Apoptosis in the Colonic Crypt, Colorectal Adenomata, and Manipulation by Chemoprevention

West, Nicholas J.; Courtney, Edward; Poullis, Andrew; Leicester, R. J.

doi:10.1158/1055-9965.epi-09-0006

Cited by 29 publications

(29 citation statements)

References 72 publications

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“…3) and 10% of the cells were undergoing apoptosis in non-cancerous mucosa (control NT) as previously demonstrated (16). A significant correlation between patient age and cleaved caspase 3 expression was observed in our study.…”

Section: Morphology Of the Colon Mucosa Differs With Aging Kwon Andsupporting

confidence: 90%

Implications of cleaved caspase 3 and AIF expression in colorectal cancer based on patient age

Perraud¹

2012

Oncol Rep

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Abstract.A high incidence of colorectal cancer (CRC) has been established in the elderly population. Apoptosis is a key event in maintaining colon homeostasis, both in aging as well as in cancer prevention. Here, we report that colon morphology is affected during the aging process: crypt loss (P=0.045) and increasing distances between crypts (P=0.0001678) were observed, associated with a tendency for mucosa reduction (P=0.083). In addition, our results show that apoptosis plays a determining role on the effect of aging during CRC. Increased expression of cleaved caspase 3 (the key factor implicated in the caspase-dependent pathway; P=0.026 for non-tumor tissues, P=0.0013 for tumor tissues) and AIF (implicated in the caspase-independent pathway; P=0.037) in tissue from elderly patients has been observed. Furthermore, elderly patients respond better to chemotherapy than younger ones (P=9.27x10 -5 ). These results suggest that patient age should be taken into account to adapt treatment of CRC.

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Section: Morphology Of the Colon Mucosa Differs With Aging Kwon Andsupporting

confidence: 90%

Implications of cleaved caspase 3 and AIF expression in colorectal cancer based on patient age

Perraud¹

2012

Oncol Rep

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“…Despite substantial advances in treatment, it remains the second most deadly disease in the Western world: the highest incidence is found in North America, Western europe, Australia/New Zealand and Japan, the lowest in Asia, Africa and an intermediate is found in parts of south America (1). In 2006, more than 200000 cases of the 1.7 million cancer deaths in europe were due to CrC without gender distinction (2). the main prognostic indicator for CrC is the tumor staging based on the invasion of the parts of the colic wall and defined by the international pathology tumor node metastasis (ptNM) classification system (3).…”

Section: Introductionmentioning

confidence: 99%

Expression of p53 and DR5 in normal and malignant tissues of colorectal cancer: Correlation with advanced stages

Perraud

Akil²,

Nouaille³

et al. 2011

Oncol Rep

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Abstract. Apoptosis has to be drastically controlled in organs with important cell turnover such as the colon. Deregulation of this process is often present in tumor progression. tissues of 82 patients treated for colorectal cancer (CrC) were analyzed using antibodies against AIF, p53, Dr4, Dr5, cleaved caspase-3 and the tUNeL method to detect apoptosis; whereas staining of Ki-67 was used as a proliferation marker. In situ immunohistochemical analyses were compared in non-tumor (Nt) cells from normal adjacent mucous membranes with tumor (t) cells from patients with stage I (n=6), stage II (n=35), stage III (n=27) and stage IV (n=14) CrC. results were correlated with the tumor stages and the treatment response of patients to improve the understanding of CrC development. p53 and Dr5 expression decreased progressively with CrC stage, suggesting that these proteins are important markers of advanced tumor stages. Moreover, p53 appears as a prognostic factor to predict recurrence-free survival. Including the detection of p53 and Dr5 for establishing the diagnosis of CrC and adapting the treatment to each patient is strongly suggested by our work.

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“…The mechanism of apoptotic cell death is complex 9 . It involves receptor-mediated protease activation, cytolytic plasma protein interactions, and ultimately distinct morphological alterations.…”

Section: Discussionmentioning

confidence: 99%

“…It involves receptor-mediated protease activation, cytolytic plasma protein interactions, and ultimately distinct morphological alterations. These alterations can be observed microscopically and include DNA degradation and margination, condensation of chromatin, cell membrane alterations and the formation of apoptotic cascade 9,10 .…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis marker positive cells were found mainly on the luminal epithelium of the normal colon and were present in crypts of the colon, in addition to the luminal epithelium, in pathological situations such as ulcerative colitis and colorectal adenomas [5][6][7][8][9] . The use of these apoptosis marker to monitor the beneficial effects of chemopreventative interventions would be to reduce the development of colorectal cancer within the context of clinical trials [5][6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

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The role of Fas ligand protein in the oxidative stress induced by azoxymethane on crypt colon of rats

et al. 2010

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PURPOSE: To study the protein Fas ligand (FasL) on the expression of apoptosis, using a model of oxidative stress induced by azoxymethane (AOM), in the crypt of colon in rats. METHODS: Wistar rats (n=14) were assigned into two groups: control (n=7) and AOM (n=7). A single subcutaneous administration of AOM (5mg/kg) or saline solution was performed at the beginning of third week and after three hours samples of proximal colon were collected. The expression of FasL was quantified (Software ImageLab) in percentage of areas in the top, base and all crypt. Results were expressed as mean ± sd (Shapiro-Wilks test and t Student test) (p < 0.05). RESULTS: In the animals of CG there was no significant difference between the FasL expression of the top (10.75±3.33) and basal (11.14±3.53) colon crypt (p=0.34293740). In the animals of AOM there was no significant difference between the FasL expression of the top (8.86±4.19) and basal (8.99±4.08) colon crypt (p=0.78486003). In the animals of CG (10.95±3.43) and AOM (8.92±4.13) there was a significant difference of the FasL expression (p=0.026466821). A significantly decrease on the FasL expression was observed in the animals of CG (10.75±3.33) and AOM (8.86±4.19) in the top crypt (p=0.00003755*). A significant decrease was also observed in the animals of CG (11.14±3.53) and AOM (8.99±4.08) in the basal colon crypt (p=0.00000381**). CONCLUSION: Azoxymethane induce the oxidative stress and the significantly decrease of FasL expression, although there is no significant difference between basal and top of colon crypt linked to consumption-activation of Fas ligand.

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Apoptosis in the Colonic Crypt, Colorectal Adenomata, and Manipulation by Chemoprevention

Cited by 29 publications

References 72 publications

Implications of cleaved caspase 3 and AIF expression in colorectal cancer based on patient age

Implications of cleaved caspase 3 and AIF expression in colorectal cancer based on patient age

Expression of p53 and DR5 in normal and malignant tissues of colorectal cancer: Correlation with advanced stages

The role of Fas ligand protein in the oxidative stress induced by azoxymethane on crypt colon of rats

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