Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer

Konstantakos, Anastasios K.; SIu, Ivanov; Pretlow, Thomas G.; Stellato, Thomas A.

doi:10.1053/gast.1996.v111.pm8780584

Cited by 49 publications

(20 citation statements)

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“…The crypts in ACF are easy to score on whole mount colon: they are two to three times larger than normal crypts, are microscopically elevated, and have a slitlike opening and a thick epithelial lining that stains darker than normal crypts, with a large pericryptal zone (17). It was demonstrated that 1) ACF were induced by all colon carcinogens in a dose-and species-dependent manner, 2) their number and growth were modified by the modulators of colon carcinogenesis, and they predicted the tumor outcome in several rodent studies, 3) they correlate with colon cancer risk and adenoma size and number in humans, 4) the morphological and genotypic features of ACF in human colons were similar to those in animal colons, and many alterations are similar in ACF and in tumors, and 5) some ACF show dysplasia, and carcinoma were observed in rodent and human ACF (18,19). The use of the ACF system to study modulators of carcinogenesis has accelerated for the last 10 years, for it provides a simple and economical tool for preliminary screening of potential chemopreventive agents, and it allows a quantitative assessment of the mechanisms of colon carcinogenesis (20).…”

Section: Introductionmentioning

confidence: 99%

Most Effective Colon Cancer Chemopreventive Agents in Rats: A Systematic Review of Aberrant Crypt Foci and Tumor Data, Ranked by Potency

Corpet¹,

Taché²

2002

Nutrition and Cancer

193

145

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Potential chemopreventive agents for colorectal cancer are assessed in rodents. We speculated that the magnitude of the effect is meaningful and ranked all published agents according to their potency. Data were gathered systematically from 137 articles with the aberrant crypt foci (ACF) end point and from 146 articles with the tumor end point. The potency of each agent to reduce the number of ACF is listed in one table and the potency of each agent to reduce the tumor incidence in another table. Both tables are shown in this review and on a website with sorting abilities (http://www.inra.fr/reseau-nacre/sci-memb/corpet/indexan.html). Potency was estimated as the ratio of the value in control rats to the value in treated rats. From each article, only the most potent agent was kept, except in articles reporting the effect of more than seven agents. Among the 186 agents in the ACF table, the median agent reduced the number of ACF by one-half. The most potent agents to reduce azoxymethane-induced ACF were Pluronic, polyethylene glycol, perilla oil with beta-carotene, and sulindac sulfide. Among the 160 agents in the tumor table, the median agent reduced the tumor incidence in rats by one-half. The most potent agents to reduce the incidence of azoxymethane-induced tumors were celecoxib, a protease inhibitor from soy, difluoromethylornithine with piroxicam, polyethylene glycol, and a thiosulfonate. For the 57 agents present in both tables, a significant correlation (r) was found between the potencies against ACF and tumors (r = 0.45, P < 0.001); without celecoxib, a major outlying point in the correlation, r = 0.68 (P < 0.001, n = 56). In conclusion, this review gathers most known chemopreventive agents, ranks the most promising agents against colon carcinogenesis in rats or mice, and further supports the use of ACF as a surrogate end point for tumors in rats.

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Section: Introductionmentioning

confidence: 99%

Most Effective Colon Cancer Chemopreventive Agents in Rats: A Systematic Review of Aberrant Crypt Foci and Tumor Data, Ranked by Potency

Corpet¹,

Taché²

2002

Nutrition and Cancer

193

145

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“…With the emergence of magnification and chromoscopy, it is now possible to perform endoscopic in vivo human studies [19][20][21][22][23][24][25][26]. Although there are a number of arguments supporting the preneoplastic nature of ACF, such as an average number that increases with age [23], a higher prevalence in patients with neoplastic lesion of the colon [23], the identification of ACF with carcinoma in situ in a patient with sporadic colon cancer [27], the presence of ACF with dysplasia and APC mutations in patients with familial adenomatous polyposis [28,29], and the occurrence of microsatellite instability in ACF picked from patients with Lynch syndrome [30], the truth is that doubt still persists with regard the preneoplastic nature of ACF, which is unquestionable only in animal models of intestinal cancer.…”

mentioning

confidence: 99%

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Figueiredo

Donato

Urbano

et al. 2008

Int J Colorectal Dis

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Background and aims Aberrant crypt foci (ACF) are preneoplastic lesions in animal models of colorectal cancer. The aim of the study is to investigate if ACF are involved in human colorectal carcinogenic process and if they can be helpful in predicting the presence of a colorectal neoplasia. Methods The study included, between 2003 and 2005, 182 patients, 62 with adenoma, 55 with colorectal carcinoma, 53 without colorectal lesions, and 12 with nonneoplastic mucosal polyps. The number of rectal ACF was determined by colonoscopy. Proliferation and apoptosis indexes were evaluated by immunohistochemistry in rectal ACF, in normal rectal mucosa, and in carcinomatous tissue. Results The mean number of rectal ACF in patients with rectal neoplasia was 12.64, significantly higher than in patients with neoplastic lesions elsewhere in the colon (p= 0.01). The apoptosis index in ACF of patients with colorectal carcinoma or adenoma aged 50 years or older was significantly lower than in younger patients (1.3% vs 2.7%, p=0.01) and, in patients with carcinoma, lower than in normal mucosa (1.1% vs 2.1%, p=0.002). The proliferation index was significantly higher in ACF of patients with colorectal neoplasia aged less than 50 years than in normal mucosa (10.9% vs 7.7%, p=0.02). The apoptosis index in ACF foci of patients with carcinoma (1.1%) was significantly lower than in patients without lesions (2.2%) and than in normal mucosa (2%). The mean number of ACF is significantly higher in patients with polyps larger than 1 cm (11.28 vs 6.27, p=0.02). Conclusion Aberrant crypt foci probably precede the appearance of neoplasia and may be helpful in predicting the presence of a colorectal neoplastic lesion.

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“…The ACF in humans ( Figures 1E and 1F) clearly resemble those seen in animals in morphology and histological appearance (Pretlow et al 1991(Pretlow et al , 1994cRoncucci et al 1991a, b;Pretlow 1994;Konstantakos et al 1996;Siu et al 1997). Although ACF from humans are enzyme-altered Pretlow et al 1991), the enzyme alterations studied to date are not as marked or consistent as those observed in F344 rats.…”

Section: Aberrant Crypt Foci In Humansmentioning

confidence: 61%

Putative Preneoplastic Changes Identified by Enzyme Histochemical and Immunohistochemical Techniques

Pretlow

1998

J Histochem Cytochem.

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SUMMARY Microscopic evaluation of whole-mount colons stained with methylene blue and ր or hexosaminidase has identified putative preneoplastic lesions in the colons of rodents treated with carcinogen and in the grossly normal colons of humans. Enzyme histochemistry with glycol methacrylate sections has permitted the identification of putative premalignant lesions in rodent livers, human and rodent colons, and human prostates. Immunohistochemistry with paraffin-embedded tissues has been used to identify and characterize putative premalignant lesions in human colons and prostates.

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Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer

Cited by 49 publications

References 0 publications

Most Effective Colon Cancer Chemopreventive Agents in Rats: A Systematic Review of Aberrant Crypt Foci and Tumor Data, Ranked by Potency

Most Effective Colon Cancer Chemopreventive Agents in Rats: A Systematic Review of Aberrant Crypt Foci and Tumor Data, Ranked by Potency

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Putative Preneoplastic Changes Identified by Enzyme Histochemical and Immunohistochemical Techniques

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