期刊论文详细信息
Biological Procedures Online
A Method for Serial Tissue Processing and Parallel Analysis of Aberrant Crypt Morphology, Mucin Depletion, and Beta-Catenin Staining in an Experimental Model of Colon Carcinogenesis
John N McGinley1  Matthew D Thompson1  Henry J Thompson1 
[1] Cancer Prevention Laboratory, Colorado State University, 1173 Campus Delivery, Fort Collins, CO 80523, USA
关键词: morphometry;    image analysis;    beta-catenin;    mucin depletion;    aberrant crypt foci;    colon carcinogenesis;   
Others  :  793425
DOI  :  10.1007/s12575-010-9032-x
 received in 2010-03-11, accepted in 2010-04-23,  发布年份 2010
PDF
【 摘 要 】

The use of architectural and morphological characteristics of cells for establishing prognostic indicators by which individual pathologies are assigned grade and stage is a well-accepted practice. Advances in automated micro- and macroscopic image acquisition and digital image analysis have created new opportunities in the field of prognostic assessment; but, one area in experimental pathology, animal models for colon cancer, has not taken advantage of these opportunities. This situation is primarily due to the methods available to evaluate the colon of the rodent for the presence of premalignant and malignant pathologies. We report a new method for the excision and processing of the entire colon of the rat and illustrate how this procedure permitted the quantitative assessment of aberrant crypt foci (ACF), a premalignant colon pathology, for characteristics consistent with progression to malignancy. ACF were detected by methylene blue staining and subjected to quantitative morphometric analysis. Colons were then restained with high iron diamine–alcian blue for assessment of mucin depletion using an image overlay to associate morphometric data with mucin depletion. The subsequent evaluation of ACF for beta-catenin staining is also demonstrated. The methods described are particularly relevant to the screening of compounds for cancer chemopreventive activity.

Additional file 1.

Format: DOCSize: 137KB Download file

This file can be viewed with: Microsoft Word ViewerOpen Data

【 授权许可】

   
2010 McGinley et al; licensee Springer

【 预 览 】
附件列表
Files Size Format View
20140705051538909.pdf 982KB PDF download
Figure 7. 207KB Image download
Figure 6. 696KB Image download
Figure 5. 480KB Image download
Figure 4. 565KB Image download
Figure 3. 222KB Image download
Figure 2. 544KB Image download
Figure 1. 246KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】
  • [1]Bird RP: Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings. Cancer Lett 1987, 37:147-151.
  • [2]Bird RP, McLellan EA, Bruce WR: Aberrant crypts, putative precancerous lesions, in the study of the role of diet in the aetiology of colon cancer. Cancer Surv 1989, 8:189-200.
  • [3]Gupta AK, Pretlow TP, Schoen RE: Aberrant crypt foci: what we know and what we need to know. Clin Gastroenterol Hepatol 2007, 5:526-533.
  • [4]Tudek B, Bird RP, Bruce WR: Foci of aberrant crypts in the colons of mice and rats exposed to carcinogens associated with foods. Cancer Res 1989, 49:1236-1240.
  • [5]Caderni G, Femia AP, Giannini A, Favuzza A, Luceri C, Salvadori M, et al.: Identification of mucin-depleted foci in the unsectioned colon of azoxymethane-treated rats: correlation with carcinogenesis. Cancer Res 2003, 63:2388-2392.
  • [6]Gupta AK, Pinsky P, Rall C, Mutch M, Dry S, Seligson D, et al.: Reliability and accuracy of the endoscopic appearance in the identification of aberrant crypt foci. Gastrointest Endosc 2009, 70:322-330.
  • [7]Mutch MG, Schoen RE, Fleshman JW, Rall CJ, Dry S, Seligson D, et al.: A multicenter study of prevalence and risk factors for aberrant crypt foci. Clin Gastroenterol Hepatol 2009, 7:568-574.
  • [8]Corpet DE, Tache S: Most effective colon cancer chemopreventive agents in rats: a systematic review of aberrant crypt foci and tumor data, ranked by potency. Nutr Cancer 2002, 43:1-21.
  • [9]Femia AP, Dolara P, Caderni G: Mucin-depleted foci (MDF) in the colon of rats treated with azoxymethane (AOM) are useful biomarkers for colon carcinogenesis. Carcinogenesis 2004, 25:277-281.
  • [10]Femia AP, Bendinelli B, Giannini A, Salvadori M, Pinzani P, Dolara P, et al.: Mucin-depleted foci have beta-catenin gene mutations, altered expression of its protein, and are dose- and time-dependent in the colon of 1, 2-dimethylhydrazine-treated rats. Int J Cancer 2005, 116:9-15.
  • [11]Femia AP, Dolara P, Luceri C, Salvadori M, Caderni G: Mucin-depleted foci show strong activation of inflammatory markers in 1, 2-dimethylhydrazine-induced carcinogenesis and are promoted by the inflammatory agent sodium dextran sulfate. Int J Cancer 2009, 125:541-547.
  • [12]Yoshimi N, Morioka T, Kinjo T, Inamine M, Kaneshiro T, Shimizu T, et al.: Histological and immunohistochemical observations of mucin-depleted foci (MDF) stained with Alcian blue, in rat colon carcinogenesis induced with 1, 2-dimethylhydrazine dihydrochloride. Cancer Sci 2004, 95:792-797.
  • [13]Paulsen JE, Loberg EM, Olstorn HB, Knutsen H, Steffensen IL, Alexander J: Flat dysplastic aberrant crypt foci are related to tumorigenesis in the colon of azoxymethane-treated rat. Cancer Res 2005, 65:121-129.
  • [14]Paulsen JE, Knutsen H, Olstorn HB, Loberg EM, Alexander J: Identification of flat dysplastic aberrant crypt foci in the colon of azoxymethane-treated A/J mice. Int J Cancer 2006, 118:540-546.
  • [15]Rijken PJ, Timmer WG, van de Kooij AJ, Van BI, Wiseman SA, Meijers M, et al.: Effect of vegetable and carotenoid consumption on aberrant crypt multiplicity, a surrogate end-point marker for colorectal cancer in azoxymethane-induced rats. Carcinogenesis 1999, 20:2267-2272.
  • [16]Bird RP: Further investigation of the effect of cholic acid on the induction, growth characteristics and stability of aberrant crypt foci in rat colon. Cancer Lett 1995, 88:201-209.
  • [17]Thompson HJ, McGinley JN, Rothhammer K, Singh M: Rapid induction of mammary intraductal proliferations, ductal carcinoma in situ and carcinomas by the injection of sexually immature female rats with 1-methyl-1-nitrosourea. Carcinogenesis 1995, 16:2407-2411.
  • [18]Thompson HJ, McGinley JN, Wolfe P, Singh M, Steele VE, Kelloff GJ: Temporal sequence of mammary intraductal proliferations, ductal carcinomas in situ and adenocarcinomas induced by 1-methyl-1-nitrosourea in rats. Carcinogenesis 1998, 19:2181-2185.
  • [19]Thompson HJ, Singh M, McGinley J: Classification of premalignant and malignant lesions developing in the rat mammary gland after injection of sexually immature rats with 1-methyl-1-nitrosourea. J Mammary Gland Biol Neoplasia 2000, 5:201-210.
  • [20]McGinley JN, Knott KK, Thompson HJ: Semi-automated method of quantifying vasculature of 1-methyl-1-nitrosourea-induced rat mammary carcinomas using immunohistochemical detection. J Histochem Cytochem 2002, 50:213-222.
  • [21]Thompson HJ, McGinley JN, Knott KK, Spoelstra NS, Wolfe P: Vascular density profile of rat mammary carcinomas induced by 1-methyl-1-nitrosourea: implications for the investigation of angiogenesis. Carcinogenesis 2002, 23:847-854.
  • [22]Magnuson BA, Carr I, Bird RP: Ability of aberrant crypt foci characteristics to predict colonic tumor incidence in rats fed cholic acid. Cancer Res 1993, 53:4499-4504.
  • [23]Hirose Y, Kuno T, Yamada Y, Sakata K, Katayama M, Yoshida K, et al.: Azoxymethane-induced beta-catenin-accumulated crypts in colonic mucosa of rodents as an intermediate biomarker for colon carcinogenesis. Carcinogenesis 2003, 24:107-111.
  • [24]Mori H, Yamada Y, Kuno T, Hirose Y: Aberrant crypt foci and beta-catenin accumulated crypts; significance and roles for colorectal carcinogenesis. Mutat Res 2004, 566:191-208.
  • [25]Femia AP, Dolara P, Giannini A, Salvadori M, Biggeri A, Caderni G: Frequent mutation of Apc gene in rat colon tumors and mucin-depleted foci, preneoplastic lesions in experimental colon carcinogenesis. Cancer Res 2007, 67:445-449.
  • [26]Magnuson BA, Bird RP: Reduction of aberrant crypt foci induced in rat colon with azoxymethane or methylnitrosourea by feeding cholic acid. Cancer Lett 1993, 68:15-23.
  • [27]Zhu Z, Haegele AD, Thompson HJ: Effect of caloric restriction on pre-malignant and malignant stages of mammary carcinogenesis. Carcinogenesis 1997, 18:1007-1012.
  • [28]Caderni G, Giannini A, Lancioni L, Luceri C, Biggeri A, Dolara P: Characterisation of aberrant crypt foci in carcinogen-treated rats: association with intestinal carcinogenesis. Br J Cancer 1995, 71:763-769.
  • [29]Carter JW, Lancaster HK, Hardman WE, Cameron IL: Distribution of intestine-associated lymphoid tissue, aberrant crypt foci, and tumors in the large bowel of 1, 2-dimethylhydrazine-treated mice. Cancer Res 1994, 54:4304-4307.
  • [30]Magnuson BA, South EH, Exon JH, Dashwood RH, Xu M, Hendrix K, et al.: Increased susceptibility of adult rats to azoxymethane-induced aberrant crypt foci. Cancer Lett 2000, 161:185-193.
  • [31]Rao CV, Hirose Y, Indranie C, Reddy BS: Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res 2001, 61:1927-1933.
  • [32]Wali RK, Khare S, Tretiakova M, Cohen G, Nguyen L, Hart J, et al.: Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin. Cancer Epidemiol Biomarkers Prev 2002, 11:1653-1662.
  • [33]Gupta AK, Schoen RE: Aberrant crypt foci: are they intermediate endpoints of colon carcinogenesis in humans? Curr Opin Gastroenterol 2009, 25:59-65.
  文献评价指标  
  下载次数:94次 浏览次数:49次