Aberrant crypt foci of the colon as precursors of adenoma and cancer

Takayama, Tetsuji; Katsuki, Shinichi; Takahashi, Yasuo; Ohi, Moton; Nojiri, Shuichi; Sakamaki, Sumio; Kato, Junji; Kogawa, Katsuhisa; Miyake, Hirotsugu; Nihsu, Yoshiro

doi:10.1097/00042737-199812000-00021

Cited by 193 publications

(384 citation statements)

References 0 publications

Supporting

Mentioning

358

Contrasting

Unclassified

Order By: Relevance

“…These results confirm our previous findings that JTE-522 significantly inhibited the development of ACF, the putative precursors of both human and experimental colon cancer, 18,19 when administered during initiation and postinitiation stages of rat colon carcinogenesis. 20 Furthermore, administration of JTE-522 during the postinitiation stage is almost equally as effective on inhibiting tubular adenocarcinomas as when it was administrated during both initiation and postinitiation stages, suggesting that JTE-522 acts to suppress adenocarcinoma formation mainly during the postinitiation phase.…”

Section: Discussionsupporting

confidence: 92%

“…14,15 This compound also inhibited liver and lung metastases of colon cancer expressing COX-2 but lacked effect on those lacking COX-2 expression in the nude mouse xenograft model. 16,17 In chemically induced colon carcinogenesis, we have previously shown that JTE-522 inhibited the development of aberrant crypt foci (ACF), the putative precursors of both human and experimental colon cancer, 18,19 when administered throughout the study. 20 In the present study, to evaluate the chemopreventive properties of JTE-522, we have investigated the efficacy of JTE-522 during different stages of rat colon carcinogenesis using colon tumor formation as an endpoint, including its effects on histopathologic pattern and growth, as well as invasion of colon tumors.…”

mentioning

confidence: 99%

See 1 more Smart Citation

JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats

Wei

Morimura

Wanibuchi

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

We have previously demonstrated that JTE-522, a selective cyclooxygenase-2 (COX-2) inhibitor, inhibited development of aberrant crypt foci (ACF) in rats, a putative preneoplastic lesion in colon, and suggested its inhibitory potential in rat colon carcinogenesis. To evaluate the chemopreventive properties of JTE-522, the present study was design to evaluate the inhibitory effects of JTE-522 on rat colon tumorigenesis induced by 1,2-dimethylhydrazine (DMH). Rats at 6 weeks of age were divided into 4 groups. One week after the start of the experiment, all rats received DMH by s.c. injection at a dose of 40 mg/kg body weight once a week for 4 successive weeks. As the initiation and postinitiation treatment groups, groups 1-3 were fed diets containing 0, 50, or 150 ppm JTE-522, respectively, from the start of the study to the end. As the postinitiation treatment group, group 4 was given 150 ppm JTE-522 from 1 week after the last DMH injection to the end of the study. Forty weeks after the start of the experiment, administration of 150 ppm JTE-522 during both initiation and postinitiation stages significantly inhibited the incidences of tubular adenocarcinomas and total carcinomas, as well as total tumors in the colon. The inhibitory effect of JTE-522 was most prominent for tubular adenocarcinomas, but was not observed in the nontubular carcinomas (signet-ring cell and mucinous carcinomas). Almost equal inhibitory effects on tubular adenocarcinomas were also observed in the rats given 150 ppm JTE-522 during the postinitiation stage, suggesting that its major anticancer action is at the postinitiation phase. However, JTE-522 had no effect on the size or invasive extent of tubular adenocarcinomas. Furthermore, microarray analyses revealed that JTE-522 had no effect on gene expression levels in DMH-induced tubular adenocarcinomas. These findings suggest that JTE-522 possesses chemopreventive activity against induction but not progression of tubular adenocarcinomas in rat colon. In view of the significant inhibitory effects of JTE-522 on ACF, its major anticancer action may occur in the postinitiation stage but before the malignant conversion stage of DMH-induced colon carcinogenesis.Key words: JTE-522; selective cyclooxynenase-2 inhibitor; colon carcinogenesis; tubular adenocarcinoma; chemoprevention Colorectal cancer leads to approximately 550,000 annual deaths worldwide 1 and is therefore a major public health problem and underlines the need for effective chemopreventive strategies. The protective effect of traditional nonsteroidal antiinflammatory drugs (NSAIDs), such as aspirin and sulindac, for colon cancer has been well documented in epidemiologic and animal studies. 2 However, their use for chemoprevention of colon cancer has been hindered by their potential gastrointestinal and renal toxicity. It is now known that nonselective NSAIDs inhibit activities of cyclooxygenases (COX), and inhibition of COX-2 may well explain their chemopreventive effect, whereas inhibition of COX-1 is believed to be responsible for man...

show abstract

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats

Wei

Morimura

Wanibuchi

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…17,18,34 ACF are preneoplastic lesions that have the propensity to progress and become neoplastic if further DNA damage occurs; they are considered to be reliable intermediate markers for tumor development in mice and humans, 40,41 as was confirmed in our previous studies. 17,18 Mice were treated with AOM at the optimal concentration of 12 mg/kg body weight, which previously was reported to be effective in promoting preneoplastic and neoplastic changes in the colonic mucosae of FVB/N mice.…”

Section: Induction Of Acf and Colonic Tumorsmentioning

confidence: 53%

Intestinal expression of mutant and wild‐type progastrin significantly increases colon carcinogenesis in response to azoxymethane in transgenic mice

Cobb

Wood

Ceci

et al. 2004

Cancer

View full text Add to dashboard Cite

Charcot–Marie–Tooth neuropathy type 1C (CMT1C) is an autosomal dominant demyelinating peripheral neuropathy caused by missense mutations in the small integral membrane protein of lysosome/late endosome (SIMPLE) gene. To investigate the prevalence of SIMPLE mutations, we screened a cohort of 152 probands with various types of demyelinating or axonal and pure motor or sensory inherited neuropathies. SIMPLE mutations were found only in CMT1 patients, including one G112S and one W116G missense mutations. A novel I74I polymorphism was identified, yet no splicing defect of SIMPLE is likely. Haplotype analysis of STR markers and intragenic SNPs linked to the gene demonstrated that families with the same mutation are unlikely to be related. The clustering of the G112S, T115N, and W116G mutations within five amino acids suggests this domain may be critical to peripheral nerve myelination. Electrophysiological studies showed that CMT1C patients from six pedigrees (n = 38) had reduced nerve conduction velocities ranging from 7.5 to 27.0m/sec (peroneal). Two patients had temporal dispersion of nerve conduction and irregularity of conduction slowing, which is unusual for CMT1 patients. We report the expression of SIMPLE in various cell types of the sciatic nerve, including Schwann cells, the affected cell type in CMT1C.

show abstract

“…Gene mutations that are commonly observed in colon cancers including K-ras and APC are also observed in a proportion of ACF (Pretlow et al, 1993;Smith et al, 1994). Aberrant crypt foci are thus considered to represent earlystage colorectal tumorigenesis (Bird, 1987;Tudek et al, 1989;Takayama et al, 1998;Bird and Good, 2000), although large or persistent ACF may have greater cancer risk (Papanikolaou et al, 2000). The present study has shown that MTCRII may reflect combined effects of chemicals within a mixture, are induced in sufficient numbers to provide statistical power from relatively small animal samples and correlate with ACF formation at 20 weeks after the initiation of treatment.…”

Section: Discussionmentioning

confidence: 99%

Metallothionein crypt-restricted immunopositivity indices (MTCRII) correlate with aberrant crypt foci (ACF) in mouse colon

Donnelly

Bardwell²,

Thomas

et al. 2005

Br J Cancer

View full text Add to dashboard Cite

Metallothionein (MT) crypt-restricted immunopositivity indices (MTCRII) are colonic crypt stem cell mutation markers that may be induced early and in abundance after mutagen treatment. Metallothionein is the endogenous reporter gene for MTCRII, but is not typically implicated in the classical pathway of colorectal tumorigenesis. Hence, the oncological relevance of MTCRII is unclear. This study tests the hypothesis that MTCRII induced by N-methyl-N-nitrosourea (MNU) and lambda carrageenan (lCgN) associate with aberrant crypt foci (ACF) in mouse colon. Undegraded lCgN and MNU were tested alone and in combination against MTCRII and ACF in Balb/c mice, at 20 weeks after the start of treatment. MTCRII were unaffected by lCgN alone. Combined lCgN/MNU treatments induced greater MTCRII (Po0.01) as well as greater number (Po0.001) and crypt multiplicity (Po0.01) of ACF than MNU alone. MTCRII were approximately 10-fold more numerous than ACF, although linear correlations were observed between these parameters (r ¼ 0.732; Po0.01). MTCRII are induced by lCgN/MNU interactions in sufficient numbers to provide statistical power from relatively small sample sizes and correlate with ACF formation. MTCRII could thus provide the basis for a novel mediumterm murine bioassay relevant to early-stage colorectal tumorigenesis.

show abstract

Aberrant crypt foci of the colon as precursors of adenoma and cancer

Cited by 193 publications

References 0 publications

JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats

JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats

Intestinal expression of mutant and wild‐type progastrin significantly increases colon carcinogenesis in response to azoxymethane in transgenic mice

Metallothionein crypt-restricted immunopositivity indices (MTCRII) correlate with aberrant crypt foci (ACF) in mouse colon

Contact Info

Product

Resources

About