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PubMed1983

Role of local prostaglandin synthesis in the modulation of proliferative activity of rat colonic epithelium.

The role of local prostaglandin (PG) synthesis in the modulation of the proliferative activity of colonic epithelium was examined in rat colon. Experimental rats were given either indomethacin (5 mg/kg s.c. every 8 h for three doses) or aspirin (0.5 g/100 g diet for 3 d). In rats treated with indomethacin or aspirin, the incorporation of [3H]thymidine (dThd) into DNA in vivo was increased approximately twofold over control in mucosal scrapings from distal colon, and approximately threefold over control in the proliferating pool of epithelial cells isolated from distal colon. [3H]dThd incorporation into DNA was also examined ex vivo immediately after distal colonic resection. It was approximately twofold higher in mucosa of colonic segments (1-h incubation) from rats treated with indomethacin or aspirin in vivo, compared with corresponding values of segments from control rats. Immunoreactive (i) prostaglandin E (PGE), the dominant PG product of colon segment incubates by high-performance liquid chromatography analysis of [14C]arachidonate metabolites, was markedly (95%) reduced in the media of 1-h colon incubates from indomethacin- or aspirin-treated rats, compared with control rats. Moreover, the cyclic (c)AMP content of mucosa of segments from indomethacin- or aspirin-treated rats was significantly lower than that of control rats. Prolonged incubation (4-24 h) of colonic segments from indomethacin-treated rats, in the absence of indomethacin in vitro, led to an eventual return of [3H]dThd incorporation into DNA, iPGE, and mucosal cAMP to control values. Conversely, inclusion of indomethacin (0.25 mM) in the incubations (6 h) of colonic segments from indomethacin-treated rats resulted in persistent suppression of iPGE and mucosal cAMP, as well as persistent enhancement of [3H]dThd incorporation into mucosal DNA. However, incubation of colonic segments from control rats (no in vivo drug exposure) with indomethacin or aspirin in vitro for periods up to 24 h failed to alter DNA synthesis, despite marked reduction in media iPGE and lower mucosal cAMP. The latter observations suggested that additional in vivo factors initiated the enhancement of DNA synthesis in indomethacin- or aspirin-treated rats. Exogenous PGE2, D2, I2, or F2 alpha, each of which increased the endogenous mucosal cAMP content of incubated colonic segments from control, indomethacin- or aspirin-treated rats, all suppressed [3H]dThd incorporation into mucosal DNA in vitro. Dibutyryl cAMP, but not dibutyryl cGMP, had an analogous suppressive effect on in vitro [3H]dThd incorporation into DNA. Thus, the present observations are consistent with an inhibitory action of endogenous colonic PG synthesis on the proliferative activity of colonic epithelium. This action may be mediated through cAMP.

Animals↗
PubMed2002

Electrophysiologic identification of the location of the colonic pacemakers. A human study.

Colonic inertia, total or segmental, is a known cause of constipation, yet its etiology is poorly understood and its treatment not satisfactory. Although the colonic electric activity has been studied by many investigators, the colonic pacemakers that are assumed to generate the electric waves, are scarcely addressed and their location, to our knowledge, has not been determined. The current communication investigates the possible sites of the colonic pacemakers, aiming at a better understanding of the mechanism of colonic motility and its disorders, notably colonic inertia. The tests were performed during the repair of huge incisional hernia in 12 subjects (mean age 37.7 +/- 10.2 years, 7 women). Monopolar silver-silver chloride electrodes were applied to the terminal ileum (TI) and cecum (C), and to the ascending (AC), transverse (TC), descending (DC) and sigmoid colon (SC); they were fixed by electrode gel to the ileal and colonic serosa. The electric activity of each of the TI, C, AC, TC, DC and SC was recorded. Electric waves in the form of slow waves or pacesetter potentials and action potentials were recorded from the TI and colon. Differences in the frequency, amplitude and conduction velocity of the waves occurred between the TI and the various segments of the colon. The change in the wave variables between the TI and C occurred at the ileocecal junction, between the C and AC at the cecocolonic junction, the AC and TC at the mid third of the TC and the DC and SC at the colosigmoid junction. The colonic electric waves are suggested to be generated by at least 4 pacemakers, which are presumably located at the ileocecal junction, the cecocolonic junction, the mid third of TC and at the colosigmoid junction. The electric waves appear to be responsible for conducting the colonic motor activity. We postulate that disordered colonic pacemakers may produce segmental or total colonic inertia, a proposition that needs further investigation.

Action Potentials↗
PubMed1992

[Secondary prevention of colon cancer].

Each year more than 6000 patients in Poland die from cancer of the colon. Morbidity due to colonic cancer increases rapidly in our country. From 1973 to 1982 there was a three-fold increase in the morbidity due to colonic cancer as compared to the years 1952-1955. Five-year relative survival in the same periods did not improve, either being 28% in men and 27% in women. To compare, in the USA with high morbidity rates due to colonic cancer where each year there are 145,000 new cases of cancer, 5-year relative survival is 42% for men and 54% for women. This raises a question whether our strategy of treatment of colonic cancer is correct. This question is even more justified now when secondary prevention of colonic cancer is of practical value. Total mortality due to colonic cancer is 60%. However, diagnosis and treatment of early forms of colonic cancer reduces mortality to 20% and below. Therefore, effective management colonic cancer should include not only the so-called primary prevention (interfering with etiological factors for instance through high fibers diet) but also secondary prevention through monitoring of precancerous changes in the colon, removal of potentially malignant lesions and early forms of colonic cancer [19]. Secondary prevention interfering with the pathogenesis of colonic cancer is the subject of the present paper. We would like to emphasize the need for a better management program for colonic cancer, especially that the data concerning colonic cancer in Poland may be underestimated due to diagnostic neglect and faulty cancer register.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Muscarinic receptors in canine colonic circular smooth muscle. I. Coexistence of M2 and M3 subtypes.

The parasympathetic neurotransmitter acetylcholine, acting postsynaptically at the smooth muscle muscarinic receptor, is a principle determinant of colonic motility. In order to elucidate the receptor signal-transduction events responsible for muscarinic receptor-induced contraction of colonic circular smooth muscle, we present here and in the accompanying work studies designed to characterize the muscarinic receptors present in colon and to determine their biochemical coupling. Muscarinic receptor subtypes in canine colonic circular smooth muscle were characterized using radioligand binding techniques. The nonselective muscarinic receptor antagonist radioligand [3H]quinuclidinyl benzilate ([3H]QNB) binds rapidly and reversibly to a single class of saturable sites in colon circular smooth muscle membranes, with an affinity (KD) for the antagonist radioligand of 79.8 +/- 12.6 pM and a density of 123.3 +/- 18.7 fmol/mg of protein. Experiments using membranes prepared from isolated cells purified from the circular smooth muscle layer of canine colon (KD = 102.4 +/- 13.5 pM) confirm the smooth muscle origin of the binding and yield a receptor density of 124,340 receptors/cell. The order of potencies of selective muscarinic receptor antagonists in competition with [3H]QNB for binding to colonic receptors is 4-diphenylacetoxy-N-methylpiperidine methobromide greater than methoctramine greater than AF-DX 116 greater than pirenzepine. Unlike other antagonists tested, pirenzepine competition of [3H]QNB binding is biphasic. The high and low affinities deduced from nonlinear fit of the binding data in colon correlate very well with affinities determined for pirenzepine in mixtures of both submandibular gland (M3) and atrium (M2), indicating the presence of two muscarinic receptor subtypes (82% M2, 18% M3) in colon circular smooth muscle. The muscarinic agonist carbachol binds to both high and low affinity sites in colon, and addition of guanine nucleotide (100 microM GTP gamma S) shifts the agonist competition curve to the right, without eliminating high affinity binding sites. Agonist competition studies with a known ratio of M2 and M3 receptors, obtained by mixing pure M2 and M3 populations, predict the result obtained in colon. cDNA probes specific for each of the muscarinic receptors m1 through m4 were hybridized to colon RNA in a Northern blot analysis. Only m2 and m3 probes hybridized to colon RNA, suggesting the presence of both M2 and M3 receptors. Our data demonstrate that the colon circular smooth muscle contains muscarinic receptors of both the M2 and M3 subtypes, which may be coupled to disparate signal transduction pathways important in the physiological actions of acetylcholine in this tissue.

Animals↗
PubMed1982

Alkaline phosphatase isoenzyme of colonic carcinoma in Wistar-Furth rats.

Wistar-Furth (WF) strain rats have been shown to have a high incidence of spontaneous colon cancer. We have compared the alkaline phosphatase (AP) isoenzymes in colonic carcinomas of these inbred WF strain rats with the isoenzymes in the non-carcinomatous colon of the same strain and the normal colon of Wistar strain rats, from which the WF strain was derived. On electrophoresis of AP specimens partially purified by acetone fractionation, the non-carcinomatous colon was found to have three main isoenzymes, while the normal colon had two. Colonic carcinomas gave one band which migrated slower than any bands from either normal or non-carcinomatous colon. The electrophoretic mobility of AP from colonic carcinomas was retarded by neuraminidase treatment. This did not influence the isoenzymes from non-carcinomatous and normal colon. The inhibition patterns of the enzyme from colonic carcinoma by amino acids, inorganic phosphate and urea were different from those of the isoenzymes in the other two tissues. AP of colonic carcinoma was also the most heat-labile. There were no significant differences in the enzymic properties of the isoenzymes from non-carcinomatous and normal colon. The enzymic properties except for electrophoretic mobility were found to be the same between APs of colonic carcinoma and the placenta.

Aging↗
PubMed1998

Differentiation of prolonged colonic transit using scintigraphy with indium-111-labeled polystyrene pellets.

UNLABELLED: Prolonged colonic transit can be caused either by slow transit constipation or by pelvic outlet obstruction needing different therapeutic regimes. The aim of this study was to prove the value of scintigraphic assessment. METHODS: Colon scintigraphy was performed in 32 patients (28 women, 4 men; age range 8-68 yr) with idiopathic constipation at 8, 24 and 48 hr in ventral and dorsal projection after oral administration of a pH-sensitive, methacrylate-coated capsule of nonresorbable 111In-labeled polystyrene (cathion exchanger) micropellets (3.5 MBq/capsule). The geometric center (GC) as the sum of products of colon segment activity and colon segment number (1 = colon ascendens; 2 = transverse colon; 3 = colon descendens; 4 = rectosigmoid colon; and 5 = stool) dividing by the total counts was used to determine the velocity of colonic transit at least at 24 hr as the proximal colonic emptying (PCE) rates. Stool activity was evaluated indirectly as decay-corrected colon activity loss between two examinations. Results were compared with data obtained from 22 healthy subjects. RESULTS: Twenty-six patients had a significant prolongation of colonic transit after 24 and 48 hr (the 95% confidence interval of the patient's GC showed no overlap to the 95% confidence interval of GC calculated from 22 healthy controls as normal range) revealing slow transit constipation. Six patients had normal or accelerated transit (GCs and PCE rates) up to the rectum but delayed rectal emptying indicating pelvic outlet obstruction. CONCLUSION: By the help of this method it was possible to differentiate the two subtypes of colon transit prolongation by use of the reported scintigraphic technique, which leads to different therapeutic management of the patients. Compared with x-ray methods (Hinton test), this method has the capability of a continuous observation of colonic transit without increasing radiation exposure.

Adolescent↗
PubMed2002

Seasonality of root fungal colonization in low-alpine herbs.

Arbuscular mycorrhizal (AM) and dark septate endophytic (DSE) fungal colonization of Alchemilla glomerulans, Carex vaginata, Ranunculus acris ssp. pumilus and Trollius europaeus growing in low-alpine meadows in the Finnish subarctic were studied at different times during the growing season. Fungal colonization was correlated to soil soluble phosphorus (P) concentration. The influence of flower bud removal on fungal colonization was investigated in A. glomerulans, C. vaginata and R. acris and the correlation between AM and DSE colonization was studied. The fungal colonization patterns were found to be species-specific. R. acris maintained a relatively high rate of fungal colonization throughout the summer, while the rates of colonization of T. europaeus were lower and decreased towards the end of the season. A. glomerulans had constant arbuscular and vesicular colonization throughout the summer, but hyphal and DSE colonization declined towards the end of the season. C. vaginata did not form arbuscular mycorrhiza, but was colonized by DSE fungi and hyaline septate hyphae throughout the season. The soil soluble P concentration showed some seasonal variation, but was also highly variable between the study sites. Bud removal decreased arbuscular colonization of R. acris, but no unique effects were seen in any other parameters or the other species studied. The root fungal parameters correlated with soil P in some species at some sites, but no consistent trend was found. DSE colonization was positively correlated with root vesicular and hyphal colonization in some cases. The differences in fungal colonization parameters may be related to species-specific phenologies.

Alchemilla↗
PubMed1996

Gnotobiotic system for studying rhizosphere colonization by plant growth-promoting Pseudomonas bacteria.

A gnotobiotic system for studying tomato rhizosphere colonization by Pseudomonas bacteria was developed. The system is based on sterile seedlings that are inoculated with one or two strains and subsequently grown in a sterile glass tube containing quartz sand. After 7 days of growth in a climate-controlled growth chamber, the number of bacteria present on the root tip was analyzed. The system was optimized with respect to root morphology, inoculation of the seedling, and isolation of root tip bacteria. With this system, rhizosphere colonization on tomato, radish, wheat, and potato was analyzed. For detailed analysis of tomato rhizosphere colonization by some representative plant growth-promoting rhizo-bacteria, the colonization of known poor, moderate, and good potato root-colonizing Pseudomonas strains and of four Rhizobium strains was determined. All strains colonized the root tips when inoculated as single strains. When inoculated in competition with the efficient root colonizer P. fluorescens strain WCS365, many strains were outcompeted. Mutants of Pseudomonas biocontrol bacteria lacking flagella or the O-antigen of lipopolysaccharide (LPS), which were isolated in previous studies and shown to be impaired in potato rhizosphere colonization in field soil systems, showed a reduced colonization ability in the gnotobiotic system also. The gnotobiotic system was used to screen a collection of 300 random P. fluorescens WCS365::Tn5 mutants for colonization-impaired mutants. Three novel mutants were found that were outcompeted by the wild-type strain in tomato root tip colonization but were not impaired in known colonization traits such as motility, amino acid auxotrophy, and presence of the O-antigenic side chain of LPS. One strain appeared to be a thiamine auxotroph, suggesting that the root does not secrete a sufficient amount of thiamine to support growth of this strain. The other two mutants had a reduced growth rate in laboratory media, suggesting that growth rate is an important colonization factor. As the system is gnotobiotic and devoid of field-soil variables, it can also be used to study the effects of selected biotic and abiotic factors on colonization.

Escherichia coli↗
PubMed1994

Sequential psychomotor skills development in laparoscopic colon surgery.

OBJECTIVES: To quantify the complexity of each of three skills used in laparoscopic colon surgery and to quantify the relative complexity of seven laparoscopic colon procedures on a graduated complexity scale. DESIGN: Five surgeons used a scale of 1 through 6 to measure the relative complexity of three laparoscopic skills (intracorporeal mobilization, intracorporeal devascularization, and intracorporeal anastomosis) to assess the relative difficulty of seven laparoscopic procedures (right colon resection, sigmoid colon resection, low anterior resection, Hartmann's procedure, left colon resection, abdominoperineal resection, and transverse colon resection) using detailed evaluation of their first 100 laparoscopic colon resections. SETTING: Three private community hospitals. MAIN OUTCOME MEASURES: The complexities of intracorporeal mobilization, intracorporeal devascularization, and intracoporeal anastomosis were recorded for seven laparoscopic colon procedures. RESULTS: The least complex procedure was right colon resection, followed in increasing complexity by sigmoid colon, Hartmann's procedure, low anterior resection, abdominoperineal resection, left colon resection, and transverse colon resection. The addition of each laparoscopic skill increased the complexity during each procedure. All three skills were not required for every procedure. CONCLUSIONS: Since all procedures do not require all three skills, skills can be learned sequentially if patients are chosen judiciously. A sequence of laparoscopic procedures performed by surgeons is recommended. The relative complexities for each procedure suggest an outline (map) for surgeons to use during laparoscopic colon surgery.

Abdomen↗
PubMed2005

Expression of NOX1, a superoxide-generating NADPH oxidase, in colon cancer and inflammatory bowel disease.

Reactive oxygen species (ROS) are at the centre of many physiological and pathological processes. NOX1, a ROS-producing NADPH oxidase, is highly expressed in the colon but its function in colonic physiology or pathology is still poorly understood. It has been suggested to play a role in host defence, but also in cell growth and possibly malignant transformation. In this study we characterized NOX1 expression in human colon samples derived from healthy control subjects and patients with colon cancer or inflammatory bowel disease (IBD). NOX1 mRNA expression was assessed by dot-blot hybridization, real-time PCR and in situ hybridization, using samples derived from surgical specimens from patients undergoing colon resection. In normal tissues, NOX1 expression was low in the ileum, intermediate in the right colon, and high in the left colon (p = 0.0056 right vs. left colon). NOX1 mRNA levels were not influenced by factors linked to colon tumourigenesis, such as age or sex. Moreover, there was no statistical difference in NOX1 expression between samples derived from adenomas, well differentiated or poorly differentiated colon adenocarcinomas. At a cellular level, NOX1 was highly expressed in colon epithelial cells, both within the crypts and on the luminal surface. In addition, a population of lymphocytes, particularly in the appendix, showed NOX1 expression. Lymphocytes in lesions of Crohn's disease and ulcerative colitis were also strongly positive for NOX1. In conclusion, NOX1 is an enzyme that is constitutively expressed in colon epithelium and is not associated with tumourigenesis. Its distribution in crypts and on the luminal surface, as well as its left-to-right gradient in the colon, suggests a role in host defence function. In addition to the known epithelial localization, we define lymphocytes as a novel site of NOX1 expression, where it may potentially be involved in the pathogenesis of inflammatory bowel diseases.

Adenocarcinoma↗
PubMed2006

Colonic manometry as predictor of cecostomy success in children with defecation disorders.

PURPOSE: The aim of this study was to define the predictive value of colonic manometry and contrast enema before cecostomy placement in children with defecation disorders. METHODS: Medical records, contrast enema, and colonic manometry studies were reviewed for 32 children with defecation disorders who underwent cecostomy placement between 1999 and 2004. Diagnoses included idiopathic constipation (n = 13), Hirschsprung's disease (n = 2), cerebral palsy (n = 1), imperforate anus (n = 6), spinal abnormality (n = 6), and anal with spinal abnormality (n = 4). Contrast enemas were evaluated for the presence of anatomic abnormalities and the degree of colonic dilatation. Colonic manometry was considered normal when high-amplitude propagating contractions (HAPC) occurred from proximal to distal colon. Clinical success was defined as normal defecation frequency with no or occasional fecal incontinence. RESULTS: Colonic manometry was done on 32 and contrast enema on 24 patients before cecostomy. At follow-up, 25 patients (78%) fulfilled the success criteria. Absence of HAPC throughout the colon was related to unsuccessful outcome (P = .03). Colonic response with normal HAPC after bisacodyl administration was predictive of success (P = .03). Presence of colonic dilatation was not associated with colonic dysmotility. CONCLUSION: Colonic manometry is helpful in predicting the outcome after cecostomy. Patients with generalized colonic dysmotility are less likely to benefit from use of antegrade enemas via cecostomy. Normal colonic response to bisacodyl predicts favorable outcome.

Adolescent↗
PubMedDate not supplied

Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases.

DNAS of some human tumours can transform NIH 3T3 fibroblast cells, thus demonstrating the transforming potential of human ras genes (Hu-rasHa, Hu-rasKi, and Hu-rasN, respectively Harvey, Kirsten and neuroblastoma ras genes). Only a small percentage of a given type of human carcinoma, however, scores positive in this assay system. Activation of ras and subsequent transformation of NIH 3T3 cells are either by a point mutation in the ras gene or enhanced expression of the normal, or proto-onc, ras gene. If the transformation of a given human tumour involves the enhanced expression of the normal or cellular ras gene and the resulting gene product, the tumour DNA would probably score negative in the NIH 3T3 transfection assay. In human colon carcinoma, for example, lesions at position 12 of Hu-rasKi have been found. None of nine colon carcinomas obtained at biopsy, however, contain the ras lesion at this position, using a Hu-rasHa probe; one other colon carcinoma does appear to contain amplified proto-onc ras, and other colon carcinomas do have increased levels of ras RNA. There are at least three explanations for these observations. Either very few colon carcinomas contain point-mutated ras, the lesion in the majority of colon carcinomas is at a position other than 12 or ras activation in many colon carcinomas involves the enhanced expression of either the point-mutated or proto-onc form of a ras gene. We have now used monoclonal antibodies directed against a synthetic peptide reflecting sequences of the human T24 ras gene product to define ras p21 protein expression in a spectrum of colonic disease states. Immunohistochemical analyses of individual cells within tissue sections reveal differences in ras p21 expression in colon carcinomas compared with normal colonic epithelium, benign colon tumours and inflammatory or dysplastic colon lesions. Our data suggest that ras p21 expression is correlated with depth of carcinoma within the bowel wall, and is probably a relatively late event in colon carcinogenesis.

Adenoma↗
PubMed1981

Carcinoma of the right colon: a change in characteristic configuration?

Carcinoma of the colon occurring to the right of the middle colic vessels is usually described as morphologically and clinically distinctive from cancers occurring in the left colon. Cancers of the right colon are characterized as polypoid tumors that are discovered in the search for occult blood loss, whereas carcinomas of the left and sigmoid colon are described as scirrhous and often annular in configuration, giving rise to obstruction as the characteristic clinical presentation. A personal experience with constricting annular lesions of the right colon that were considered atypical has led to a review of the total experience in colonic resections for cancer (excluding abdominoperineal resections for carcinoma of the rectum) at one metropolitan university medical center. Of 152 colonic resections for cancer within 39-month interval, 57 resections were for cancer of the right colon and 95 for cancer of the left colon. One half of the cancers of the right colon were annular, whereas only one third of those of the left colon were so described by operative, pathologic, and radiologic criteria. Differences in clinical presentation of cancers of the right and left colon are probably attributable more to the form and function of the colon in each anatomic region than to any characteristic configuration of the tumor itself.

Adenocarcinoma↗
PubMed1999

Increased expression of angiogenic factors in human colonic angiodysplasia.

OBJECTIVE: Angiodysplasia of the colon is a distinct vascular abnormality characterized by focal accumulation of ectatic vessels in the mucosa and submucosa. To investigate whether angiogenesis contributes to the pathogenesis of human colonic angiodysplasia, we examined the expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), and its endothelial cell receptors flt-1 and KDR. METHODS: Immunohistochemistry was performed in sections of specimens obtained from 18 patients with colonic angiodysplasia and from eight patients with colon cancer and its adjacent, histologically normal margins of resection. We used affinity-purified rabbit polyclonal antibodies and a streptoavidin-biotin peroxidase method. RESULTS: We detected strong immunoreactivity for vascular endothelial growth factor, homogeneously distributed in the endothelial lining of blood vessels of all sizes in 16 (89%) specimens of colonic angiodysplasia and in seven (88%) patients with colon cancer. In contrast, very limited immunoreactivity was found in normal colon. Vascular staining for flt-1 was observed in eight (44%) and one (12.5%) of the colonic angiodysplasia or colon cancer specimens, respectively, but not in normal colon. Vascular immunoreactivity for basic fibroblast growth factor was observed in seven (39%) specimens from patients with colonic angiodysplasia, whereas either very limited or no immunostaining was found in sections from specimens of patients with colon cancer and its normal margins. CONCLUSIONS: In human colonic angiodysplasia, increased expression of angiogenic factors is likely to play a pathogenic role.

Adenocarcinoma↗
PubMedDate not supplied

Role of prostaglandin E2 in rat colon carcinoma.

BACKGROUND/AIMS: It has previously been reported that prostaglandin E2 (PGE2) promotes colon carcinogenesis. We therefore studied the effects of long-term administration of prostaglandin E2 (PGE2) on colon carcinogenesis in rats. METHODOLOGY: Rats received intrarectal n-methyl-n-nitrosourea (MNU) or n-methyl-n-nitrosoguanidine (MNNG) to induce the formation of colonic tumors. Rates then received indomethacin (IND) and/or PGE2, or nothing. After 44 weeks (MNU group) or 46 weeks (MNNG group), colon lesions were identified histologically and colonic mucosa PGE2 concentrations were measured by radioimmunoassay. RESULTS: The incidence of colon carcinoma in the control, MNU, MNU + IND, MNU + PGE2, and MNU + IND + PGE2 groups was 0/14, 5/15, 0/14, 4/10, and 2/9, respectively. In the MNNG group, no tumors were observed. Induction of colon carcinomas by MNU was completely inhibited by IND, while exogenous PGE2 blocked the inhibitory effect of IND. However, PGE2 administration did not accelerate colon carcinogenesis. Neither MNU nor MNNG alone resulted in increased colonic mucosal PGE2 concentrations, whereas exogenous PGE2 administration significantly increased mucosal PGE2 concentrations. IND significantly decreased the mucosal concentration of PEG2 with or without PGE2 administration. CONCLUSIONS: These results suggest that endogenous PGE2 in colon mucosa may be adequate to promote colon carcinoma. To block colon carcinogenesis, PGE2 levels in colonic mucosa must be decreased to less than endogenous levels.

Animals↗
PubMed1992

Comparison of mouse and human colon tumors with regard to phase I and phase II drug-metabolizing enzyme systems.

Since human colorectal tumors are insensitive to most chemotherapeutic agents, there is a need for the discovery of new drugs that would show activity against this disease. In an attempt to better appreciate the relevance of a widely used mouse colon tumor (colon adenocarcinoma Co38) as a screening model for human colorectal tumors, we compared the main phase I and phase II drug-metabolizing enzyme systems in both tumoral and nontumoral colon tissues. The following enzymes were assayed by Western blot: cytochromes P-450 (1A1/A2, 2B1/B2, 2C, 2E1, and 3A), epoxide hydrolase, and glutathione-S-transferases (GST-alpha, -mu, and -pi). The activities of the following enzymes or cofactors were determined by spectrophotometric or fluorometric assays: total cytochrome P-450, 1-chloro-2,4-dinitrobenzene-GST, selenium-independent glutathione peroxidase, 3,4-dichloronitrobenzene-GST, ethacrynic acid-GST, total glutathione, epoxide hydrolase, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. Results obtained by Western blot showed that mouse colon adenocarcinoma Co38 did not express any of the probed cytochromes P-450, whereas human colorectal tumors expressed only low levels of cytochrome P-450 3A. GST-alpha and GST-pi were detected in all tumoral and nontumoral tissues of both species. The neutral GST-mu was expressed in all murine tissues investigated and was found to be polymorphic in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzyme levels, whereas mouse colon adenocarcinoma Co38 had a lower expression of GST-mu and GST-pi, compared to normal mouse colon. Enzymatic activities for glutathione peroxidase, 3,4-dichloronitrobenzene-GST, and ethacrynic acid-GST confirmed the Western blot results for GST-alpha, GST-mu, and GST-pi, respectively. Total GSH levels were similar between murine and human tumors but were 3-fold higher in human tumors than in peritumoral tissues, whereas they were 7-fold lower in mouse colon tumor Co38, compared to normal mouse colon. Epoxide hydrolase was not expressed in either mouse colon adenocarcinoma Co38 or normal mouse colon tissues, whereas it was expressed in human colon peritumoral and tumoral tissues at similar levels. No significant difference was observed between human tumors and peritumoral tissues for UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. For murine colon tissues, the conjugation pathways (UDP-glucuronosyltransferase and sulfotransferase) were lower in colon adenocarcinoma Co38, whereas the converse was observed for the corresponding hydrolytic enzymes (beta-glucuronidase and sulfatase).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed2004

[Anatomic variations of the colon detected on abdominal CT scans].

PURPOSE: The frequency of anatomic variations of the colon detected on abdominal CT scans was examined. MATERIALS AND METHODS: 296 consequtive abdominal tomography were evaluated prospectively for the presence of retrorenal colon, retrogastric (pancreaticogastric interposition or retrosplenic) colon, high positioned colon, interposition of the colon between the psoas muscle and the kidney and hepatodiaphragmatic interposition (anterior or posterior). RESULTS: We observed 2 retrogastric colon [1 pancreaticogastric (0.3%), 1 retrosplenic (0.3%)], 7 retrorenal colon (1.2%) being bilateral in two cases, 2 interposition of colon between the psoas muscle and the kidney (0.7%), 1 posterior (0.3%) and 6 anterolateral hepatodiaphragmatic interposition (2.1%) and 12 high positioned cecum (4.2%) (in 4 of them cecum was totally subhepatic in location). Terminal ileum was lying in Morrison's pouch and anterior to renal hilus in two of the cases with subhepatic cecum. CONCLUSION: Anatomic variations of the colon probably result due to mild embryologic abnormalities of bowel rotation and fixation, short transvers mesocolon, intraperitoneal ascending or descending colon, increased intraperitoneal pressure or decreased retroperitoneal fat. Pancreaticogastric interposition occurs in approximately 0.2%, partial retrorenal colon in 9-10%, complete retrorenal colon 1%, interposition between psoas muscle and kidney in 0.7-1.7%, anterolateral hepatodiaphragmatic interposition in 1.3-3% of individuals. When located in lesser sac it simulates several pathologies of this area. On intravenous urography images it may cause mass effect. In percutaneous interventions and surgical procedures colon may be perforated. For these reasons tomography images should be evaluated for the presence of these anatomic variations.

Adult↗
PubMed1987

Effects of chronic dietary beer and ethanol consumption on experimental colonic carcinogenesis by azoxymethane in rats.

Epidemiological studies have shown an association between consumption of alcoholic beverages, particularly beer, and carcinoma of the large bowel, especially the rectum. We studied the effects of chronic dietary beer and ethanol consumption on experimental colonic carcinogenesis, fecal bile acid and neutral sterol levels, fecal bacterial flora, and colonic epithelial DNA synthesis. Ten-week-old male Fischer 344 rats were pair fed throughout the study with Lieber-DeCarli-type liquid diets providing comparable total carbohydrates, proteins, fats, and calories. The diets provided 23 or 12% of calories as alcohol in beer (Hi-Beer and Lo-Beer groups), 18 or 9% of calories as reagent ethanol (Hi-EtOH and Lo-EtOH groups), or no alcohol (control group). After 3 weeks of dietary acclimatization, 10 weekly s.c. injections of the bowel carcinogen azoxymethane, 7 mg/kg, were given (weeks 1-10). At necropsy in week 26, the high alcohol groups (Hi-Beer and Hi-EtOH) showed a significantly reduced incidence of tumors in the right colon (42 and 46% versus 81% in control, P less than 0.01 and P = 0.02) but no effect on left colonic tumorigenesis. By contrast, the low alcohol groups (Lo-Beer and Lo-EtOH) showed a trend toward increased incidence and proportion of tumors in the left colon (incidence of 42 and 35% versus 15% in control, P = 0.06 for Lo-Beer; 28 and 30% of tumors in left colon versus 11%, P = 0.08 and P = 0.07) but no effect on right colonic tumorigenesis. Numbers of right colonic tumors were inversely correlated with alcohol consumption of all rats (r = -0.350, P less than 0.001), but left colonic tumors were not correlated. Fecal bile acid and neutral sterol levels, fecal bacterial counts, and colonic epithelial DNA synthesis did not correlate with the effects of alcohol consumption on colonic tumorigenesis. Our findings suggest that: modulation of experimental colonic tumorigenesis by chronic dietary beer and ethanol consumption was due to alcohol rather than other beverage constituents; tumorigenesis in the right and left colon was affected differentially by the levels of alcohol consumption, reflecting complex interactions among the potential mechanisms for alcohol effects in the model used.

Alcohol Drinking↗