Putative Preneoplastic Changes Identified by Enzyme Histochemical and Immunohistochemical Techniques

Pretlow, Theresa P.; Pretlow, Thomas G.

doi:10.1177/002215549804600503

Cited by 6 publications

(3 citation statements)

References 28 publications

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“…These lesions were first described in the colon of rodents treated with colon-specific genotoxic or non-genotoxic carcinogens and later observed at a high incidence in the colon of patients with sporadic and inherited colon cancer [13][14][15][16]. Biochemical, genetic, and morphological studies have shown that ACF and colon tumors share similar alterations, further supporting the hypothesis that the ACF are precursors of colorectal cancer [17][18][19]. A number of natural compounds that inhibit ACF development have been proved to prevent colon cancer in rodents [20,21].…”

Section: Introductionmentioning

confidence: 82%

Protective action of propolis on the rat colon carcinogenesis

Bazo

Rodrigues

Sforcin

et al. 2002

Teratog Carcinog Mutagen

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Propolis is a honeybee product with several biological and therapeutical properties. Its effect on the process of colon carcinogenesis and DNA damage were evaluated in the male Wistar rats using the aberrant crypt foci (ACF) assay and the comet assay, respectively. For both tests, animals were treated with the colon carcinogen 1,2 dimethylhydrazine (DMH, 40 mg/kg, s.c.) for 2 weeks (two injections/week) in order to induce both DNA damage and ACF. The animals were divided into groups that received propolis (ethanolic extract) at three different doses (10, 30, and 90 mg/kg b.w., by gavage), either simultaneously or after DMH treatment. For the comet assay, peripheral blood samples were collected 4 h after the last DMH treatment. All animals were sacrificed at the 5th week for evaluation of ACF. The results show that only the intermediate dose (30 mg/kg) of propolis, administered after DMH initiation, is significantly associated to a smaller number of aberrant crypts in the distal colon. No effect on DNA damage in peripheral blood cells, however, was verified by the comet assay. These data suggest that propolis has a protective influence on the process of colon carcinogenesis, suppressing the development of preneoplastic lesions, and probably exerts no protection against the initiation of carcinogenesis.

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Section: Introductionmentioning

confidence: 82%

Protective action of propolis on the rat colon carcinogenesis

Bazo

Rodrigues

Sforcin

et al. 2002

Teratog Carcinog Mutagen

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“…A study by Pretlow et al (49) showed that APC mutations are involved in the initiation of aberrant crypt foci, which are precursors to adenoma and colon adenocarcinoma. Goblet cells were already absent from aberrant crypt foci (50). Together, it is possible that the loss of Hath1 expression in aberrant crypt foci may represent an early event in tumorigenesis.…”

Section: Discussionmentioning

confidence: 98%

Hath1, Down-Regulated in Colon Adenocarcinomas, Inhibits Proliferation and Tumorigenesis of Colon Cancer Cells

et al. 2004

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A striking feature of colon tumors is the significant reduction of goblet cells. Although targeted deletion of Math1 in mice leads to a loss of intestinal secretory cells, including goblet cells, the role of Hath1 in colon tumorigenesis remains unknown. Here we report that Hath1, the human ortholog of Math1, was dramatically down-regulated in colon tumor samples and colon cancer cell lines. Overexpression of Hath1 in HT29, an aggressive colon cancer cell line, resulted in a significant inhibition on cell proliferation, anchorage-independent growth in soft agar and, more importantly, growth of human colon cancer cell xenografts in athymic nude mice. Such inhibition was accompanied by altered expression of a goblet cell differentiation marker, MUC2, and cell cycle regulators cyclin D1 and p27 kip1 . Hath1 expression also was up-regulated on inhibition of the Wnt pathway, which has been well implicated in colon tumorigenesis. Hence, this study suggests that Hath1 may be a novel factor downstream of the Wnt pathway capable of suppressing anchorage-independent growth of colon cancer cell lines. More importantly, this study is the first to establish a link between down-regulation of Hath1 expression and colon tumorigenesis.

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“…Consistent with our findings, a recent microarray study examining the gene expression profile of Wnt signaling inhibition in LS174T colon cancer cells revealed an increase in MUC2 expression 40. Interestingly, Pretlow and Pretlow41 show that goblet cells are already absent from aberrant crypt foci (ACF), which are precursors to adenoma and colon adenocarcinoma. Since APC mutation is also involved in the initiation of ACF,41 it is possible that the loss of Hath1 expression in aberrant crypt foci may represent an early event in colon tumorigenesis.…”

Section: Relationship Between Hath1 and Wnt Signaling In Colon Adenocmentioning

confidence: 99%

A Role for Hath1, a bHLH Transcription Factor, in Colon Adenocarcinoma

Leow

Polakis

Gao

2005

Annals of the New York Academy of Sciences

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A significant reduction or loss of goblet cells is often observed in clinical samples of colon adenocarcinomas, which is the predominant form of colon carcinoma. Mice lacking Math1, a bHLH transcription factor downstream of the Notch signaling pathway, demonstrates that Math1 is necessary for cell fate determination of the intestinal secretory cells, including goblet cells. Examination of Hath1, the human orthologue of Math1, expression in multiple colon tumor samples and colon cancer cell lines reveals a dramatic decrease in Hath1 expression in colon tumor samples and colon cancer cell lines. Hath1 expression in the HT29 colon cancer cell line can significantly inhibit its proliferation and anchorage-independent growth both in vitro and in vivo. At the molecular level, Hath1 may regulate the expression of MUC2, a mucin secreted by goblet cells, and Hath1 may also be a novel factor normally repressed as a consequence of activation of the Wnt signaling pathway, which has been clearly implicated in colon tumorigenesis.

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Putative Preneoplastic Changes Identified by Enzyme Histochemical and Immunohistochemical Techniques

Cited by 6 publications

References 28 publications

Protective action of propolis on the rat colon carcinogenesis

Protective action of propolis on the rat colon carcinogenesis

Hath1, Down-Regulated in Colon Adenocarcinomas, Inhibits Proliferation and Tumorigenesis of Colon Cancer Cells

A Role for Hath1, a bHLH Transcription Factor, in Colon Adenocarcinoma

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