This project is an extension of an on-going randomized, double-blind, placebo-controlled chemoprevention trial initiated in 1991 in a population at high risk of gastric cancer living in the Colombian Andes mountains. This trial seeks to determine the efficacy of chemoprevention on the progression of premalignant gastric lesions by antioxidant supplementation and/or anti-Helicobacter pylori treatment. Using a factorial design, 863 subjects with histopathologically-determined premalignant lesions (multifocal chronic atrophic gastritis, intestinal metaplasia, mild/moderate dysplasia) were randomly-allocated to treatment with ascorbic acid (2 g/day) or placebo, beta-carotene (30 mg/day) or placebo, and anti-Helicobacter pylori treatment (bismuth plus antibiotics) or no treatment. Study subjects have been treated for a total of 3 years (1991/92-1994/95) with an endoscopy and biopsy after 3 years. They will continue on treatment for an additional three years (1994/95-1997/98) with no interruption of treatment because drugs needed for a 3-year extension have been provided. Study subjects will undergo a final endoscopy with biopsies at the end of six years of treatment. The effects of each treatment versus its placebo will be evaluated by comparing baseline and post-treatment endpoints. The primary endpoint is global histopathology and its progression rate. Secondary endpoints include expression of sulfomucins, degree of cell replication (Ki67), frequency of expression of genetic abnormalities (p53, TPR-MET, microsatellite destabilization), indicators of DNA-damage (8-hydroxyguanine adducts) and the presence and quantity of indicators of oxidative stress (iNOS, nitrotyrosine, and apoptosis).

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Singh, Kshipra; Coburn, Lori A; Asim, Mohammad et al. (2018) Ornithine Decarboxylase in Macrophages Exacerbates Colitis and Promotes Colitis-Associated Colon Carcinogenesis by Impairing M1 Immune Responses. Cancer Res 78:4303-4315
Ge, Zhongming; Sheh, Alexander; Feng, Yan et al. (2018) Helicobacter pylori-infected C57BL/6 mice with different gastrointestinal microbiota have contrasting gastric pathology, microbial and host immune responses. Sci Rep 8:8014
Gobert, Alain P; Al-Greene, Nicole T; Singh, Kshipra et al. (2018) Distinct Immunomodulatory Effects of Spermine Oxidase in Colitis Induced by Epithelial Injury or Infection. Front Immunol 9:1242
Estevez-Ordonez, Dagoberto; Montalvan-Sanchez, Eleazar E; Wong, Rochelle E et al. (2018) Health Barriers and Patterns of Gastric Cancer Care in Rural Central American Resource-Limited Settings. JAMA Oncol 4:1131-1133
Scoville, Elizabeth A; Allaman, Margaret M; Brown, Caroline T et al. (2018) Alterations in Lipid, Amino Acid, and Energy Metabolism Distinguish Crohn's Disease from Ulcerative Colitis and Control Subjects by Serum Metabolomic Profiling. Metabolomics 14:
Sierra, Johanna C; Asim, Mohammad; Verriere, Thomas G et al. (2018) Epidermal growth factor receptor inhibition downregulates Helicobacter pylori-induced epithelial inflammatory responses, DNA damage and gastric carcinogenesis. Gut 67:1247-1260
Blosse, Alice; Lehours, Philippe; Wilson, Keith T et al. (2018) Helicobacter: Inflammation, immunology, and vaccines. Helicobacter 23 Suppl 1:e12517
Piñeros, Marion; Frech, Silvina; Frazier, Lindsay et al. (2018) Advancing Reliable Data for Cancer Control in the Central America Four Region. J Glob Oncol :1-11
González-Pons, María; Soto-Salgado, Marievelisse; Sevilla, Javier et al. (2018) Seroprevalence of Helicobacter pylori in Hispanics living in Puerto Rico: A population-based study. Helicobacter 23:
Coburn, Lori A; Singh, Kshipra; Asim, Mohammad et al. (2018) Loss of solute carrier family 7 member 2 exacerbates inflammation-associated colon tumorigenesis. Oncogene :

Showing the most recent 10 out of 278 publications