Aberrant Crypt Foci: The Case for Inclusion as a Biomarker for Colon Cancer

Wargovich, Michael J.; Brown, Vondina R.; Morris, Joseph E.

doi:10.3390/cancers2031705

Cited by 42 publications

(31 citation statements)

References 64 publications

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“…However, a few years later, the same author suggested and others confirmed that AFC in fact was part of the sequential evolution of colon carcinogenesis, which can become dysplastic, which can give rise to adenomas and colorectal carcinoma in that order, serving then as a model of early lesions, that is, pre-neoplastic lesions in colorectal carcinogenesis 20,21 .…”

Section: Discussionmentioning

confidence: 98%

Carcinogenesis in rats subjected to a new model ureterosigmoidostomy and treated with L-lysine

Santos¹,

Coelho

Azevedo

et al. 2016

Acta Cir. Bras.

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PURPOSE:To evaluate the effects of L-lysine on the intestinal and urothelial epithelium of rats subjected to ureterosigmoidostomy (new model for surgical carcinogenesis). METHODS:Forty-two rats, 9 weeks of age, were divided into 6 groups. Animals in groups A, B, C were subjected to ureterosigmoidostomy (US) and treated with L-lysine, celecoxib and H 2 O, respectively. Groups D, E and F (non-operated controls) received L-lysine, celecoxib and H 2 O, respectively. The L-lysine dose was 150 mg/kg and that of celecoxib was 20 mg/kg. The colon was analyzed for the presence of aberrant crypt foci (ACF) under a stereomicroscope.The tissue was stained with hematoxylin and eosin and PAS alcian blue. RESULTS:There were rare ACF, and there was no statistically significant difference between the groups. Histopathologic study of the ureteral epithelium identified moderate to severe urothelial hyperplasia in rats with ureterosigmoidostomy. Transitional hyperplasia in the ureters of animals receiving L-lysine (A) showed an apparent difference compared to the control (C) (P=0.2424). There was no dysplasia or atypia.CONCLUSION: L-lysine does not promote carcinogenesis of the intestinal and urethelial epithelium of rats subjected to ureterosigmoidostomy at the doses and times studied.

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Section: Discussionmentioning

confidence: 98%

Carcinogenesis in rats subjected to a new model ureterosigmoidostomy and treated with L-lysine

Santos¹,

Coelho

Azevedo

et al. 2016

Acta Cir. Bras.

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“…Data with respect to ACF formation partly support this conjecture; however, the effects of nCDase were intermediate: nCDase ‐/‐ mice had 50% fewer ACFs, suggesting a role for nCDase early in tumor initiation. However, the proposed role of ACFs as an early mediator of adenocarcinoma development in the AOM model is disputed (43, 58). Second, the significance of deletion of nCDase in colon cancer development, but not for normal intestine and colon development, suggests that oncogenically transformed cells become “addicted” to the action of nCDase.…”

Section: Discussionmentioning

confidence: 99%

Role of neutral ceramidase in colon cancer

et al. 2016

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Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of sphingolipid metabolism may emerge as novel regulators and targets in colon cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that hydrolyzes ceramide into sphingosine, is highly expressed in the intestine; however, its role in colon cancer has not been defined. Here we show that molecular and pharmacological inhibition of nCDase in colon cancer cells increases ceramide, and this is accompanied by decreased cell survival and increased apoptosis and autophagy, with minimal effects on noncancerous cells. Inhibition of nCDase resulted in loss of β-catenin and inhibition of ERK, components of pathways relevant for colon cancer development. Furthermore, inhibition of nCDase in a xenograft model delayed tumor growth and increased ceramide while decreasing proliferation. It is noteworthy that mice lacking nCDase treated with azoxymethane were protected from tumor formation. Taken together, these studies show that nCDase is pivotal for regulating initiation and development of colon cancer, and these data suggest that this enzyme is a suitable and novel target for colon cancer therapy.-García-Barros, M., Coant, N., Kawamori, T., Wada, M., Snider, A. J., Truman, J.-P., Wu, B. X., Furuya, H., Clarke, C. J., Bialkowska, A. B., Ghaleb, A., Yang, V. W., Obeid, L. M., Hannun, Y. A. Role of neutral ceramidase in colon cancer.

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“…size and number of ACF and the severity of colon cancer (Alrawi et al, 2006;Gupta and Schoen, 2009;Wargovich et al, 2010). It has been reported that HLF may induce apoptosis and reduce cancer volume in experimentally induced colon cancer in the nude mouse (Chen et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

“…The size and number of ACF increase as the cancer progresses, so they provide information about the stage of the cancer. There is a positive correlation between the incidence of ACF and cancer severity (Alrawi et al, 2006;Gupta and Schoen, 2008;Wargovich et al, 2010). Treatment outcomes may be evaluated according to the number, size and multicrypt features of ACF (Raju, 2008).…”

Section: Introductionmentioning

confidence: 99%

Halofuginone may suppresses azoxymethane-induced serum tumor necrosis factor-a synthesis and aberrant crypt foci progression in rat colon

Çorum

Yazar

2017

IJAR

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The aim of this research was to investigate the effect of halofuginone on the progression of azoxymethane-induced colon cancer in rats. A total of 38 male Wistar albino rats were divided into 4 groups: Control (n=8), Halofuginone (n=10, 0.4 mg/ kg, PO, SID), Cancer (n=10, azoxymethane, 15 mg/kg, IP, once a week for two weeks) and Cancer + Halofuginone (n=10). After 18 weeks, blood samples were taken under anesthesia and all animals were sacrificed. Aberrant crypt foci in the colon were stained with methylene blue. Blood cytokines, thiobarbituric acid reactive substances, 13,14-dihydro-15-ketoprostaglandin F2 levels, hemogram and biochemical values were measured. The tumor necrosis factor-a level in the Cancer group was higher (P<0.05) than in other groups, while higher numbers of aberrant crypt foci were found in the Cancer group compared with the Cancer + Halofuginone group (P<0.05). In summary, it may be stated that halofuginone may warrant evaluation as a supportive drug in the treatment of colon cancer in the future.

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Aberrant Crypt Foci: The Case for Inclusion as a Biomarker for Colon Cancer

Cited by 42 publications

References 64 publications

Carcinogenesis in rats subjected to a new model ureterosigmoidostomy and treated with L-lysine

Carcinogenesis in rats subjected to a new model ureterosigmoidostomy and treated with L-lysine

Role of neutral ceramidase in colon cancer

Halofuginone may suppresses azoxymethane-induced serum tumor necrosis factor-a synthesis and aberrant crypt foci progression in rat colon

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