Colon Carcinogenesis: Modulation of Progression

Cameron, Ivan L.; Ord, Virginia A.; Hunter, Keithley E.; Heitman, David W.

doi:10.1016/b978-0-12-509375-0.50009-4

Cited by 8 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This recovery time was necessary to allow the epithelium to reach a steady state after DMH injection (Wright and Alison, 1984;Deschner, 1987;Cameron et al, 1990), and to enable the evaluation of longer lasting rather than immediate effects of the other drugs. Given the relatively short half-lives of the drugs administered (Insel, 1996) and the lack of any significant difference in total cyclo-oxygenase activity between the treatment groups, any changes in proliferation may have been due to a long-term influence of the NSAID rather than to a short-term NSAID suppression of prostaglandin synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…On the fourth morning, half of the rats in each group (n = 6) were given a s.c. injection of DMH (12 mg base per kg bw) and the other half were injected with DMH vehicle alone (4 ml kg-'). This weekly pattern was repeated for 8 weeks according to an established protocol for inducing rat colon cancer (Cameron et al, 1990). At the start of week 9 (i.e.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…A tumour is generally considered to be a lesion that arises as a result of an imbalance between cell proliferation and cell death. Increased epithelial cell proliferation is an established risk factor for colon cancer development (Deschner and Maskens, 1982; Wright and Alison, 1984;Cameron et al, 1990). NSAIDs have been shown to reduce cell proliferative parameters in colon crypts (Barnes et al, 1995) and to stall cultured colon adenocarcinoma cells in the GO/GI phase of the cell cycle (Shiff et al, 1996).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Non-steroidol anti-inflammatory drug effect on crypt cell proliferation and apoptosis during initiation of rat colon carcinogenesis

Barnes

Cameron²,

Hardman³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary Sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colorectal cancer. However, the optimal drug, period of efficacy and mechanism(s) of action are unknown. Experiments were undertaken to determine which of several NSAIDs would modulate colon crypt cell proliferation or apoptosis when given during the initiation phase of 1,2-dimethylhydrazine (DMH)-induced rat colon cancer. Colon crypts located both away from and over an aggregate of lymphoid nodules (ALN) were examined. Rats were injected with aspirin, indomethacin, nabumetone, sodium salicylate, 16,16-dimethyl prostaglandin E2 or saline for 3 days and DMH or DMH vehicle on day 4 of each week for 8 weeks, then killed 3 days after the last DMH injection. At the time of killing, DMH had significantly increased crypt cell proliferation but not apoptosis. There was significantly more cell proliferation and apoptosis in crypts over the ALN than away from the ALN. Aspirin and salicylate increased proliferation and apoptosis in crypts over the ALN. Finally, the distributional peaks of cell proliferation and apoptosis were shifted significantly closer together after DMH. Thus, DMH increases proliferation and alters the distribution of proliferating and apoptotic cells in colon crypts early in carcinogenesis. Aspirin may suppress tumour incidence via salicylate by enhancing apoptosis in carcinogen-initiated cells.Keywords: colon cancer; proliferation; apoptosis; non-steroidal anti-inflammatory drugs; lymphoid nodules; 1,2-dimethylhydrazine Data from human epidemiological research (Thun, 1994;Giovannucci et al, 1995) and from rodent experimental research (Craven and DeRubertis, 1992;Reddy et al, 1993) have demonstrated both correlative and direct evidence of a role for aspirin and possibly other non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention of colon and rectal cancer morbidity and mortality. However, the optimal NSAID, the dose, the period of efficacy and the mechanism of this putative chemopreventive activity remain to be established (Earnest et al, 1992;Giardiello et al, 1995).One potential mechanism for this chemopreventive effect lies in the ability of aspirin and other NSAIDs to inhibit prostaglandin production by blocking the activity of one or both of the prostaglandin endoperoxide G/H synthase (PGHS) isozymes, PGHS-1 and PGHS-2 (Meade et al, 1993). PGHS-l is the constitutive form of the enzyme and is expressed in most tissues, whereas PGHS-2 is induced by mitogenic stimuli in inflammatory situations (Smith and DeWitt, 1996) and is expressed at high levels in colon tumour tissue (Eberhart et al, 1994;Kargman et al, 1995;Dubois et al, 1996). Aspirin covalently and irreversibly modifies the cyclo-oxygenase active site of both PGHS-1 and PGHS-2 by acetylation, whereas other NSAIDs reversibly block PGHS function and thus prostaglandin production via steric hindrance of the cyclo-oxygenase active site (Smith and DeWitt, 1996 (Marnett, 1992). These include: evidence that PGs stimulate proliferation of human colon can...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Experimental Protocolmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Non-steroidol anti-inflammatory drug effect on crypt cell proliferation and apoptosis during initiation of rat colon carcinogenesis

Barnes

Cameron²,

Hardman³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Unravelling the mechanisms through which dietary factors alter the gastrointestinal environment to prevent or promote tumour formation is a major challenge and may never be completely performed using in vivo experimentation. However, in vitro models may provide clues to help us understand these mechanisms (Cameron, 1990).…”

mentioning

confidence: 99%

Growth inhibitory effects of casein hydrolysates on human cancer cell lines

Phelan

Aherne

O’Sullivan

et al. 2010

Journal of Dairy Research

View full text Add to dashboard Cite

The aim of this study was to investigate the effects of unhydrolysed/intact casein and eight different sodium casein hydrolysates (a-h) on the viability and growth of human cancer cell lines. Both human Jurkat T cells and Caco-2 cells were incubated with increasing concentrations of the test compounds (0 . 5-10 % v/v) for 24 h. Cell viability was assessed using the MTT, lactate dehydrogenase (LDH) release and Trypan Blue assays. Cell growth was monitored using the MTT, Trypan Blue and Bromodeoxyuridine (BrdU) proliferation assays. Casein hydrolysates b, c and f had an inhibitory effect on the viability and growth of both cell lines. The casein hydrolysates did not negatively affect the membrane integrity of both Jurkat and Caco-2 cells. In Jurkat cells hydrolysates a and h had an inhibitory effect on DNA synthesis after 24 h, while in Caco-2 cells DNA synthesis was not affected. In conclusion, we found that the different casein hydrolysates had cell-specific effects which target particular functions within the cell. Overall, casein hydrolysates had no effect on membrane integrity while they had varied effects on mitochondrial activity and DNA synthesis in the different cell lines.

show abstract

“…Soluble fibres are well fermented by anaerobic bacteria in the proximal colon and seem to provide less protection against the development of colorectal cancer 78 In many studies, soluble fibres have shown an increase in tumorigenesis with only few showing any protection 910 Guar gum, oat bran and pectin are examples of soluble fibres which are fermented in the proximal colon and have little effect on tumorigenesis in distal colon 11…”

mentioning

confidence: 99%

Effect of cereal fibre source and processing on rectal epithelial cell proliferation

Macrae

Kilias

Selbie

et al. 1997

Gut

View full text Add to dashboard Cite

Background-Low fat and wheat bran interventions significantly reduced the growth of small to large adenomas and modestly suppressed rectal epithelial cell proliferation in the Australian Polyp Prevention Project. Aim-To study the eVect of unprocessed wheat bran, unprocessed oat bran and processed wheat bran (Kellogg's All Bran) on rectal epithelial cell proliferation. Patients-Twenty subjects with recent adenomas and a high fat background diet were recruited. Methods-Rectal biopsy specimens were taken at entry and at the end of three sixweek periods of oat bran (64 g/day), wheat bran (25 g/day) and All Bran (38 g/day), all in association with a diet <25% energy as fat, in a randomised cross-over trial. Each of the bran supplements had a total of 11 g dietary fibre. The biopsy specimens were fixed in methacarn and stained immunohistochemically for presence of the proliferating cell nuclear antigen (PCNA). The kinetics used to measure proliferation were labelling index, whole distribution of labelled cells, and labelled cells in the top two-fifths of crypts using analysis of variance. Results-There were no significant diVerences in mean labelling indexes between the four diets or in the percentage of labelled cells in the top two-fifths (p=0.59), but activity in the top two-fifths of crypts was lowest with wheat bran. The mean (SD) labelling indexes were 2.23 (0.11)% for control, 2.13 (0.08)% for wheat bran, 2.19 (0.09)% for oat bran, and 2.12 (0.08)% for All Bran. The proportion in the top two-fifths of the crypts was 2.6 (0.6)% for control, 2.15 (0.5)% for wheat bran, 3.3 (0.9)% for oat bran, and 3.1 (0.9)% for All Bran. On analysis of whole distribution, there was no significant overall eVect of diets but there was a diVerence between subjects. Analysis including total fibre intake also did not identify eVects on proliferation. Conclusion-In this study of high risk subjects with initial high fat diets, dietary fibre in association with a low fat diet had no eVect on rectal epithelial cell proliferation, although wheat bran had the greatest eVect on percentage of labelled cells in the top two-fifths of crypts.

show abstract

Colon Carcinogenesis: Modulation of Progression

Cited by 8 publications

References 20 publications

Non-steroidol anti-inflammatory drug effect on crypt cell proliferation and apoptosis during initiation of rat colon carcinogenesis

Non-steroidol anti-inflammatory drug effect on crypt cell proliferation and apoptosis during initiation of rat colon carcinogenesis

Growth inhibitory effects of casein hydrolysates on human cancer cell lines

Effect of cereal fibre source and processing on rectal epithelial cell proliferation

Contact Info

Product

Resources

About