Pattern of cell kinetics in colorectal mucosa of patients with different types of adenomatous polyps of the large bowel

Roncucci, Luca; Scalmati, Alessandra; Leòn, Maurizio Ponz de

doi:10.1002/1097-0142(19910815)68:4<873::aid-cncr2820680433>3.0.co;2-p

Cited by 31 publications

(17 citation statements)

References 26 publications

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“…These observations are consistent with those of Roncucci and colleagues 34. Terpstra and colleagues23 found intraregional differences in the TLIs of patients with adenomas <1 cm but not in those with a history of large adenomas (>1 cm).…”

Section: Discussionsupporting

confidence: 91%

Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas

Anti

Armuzzi²,

Morini³

et al. 2001

Gut

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Background-Alterations in epithelial proliferation and apoptosis in colonic mucosa are associated with an increased risk of colon cancer. It is unclear if these alterations represent a generalised "field defect". Aims-To analyse segmental patterns of cell proliferation and apoptosis in the colon of subjects with a high and no apparent risk of colon cancer. Methods-Pancolonoscopywas performed in 15 patients with resected adenomas (>1.5 cm) and in nine subjects without an apparent risk of colorectal cancer. Mucosal biopsies were taken from the right colon, left colon, and sigmoid rectum. Crypt cell proliferation and apoptosis were evaluated, respectively, with bromodeoxyuridine immunohistochemistry and terminal deoxyuridine nucleotidyl nick end labelling of DNA strand breaks. Results are expressed as total labelling index (TLI) and labelling index (LI) for each of the five compartments in which colonic crypts were divided (fourth and fifth compartments were evaluated together) for cell proliferation and as apoptotic index (AI) for apoptosis assessment. Results-No significant segmental variations in proliferation were found in either group. Compared with controls, adenoma patients had higher TLIs for the right (p>0.05), left (p<0.005), and sigmoid rectum (p<0.05) segments, and higher left colon LIs for crypt compartments (compartment 1, p<0.01; compartment 2, p<0.005; compartment 3, p<0.001; compartments 4-5, p<0.01). Control AIs were similar in all segments but in the adenoma patients left colon and sigmoid rectum AIs were lower than their right colon indexes (p<0.05, p<0.05) and corresponding values for controls (p<0.01, p<0.05). Conclusions-The colonic mucosa of patients with past adenomas presents diVuse hyperproliferation and, distally, abnormally distributed proliferating cells and markedly reduced apoptosis. These changes represent a significant risk for malignancies and could account for the high prevalence of left colon tumours. (Gut 2001;48:238-246)

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Section: Discussionsupporting

confidence: 91%

Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas

Anti

Armuzzi²,

Morini³

et al. 2001

Gut

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“…As far as tumor site is concerned, proximal and distal segments in the large bowel have different embryological origins and show development and biological differences (21). It has been postulated that these segments may have different susceptibilities to neoplastic transformation.…”

Section: Discussionmentioning

confidence: 66%

EGF, TGF-a, and EGF-R in Human Colorectal Adenocarcinoma

Messa¹,

Russo²,

Caruso³

et al. 1998

Acta Oncologica

229

121

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“…This has not been confirmed in other studies, including the present study. Alteration in the distribution of mitotic cells in the crypts in normal flat mucosa is one of the earliest detectable premalignant changes occurring in the colon and is observed in the macroscopically normal appearing flat colonic mucosa in patients with CRC 26 29 – 31. In the present study, the proportion of mitotic cells in the top half of the crypt was reduced markedly (p = 0.028) following RS treatment, and adds support to the hypothesis that RS has antineoplastic effects in the human large bowel 32…”

Section: Discussionmentioning

confidence: 99%

Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial

Dronamraju

Coxhead

Kelly

et al. 2008

Gut

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Objective: This study investigated the effects of oral supplementation of resistant starch (RS) on tumour cell and colonic mucosal cell kinetics and on gene expression in patients with colorectal cancer (CRC), and its potential role in colon cancer prevention. Methods: 65 patients with CRC were randomised to treatment with RS or ordinary starch (OS) and were given starch treatment for up to 4 weeks. Pretreatment and post-treatment biopsies were obtained from the tumour and colonic mucosa, and the effects of the starch treatment on cell proliferation and expression of the cell cycle regulatory genes CDK4 (cyclin-dependent kinase 4) and GADD45A (growth arrest and DNA damage-inducible, alpha) were investigated. Results: The proportion of mitotic cells in the top half of the colonic crypt was significantly lower following RS treatment (3.1 (1.5), mean (SEM)) as compared with OS treatment (13.7 (3.2)) (p = 0.028). However, there was no effect of RS treatment on crypt dimensions and tumour cell proliferation index. There was significant upregulation in expression of CDK4 (p,0.01) and downregulation in expression of GADD45A (p,0.001) in the tumour tissue when compared with macroscopically normal mucosa. Following RS treatment, CDK4 expression in tumours (0.88 (0.15)) was twofold higher than that in the OS group (0.37 (0.16)) (p = 0.02). The expression of GADD45A, which was downregulated in the presence of cancer, was significantly upregulated (p = 0.048) following RS treatment (1.41 (0.26)) as compared with OS treatment (0.56 (0.3)). However, there were no significant differences in the expression of these genes in the normal mucosa following starch treatment. Conclusions: Cell proliferation in the upper part of colonic crypts is a premalignant marker and its reduction by RS supplementation is consistent with an antineoplastic action of this food component. Differential expression of the key cell cycle regulatory genes may contribute to the molecular mechanisms underlying these antineoplastic effects of RS. Trial registration number: ISRCTN93586244.Resistant starch (RS) is defined as the fraction of dietary starch which resists digestion in the small intestine of healthy individuals.1 This undigested starch forms a major substrate for microbial fermentation in the large bowel, leading to the production of short chain fatty acids (SCFAs) including acetate, propionate and butyrate.2 3 RS has a number of physiological effects in the colon, most of which are thought to be due to the SCFAs, particularly butyrate. There is compelling evidence that butyrate causes a dose-dependent suppression of proliferation of colon cancer cell lines, 4-8 and RS has antineoplastic effects against colon cancer in animal models. 9-11Recent studies in rat have shown that feeding RS reduced the incidence and multiplicity of azomethane-induced colon cancers and reduced the tumour-enhancing effects of indigestible protein and red meat.12-14 These protective effects of RS were thought to be secondary to fermentation of RS to butyrate in th...

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Pattern of cell kinetics in colorectal mucosa of patients with different types of adenomatous polyps of the large bowel

Cited by 31 publications

References 26 publications

Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas

Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas

EGF, TGF-a, and EGF-R in Human Colorectal Adenocarcinoma

Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial

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