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At least 433 records · Page 24Linked to original sources
PubMed1984

Characterization of plasminogen activators from normal human breast and colon and from breast and colon carcinomas.

Triton X-100 and NaSCN extracts of 18 normal breast and colon tissues and of 20 breast and colon carcinomas were fractionated by SDS-PAGE and plasminogen activators (PA) revealed by a zymographic method. Four different lysis bands, corresponding to MWs of 54,000, 68,000, 95,000 and 110,000 were observed. Using immunoadsorption with specific antisera against urokinase (UK) and tissue PA (t-PA), we found that all normal tissue extracts contained free t-PA (68 kd). Some of these revealed, in addition, a complex (110 kd) of t-PA with a 40-kd component. The latter presumably represents the fast-acting specific inhibitor of t-PA and UK. Most carcinoma extracts contained, in addition to the two t-PA-related lysis bands, the UK-related 54 kd PA, and some a 95 kd complex of UK with the 40 kd component. For each extractant, mean total fibrinolytic activity of normal and tumor tissue was comparable when measured on conventional fibrin plates, but breast and colon carcinomas contained higher concentrations of UK-related PA. PA activity was higher in normal and carcinoma NaSCN extracts than in the corresponding Triton X-100 extracts. In general, Triton X-100 but not NaSCN extracts of malignant tissue contained a high concentration of fibrinolytic inhibitors. Mixing experiments revealed that the inhibitory activity was mainly directed against UK. It was abolished by acidification of the carcinoma extracts. The anti-UK inhibitory activity was absent in extracts of normal breast or colon and appears to be different from the 40 kd fast-acting PA inhibitor. These studies show that malignant transformation of breast and colon is accompanied by important changes of the production of a UK-related PA and of an inhibitory activity directed against UK.

Breast↗
PubMed1994

Expression of multiple isoforms of protein kinase C in normal human colon mucosa and colon tumors and decreased levels of protein kinase C beta and eta mRNAs in the tumors.

Previous studies have suggested that protein kinase C (PKC) may play an important role in colon carcinogenesis and that human colon tumors have less total PKC enzyme activity than normal tissue. Because PKC is a multigene family that encodes for at least 11 distinct isoforms, in the study reported here we analyzed the expression of six of these isoforms at the mRNA level by northern blot hybridization in 22 pairs of primary colon tumors (of various stages), and adjacent normal mucosa samples. We found that the normal mucosa samples expressed the mRNAs of the following isoforms of PKC, in decreasing order of abundance: PKC delta > PKC eta > PKC alpha > PKC beta > PKC epsilon. There was no consistent difference in the levels of PKC alpha, PKC delta, and PKC epsilon mRNAs between the normal mucosa and the tumor samples. PKC gamma was expressed at a very low level in two of the colon tumors but could not be detected in the remaining tumors or any of the normal mucosa samples. The levels of both PKC beta and PKC eta mRNAs were significantly lower in the tumor samples than in the normal mucosa samples, and this was true of adenomas as well as Dukes' stage A, B, and C adenocarcinomas. Furthermore, the decrease in PKC eta mRNA appeared to be greater in the more poorly differentiated carcinomas. This finding is of interest because PKC eta is normally expressed in the more differentiated cells of epithelial tissues. The decreased levels of both PKC beta and PKC eta mRNAs occurred early in the multistage process of colon carcinogenesis, as it was also seen in adenomas. The functional significance of these changes remains to be determined.

Adenoma↗
PubMed1985

[Current aspects of the surgical treatment of colonic ileus caused by stenosing colonic carcinoma].

Formerly it was considered dangerous to undertake resection in the presence of colonic obstruction. This idea has been abandoned. Immediate right hemicolectomy is the accepted treatment for obstructed lesions of the right colon. For obstruction of the left colon proximal colostomy or caecostomy are being challenged by immediate resection as a Hartmann operation with iliac colostomy or finished with a colo-colonic or colo-rectal anastomosis. A subtotal colectomy with ileo-sigmoid or ileo-rectal anastomosis is a further method with encouraging experiences. From 1979-1984 a series of 33 patients with obstruction from a carcinoma of the left colon underwent emergency abdominal colectomy with primary ileosigmoidostomy or ileorectostomy without diversion. The mortality and morbidity was favourable compared with those reported in series of similar cases treated by stages procedures or primary resection. Several advantages of this method are explained and further encouraging experiences from other centers are reported.

Adenocarcinoma↗
PubMed1994

Characterization of distal colonic motility in early postoperative period and effect of colonic anastomosis.

Under standardized conditions, the manometric motility of the distal colon following rectosigmoid anastomosis (N = 11, median age 70 years, range 47-80), was compared to that following laparotomies not involving colonic anastomosis (N = 9, 56 years, 32-65). Microtransducer probes were inserted peroperatively and colonic activity recorded continuously (median 96 hr, range 48-109 anastomotic and 75 hr, range 46-107 control group) employing an ambulatory system. Quantitative indices of motility were calculated with an automated analysis program. Total postoperative analgesic doses and duration of surgery were similar in both groups. The first return in the anastomotic group of isolated waveforms [median 1.8 hr, interquartile range (IQR) 1-3] and propagated waves (92 hr, 79-100), was comparable to the control group (4 hr, 1.8-7, and 73 hr, 72-101, respectively). Motor complexes, characterized by bursts of regular contractile activity at 3-5 cpm, returned faster in the control group (3 hr, 2-24 vs 24 hr, 19-30, P < 0.05). Motility index was significantly depressed during the first 72 hr following surgery in the anastomotic group compared to controls (P < 0.001). Flatus was passed at a median of 72 hr (IQR 45-79) in the control and 94 hr (81-105) in the anastomotic group (P = 0.05). The presence of a left-sided colonic anastomosis has a major inhibitory effect on distal colonic motility, compared to nonanastomotic surgery of similar severity, in the early postoperative period.

Aged↗
PubMed1989

The place of intraoperative antegrade colonic irrigation in emergency left-sided colonic surgery.

The healing of colonic or colorectal anastomoses depends, at least partially, on the volume of fecal residue. Intraoperative antegrade colonic irrigation enables the surgeon to prepare the colon adequately at the time of surgery and to perform safely an immediate resection and primary anastomosis in obstructive lesions of the left colon. Its indications have been extended to other left-sided colonic emergencies, especially perforation and hemorrhage. The technique is described in this study and its value is assessed in the light of available experimental and clinical evidence.

Anastomosis, Surgical↗
PubMed1982

The influence of androgens, anti-androgens, and castration on cell proliferation in the jejunal and colonic crypt epithelia, and in dimethylhydrazine-induced adenocarcinoma of rat colon.

Androgenic hormones have previously been shown to promote cell proliferation in the small intestine of rat and androgen receptors have been demonstrated in carcinomata of the large intestine of rat. In this study the influence of testosterone and of castration on epithelial cell proliferation in the small intestine, the large intestine and in dimethylhydrazine-induced colonic tumours is compared. Cell proliferation in the small intestine and in colonic tumours was accelerated by testosterone treatment, and cell proliferation in colonic tumours, but not in the small intestine, was retarded following castration. Cell proliferation in colonic tumours was also inhibited by the anti-androgenic drug, Flutamide. Testosterone and castration each failed to influence cell proliferation in the colonic crypt epithelium of both normal and carcinogen-treated animals.

Adenocarcinoma↗
PubMed1993

Characterization of the inflammatory cell populations in normal colon and colonic carcinomas.

UNLABELLED: Little is known about the nature of the mucosa-associated immune system within the normal colon, or about the immune response to colon carcinoma. In this study inflammatory cells (ICs) in 14 normal colons and 14 carcinomas were characterized. Overall inflammation, lymphocytes, plasma cells, neutrophils, and eosinophils were graded in routine H & E sections. Frozen sections were stained by an immunoperoxidase technique using antibodies to the T cell associated antigens CD2, CD7, CD4, CD8, and T cell receptors alpha beta and gamma delta. B cells were identified with CD20, macrophages with CD68, and Class II antigen with anti-HLA DR. Each cell type was semiquantitatively graded in 10 high power fields (HPFs) in the lumenal half (LH) or basal half (BH) of the normal mucosae, and in epithelium or stroma of the carcinomas. In normal colons, ICs were more frequent in LH than in BH. Plasma cells, lymphocytes and monocytes predominated. Subtyping of lymphocytes showed that CD4+ TCR alpha beta + T lymphocytes were most numerous in the lamina propria. Lymphocytes within the epithelium were CD8+ T cells. Around carcinomas the overall grade of ICs was 1+ in the majority of cases. Plasma cells, CD4+ and CD8+ cells with the TCR alpha beta receptor, and macrophages were most frequent. Lymphoid aggregates of both T and B cells were frequent. CONCLUSIONS: 1. Normal colon contains a diffuse luminally oriented population of TCR alpha beta+ CD4+ T cells, plasma cells, macrophages and class II antigen-expressing cells in the lamina propria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed2005

Experimental inflammation of the rat distal colon inhibits ion secretion in the proximal colon by affecting the enteric nervous system.

Intestinal inflammation causes hyporesponsiveness of the inflamed tissue to secretagogues but little is known about the behaviour of the areas proximal to the site of inflammation. We studied the responses of the proximal segment of the colon to carbachol, histamine, isobutylmethylxanthine (IBMX) and vasoactive intestinal peptide (VIP) in rats with trinitrobenzenesulphonic acid (TNBS)-induced, chronic inflammation of the distal colon. Macroscopic and biochemical analysis ruled out the presence of inflammation in the proximal colon. When mounted in Ussing chambers under voltage-clamp conditions, basal transport and conductance were not affected. However, the maximum response in the concentration/response curves (short-circuit current) for carbachol and histamine was reduced in TNBS-treated rats, without changes in the EC(50). This effect corresponded to reduced chloride secretion, as demonstrated by ion substitution experiments. The responses to IBMX and VIP were virtually unaffected. The inhibitory effect was abolished by pretreatment with the neural blockers tetrodotoxin and lidocaine but not indomethacin, suggesting that the enteric nervous system is responsible for the inhibition. In conclusion, chronic distal inflammation of the distal colon results in inhibition of calcium-dependent secretion in the proximal colon via a reduction of the contribution of the enteric nervous system.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Nuclear and cytosolic estrogen receptors in human colon carcinoma and in surrounding noncancerous colonic tissue.

The measurement of estrogen as well as progesterone receptors has been applied clinically to predict the effectiveness of endocrine therapy in patients with breast or endometrial carcinoma. The presence of cytosolic estrogen receptors in human colorectal carcinomas has been reported by several different groups during the past 10 yr. The aim of our current study was to evaluate the estrogen binding activity in the nuclear and cytosolic fractions of these carcinomas, as well as in surrounding noncancerous colonic tissue. Twenty-six patients, operated on for colorectal carcinoma, were studied: 16 were men and 10 were postmenopausal women, mean age 61 yr (range 43-78 yr). In neoplastic tissue, cytosolic estradiol receptors were detected in 42.3% of the patients (women 40%, men 43.7%). The values for cytosolic estrogen receptor ranged from 118 to 1214 fmol/g wet colon. Nuclear estrogen receptors were detectable in 46.1% of the patients (women 40%, men 50%) and their values displayed a range from 3.4 to 2554 fmol/g wet colon. In 30.7% of the patients, both nuclear and cytosolic receptors were demonstrated. In 38.4% of the patients, receptors were found in neither cytosol nor nuclei. Receptor positivity in men was most frequently associated with tumors removed from the rectum, and those with Dukes' classification of C1. In the surrounding noncancerous tissue cytosolic estrogen receptors were also detected (range 133-1105 fmol/g wet colon) and were present in 34.6% of the patients (women 30%, men 37.5%). Nuclear estrogen receptors (range 225-1105 fmol/g wet colon) were detected in 57.6% of the patients (women 40%, men 68.7%). In 23% of the patients, both nuclear and cytosolic receptors were demonstrated. In 30.7% of the patients, no receptors were found in either cytosol or nucleus. Therefore, the presence of cytosolic or nuclear estrogen receptors, or both, in 61.6% of human colorectal cancer specimens emphasizes the need to evaluate both forms of these receptors for studies of potential hormone dependence in these tumors.

Adenocarcinoma↗
PubMed1988

Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer.

Rectal biopsies and fecal collections were obtained from a consecutive series of 34 outpatients prior to colonoscopy at a gastroenterology clinic. Subsequently, 14 were found to have no colonic pathology, 13 had adenomatous polyps, (3 of those had a previous history of colon cancer) and 7 were diagnosed with colon cancer. In confirmation of earlier studies the tritiated thymidine labelling index was higher in patients with tumors than in those without pathology (7.9% vs. 5.8% with P = 0.06). The patients with colonic tumors also had significantly higher levels of deoxycholic acid (P = 0.01) and lithocholic acid (P = 0.005) in the aqueous extract of their feces. This study shows that these biochemical measures may indicate colon cancer risk.

Bile Acids and Salts↗
PubMed2000

Induction of angiogenesis by hyperplastic colonic mucosa adjacent to colon cancer.

We determined whether hyperplastic mucosa adjacent to colon cancer contributes to neoplastic angiogenesis. Surgical specimens of human colon cancer (40 Dukes' stage B and 34 Dukes' stage C) were analyzed by immunohistochemistry for expression of proliferative and angiogenic molecules. The mucosa adjacent to Dukes' stage C tumors (but not Dukes' stage B tumors) had a higher Ki-67 labeling index and a higher expression of epidermal growth factor receptor and transforming growth factor-alpha than distant mucosa. The expression levels of vascular endothelial growth factor, basic fibroblast growth factor, interleukin-8, and the vascular density in the adjacent mucosa were similar to those in the tumor lesions and significantly higher than those in the distant mucosa. The expression of interferon-beta inversely correlated with the level of pro-angiogenic molecules and the vascular density. The injection of metastatic human colon cancer cells and murine colon cancer cells into the cecal wall of mice induced hyperplastic changes in the adjacent mucosa which expressed higher levels of epidermal growth factor receptor, basic fibroblast growth factor, and vascular endothelial growth factor, and lower levels of interferon-beta than did the control mucosa, which directly correlated with the degree of hyperplasia. These data suggest that metastatic human colon cancer cells can induce hyperplasia in the adjacent mucosa, which in turn produces angiogenic molecules that contribute to neoplastic angiogenesis.

Animals↗
PubMed2003

Expression of Musashi-1 in human normal colon crypt cells: a possible stem cell marker of human colon epithelium.

Musashi has been identified as an RNA-binding protein thought to be involved in asymmetric divisions during Drosophila neural development. To analyze expression patterns of mammalian Musashi homolog Musashi-1 in human normal colon crypt, 155 colon crypts separated from biopsy specimens of normal colonic mucosa were evaluated. Specimens were fixed, microdissected to isolate a few crypts, immunostained with anti-Musashi-1 antibody (14H1), and examined under confocal laser scan microscopy. The number of Musashi-1-positive cells in each crypt was 19.0 +/- 7.53 (mean +/- SD). Most Musashi-1 positive cells were located at the crypt base, between cell positions 1 and 10. Distribution of Musashi-1-positive cells corresponded with that of stem cells, as outlined in previous reports, implying that Musashi-1 is a key control element of asymmetrical division within the colon crypt. This is the first report outlining expression of Musashi-1 in human colon crypt cells.

Aged↗
PubMed1996

Modulation of colonic aberrant crypt foci and proliferative indexes in colon and prostate glands of rats by vitamin E.

The effect of a high vitamin E diet on the early stages of colon carcinogenesis and on the proliferative indexes in the colon and in the prostate glands was investigated in rats. F344 male rats were injected with azoxymethane (AOM, 15 mg/kg sc). One week later, animals were randomly allocated into two dietary groups (n = 8 rats/group): normal vitamin E (50 IU/kg diet) and high vitamin E (200 IU/kg diet). The basal diet was the AIN-76 diet modified to contain high corn oil (23% wt/wt). After eight weeks of feeding, concentrations of vitamin E in plasma, liver, and prostate were analyzed. Enumeration of aberrant crypt foci (ACF) in colons and proliferative indexes of colons and prostate glands were determined. The total number of ACF and the average number of aberrant crypts (AC) per focus were similar in both dietary groups. ACF were classified as small (1-3 crypts/focus), medium (4-6 crypts/focus), or large (> or = 7 crypts/focus). Only the ACF in the small category showed a significant treatment effect, with values being lower in the high vitamin E group than in the control group (p < or = 0.05). No significant difference was observed in colonic proliferative indexes assessed by enumeration of metaphase cells, S phase cells, or cells exhibiting proliferative cell nuclear antigen (PCNA). The PCNA labeling index in the prostate glands and the activity of prostatic acid phosphatase in plasma were higher in high vitamin E-fed rats (p < or = 0.05) than in control animals. The present study demonstrates that additional vitamin E does not inhibit the induction and growth of ACF; also it enhances the proliferative status of the prostate glands.

Acid Phosphatase↗
PubMed1999

Overexpression of protein kinase C betaII induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis.

Protein kinase C betaII (PKC betaII) has been implicated in proliferation of the intestinal epithelium. To investigate PKC betaII function in vivo, we generated transgenic mice that overexpress PKC betaII in the intestinal epithelium. Transgenic PKC betaII mice exhibit hyperproliferation of the colonic epithelium and an increased susceptibility to azoxymethane-induced aberrant crypt foci, preneoplastic lesions in the colon. Furthermore, transgenic PKC betaII mice exhibit elevated colonic beta-catenin levels and decreased glycogen synthase kinase 3beta activity, indicating that PKC betaII stimulates the Wnt/adenomatous polyposis coli (APC)/beta-catenin proliferative signaling pathway in vivo. These data demonstrate a direct role for PKC betaII in colonic epithelial cell proliferation and colon carcinogenesis, possibly through activation of the APC/beta-catenin signaling pathway.

Animals↗
PubMed2003

Mucin-depleted foci (MDF) in the colon of rats treated with azoxymethane (AOM) are useful biomarkers for colon carcinogenesis.

Crypt foci with absent or scant mucous production (mucin-depleted foci, MDF) were recently described by our group in the colon of azoxymethane (AOM)-treated rats. Since MDF are dysplastic and easy to quantify, we think that MDF are pre-neoplastic lesions that could be used as biomarkers for carcinogenesis. To test this hypothesis, we studied MDF in azoxymethane (AOM)-initiated rats treated with cholic acid (CHA), a promoter of colon carcinogenesis or with piroxicam (PXC), a colon cancer-inhibiting drug. Aberrant crypt foci (ACF) were determined as well. F344 male rats were treated with AOM (15 mg/kg x 2, s.c.) and then divided into: controls, which were fed AIN76 diet; CHA group, which was fed AIN76 diet containing CHA 0.5% w/w; PXC group, which was fed AIN76 diet containing PXC 0.02% w/w. Ten weeks after the first dose of AOM, the total number of MDF was significantly increased in rats treated with CHA (P<0.05) and drastically reduced (P<0.01) in rats treated with PXC (MDF/colon were 6.10 +/- 1.26, 10.59 +/- 1.96 and 1.31 +/- 0.21 in controls, CHA and PXC groups, respectively, means +/- SE). The multiplicity of MDF was also increased in CHA-treated rats. On the contrary, ACF multiplicity was significantly decreased by CHA. In PXC-treated rats there were fewer ACF with lower multiplicity. The effect of PXC was also investigated 15 weeks after the first AOM dose and the results showed that the total number of MDF in the PXC group was significantly lower than in controls. The number of 'large' MDF, formed by 12 or more crypts, was also reduced (P<0.01) by PXC ('large' MDF were 1.7 +/- 0.5 and 0.4 +/- 0.2 in control and PXC groups, respectively). Since CHA promotes and PXC reduces colon cancer, MDF are correlated with carcinogenesis and can be proposed as endpoints to study the modulation of colon carcinogenesis in short-term experiments.

Animals↗
PubMed1991

A follow-up study of colonic epithelial proliferation as a biomarker ina Native-American family with hereditary nonpolyposis colon cancer.

A 7-year follow-up study of colonic mucosa proliferation markers was conducted on members of a Native-American family with hereditary nonpolyposis colon cancer. Reproducibility of a tritiated thymidine autoradiography assay for labeling indexes during this 7-year biologically significant time frame was established. A good correlation between tritiated thymidine and a newer technique, bromodeoxyuridine immunoperoxidase staining, was seen. No confounding effect could be attributed to standard colon preparation. On average, both baseline and follow-up values for epithelial proliferation were within the accepted normal range. The presence of essentially normal labeling indexes among colon cancer patients and their high-risk offspring suggests the possibility of the significant effect of dietary factors in reducing proliferation. Such factors may account for the low risk of colon cancer that characterizes the Native-American population in the American Southwest.

Adult↗
PubMed2006

Chemopreventive potential of diallylsulfide, lycopene and theaflavin during chemically induced colon carcinogenesis in rat colon through modulation of cyclooxygenase-2 and inducible nitric oxide synthase pathways.

Chemoprevention of colorectal cancer has become essential in the modern industrialized world as cancer of the large bowel has become one of the major causes of cancer mortality, second only to lung cancer. Colon cancer integrates lifestyle factors and multistep genetic alterations, and without preventive intervention, a substantial part of the population is likely to develop colorectal cancer at some point during their lives. Diet and nutrition clearly play a role in the etiology of colon cancer. Inhibitory activity of aqueous suspensions of garlic, tomato and black tea was tested on azoxymethane-induced colon carcinogenesis in Sprague-Dawley rats during earlier studies. In the present study, the protective activity of diallylsulfide and lycopene and theaflavin, important antioxidative ingredients of garlic, tomato and black tea, respectively, was assessed during colon carcinogenesis. The effect was observed on aberrant crypt foci, the preneoplastic lesion. As inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activities is correlated with the prevention of colon cancer, the study continues with the determination of the change in the expression of these proteins. Following treatment, significant reduction in the incidences of aberrant crypt foci (by 43.65% in diallylsulfide, 57.39% in lycopene and 66.08% in theaflavin group) was observed, which was in accordance with the reduced expression of cyclooxygenase-2 and inducible nitric oxide synthase. The effect of the intact source was found to be more pronounced than their components used separately.

Allyl Compounds↗
PubMed1970

The transport of colonic contents in the irritable colon syndrome.

The mean distance of travel and hourly incidence of propulsive and retropulsive movements of colonic contents have been assessed by means of time-lapse cinefluorography and compared in 98 patients with the irritable colon syndrome and in 90 control subjects.Net propulsion in patients with the irritable colon syndrome was less than in the controls at rest, similar to the controls after feeding, and greater than in the controls after an injection of carbachol. In both clinical groups, food and carbachol increased the incidence of propulsive and retropulsive movements but did not alter the average distance over which they travelled.The figures suggest that at least two-thirds of all net propulsion of colonic contents in the irritable colon syndrome takes place under circumstances not reproduced in the present study.

Barium Sulfate↗