Predictive value of proliferation, differentiation and apoptosis as intermediate markers for colon tumorigenesis

Chang, Wen‐Chi L.; Chapkin, Robert S.; Lupton, Joannè R.

doi:10.1093/carcin/18.4.721

Cited by 196 publications

(192 citation statements)

References 9 publications

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“…dose of BrdUrd (160 g͞kg body weight in DMSO) 3 h before killing. Tissue for immunohistochemistry was taken from the distal end of the colon (1 cm) and fixed in 10% (vol͞vol) PBS-buffered formalin overnight, followed by BrdUrd staining, as described (22). Labeling index [(no.…”

Section: Measurement Of Proliferation Of Different Tissues Proliferamentioning

confidence: 99%

Measurement in vivo of proliferation rates of slow turnover cells by ² H ₂ O labeling of the deoxyribose moiety of DNA

Neese

Misell

Turner

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

255

330

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We describe here a method for measuring DNA replication and, thus, cell proliferation in slow turnover cells that is suitable for use in humans. The technique is based on the incorporation of 2 H2O into the deoxyribose (dR) moiety of purine deoxyribonucleotides in dividing cells. For initial validation, rodents were administered 4% 2 H2O in drinking water. The proliferation rate of mammary epithelial cells in mice was 2.9% per day and increased 5-fold during pregnancy. Administration of estradiol pellets (0 -200 g) to ovariectomized rats increased mammary epithelial cell proliferation, according to a doseresponse relationship up to the 100 g dose. Similarly, proliferation of colon epithelial cells was stimulated in a dose-response manner by dietary cholic acid in rats. Bromodeoxyuridine labeling correlated with the 2 H2O results. Proliferation of slow turnover cells was then measured. Vascular smooth muscle cells isolated from mouse aorta divided with a half-life in the range of 270 -400 days and die-away values after 2 H2O wash-out confirmed these slow turnover rates. The proliferation rate of an adipocyte-enriched fraction from mouse adipose tissue depots was 1-1.5% new cells per day, whereas obese ad libitum-fed ob͞ob mice exhibited markedly higher fractional and absolute proliferation rates. In humans, stable long-term 2 H2O enrichments in body water were achieved by daily 2 H2O intake, without toxicities. Labeled dR from fully turned-over blood cells (monocytes or granulocytes) exhibited a consistent amplification factor relative to body 2 H2O enrichment (Ϸ3.5-fold). The fraction of newly divided naive-phenotype T cells after 9 weeks of labeling with 2 H2O was 0.056 (CD4 ؉ ) and 0.043 (CD8 ؉ ) (replacement rate <0.1% per day). In summary, 2 H2O labeling of dR in DNA allows safe, convenient, reproducible, and inexpensive measurement of cell proliferation in humans and experimental animals and is well suited for slow turnover cells. deuterated water ͉ cell proliferation ͉ DNA synthesis ͉ adipogenesis ͉ vascular smooth muscle cell proliferation

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Section: Measurement Of Proliferation Of Different Tissues Proliferamentioning

confidence: 99%

Measurement in vivo of proliferation rates of slow turnover cells by ² H ₂ O labeling of the deoxyribose moiety of DNA

Neese

Misell

Turner

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

255

330

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“…Calcium also reduces the number of guanine-to-adenine mutations in the K-ras gene in colorectal neoplasms of the rat (Llor et al, 1991). Calcium may increase the rate of apoptosis occurring in colonic epithelial cells which, itself, could normalize a possible discrepancy between the proliferation=apoptosis ratio in preneoplastic mucosa (Chang et al, 1997).…”

Section: Principal Hypotheses Linking Dairy Products Intake and Colormentioning

confidence: 99%

Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence

2003

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Objectives: This review provides an overview of the principal hypotheses and epidemiological evidence of the possible links between colorectal cancer and intake of milk and=or dairy products. Methods: The first section outlines the main hypotheses about the possible effect of calcium, vitamin D, fats and other milk components. The possible role of acid lactic bateria in fermented products is also discussed. The second section is a summary of the published epidemiological evidence. The results on milk, cheese and yoghurt are summarized using a meta-analytical approach. The results of studies on calcium and vitamin D are briefly described. Results: Case -control studies are heterogeneous and, on average, do not provide evidence of association between total intake of total dairy products, milk, cheese or yoghurt and colorectal cancer risk. The average result from cohort studies support the hypothesis of a protective effect of total dairy products (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.52 -0.74; P heterogeneity test: 0.93) and for milk (OR: 0.80; 95% CI: 0.68 -0.95; P heterogeneity: 0.77). No association was found between cheese (OR: 1.10; 95% CI: 0.88 -1.36; P heterogeneity: 0.55) or yoghurt (OR: 1.03; 95% CI: 0.83 -1.28; P heterogeneity: 0.69) in cohort studies. Conclusions: Cohort studies consistently found a protective effect of total dairy products and milk intake, but the evidence is not supported by case -control studies. No relationship was found with cheese or yoghurt intake. As the number of cohort studies is still limited, their results need to be confirmed by other prospective studies.

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“…5,6 Several in vivo studies hypothesize that a high amount of x-6 PUFA, such as LA, might enhance colorectal carcinogenesis via stimulation of colonic epithelial cell proliferation. [7][8][9][10] Indeed, rats treated with AOM and fed a diet supplemented with LA developed more tumors than animals treated with AOM alone. 11 AOM is a potent carcinogen, which induces colorectal cancers at high incidence in rats and mice.…”

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confidence: 99%

Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment

Sasaki

Yoshida

Sasaki

et al. 2005

Intl Journal of Cancer

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The effect of linoleic acid (LA) on growth and transformation of IEC6 intestinal cells was examined. IEC6 cells expressed mRNAs of 15-lipooxygenase (LOX15) and peroxisome proliferator-activated receptor (PPAR)c but not COX-2. Cell growth was suppressed by LA in a dose-dependent manner in IEC6 cells. Threeweek treatment with LA provided IEC6 cells a quiescent state. LA-induced growth inhibition was abrogated by exposure to antisense S-oligodeoxynucleotides (S-ODNs) for LOX15 and/or PPARc. In an in vitro carcinogenesis model, IEC6 cells, which had confirmed CYP2E1 expression and activity, were continuously treated with AOM and/or LA for 40 weeks. DNA injury in AOMtreated cells was suppressed to the control level by concurrent LA treatment. Colony formation of AOM-treated cells in soft agar was suppressed by treatment with LA, which was reversed by exposure to antisense S-ODNs for LOX15 and/or PPARc. AOMtreated IEC6 cells formed s.c. tumors in 9 of 12 mice, whereas AOM1LA-treated cells formed no tumor. IEC6 cells showed no remarkable alteration of protein production by AOM treatment, whereas cells treated with AOM1LA showed decreased epidermal growth factor receptor (EGFR) and phospho-EGFR and increased BAX. These findings suggest that LA inhibited AOMinduced transformation of COX-2-negative IEC6 cells, which was possibly mediated with PPARc ligands generated by LOX15 from LA. ' 2005 Wiley-Liss, Inc.Key words: linoleic acid; azoxymethane; colon cancer; transformation; peroxisome proliferator-activated receptor Colorectal cancer is the third most common malignant neoplasm worldwide and the third leading cause of cancer deaths in Japan. 1 The frequency of colon cancer in Japan is continuously increased along with the alteration of lifestyle from traditional Japanese to Western. In particular, the increase of fat intake and decrease of fiber intake have been regarded as the most important nutritional influence on colorectal cancer development. 2,3 Prostaglandins are bioactive lipids derived from the metabolites of membrane PUFAs and play important roles in a number of biologic processes. 4 COX-2-dependent overproduction of PGE 2 is hypothesized to be an important part of sustained proliferative and chronic inflammatory conditions. 5,6 Several in vivo studies hypothesize that a high amount of x-6 PUFA, such as LA, might enhance colorectal carcinogenesis via stimulation of colonic epithelial cell proliferation. 7-10 Indeed, rats treated with AOM and fed a diet supplemented with LA developed more tumors than animals treated with AOM alone. 11 AOM is a potent carcinogen, which induces colorectal cancers at high incidence in rats and mice. Adduct formation (mainly O 6 -methylguanine) by AOM induces point mutations in multiple genes such as K-ras and b-catenin. 12 In the present study, we used AOM as a carcinogen in the in vitro carcinogenesis model.The oxidative metabolites of LA, particularly 9-HODE, 13-HODE and 13-OXO, have biologic effects as PPARg ligands. 13 CLA, a strong ligand for PPARg, has a substantial anticarcin...

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Predictive value of proliferation, differentiation and apoptosis as intermediate markers for colon tumorigenesis

Cited by 196 publications

References 9 publications

Measurement in vivo of proliferation rates of slow turnover cells by ² H ₂ O labeling of the deoxyribose moiety of DNA

Measurement in vivo of proliferation rates of slow turnover cells by ² H ₂ O labeling of the deoxyribose moiety of DNA

Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence

Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment

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Predictive value of proliferation, differentiation and apoptosis as intermediate markers for colon tumorigenesis

Cited by 196 publications

References 9 publications

Measurement in vivo of proliferation rates of slow turnover cells by 2 H 2 O labeling of the deoxyribose moiety of DNA

Measurement in vivo of proliferation rates of slow turnover cells by 2 H 2 O labeling of the deoxyribose moiety of DNA

Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence

Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment

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Measurement in vivo of proliferation rates of slow turnover cells by ² H ₂ O labeling of the deoxyribose moiety of DNA

Measurement in vivo of proliferation rates of slow turnover cells by ² H ₂ O labeling of the deoxyribose moiety of DNA