1% vs 78.3%, p<0.05). Advanced TNM stage, postoperative recurrence, and overexpression of HER-2/neu were found to be independently related to survival by multivariate analysis. CONCLUSION: HER-2/neu overexpression may constitute an independent prognostic factor in colorectal cancer patients, and patients exhibiting HER-2/neu overexpression might constitute potential candidates for a new adjuvant therapy which involves the use of humanized monoclonal antibodies.

Adult↗
PubMed2006

HER-2/neu amplification is an independent prognostic factor in gastric cancer.

The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth and is extensively homologous and related to the epidermal growth factor receptor. HER-2/neu protein expression has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease, and with a poor prognosis, and constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationship between the expression of HER-2/neu and the clinicopathological characteristics of tumors, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for gastric cancer patients. HER-2/neu overexpression and gene amplification was examined with semiquantitative standardized immunohistochemical staining, chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH) in 182 gastric cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. Twenty-nine (15.9%) of 182 patients expressed the HER-2/neu protein by immunohistochemistry. HER-2/neu gene amplification was detected in seven patients by CISH and FISH. Intestinal-type cancers exhibited higher rates of HER-2/neu amplification than did diffuse-type cancers (P < 0.05). Tumors with HER-2/neu amplification were associated with poor mean survival rates (922 vs 3243 days) and 5-year survival rates (21.4% vs 63.0%; P < 0.05). Age, TNM stage, and amplification of HER-2/neu were found to be independently related to survival by multivariate analysis. HER-2/neu amplification may constitute an independent prognostic factor in gastric cancer patients, and patients exhibiting HER-2/neu amplification might constitute potential candidates for new adjuvant therapies which involve the use of humanized monoclonal antibodies.

Adult↗
PubMed2006

Assessment of microsatellite instability in very small microdissected samples and in tumor samples that are contaminated with normal DNA.

Microsatellite instability (MSI) testing is important for the management of young patients with colonic adenocarcinoma. Biopsies can be small and can be contaminated by normal cells. It is not known how sample size or contamination by non-neoplastic cell populations affects the interpretation of MSI assays. Serial microdissection targets (0.75 to 5.5 mm) were obtained from cases with high-level MSI. Polymerase chain reaction was performed for the standard National Cancer Institute recommended markers and products were analyzed by capillary electrophoresis. DNA from a patient with a BAT25 polymorphism was used to determine the sensitivity of detecting an aberrant allele in otherwise normal DNA. In small targets, MSI was seen sporadically in the setting of low DNA concentration. The results for small targets ranged from 1/4 to 5/5 loci with MSI, secondary to allelic dropout. In the sensitivity study, the aberrant allele was detected only when present at a concentration of above 10%. Allelic dropout can lead to under-estimation of the presence of MSI in small tissue samples or samples with low DNA concentration. Contaminating normal cell DNA can mask the presence of MSI. MSI testing on tissue fragments that are <5.5 mm can lead to a false-negative MSI test.

Alleles↗
PubMed2006

Demonstration and characterization of mutations induced by Helicobacter pylori organisms in gastric epithelial cells.

BACKGROUND: Helicobacter pylori gastritis increases gastric cancer risk. Microsatellite instability-type mutations are secondary to deficient DNA mismatch repair. H. pylori gastritis is more frequent in patients with microsatellite instability-positive gastric cancers, and H. pylori organisms independently of inflammation can reduce DNA mismatch repair protein levels, raising the hypothesis that H. pylori organisms might lead to mutagenesis during infection. MATERIALS AND METHODS: Mutations were detected using a green fluorescent protein reporter vector (pEGFP-CA13). Gastric cancer AGS cells transfected with pEGFP-CA13 were cocultured with H. pylori or Escherichia coli. The numbers of green fluorescent protein (GFP)-positive cells were determined, and GFP, hMSH2, and hMLH1 protein levels were measured by Western blot. The effect of H. pylori on CpG methylation status of hMLH1 was determined by methylation-specific polymerase chain reaction. RESULTS: GFP levels and GFP-positive cell numbers in AGS cells cocultured with H. pylori significantly increased, as the levels of hMLH1 and hMSH2 dropped. H. pylori cocultures induced low-level CpG methylation of the hMLH1 promoter. Sequence analysis of cells cocultured with H. pylori showed an increased number of frameshift mutations and point mutations as compared to cells not cocultured with H. pylori (p = .03 and p = .001, respectively). CONCLUSIONS: This is the first report showing that H. pylori bacteria may lead to accumulation of genomic mutations, independently of underlying inflammation. This is associated with reduced DNA mismatch repair, and is at least in part associated with CpG methylation of the hMLH1 promoter. These data support the notion that H. pylori-induced mutations and epigenetic alterations in gastric epithelial cells during chronic gastritis may contribute to an increased risk of gastric cancer associated with H. pylori infection.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway.

Heme oxygenase (HO)-1 and its metabolic product carbon monoxide (CO) play regulatory roles in acute inflammatory states. In this study, we demonstrate that CO administration is effective as a therapeutic modality in mice with established chronic colitis. CO administration ameliorates chronic intestinal inflammation in a T helper (Th)1-mediated model of murine colitis, interleukin (IL)-10-deficient (IL-10(-/-)) mice. In Th1-mediated inflammation, CO abrogates the synergistic effect of interferon (IFN)-gamma on lipopolysaccharide-induced IL-12 p40 in murine macrophages and alters IFN-gamma signaling by inhibiting a member of the IFN regulatory factor (IRF) family of transcription factors, IRF-8. A specific signaling pathway, not previously identified, is delineated that involves an obligatory role for HO-1 induction in the protection afforded by CO. Moreover, CO antagonizes the inhibitory effect of IFN-gamma on HO-1 expression in macrophages. In macrophages and in Th1-mediated colitis, pharmacologic induction of HO-1 recapitulates the immunosuppressive effects of CO. In conclusion, this study begins to elucidate potential etiologic and therapeutic implications of CO and the HO-1 pathway in chronic inflammatory bowel diseases.

Administration, Inhalation↗
PubMed2005

Microsatellite instability and DNA mismatch repair deficiency testing in hereditary and sporadic gastrointestinal cancers.

The reference cancers associated with DNA mismatch repair (MMR)deficiency are the adenocarcinomas of patients with hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome. Sporadic gastrointestinal (GI) carcinomas, most commonly colorectal and gastric carcinomas, may also be associated with deficiencies of DNA mismatch repair. Deficiency in cellular MMR leads to wide-spread mutagenesis and neoplastic development and progression. An important diagnostic feature of MMR-deficient tumors is the high rate of mutations that accumulate in repetitive nucleotide regions, and these mutations are known as microsatellite instability(MSI). A standard panel of markers to test for MSI in tumors has been recommended and efficiently separates tumors into those with high, low, or no microsatellite instability (MSI-H, MSI-L, or MSS). Tumors characterized by MSI-H characteristically show loss of one of the main DNA MMR proteins, mLH1 or MSH2, and rarely MSH6 and PMS2, detected by immunohistochemistry (IHC). The combination of MSI testing and IHC for MMR proteins in tumors tissues is used to identify underlying DNA MMR deficiency andis clinically relevant screen patients who might have hereditary non-polyposis colorectal cancer for DNA repair gene germline testing. Increasing evidence demonstrates that tumors with a positive MSI status have lower lymph node metastases burden, and these patients have an overall improved survival, suggesting that the MSI and MMR status may contribute to decision making regarding treatment approaches. Updated guidelines for MSI and IHC for DNAMMR testing, and the biological and potential clinical implications of MMR deficiency and microsatellite instability in GI polyps and cancers are reviewed.

Adenocarcinoma↗
PubMed2005

Molecular markers in Helicobacter pylori-associated gastric carcinogenesis.

Helicobacter pylori infection is a known risk factor of gastric carcino-genesis. This article presents early molecular alterations associated with H. pylori chronic gastritis and advances in the molecular characterization of preneoplastic intestinal metaplasia (IM) and premalignant gastric mucosal lesions. H. pylori infection induces changes in gene expression, genomic instability and accumulation of gene mutations in the stomach epithelium. Mutations, including LOH and microsatellite instability, and gene hypermethylation are seen not only in gastric cancer, but are already detectable in IM and gastric dysplasia/adenoma. Recent reports using microarray expression analysis identified several gastric epithelial genes that are regulated by H. pylori. Among the many genes showing altered epithelial expression in response to H. pylori, some might be useful as markers to assess gastric cancer risk. Profiles of mutagenesis and gene expression in IM and dysplasia/adenoma have been characterized and represent potential markers of preneoplastic and premalignant lesions during gastric carcinogenesis.

Adenocarcinoma↗
PubMed2005

Bacillus clausii effect on gene expression pattern in small bowel mucosa using DNA microarray analysis.

BACKGROUND: Probiotics are widely used for the cure or prevention of several clinical conditions. However, clinical decisions need to be substantiated by an analysis of the complex bacteria-host interplay in the intestinal lumen. AIMS: To identify the gene expression pattern induced by Bacillus clausii in the intestinal mucosa of healthy individuals. METHODS: Six male patients (mean age 38+/-5 years) affected by endoscopically confirmed mild oesophagitis were treated for one month with esomeprazole, and were randomly selected to receive or not B. clausii (groups I and II, respectively). Duodenal biopsies were taken pre and post-treatment to identify the modification of gene expression, using the GeneChip Human U133A array. To validate the microarray analysis, real-time reverse transcriptase-polymerase chain reaction (PCR) of five target genes was performed. RESULTS: After B. clausii administration, a total of 158 and 265 genes were up and downregulated, respectively. Quantitative PCR confirmed the microarray data. B. clausii mainly affected the expression of genes involved in immune response and inflammation, apoptosis and cell growth, cell differentiation, cell-cell signalling, cell adhesion, signal transcription and transduction. CONCLUSIONS: Our data represent the first global analysis of B. clausii effects on the gene expression profile in normal intestine, and provide the basis to identify the mechanisms by which these agents interact with the host and exert their beneficial effects. Future studies are needed to clarify the B. clausii-induced gene pattern in the clinical disorders in which probiotics have proved to be effective.

Adult↗
PubMed2005

Helicobacter heilmannii gastritis: a case study with review of literature.

H. heilmannii belongs to the Helicobacter family and is found in a small number of gastric biopsies. This bacterium is generally found in primates, cats, pigs, and carnivorous mammals. About 0.5% to 6% of human gastric infections have been attributed to H. heilmannii. The bacterium usually induces mild chronic gastritis but may be associated with peptic ulceration, and rare cases were reported in association with gastric carcinoma and mucosa-associated lymphoid tissue lymphoma. We report a case of H. heilmannii chronic gastritis in a 44-year-old man with a history of chronic heartburn, found to have erythema and granularity in the antrum. Antral biopsy showed mild chronic gastritis with prominent lymphoid aggregates, and rare long, thin, spiral bacilli were present adjacent to the surface epithelium. The long tightly coiled morphology suggestive of H. heilmannii was obvious at 1000 x magnification. The lack of information in the literature regarding cross-reactivity of H. heilmannii to commercially available antibodies used for immunohistochemical detection of H. pylori prompted us to evaluate whether commercially available polyclonal anti-H. pylori antibodies show cross-reactivity between the two organisms. The H. pylori immunostain highlighted H. heilmannii organisms and their characteristic morphology, confirming cross-reactivity with the anti-H. pylori polyclonal antibody. This case illustrates the potential contribution of commercially available polyclonal antibodies against H. pylori to help confirm a diagnosis of H. heilmannii gastritis. The use of immunohistochemical stain to identify H. heilmannii may be useful in cases with a paucity of organisms, with suggestive but not diagnostic forms on routine hematoxylin and eosin stain.

Adult↗
PubMed2005

Effect of Helicobacter pylori infection on the expression of DNA mismatch repair protein.

BACKGROUND: Helicobacer pylori infection is a major gastric cancer risk factor. Deficient DNA mismatch repair (MMR) caused by H. pylori may underlie microsatellite instability (MSI) in the gastric epithelium and may represent a major mechanism of mutation accumulation in the gastric mucosa during the early stages of H. pylori-associated gastric carcinogenesis. In this study, we examined the expression of DNA MMR protein (hMLH1 and hMSH2) in patients with chronic H. pylori infection before and after eradication of the infection. MATERIALS AND METHODS: Gastric tissue samples were collected from 60 patients with H. pylori gastritis and peptic ulcer disease before and after eradication of the infection. The DNA MMR protein expression (hMLH1 and hMSH2) was determined by immunohistochemical staining in 60 patients before and after H. pylori eradication. The percentage of epithelial cell nuclei and intensity of staining were then compared in gastric biopsies before and after eradication. RESULTS: The percentage of hMLH1 (76.60 +/- 20.27, 84.82 +/- 12.73, p=.01) and hMSH2 (82.36 +/- 12.86, 88.11 +/- 9.27, p<.05) positive epithelial cells significantly increased in 53 patients who became H. pylori-negative after eradication therapy. However, the intensity of hMLH1 and hMSH2 staining was not significantly different. In those 7 patients, who did not respond to the eradication therapy and were still H. pylori-positive, the percent positivity and intensity of hMLH1 and hMSH2 staining did not change. CONCLUSIONS: The expression of DNA MMR proteins increased in the gastric mucosa after H. pylori eradication, indicating that H. pylori gastritis may be associated with a reduced DNA MMR system during infection. The effect of H. pylori infection on MMR protein expression appears to be at least partially reversible after H. pylori eradication. These data suggest that H. pylori gastritis might lead to a deficiency of DNA MMR in gastric epithelium that may increase the risk of mutation accumulation in the gastric mucosa cells during chronic H. pylori infection.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability.

CONTEXT: Criteria for microsatellite instability (MSI) testing to rule out hereditary nonpolyposis colorectal cancer were recently revised and include parameters such as age and specific histologic features that can be identified by the pathologist, triggering reflex MSI testing. OBJECTIVE: To review the performance of the revised Bethesda guidelines to identify MSI-positive colorectal cancers. DESIGN: Seventy-five patients with colorectal cancer were included; 68 patients younger than 50 years and 7 patients between 50 and 60 years were selected based on histopathologic criteria. Microsatellite instability testing with the National Cancer Institute--recommended panel and immunohistochemistry for hMLH1 and hMSH2 were performed. Tumors were classified into microsatellite instability high (MSI-H), low (MSI-L), or stable (MSS) categories. RESULTS: Overall, 17 (23%) of 75 colorectal cancer cases were classified as MSI-H, including 13 patients younger than 50 years and 4 patients between 50 and 60 years. Among the MSI-H tumors, 10 (59%) were characterized by loss of hMLH1 and 6 (35%) were hMSH2 negative. Histologic features suggestive of MSI-H phenotype were present in 80% of MSI-H and 35% of MSS/MSI-L tumors. The number of positive lymph nodes was higher in MSS/MSI-L adenocarcinomas (P = .04). CONCLUSIONS: By selecting for age and histologic features, we detected MSI-H tumors in approximately one quarter of colorectal cancer cases meeting the revised Bethesda guidelines and identified 17 MSI-H cases, whereas only 8 would have been recognized by the prior guidelines. These data indicate that reflex testing requested by pathologists based on the revised Bethesda guidelines increases the detection of MSI-H and potential hereditary nonpolyposis colorectal cancer cases.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Alterations of DNA mismatch repair proteins and microsatellite instability levels in gastric cancer cell lines.

Alterations in DNA mismatch repair (MMR) proteins result in microsatellite instability (MSI), increased mutation accumulation at target genes and cancer development. About one-third of gastric cancers display high-level microsatellite instability (MSI-High) and low-level microsatellite instability (MSI-Low) is frequently detected. To determine whether variations in the levels of MMR proteins or mutations in the main DNA MMR genes are associated with MSI-Low and MSI-High in gastric cancer cell lines, the MSI status (MSI-High, MSI-Low or MS-Stable (MSS)) of 14 gastric cancer lines was determined using multiple clone analysis with a panel of five microsatellite markers. Protein levels of hMLH1, hMSH2, hMSH6, hPMS2 and hPMS1 were determined by Western blot. Sequence analysis of hMLH1 and hMSH2 was performed and the methylation status of the hMLH1 promoter was examined. The cell lines SNU1 and SNU638 showed MSI-High, decreased to essentially absent hMLH1 and hPMS2 and reduced hPMS1 and hMSH6 protein levels. The hMLH1 promoter region was hypermethylated in SNU638 cells. The MKN28, MKN87, KATOIII and SNU601 cell lines showed MSI-Low. The MMR protein levels of cells with MSI-Low status was similar to the levels detected in MSS cells. A marked decrease in the expression levels of MutL MMR proteins (hMLH1, hPMS2 and hPMS1) is associated with high levels of MSI mutations in gastric cancer cells. Gastric cancer cell lines with MSI-Low status do not show significant changes in the levels of the main DNA MMR proteins or mutations in the DNA mismatch repair genes hMSH2 and hMLH1. These well-characterized gastric cancer cell lines are a valuable resource to further our understanding of DNA MMR deficiency in cancer development, progression and prognosis.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Detection of Chlamydiae pneumoniae but not Helicobacter pylori DNA in atherosclerosis plaques.

Chronic infections have been associated with cardiovascular disease. We used bacterial culture, polymerase chain reaction (PCR), and immunohistochemical staining with anti-vacA and anticagA antibodies to search for Helicobacter pylori and Chlamydiae pneumoniae in atherosclerotic plaques obtained at endarterectomy. Serum IgG antibodies to H. pylori and C. pneumoniae were also determined. Thirty-two patients were enrolled. Anti-H. pylori and anti-C. pneumoniae IgG were present in 72% and 81%, respectively. Culture and PCR for H. pylori of vessel walls and plaques were negative. Atherosclerotic plaque and normal vessel sections from H. pylori-negative and- positive patients showed reactivity with anti-vacA and anti-cagA antibodies. C. pneumoniae DNA was amplified in three atherosclerotic lesions. These findings suggest that the association between H. pylori infection and atherosclerosis does not result from continuing direct effects of H. pylori antigens in the vessel walls. Antigens within vessel atherosclerotic plaques cross-react with H. pylori virulence factors and could act as cofactors in determining instability for the atherosclerotic plaques.

Aged↗
PubMed2003

Cyclooxygenase expression during Helicobacter pylori infection in Mongolian gerbils.

We investigated the expression of cyclooxygenase-2 (COX-2) and COX-1 mRNAs during longterm Helicobacter pylori infection of the Mongolian gerbil (18 months) as well as the effect of eradication therapy and the cag pathogenicity island on COX mRNA expression. COX mRNA levels were determined by reverse transcription-polymerase chain reaction. Pyloric channel ulcers were noted in one of 10 gerbils (10%) at 3 months, 33% at 6 months, 50% at 9 months, 17% at 10 months, 40% at 12 months and 25% at 18 months after inoculation of parental strains. Nineteen of 21 gerbils had successful H. pylori eradication and showed significant reduction of inflammation and no ulcerations. There were no significant differences in COX-1 mRNA expression between the groups. COX-2 mRNA expression was significantly increased 1 and 3 months after inoculation and then decreased to basal levels. In control animals, COX-2 mRNA expression was significantly higher at 12 and 18 months compared to younger animals. cagE knockout mutants did not induce gastric inflammation and induced significantly lower COX-2 mRNA expression compared to parental strains. COX-2 mRNA was induced early in H. pylori infection and then declined. COX-2 mRNA expression was also induced with aging.

Animals↗
PubMed2003

Celecoxib and rofecoxib potentiate chronic colitis and premalignant changes in interleukin 10 knockout mice.

Nonsteroidal anti-inflammatory drugs decrease sporadic colorectal carcinoma and adenomas in patients with familial adenomatous polyposis and in rodent models of sporadic colon cancer and familial adenomatous polyposis. Similarly, selective cyclooxygenase 2 inhibitors decrease adenomas in humans and rodents. However, their effects on chronic colitis and colitis-associated neoplasia are unknown. Interleukin 10-/- mice (C57/B6) were fed regular chow (n = 20) or chow with celecoxib (1,500 ppm, n = 18) or rofecoxib (75 ppm, n = 20) for 12 weeks. Twenty-eight percent of the celecoxib group died versus 5% of the control and rofecoxib groups (p < 0.05 compared with control). Celecoxib and rofecoxib increased the incidence of colitis (26% vs. 92% and 68%, p < 0.01), colitis score (0.4 +/- 0.2 vs. 2.5 +/- 0.3 and 2 +/- 0.4, p < 0.01), aberrant crypt foci (0.5 +/- 0.3 vs. 3.7 +/- 2.6 and 2.8 +/- 0.7, p < 0.01), aberrant crypts per mouse (4.11 +/- 2.1 vs. 41.2 +/- 9.7 and 27.1 +/- 7.5, p < 0.01) and dysplasia (11% vs. 54% and 42%, p < 0.01). Similarly, indomethacin (9 ppm, n = 15) increased colitis score, aberrant crypt foci, and dysplasia after 27 days of treatment. Two selective cyclooxygenase 2 inhibitors exacerbate colitis and premalignant changes in the interleukin 10-/- mouse model of chronic colitis and colitis-associated colon carcinoma.

Animals↗
PubMed2003

Effects of Helicobacter pylori infection on the link between regenerating gene expression and serum gastrin levels in Mongolian gerbils.

Although regenerating gene (Reg) protein is reported to have a trophic effect on gastric epithelial cells, its involvement in human gastric diseases is not clear. We have recently shown that both gastrin and gastric mucosal inflammation enhance Reg gene expression in the fundic mucosa in rats. This study was designed to clarify whether Reg protein is involved in Helicobacter pylori-induced gastritis and whether Reg gene expression is linked to serum gastrin levels in this condition. Mongolian gerbils were inoculated with an H. pylori strain isolated from a gastric cancer patient. Four weeks later, some of the gerbils with H. pylori infection were eradicated by lansoprazole, amoxicillin, and clarithromycin. The time courses of changes in Reg gene expression, serum gastrin levels, gastric acidity, and histopathologic factors were examined. Four weeks after H. pylori infection, gastritis started spreading to the fundic mucosa, and gastric acidity started reducing. Serum gastrin levels and Reg mRNA expression in the fundus were significantly increased 6 weeks after infection. Reg mRNA expression in the fundus correlated significantly with both serum gastrin levels and the severity of fundic mucosal inflammation. After H. pylori eradication, serum gastrin levels and fundic mucosal inflammation were normalized, and the increase in Reg mRNA expression was abolished. The Reg gene is associated with hypergastrinemia and fundic mucosal inflammation and may be involved in H. pylori-induced gastritis.

Animals↗