Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “colonization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed1992

Mr 40,000 human colonic epithelial protein expression in colonic mucosa and presence of circulating anti-Mr 40,000 antibodies in cotton top tamarins with spontaneous colitis.

Saguinus oedipus, Callithrix jacchus, and Saguinus fuscicollis are three species of New World monkeys which develop a form of colitis that is similar to human ulcerative colitis. Only S oedipus, however, develop colon cancer. We examined intestinal tissues from these animals for the presence of an antigen cross reacting to the Mr 40,000 human colonic epithelial protein that acts as an autoantigen in ulcerative colitis. Using an anti-Mr 40,000 monoclonal antibody (7E12H12, IgM isotype), by an immunoperoxidase assay we showed that all colon specimens from S oedipus reacted with 7E12H12; however, the colonic tissue from C jacchus and S fuscicollis did not. In immunotransblot analysis eluted IgG antibody bound to human ulcerative colitis colon (CCA-IgG) reacted with Mr 40,000 protein(s) present in the extracts of colon from S oedipus animals and humans. Small intestinal tissue reacted neither with 7E12H12 nor with CCA-IgG. In S oedipus, the Mr 40,000 protein was localised exclusively to colonic epithelial cells. Preincubation of seven S oedipus colon specimens with eight of 10 sera from animals with acute or chronic colitis and 0 of four sera from animals without colitis almost completely inhibited the binding of 7E12H12 to the colonic epithelium. Four of these 10 sera inhibited the binding of 7E12H12 to the autologous colon. These results show the presence of circulating autoantibodies in S oedipus with colitis against an epitope(s) on Mr 40,000 protein shared by human and S oedipus colon.

Animals↗
PubMed2000

Migrating site of bleeding in a right colon demonstrating angio-dysplasia following a segmental resection of the colon. A unique variant of angiodysplasia.

BACKGROUND/AIM: A case of angiodysplasia of the right colon presenting with a migrating site of bleeding following a segmental resection of the colon in a 38-year-old Japanese is herein reported. METHODS: The case records of a patient with severe intestinal bleeding and multiple surgeries were reviewed, and then the histologic features were compared with the operative findings. The patient received many units of packed red blood cells and had also undergone three segmental colectomies and most recently a curative ileocolostomy. Despite an exhaustive evaluation, the bleeding sites could not be detected clinically. RESULTS: Ectatic, tortuous submucosal veins were presented in four sections of the colon (cecum, ascending colon and transverse colon, respectively) out of a total of 30 sections that were examined. These veins pierced the proper muscle layer of the colon, but did not traverse the muscularis mucosa. Our case of segmental microscopic angiodysplasia may represent a previously unreported unique variant, because the angiodysplastic lesions were present in the segmental colon and they developed bleeding from the distal remnant colon immediately after each segmental colectomy until an extended right hemicolectomy containing the oral part of the descending colon was done. In spite of the severe bleeding, the mucosa of the colon appeared to be essentially normal during a macroscopic inspection. CONCLUSION: Gastrointestinal bleeding from angiodysplasia is generally assumed to arise from macroscopically visible vascular lesions within the mucosa. However, angiodysplastic lesions are often unrecognizable and multiple in the gastrointestinal tract, and especially tend to affect both the cecum and ascending colon. When this disease process is recognized, a subtotal colectomy may thus be called for to control bleeding.

Adult↗
PubMedDate not supplied

The interactions of diet and colonic microflora in regulating colonic mucosal growth.

The colonic mucosa can adapt its growth to alterations in diet. Metabolites from colonic microflora are frequently implicated as the primary factor in mediating the colonic mucosal response to diet; however, there is also evidence indicating that diet may have a direct effect in mediating this response. The aim of this study was to determine the role of diet, microflora, and microflora metabolites in altering the growth of the colonic mucosa. Two 28-day feeding studies were conducted using Sprague-Dawley rats. The first study compared the growth of the colonic mucosa in germ-free and conventional rats fed 6 different diets. The second study compared the growth of the colonic mucosa to the concentration of bacterial-derived short-chain fatty acids (SCFs), bile acids, and ammonia. The diets that were fed consisted of (1) AIN-76a diet without dietary fiber; (2) standard AIN-76a diet, which contained 5% cellulose; (3) AIN-76a diet with 5% guar gum; (4) a "Western" human diet with 20% fat and 10% cellulose; (5) AIN-76a diet formulated to mimic Diet 4 in fat content but with 2.5% cellulose; and (6) Purina Rodent Chow. Quantitative volumetric and stereologic analysis was used to assess changes in total colonic mucosal volume as a measure of mucosal growth. In germ-free rats, Diets 2-4 and 6 induced a significant increase (18-38%) in mucosal volume compared to Diet 1. In conventional animals, only Diets 4 and 6 induced a significant increase (up to 63%) in mucosal volume compared to Diet 1. Relative to the germ-free animals, only conventional animals on Diets 4 and 6 had an increase in mucosal volume. The increases in mucosal volume in Diets 4 and 6 were not consistently associated with increased SCFAs, ammonia, or bile acids. There was a wide range in the colonic concentrations of SCFAs (2-fold), ammonia (6-fold), and bile acids (10-fold). The presence of colonic microflora in and of itself does not lead to enhanced colonic mucosal growth. Rather, there are unique interactions between specific types of diet and microflora that lead to a growth-promoting effect. This effect could not be explained by alterations in the concentration of SCFAs, ammonia, or bile acids in colonic contents.

Ammonia↗
PubMed2003

Colonic pacing in patients with constipation due to colonic inertia.

BACKGROUND: The colon exhibits electrical activity in the form of pacesetter potentials (PPs) and action potentials (APs); no activity is recorded in total colonic inertia (TCI). Electrical activity mediates colonic motility. We have elsewhere demonstrated that 4 pacemakers initiate colonic electric activity. We investigated the hypothesis that the absence of electric activity in TCI is due to non-functioning pacemakers and that their stimulation produces colonic motility and defecation. MATERIAL/METHODS: 19 patients with TCI were divided into 2 groups: a study group of 11 patients (age 42.6 +/- 6.8 years; 7 women) and a control group of 8 patients (age 41.4 +/- 6.3 years, 5 women). 7 healthy volunteers (age 40.9 +/- 6.1 years, 5 women) were also studied. Pacing electrodes were endoscopically hooked to colonic mucosa: one stimulating and 2 or 3 recording. Stimulating electrodes were applied to the 4 potential pacemaker sites located at the cecal pole, the cecocolonic junction, the mid-transverse colon, and the colosigmoid junction. Electrical activity was recorded before and during electrical stimulation. RESULTS: Colonic pacing of healthy volunteers caused a significant increase in the frequency, amplitude and conduction velocity of basal electric waves. Colonic pacing in the study group produced PPs and APs, which varied between colonic segments. No waves were recorded from the control group in which the pacemakers were not activated. CONCLUSIONS: Colonic pacing produces electrical activity in patients with TCI. This method can be applied for the treatment of constipation in these patients.

Action Potentials↗
PubMed1985

E. coli colonization of the mammalian colon: understanding the process.

Overall, the risk assessment data have shown not only that recombinant DNA research using E. coli strains is safe but also that E. coli strains, in general, including K-12 strains, can colonize the mammalian colon in individuals undergoing antibiotic treatment. However, very little is known about how E. coli colonizes the mammalian colon and it is possible that different strains use different adhesins and different colonic receptors in the process. Through the approach described here it has been possible to begin to identify both E. coli adhesins and colonic receptors which may play an important role in the colonization process. Hopefully, continued research into the molecular basis of E. coli colonic colonization will lead to the development of healthy E. coli strains for recombinant DNA research which are unable to colonize the human colon under any circumstance.

Adhesiveness↗
PubMed1988

Alterations of the biological characteristics of a colon carcinoma cell line by colon-derived substrata material.

This study documents the ability of substrata material derived from well but not poorly differentiated colon carcinoma cells to alter the biological characteristics of a separate colon carcinoma cell line (MOSERSF). To assess changes induced by the presence of these substrata, MOSERSF cells were screened for (a) morphological features, (b) secretion of carcinoembryonic antigen (CEA), (c) alteration of urokinase levels, and (d) sensitivity to the growth-inhibitory peptide transforming growth factor beta. Morphologically, MOSERSF cells grown on plastic displayed a rounded shape and could be detached by agitation. Subculturing of these cells onto substrata laid down by well differentiated (mature) colon carcinoma cells resulted in cell attachment and spreading. These changes did not manifest themselves when cells were plated on material derived from poorly differentiated (primitive) colon cells. Conditioned medium from MOSERSF cells grown on plastic or on colon-derived material from the well and poorly differentiated colon cells were compared for CEA levels. Substrata derived from undifferentiated cells were without effect on assayable CEA (substrata absent, 1.4 ng/ml/10(6) cells/72 h; substrata present, 1.4-1.7 ng/ml/10(6) cells/72 h). However, growth of MOSERSF cells on material deposited by well differentiated colon cells resulted in a 3-fold increase in the level of CEA. Spent medium was also analyzed for urokinase. A high level of the protease (20.3 ng/ml/10(6) cells/72 h) was expressed by MOSERSF cells. The concentration of the enzyme was reduced by over 50% when MOSERSF cells were propagated on substrata laid down by well differentiated cells. An enhanced sensitivity to the growth-retarding effects of transforming growth factor beta was seen with certain substrata. On plastic, transforming growth factor beta inhibited proliferation of MOSERSF cells with a median effective concentration of 0.65 ng/ml. However, on substrata from mature but not primitive cells, MOSERSF cells exhibited an increased sensitivity to the peptide (median effective concentration, 0.16 ng/ml). Colon-derived material obtained from both well differentiated and poorly differentiated colon carcinoma cells was compared after [35S]-methionine metabolic labeling. More [35S]methionine was incorporated into the material from the "mature" colon cells. The substrata could also be distinguished by quantitative differences in a number of high molecular weight proteins. Immunofluorescence of colon-deposited material revealed the presence of laminin and fibronectin.

Carcinoembryonic Antigen↗
PubMed1984

Fecal bile acid excretion in patients with colon cancer, colon polyp and peptic ulcer.

Fecal bile acids were analyzed by gas chromatography in 10 patients with colon cancer, 25 patients with colon polyp and 10 patients with peptic ulcer. On admission total bile acid excretion in patients with colon cancer was significantly higher than in patients with peptic ulcer (P less than 0.01). Also, concentration of cholic acid, chenodeoxycholic acid and primary bile acids in patients with colon cancer were significantly higher than those in patients with peptic ulcer (P less than 0.05, P less than 0.025) and in patients with colon polyp (P less than 0.005). Primary bile acids in patients with colon cancer significantly decreased under ward conditions after admission (P less than 0.05). Total bile acids in patients with colon cancer decreased after admission though there was no significant difference. It is of considerable interest that the fecal bile acid composition of colon cancer patients was different from that of colon polyp and peptic ulcer patients. Fecal bile acids may be involved in the pathogenesis of colon cancer.

Adenoma↗
PubMed1990

Nonobstructing colonic dilatation and colon perforations following renal transplantation.

Nonobstructing colonic dilatation has not been commonly reported following renal transplantation, and colon perforations carry a high morbidity and mortality in this population. During a 7-year period, nonobstructing colonic dilatation developed in 13 adults 1 to 13 days after renal transplantation. Twelve (92%) of the 13 had poorly functioning allografts. Five (83%) of the 6 with and 2 (29%) of the 7 without colonoscopy had resolution of nonobstructing colonic dilatation. Of the seven right-sided colon perforations during this period, six were associated with nonobstructing colonic dilatation. An additional 4 patients had diverticular perforations in the left colon. Of a total of 11 patients with colon perforation, 7 had surgery within 24 hours of the perforation and 6 (86%) of these survived. Only 1 (25%) of the 4 having surgery more than 24 hours later survived. Six of the survivors retained functioning allografts. Nonobstructing colonic dilatation seems to be a potential complication of poor graft function after renal transplantation, and colonoscopy is effective in its treatment. In patients with colon perforations, early surgery and reduced immunosuppression are essential in decreasing mortality.

Adult↗
PubMed2002

Primary repair for penetrating colon injuries.

BACKGROUND: Primary repair of penetrating colon injuries is an appealing management option, however uncertainty about its safety persists. OBJECTIVES: The objective of this review was to compare the morbidity and mortality of primary repair to fecal diversion in the management of penetrating colon injuries using a meta-analysis of randomized controlled trials. SEARCH STRATEGY: We searched MEDLINE (1966 to November 2001), the Cochrane Controlled Trials Register, and EMBASE using the terms colon, penetrating, injury, colostomy, prospective, and randomized. SELECTION CRITERIA: Studies were included if they were randomized controlled trials comparing the outcomes of primary repair versus fecal diversion in the management of penetrating colon injuries. Five studies were included. DATA COLLECTION AND ANALYSIS: Reviewers performed data extraction independently. Outcomes evaluated from each trial included mortality, total complications, infectious complications, intra-abdominal infections, wound complications, penetrating abdominal trauma index (PATI), and length of stay. Peto odds ratios for combined effect were calculated with a 95% confidence interval for each outcome. Heterogeneity was assessed for each outcome using a chi-squared test. MAIN RESULTS: The Penetrating Abdominal Trauma Index (PATI) of included subjects did not significantly differ between studies. Mortality was not significantly different between groups (OR 1.70, 95% CI 0.51,5.66). However, total complications (OR 0.28 95% CI 0.18,0.42), total infectious complications (OR 0.41, 95% CI 0.27, 0.63), abdominal infections including dehiscence (OR 0.59, 95% CI 0.38,0.94), abdominal infections excluding dehiscence (OR 0.52 95% CI 0.31,0.86), wound complications including dehiscence (OR 0.55, 95% CI 0.34,0.89), and wound complications excluding dehiscence (OR 0.43, 95% CI 0.25,0.76) all significantly favored primary repair. REVIEWER'S CONCLUSIONS: Meta-analysis of currently published randomized controlled trials favors primary repair over fecal diversion for penetrating colon injuries.

Colon↗
PubMed1994

The effects of bile acids on phospholipase C activity in extracts of normal human colon mucosa and primary colon tumors.

Phospholipase C (PLC) activity and its response to stimulation by bile acids was assayed in cellular extracts from 16 primary human colon tumors of various Duke's stages and paired adjacent normal mucosal samples. In the absence of bile acid, there was negligible degradation of phosphatidylinositol (PI) 1-stearoyl-2-[14C]-arachiodonoyl by tumor or normal tissue, but the addition of deoxycholic acid (DCA) or taurocholic acid (TCA) resulted in concentration-dependent and time-dependent stimulation of diacylglycerol (DAG) formation at optimal concentrations of 2 mM DCA and 4 mM TCA. Triton X-100 (0.125-1.0%) inhibited rather than enhanced the PI-degrading activity of these extracts, indicating that the stimulatory effects of DCA and TCA were not simply due to a detergent effect. Under the same assay conditions there was only a small amount of labeled monoacylglycerol or free arachidonic acid produced by extracts incubated in the absence or presence of DCA or TCA. No major differences in DAG production from PI were seen between paired samples of normal colon mucosa and primary colon tumors, in assays done in the presence of 2 mM TCA. Extracts from tumors in the distal part of the colon had higher activity than those from the proximal colon. This was also true for the extent of release of free arachidonic acid from labeled PI. Under the same conditions, labeled phosphatidylcholine or phosphatidylethanolamine did not serve as substrates for the colon mucosa or tumor extracts. Nor was there significant hydrolysis of the labeled DAG (1-stearoyl-2-14C-arachidonoylglycerol) by normal colon mucosa or tumor extracts, in the absence or presence of DCA or TCA. On the other hand, a low level of DAG lipase activity was detected in the presence of Triton X-100. These findings provide the first evidence that normal human colon mucosa and primary colon tumors contain a PI-specific PLC activity that is markedly stimulated by bile acids. Our results also suggest that bile acids may enhance colon carcinogenesis by acting on this enzyme system, thereby influencing signal transduction pathways in the target cells.

Aged↗
PubMed1986

Effect of dietary components on the pathobiology of colonic epithelium: possible relationship with colon tumorigenesis.

The concept that diet plays an important role in the initiation and/or development of various types of tumors in man and experimental animals is well documented. The etiology of colon cancer is complex and multifactorial in nature, and there is little information on the dietary components that may act as initiators during colon tumorigenesis. We have evaluated various dietary heterocyclic mutagenic amines present in a typical "Western" diet for their nuclear damaging effect (presumably a genotoxic response) on the colonic epithelium of C57BL/6J mice in vivo. Among the mutagenic amines studied 2-amino-3,4-dimethylimidazo(4,5-f)quinoline and 2-amino-3-methylimidazo(4,5-f)quinoline were very potent inducers of nuclear aberrations. These observations provide us with clues that our daily diet may contain colon-specific genotoxic components. Promotional effects of dietary fat and/or bile acids on colon tumorigenesis have been well studied. Dietary levels of calcium (0.1, 0.5 or 1.0% by weight) appear to modify the toxicity of orally administered fat or cholic acid (assessed by quantifying cell proliferation). The colons of animals consuming 0.1% or 0.5% calcium diet were more susceptible to the toxicity, whereas the colons of those consuming a 1.0% calcium diet appeared more like control colons. These studies demonstrate a profound effect of dietary constituents on the pathobiology of the colonic epithelium which may have a marked influence on the colon tumorigenesis.

Animals↗
PubMed1987

Ion transport in human cecum, transverse colon, and sigmoid colon in vitro. Baseline and response to electrical stimulation of intrinsic nerves.

In a flux chamber study of ion transport in human colon, we compared baseline rates with those measured during electrical stimulation of intrinsic nerves. In baseline studies, sodium was absorbed throughout, but maximally in transverse colon. In cecum, sodium absorption accounted for the short circuit current and chloride was not absorbed. Chloride was absorbed in transverse and sigmoid colon, however. Residual current was minimal in cecum and transverse colon, but increased in sigmoid colon. Neural stimulation caused chloride secretion in cecum, reduced chloride absorption in sigmoid colon, but caused no change in transverse colon; sodium absorption decreased in cecum. A neurotransmitter of unknown identity affects baseline short circuit current in sigmoid colon. Half of the increase in short circuit caused by neural stimulation in sigmoid colon is mediated by muscarinic receptors. The identity of the other transmitter(s) is not known. It is not substance P or histamine. The three divisions of the colon differ in relative rates of baseline ion transport and in their transport responses to intrinsic nerve stimulation.

Cecum↗
PubMed2000

The mRNA of L-type calcium channel elevated in colon cancer: protein distribution in normal and cancerous colon.

Previous reports indicate that the mRNA for the cardiac isoform of the voltage-gated L-type calcium channel (alpha(1C)) is elevated in colon cancer. The aim of these experiments was to verify that the mRNA for alpha(1C) was significantly increased in tumors of two separate populations of patients when compared to normal adjacent mucosa. The second aim was to measure the distribution of alpha(1C) using immunocytochemistry in normal human colon and in colon cancer and to determine what might regulate the channel expression. Biopsies were taken from patients with various stages of colon cancer and nearby normal mucosa were used as control. RNA was prepared and mRNA level measured by semiquantitative reverse transcriptase-polymerase chain reaction. The mRNA of the calcium channel was compared with other markers including beta-actin. The mRNA for alpha(1C) was increased significantly in colon cancers compared to nearby adjacent mucosa. Using confocal microscopy alpha(1C) was localized mainly at the apical membrane in the surface epithelium of normal human colon with less distribution on the lateral and basal membranes. The channel was localized on the lateral and basal membranes in crypt cells. Calcium channel localization appeared to be nearer nuclei in colon cancer samples, in part because of the smaller size of the cells. Likewise, cultured Caco-2 and T84 cells showed a membrane distribution. Western blotting indicated that alpha(1C) protein was increased in nonconfluent cultures of colonic carcinoma cells compared to confluent cells and immunocytochemistry confirms that there is more calcium channel protein in cells that are nonconfluent. We conclude that the increase in mRNA of alpha(1) subunit of the cardiac isoform of the L-type calcium channel may be a useful marker of colon cancer compared to other markers because the increase is large and this increase can be documented on small samples using a simple semiquantitative reverse transcriptase-polymerase chain reaction. We found that alpha(1C) protein is increased when colonic cells are nonconfluent or dividing which may account for the increase in cancer.

Blotting, Western↗
PubMed2006

Minimal-preparation CT colon in detection of colonic cancer, the Oxford experience.

BACKGROUND: the main colonic imaging modalities, including barium enema, colonoscopy and computed tomography colonography, require bowel preparation. Performing these imaging procedures in the elderly can difficult due to immobility, incontinence and poor tolerance of bowel cleansing. Minimal preparation CT (MPCT) colon was introduced in the early 1990s in the UK. Much of the published literature on MPCT colon is limited by small patient numbers and short duration of follow-up. OBJECTIVE: the aim of this study is to review our experience with the MPCT technique involving a large consecutive cohort of patients with long follow-up. METHODS: all studies of MPCT performed in a 1-year period between July 2000 and July 2001 at our institution were reviewed retrospectively. MPCT reports were cross-referenced with the cancer registry to allow for an average period of 30 months follow-up. A definite diagnosis of cancer was only given following the appearance on the cancer registry. Those patients who had negative MPCT colon were assumed to be true negatives if no corresponding name was identified on the cancer registry. In the event of data mismatch, patient notes were reviewed to ascertain a diagnosis. RESULTS: 391 MPCT examinations were performed during the period of the study (209 males, median age 82: age range 56-91 years). Thirty-four patients who had MPCT colon during the study period appeared on the cancer registry. A further three patients with disseminated colorectal malignancy identified on MPCT colon died without histological confirmation (tumour prevalence = 9.5%). Thirty-two of the registry confirmed 34 cases were detected on MPCT colon, giving a sensitivity of 0.94 (95% confidence interval 0.86-1.00). Including the three cases without histological confirmation gives a slightly higher sensitivity of 0.95. There were seven patients with definitely abnormal MPCT colons, who did not appear on the registry, resulting in specificity for definite abnormality of 0.98 (confidence interval 0.97-1.0). However, three of these seven are those who died of disseminated colorectal malignancy as above, raising the specificity to 0.99. Fourteen cases (3.5%) of extra-colonic malignancies were observed in this study. CONCLUSION: even with the longer follow-up of this large cohort of patients the sensitivity and specificity in our study for the diagnosis of colorectal cancer with MPCT remains comparable with that of other studies and this technique competes well with other common colonic imaging modalities.

Aged↗
PubMed1991

Role of the transitional mucosa of the colon in differentiating primary adenocarcinoma from carcinomas metastatic to the colon. An immunohistochemical study.

Differentiation between primary colonic adenocarcinoma arising in flat mucosa and carcinoma metastatic to the colon is often difficult. Examination of the mucosa adjacent to the tumor, the so-called transitional mucosa (TM), may be helpful. The morphologic, ultrastructural, and histochemical characteristics of the TM have been reported previously in detail. In this study the morphologic and immunohistochemical characteristics of the TM have been compared in 18 cases of primary colonic adenocarcinoma and 13 cases of metastasis to the colon. Five immunophenotypic markers were used: carcinoembryonic antigen (CEA), Lewis (x) and (y) blood group antigens, ras oncogene p21, and tumor-associated glycoprotein (TAG-72). Neoplastic transformation of colonic epithelium is associated with altered expression of these antigens. The morphologic and immunohistochemical profile of the TM was similar in both primary colonic adenocarcinomas and metastases to the colon. In some cases the TM adjacent to colonic metastases stained with one or more antibodies while the metastatic tumor was negative. Therefore, in cases where differentiation between primary colonic adenocarcinoma arising in flat mucosa and metastasis is difficult, the use of these reagents, particularly CEA, TAG-72, or ras oncogene p21, may be helpful. The similar immunohistochemical staining pattern of the TM in both primary and metastatic colon lesions supports a reactive, non-neoplastic origin of the TM. Furthermore, expression of these antigens is not limited to neoplastic epithelial cells.

Adenocarcinoma↗
PubMed2002

Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor.

BACKGROUND AND AIMS: Galectins are beta-galactoside binding proteins. This ability may have a bearing on cell adhesion and migration/proliferation in human colon cancer cells. In addition to galectins-1 and -3 studied to date, other members of this family not investigated in detail may contribute to modulation of tumour cell features. This evident gap has prompted us to extend galectin analysis beyond the two prototypes. The present study deals with the quantitative determination of immunohistochemical expression of galectin-8 in normal, benign, and malignant human colon tissue samples and in four human colon cancer models (HCT-15, LoVo, CoLo201, and DLD-1) maintained both in vitro as permanent cell lines and in vivo as nude mice xenografts. The role of galectin-8 (and its neutralising antibody) in cell migration was investigated in HCT-15, LoVo, CoLo201, and DLD-1 cell lines. METHODS: Immunohistochemical expression of galectin-8 and its overall ability to bind to sugar ligands (revealed glycohistochemically by means of biotinylated histochemically inert carrier bovine serum albumin with alpha- and beta-D-galactose, alpha-D-glucose, and lactose derivatives as ligands) were quantitatively determined using computer assisted microscopy. The presence of galectin-8 mRNA in the four human colon cancer cell lines was examined by reverse transcriptase-polymerase chain reaction. In vitro, cellular localisation of exogenously added galectin-8 in the culture media of these colon cancer cells was visualised by fluorescence microscopy. In vitro galectin-8 mediated effects (and the influence of its neutralising antibody) on migration levels of living HCT-15, LoVo, CoLo201, and DLD-1 cells were quantitatively determined by computer assisted phase contrast microscopy. RESULTS: A marked decrease in immunohistochemical expression of galectin-8 occurred with malignancy development in human colon tissue. Malignant colon tissue exhibited a significantly lower galectin-8 level than normal or benign tissue colon cancers; those with extensive invasion capacities (T3-4/N+/M+) harboured significantly less galectin-8 than colon cancers with localised invasion capacities (T1-2/N0/M0). The four experimental models (HCT-15, LoVo, CoLo201, and DLD-1) had more intense galectin-8 dependent staining in vitro than in vivo. Grafting the four experimental human colon cancer models onto nude mice enabled us to show that the immunohistochemical expression of galectin-8 was inversely related to tumour growth rate. In vitro, galectin-8 reduced the migration rate of only those human experimental models (HCT-15 and CoLo201) that exhibited the lowest growth rate in vivo. CONCLUSIONS: Expression of galectin-8 correlated with malignancy development, with suppressor activity, as shown by analysis of clinical samples and xenografts. In vitro, only the two models with low growth rates were sensitive to the inhibitory potential of this galectin. Future investigations in this field should involve fingerprinting of these newly detected galectins, transcending the common focus on galectins-1 and -3.

Animals↗
PubMed1990

Proliferation rate of colonic mucosa in normal subjects and patients with colonic neoplasms: a refined immunohistochemical method.

An increased colonic epithelial proliferation rate and an increase of the cryptal proliferative zone are probable markers of increased susceptibility to colonic cancer. In this study an immunohistochemical method using 5-bromo-deoxyuridine (BrdUrd) to measure the proliferation rate of colonic mucosa in vitro was used. Fresh endoscopic colonic biopsy specimens were incubated with BrdUrd and then processed for immunohistochemistry using a monoclonal antibody. Essential procedures with respect to the equal distribution of nuclei stained with BrdUrd in the biopsy specimens proved to be the cutting of the specimens before incubation and the use of a microwave oven at the beginning of incubation. The use of the procedure of the running average showed that 12 length cut crypts are sufficient to determine reliably the proliferation rate, expressed as the labelling index (LI). This was determined in the biopsy specimens of 10 subjects without organic colonic disease, eight patients with adenomatous colonic polyps, and in six patients with (recent) colonic carcinoma. Mean LI in the controls was significantly lower than in patients with colonic polyps and in those with colon cancer. It is concluded that this method is promising for screening persons at risk for colon cancer and will be of great potential in performing dietary intervention studies in these subjects.

Adolescent↗
PubMed2005

Decreased expression of cytochrome P450 protein in non-malignant colonic tissue of patients with colonic adenoma.

BACKGROUND: Cytochrome P450 (CYP) enzymes in epithelial cells lining the alimentary tract play an important role in both the elimination and activation of (pro-)carcinogens. To estimate the role of cytochrome P450 in carcinogenesis of the colon, expression patterns and protein levels of four representative CYPs (CYP2C, CYP2E1, CYP3A4 and CYP3A5) were determined in colon mucosa of normal and adenomatous colonic tissue of patients with adenomas and disease-free controls. METHODS: Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 in colon mucosa of normal and adenomatous colonic tissue of patients with adenoma and disease-free controls was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot. RESULTS: With the exception of CYP3A5, expression of CYP mRNA was similar among groups and tissues (e.g. normal colon mucosa and adenoma). CYP3A5 mRNA expression was significantly higher in adenoma in comparison to normal tissue of patients with adenoma (approximately 48%). When comparing protein concentrations of CYPs measured in adenomas with neighboring normal colonic mucosa no differences were found. However, in normal tissue of patients with adenomas, protein levels of CYP2C8, CYP3A4 and CYP3A5, but not that of CYP2E1, were significantly lower than in biopsies obtained from disease-free controls. Specifically, in normal colonic mucosa of patients protein concentrations of CYP2C8, CYP3A4, and CYP3A5 were approximately 86%, approximately 69%, and approximately 54%, respectively, lower than in disease-free controls. CONCLUSION: In conclusion, among other factors, the altered protein levels of certain CYPs (e.g. CYP2C8, CYP3A4 and CYP3A5) in colon mucosa might contribute to the development of neoplasia in the colon.

Adenoma↗