Aberrant Crypt Foci: Detection, Gene Abnormalities, and Clinical Usefulness

Takayama, Tetsuji; Miyanishi, Koji; Hayashi, Tsuyoshi; Kukitsu, Takehiro; Takanashi, Kunihiro; Ishiwatari, Hirotoshi; Kogawa, Takahiro; Abe, Tomoyuki; Niitsu, Yoshiro

doi:10.1016/s1542-3565(05)00257-0

Cited by 44 publications

(43 citation statements)

References 7 publications

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“…A number of evidences support the conclusion that AC constitute initial lesions that may give rise to adenomas and carcinomas in advanced steps (Takayama et al, 2005). The usefulness of evaluating these lesions also relies on the shorter time of experimentation compared with the classical methods for studying tumor development, as well as in the similarity of AC in experimental animals as compared with the observed in humans (Pretlow et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…This result agrees with the fact that the initial genetic damage by the carcinogen could be organ-specific, is of epigenetic type, or/and that defects in chromosomal segregation are produced later in the pathogenesis, probably during the adenoma-carcinoma phase. In fact, the molecular mechanism that act at the colon cancer initiation are complex and not homogeneous, for example, K-ras mutations can be present in most sporadic AC, in contrast with adenomatous polyposis where APC mutations are preponderant (Takayama et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

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Grapefruit Juice Suppresses Azoxymethane-induced Colon Aberrant Crypt Formation and Induces Antioxidant Capacity in Mice

Madrigal-Bujaidar¹,

Roaro²,

García-Aguirre³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Grapefruit Juice Suppresses Azoxymethane-induced Colon Aberrant Crypt Formation and Induces Antioxidant Capacity in Mice

Madrigal-Bujaidar¹,

Roaro²,

García-Aguirre³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…The rather long-term recruitment period was because of the delay in approval by the institutional review board in 3 hospitals and the delay in dispensing the drug to 1 hospital. According to reduction rates in ACF number by sulindac administration in our preliminary trials (20,21), we estimated that 360 subjects would generate 90% power for a difference in the ACF number among the groups. Because it was possible that the estimate of an adequate sample size to show significant efficacy of the investigational drug was too conservative, a planned interim analysis was carried out when half of the subjects had been enrolled.…”

Section: Study Design and Subjectsmentioning

confidence: 99%

“…We then, though preliminarily, showed that ACF could be eradicated by short-term administration of sulindac (20,21) and proposed the possibility that discontinuous use of the drug may be just as effective as continuous use and may make the daunting task of chemoprevention more realistic. However, results of multicenter trials of chemoprevention by others have raised controversy over the ACF-adenoma-carcinoma sequence theory or the use of ACF as biomarkers for recurrent colorectal adenomas (22,23).…”

Section: Introductionmentioning

confidence: 99%

Randomized Double-Blind Trial of Sulindac and Etodolac to Eradicate Aberrant Crypt Foci and to Prevent Sporadic Colorectal Polyps

Takayama

Nagashima

Maeda

et al. 2011

Clinical Cancer Research

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Purpose: On the basis of the results of our preliminary trial suggesting that aberrant crypt foci (ACF) could be eradicated by short-term administration of sulindac, in the present study, we explored the feasibility of using ACF as surrogate markers for chemoprevention of colorectal cancer.Experimental design: Randomly assigned to sulindac (300 mg daily), etodolac (400 mg daily), and placebo groups were 189 subjects without polyps or who had undergone polypectomy. Drugs were administered for 2 months. ACF in the rectal region were counted by magnifying endoscopy. Occurrence of polyps was evaluated at 12 months. A planned interim analysis was conducted.Results: ACF number at 2 months was significantly suppressed in the sulindac group (P ¼ 0.0075), but not in the etodolac group (P ¼ 0.73). In the sulindac group, the numbers of adenomas plus hyperplastic polyps (total polyps) and adenomas at 12 months were significantly (P ¼ 0.02) and marginally (P ¼ 0.064) lower, respectively, in comparison with the placebo group; no such difference was observed in the etodolac group. In analysis of only polypectomized subjects, the numbers of total polyps and adenomas in the sulindac group were even more markedly lower, with P values of 0.014 and 0.034, respectively. A similar tendency was confirmed by analyses of the incidence of polyps at 12 months. Suppression rates of total polyps and adenomas in ACF responders to sulindac were significantly greater than in nonresponders. In all groups, compliance was more than 90% and no intolerable adverse effects were observed.Conclusions: ACF may be useful as surrogate lesions for chemoprevention of colorectal cancer. Clin Cancer Res; 17(11); 3803-11. Ó2011 AACR.

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“…Colorectal cancer remains the second leading cause of cancer-related mortality in Western countries, and it develops mainly from adenomatous polyps and shows a morphological and genetic progression through an adenoma-carcinoma sequence, both in hereditary and in sporadic colorectal cancer (15 genetic and epigenetic alterations (16)(17)(18)(19). The purpose of the present study was two-fold: (i) to determine whether BCL6 is expressed during malignant transformation of the large bowel and (ii) to assess whether, and to what extent, BCL6 immunoreactivity is related to the different stages of neoplastic progression.…”

Section: Introductionmentioning

confidence: 99%

Morphological and quantitative analysis of BCL6 expression in human colorectal carcinogenesis

et al. 2013

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Abstract. The aim of the present study was to determine whether BCL6 is expressed during malignant transformation of the large bowel and to assess whether, and to what extent, immunoreactivity is related to the different stages of neoplastic progression. Samples of normal colorectal mucosa (n=22), microadenomas (n=22) and colorectal cancer (n=22), were analyzed by immunohistochemistry, immunofluorescence coupled with confocal microscopy and western blotting. Our results clearly outlined the marked increase occurring in both intensity and density of BCL6 protein expression in the normal mucosa-microadenoma-carcinoma sequence. Immunohistochemistry and immunofluorescence analyses showed that BCL6 is expressed at low levels in normal mucosa and increases in microadenoma and in cancer with statistical significance. These results were confirmed by western blotting data. The increasing expression of BCL6 in human colorectal cancer development suggests the involvement of BCL6 in tumor progression, from the earliest stages of carcinogenesis with significant increase in cancer. The enhanced understanding of the biological role of BCL6, previously shown to exert a key role in lymphomagenesis, may lead to a re-evaluation of this protein and may highlight the importance of performing further studies in order to identify novel therapeutic targets for colorectal cancer.

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Aberrant Crypt Foci: Detection, Gene Abnormalities, and Clinical Usefulness

Cited by 44 publications

References 7 publications

Grapefruit Juice Suppresses Azoxymethane-induced Colon Aberrant Crypt Formation and Induces Antioxidant Capacity in Mice

Grapefruit Juice Suppresses Azoxymethane-induced Colon Aberrant Crypt Formation and Induces Antioxidant Capacity in Mice

Randomized Double-Blind Trial of Sulindac and Etodolac to Eradicate Aberrant Crypt Foci and to Prevent Sporadic Colorectal Polyps

Morphological and quantitative analysis of BCL6 expression in human colorectal carcinogenesis

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