Proliferating cell nuclear antigen expression in normal, preneoplastic, and neoplastic colonic epithelium of the rat

Yamada, Kyoji; Yoshitake, Kenzo; Sato, Masaki; Ahnen, Dennis J.

doi:10.1016/0016-5085(92)91109-h

Cited by 86 publications

(29 citation statements)

References 12 publications

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“…Using [3H]thymidine labeling Deschner and co-workers have shown that in high-risk sub jects labeled S-phase cells are not confined to the lower thirds of the colonic crypts but are scattered throughout the entire length of the crypts [19,20]. Similar data were obtained in experimental studies in rats using PCNA and BrdUrd as a marker [ 16], Therefore, determi nation of the LI alone is probably not the opti mal parameter for the assessment of cancer risk. For this reason we had chosen to assess the LI by visual inspection in association with the evaluation of the proliferative pattern.…”

Section: Resultssupporting

confidence: 69%

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Nijs

Mengs²,

Geboes

et al. 1993

Pharmacology

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Experimental studies indicate that laxatives may induce epithelial damage. In addition, some laxatives induce the release of prostaglandins. Epithelial cell damage and release of prostaglandins are two pathways by which epithelial cell proliferation could be influenced. Furthermore, fermentable laxatives like lactulose may influence large intestine cell proliferation by the trophic effect of the fermentation products such as short-chain fatty acids. For these reasons an in vivo study in rats was performed to compare the short- and long-term effect of sennosides, bisacodyl, sodium picosulfate and lactulose on epithelial cell proliferation in the ileum and large intestine. Cell proliferation was examined by the BrdUrd labelling technique after 2, 6 and 12 weeks of continuous treatment. Studies in control animals show that the Labeling Index (LI) is higher in the cecum compared with other segments of the colon, and higher in the ileum than in the colon. Treatment with sennosides, bisacodyl and sodium picosulfate does not influence the LI in the ileum and induces no statistically significant increase of the LI when the treated groups are compared with the control group. The proliferative pattern along the crypts remains unchanged with all the laxatives throughout the study. It appears therefore that ‘contact’ laxatives have no major influence on ileal and colonic epithelial cell proliferation and should not be regarded as tumor-promoting substances.

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Section: Resultssupporting

confidence: 69%

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Nijs

Mengs²,

Geboes

et al. 1993

Pharmacology

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“…In the present study, PCNA + epithelial cells were more frequently found in the intestinal crypts with indigenous bacteria than in those without indigenous bacteria in MAM. Furthermore, PCNA + epithelial cells were located from the middle to apical portions of the intestinal crypts without indigenous bacteria in MAM, as in the previous reports [23,31,36], but in the whole portions of the intestinal crypts with indigenous bacteria in MAM. Rapid migration and turnover of epithelial cells by the increase of epithelial proliferation is one of the host defense in the intestine [16,26].…”

Section: Discussionsupporting

confidence: 82%

Histoplanimetrical Study on the Relationship between Invasion of Indigenous Bacteria into Intestinal Crypts and Proliferation of Epithelial Cells in Rat Ascending Colon

Mantani

Takahara

Takeuchi

et al. 2013

The Journal of Veterinary Medical Science

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ABSTRACT. The relationship between the invasion of indigenous bacteria into intestinal crypts and the proliferation of epithelial cells was histoplanimetrically investigated in the rat ascending colon. Indigenous bacteria preferentially adhered to the intestinal superficial epithelial cells in the mesenterium-attached mucosa (MAM) compared to those in the mesenterium-non-attached mucosa (MNM). Intestinal crypts with indigenous bacteria were also significantly more frequently found in MAM than in MNM. Total epithelial cells, columnar epithelial cells and goblet cells were significantly more abundant in the intestinal crypts with no-indigenous bacteria in MAM (MAM-C) than those in MNM (MNM-C), whereas the columnar epithelial cells were less abundant in MAM-C than in the intestinal crypts with indigenous bacteria in MAM (MAM-C-B). Columnar epithelial cells and goblet cells immuno-positive for proliferating cell nuclear antigen (PCNA) in MAM-C were more abundant than those in MNM-C, but less abundant than those in MAM-C-B. Toll-like receptor (TLR)-2, -4 and -9 were immuno-positive in the striated borders of the intestinal superficial epithelial cells, but their positive intensities were weaker in MAM than in MNM. From these findings, indigenous bacteria were confirmed to preferentially settle on the intestinal superficial epithelium of MAM in the rat ascending colon, and low TLRs-expression might contribute to the preferential settlement of indigenous bacteria in MAM. The increase of proliferating epithelial cells is probably induced by the invasion of indigenous bacteria into the intestinal crypts of MAM. KEY WORDS: ascending colon, epithelial proliferation, indigenous bacteria, rat, Toll-like receptor.doi: 10.1292/jvms.13-0036; J. Vet. Med. Sci. 75(7): [939][940][941][942][943][944][945][946][947] 2013 A large number of indigenous bacteria settle in the animal alimentary tract. The bacterial settlement initiates immediately after birth by bacteria derived from mother, and the number and composition of indigenous bacteria are stable in the adult alimentary tract [4]. The number of indigenous bacteria in the chyme increases toward the caudal alimentary tract, that is, 0-10 5 colony forming unit (CFU)/ml in the stomach to jejunum, 10 3 -10 9 CFU/ml in the ileum and 10 10 -10 12 CFU/ml in the colon of human [28], resulting in total 2 kg of indigenous bacteria in the human alimentary tract [11]. From histoplanimetrical investigation along the longitudinal axis of the rat intestine, indigenous bacteria settle on the intestinal superficial epithelium, whose apical surface expresses special sugars throughout the large intestine, and indigenous bacteria also reside in the intestinal crypts in the cecum and proximal 30% of the colon [34,35]. Additionally, numerous indigenous bacteria exist between the mucosal folds in the rat ascending colon [27]. However, the detailed distribution of the settlement sites of indigenous bacteria has not been investigated in the ascending colon.The settlement of indigenous or exogenous bac...

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“…In general, more PCNA positivity was seen with in higher grade lesions. No definitive difference in PCNA staining in primary versus metastatic lesions could be detected in concordance with a previous study showing no difference in the percentage of PCNA-positive cells in pri mary colorectal carcinoma versus lymph node metastases [ 19], The pattern of PCNA staining in the lesions we stud ied showed marked intra-and interlcsional heterogeneity similar to that seen in previous studies [15][16][17], Examina tion of the adenomas and carcinomas reported in Bronner et al [3] reveals similar intra-and intcrtumoral heteroge neity in bcl-2 staining. Within the same lesion, areas of complete negativity were frequently seen adjacent to areas where the majority of lesional cells stained intensely for PCNA as was also reported by Diebold et al [ 15].…”

Section: Discussionsupporting

confidence: 79%

“…As has been previously reported, we found that in nor mal tissues PCNA expression was localized within the colonic and small bowel crypts and within the neck region of the stomach [15][16][17][18] in the same location as bcl-2 expression. Yamada et al [17] reported a difference in PCNA localization between the normal epithelium of the proximal and distal colon in rats: PCNA staining in the proximal colon was localized within the midcrypt with a PCNA-negative compartment present at the base in com parison to the distal colon where PCNA staining was con fined to the base. We found no difference in the pattern of PCNA staining between the normal epithelium of proxi mal and distal colon in agreement with the results of Diebold et al [ 15], We observed randomly distributed PCNA-positive cells along the epithelium of the pancreat ic ducts and bilary tree, previously observed by Hall et al [16], suggesting that the proliferating stem cells are ran domly distributed along the epithelium in these tissues rather than being found in a discrete proliferative com partment as is seen in other epithelia within the gastroin testinal tract [16].…”

Section: Discussionsupporting

confidence: 68%

Expression of Proliferating Cell Nuclear Antigen in Gastrointestinal Tract Lesions and Its Relationship to bcl-2 Expression

Bell

Bronner²,

Pasha³

et al. 1996

Pathobiology

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We report the relationship between proliferation as measured by the expression of proliferating cell nuclear antigen (PCNA) and the proto-oncogene bcl-2 in inflammatory and neoplastic lesions of the gastrointestinal tract and associated normal tissues. We found that (1) PCNA and bcl-2 are coexpressed in the stem cell-regenerative compartments of normal tissues but are not coexpressed in carcinomas or adjacent histologically normal epithelium, (2) there is marked heterogeneity of PCNA and bcl-2 expression in neoplastic lesions of the gastrointestinal tract, and (3) overexpression of PCNA is frequently seen in histologically inactive ulcerative colitis. We postulate (1) increased bcl-2 expression in epithelium adjacent to tumors represents an inherent change in the morphologically normal epithelium because it occurs without the corresponding high proliferative state seen in the normal crypt-regenerative compartment, (2) heterogeneity may provide a mechanistic explanation for chemotherapeutic resistance in tumors since cells having high bcl-2 but low proliferative activity would have prolonged survival and might show resistance to chemotherapeutic agents, and (3) the increased proliferative state in histologically inactive ulcerative colitis may provide a partial explanation for the increased risk of colon carcinomas in these patients.

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Proliferating cell nuclear antigen expression in normal, preneoplastic, and neoplastic colonic epithelium of the rat

Cited by 86 publications

References 12 publications

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Histoplanimetrical Study on the Relationship between Invasion of Indigenous Bacteria into Intestinal Crypts and Proliferation of Epithelial Cells in Rat Ascending Colon

Expression of Proliferating Cell Nuclear Antigen in Gastrointestinal Tract Lesions and Its Relationship to bcl-2 Expression

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Proliferating cell nuclear antigen expression in normal, preneoplastic, and neoplastic colonic epithelium of the rat

Cited by 86 publications

References 12 publications

Effects of &lsquo;Contact Laxatives&rsquo; on Intestinal and Colonic Epithelial Cell Proliferation

Effects of &lsquo;Contact Laxatives&rsquo; on Intestinal and Colonic Epithelial Cell Proliferation

Histoplanimetrical Study on the Relationship between Invasion of Indigenous Bacteria into Intestinal Crypts and Proliferation of Epithelial Cells in Rat Ascending Colon

Expression of Proliferating Cell Nuclear Antigen in Gastrointestinal Tract Lesions and Its Relationship to bcl-2 Expression

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Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation