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Writing the Introduction Section
Example of a Well-Written Introduction (Basic Science Study)
Ulcerative colitis (UC) is a chronic disease characterized by inflammation of the mucosa and submucosa of the large intestine. Increasing duration and severity of UC correlate directly with an increased propensity to develop colorectal carcinoma (1,2). For patients who have had UC for >20 years, the incidence of colorectal cancer is 10- to 20-fold greater than that of the general population, and the average age of onset is 20 years earlier (3). Unlike sporadic colorectal carcinoma, which arises from adenomatous polyps, UC-associated colorectal carcinoma progresses from areas of dysplastic mucosa. Although the molecular events that facilitate the progression of adenoma to carcinoma in sporadic colorectal cancer have been well investigated (4), it is not known whether the same events underlie the progression of UC mucosa to dysplasia and carcinoma. Identifying the events involved in this progression would allow us to identify patients with UC at increased risk for developing colorectal carcinoma. One such event, inactivation of the p53 tumor suppressor gene, is common in both sporadic and UC- associated colorectal carcinoma (4–6). Although point mutation and loss of heterozygosity are the most commonly reported mechanisms resulting in p53 inactivation, other genetic and epigenetic factors have been shown to modify p53 activity as well. Amplification of the MDM-2 gene (the protein product of which tags p53 for degradation) and expression of viral oncoproteins (which sequester p53) are 2 such examples (7). MDM-2 is inhibited by p14 ARF (8). Homozygous deletion of the p14 ARF locus has been reported in a variety of cancers (9–13), and gene knockout of p14 ARF correlates with tumorigenesis (14). In addition to mutation, the p14 ARF gene can be epigenetically inactivated through hypermethylation of its normally unmethylated CpG island. Esteller et al. (15) demonstrated that p14 ARF hypermethylation occurs frequently in sporadic colorectal cancer. We therefore hypothesized that p14 ARF hypermethylation occurs during the progression of UC mucosa to carcinoma. To test this hypothesis, we determined the frequency and timing of p14 ARF hypermethylation in clinical samples ranging from nonneoplastic UC mucosa to colorectal carcinoma.
Reprinted with permission from Fumiaki Sato F et al. Hypermethylation of the p14 ARF gene in ulcerative colitis–associated colorectal carcinogenesis. Cancer Res 62:1148–1151, 2002.
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