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At least 811 records · Page 45Linked to original sources
PubMed1994

Therapeutic effect of a vaccinia colon oncolysate prepared with interleukin-2-gene encoded vaccinia virus studied in a syngeneic CC-36 murine colon hepatic metastasis model.

Vaccinia CC-36 murine colon oncolysate (VCO) prepared with interleukin-2-gene encoded recombinant vaccinia virus (IL-2VCO) was used in the treatment of a syngeneic murine colon adenocarcinoma (CC-36) hepatic metastasis to test the beneficial effect of the interleukin-2-gene encoded vaccinia virus over a control recombinant vaccinia virus in producing a vaccinia oncolysate tumor cell vaccine. Results suggest that the IL-2VCO treatment significantly reduced the hepatic tumor burden in comparison with the controls that received either IL-2-gene-encoded recombinant vaccinia virus or a plain recombinant vaccinia virus or vaccinia oncolysate prepared with the plain recombinant virus. The survival of mice treated with IL-2VCO was also improved in comparison with mice treated with other preparations. The induction of a cytolytic T lymphocyte response was examined to elucidate the mechanism of the induction of antitumor responses in IL-2VCO-treated mice. Fresh peripheral blood lymphocytes (PBL) isolated from IL-2VCO-treated mice showed a higher cytolytic activity against CC-36 tumor cell target when compared to PBL from the mice of other treatment groups, suggesting that the IL-2VCO induced an antitumor cytolytic T lymphocyte response. These results suggest that a vaccinia oncolysate, prepared with recombinant vaccinia virus encoding an immunomodulating cytokine gene will enhance antitumor responses in the host.

Adenocarcinoma↗
PubMed1989

Single chloride channels in colon mucosa and isolated colonic enterocytes of the rat.

Chloride channels from rat colonic enterocytes were studied using the patch-clamp technique. After removal of mucus, inside-out patches were excised from the apical membrane of intact epithelium located at the luminal surface. They contained spontaneously switching Cl- channels with a conductance of 35-40 pS. The channels were blocked reversibly by anthracene-9-carboxylic acid (1mM). In excised patches from single enterocytes, isolated by calcium removal, the Cl- channels were studied in more detail. The I-V relation was linear between +/- 80 mV. The selectivity was I- greater than Br- greater than Cl- = NO3- greater than F- = HCO3-. Thirty pS Cl- channels were also found on the basolateral membrane of crypts isolated by brief calcium removal. The I-V curve of these Cl- channels was also linear. The results provide direct evidence for the existence of Cl- channels in the apical membrane of surface cells in colonic mucosa. The properties of these channels are similar to those previously observed when incorporating membrane vesicles into planar lipid bilayers. Both results support the validity of the theoretical models describing intestinal secretion.

Animals↗
PubMed2000

Congenital short colon with imperforate anus (pouch colon). Report of a case.

We report a case of a persistent cloaca and pseudoexstrophy associated with congenital pouch colon in a native-born American female child. This unusual anomaly occurs in two clinical settings. It has been reported in India as an isolated anomaly occurring primarily in males. Pouch colon also occurs in female patients with pseudoexstrophy or closed cloacal exstrophy. The typical anatomic features of this anomaly are discussed.

Abnormalities, Multiple↗
PubMed2002

Therapeutic effect of colon tumor cells expressing FLT-3 ligand plus systemic IL-2 in mice with syngeneic colon cancer.

Flt-3 ligand (FL) and interleukin-2 (IL-2) have been shown to enhance individually the antitumor response against several cancers. Therefore, treatment with a combination of FL gene-transduced tumor cell plus soluble IL-2 was studied in a murine colon adenocarcinoma model. The human full-length FL cDNA was cloned from FL-expressing cell line AML-193 by reverse transcription-polymerase chain reaction (RT-PCR). CC-36 colon tumor cells were transduced with the FL gene (CC-36-FL). In vivo and in vitro secretion of FL from CC-36-FL was confirmed by enzyme-linked immunosorbent assay (ELISA). Moreover, enhancement of dendritic cells in vivo was evaluated in mice transplanted with CC-36-FL. The therapeutic efficacy of CC-36-FL plus systemic IL-2 was tested using six groups ( n=12-13/group) of 10-week-old male Balb/c mice transplanted with 10(3) CC-36 tumor cells. Mice were treated subcutaneously with 10(6) irradiated CC-36 cells, 10(6) irradiated CC-36 cells+IL-2, 10(6) irradiated CC-36-FL cells, 10(6) irradiated CC-36-FL+IL-2, or IL-2 alone on days 4, 10 and 18 after tumor transplantation. A group of mice with no treatment served as a control. All of the treatment injections were performed subcutaneously in the left flank. IL-2 (2 x 50,000 IU) was administered intraperitoneally in 3-day cycles (days 4-6, 10-12, 17-19). Tumor growth was determined by measuring the tumor diameter. A survival experiment was performed with the same treatments, and mice were observed for survival for 100 days. The group of mice treated with the combination of CC-36-FL+IL-2 showed a significant reduction in tumor burden when compared to the no treatment group and the other control treatment groups ( P<0.05). Similarly, the group of mice treated with CC-36-FL+IL-2 displayed significant survival when compared with the other control groups (P<0.05). In Balb/c mice, the CC-36-FL plus systemic IL-2 therapy significantly decreased the tumor burden and increased the survival rate when compared to mice treated by control therapies or mice that received no treatment.

Animals↗
PubMed1982

Atherosclerosis and polyps of the colon. Quantification of precursors of coronary heart disease and colon cancer.

The prevalence of adenomatous and hyperplastic polyps of the colon and the degree of involvement of the aorta by atherosclerotic lesions were evaluated in 842 autopsies from New Orleans. A positive statistical association between the two variables was found in white males under 75 years of age. In black males a positive correlation between atherosclerotic lesions and adenomatous (but not hyperplastic) polyps was found. The most extensive involvement of the aorta by atherosclerosis was found in patients in whom adenomatous and hyperplastic polyps coincided. The possibilities that dietary factors may account for these findings and its relevance in relation to colon cancer and coronary heart disease are discussed.

Adult↗
PubMed1994

Recto-vagino-vestibuloplasty using a vagino-colonic flap with double colonic implantation for rectocloacal fistula.

This technique was devised to obtain a good cosmetic appearance of the perineum and a functional neovagina, without any need for a dilator, by using a vaginocolonic flap marsupialized to the perineum and by creating a vestibule with noncornifying squamous epithelium. The technique was used to treat a 2 year old girl who had a single small orifice in the upper part of a featureless perineum, with a high-confluence rectocloacal fistula between a short urethra and double vagina, which was separated by a septum. A long inverted U-shaped flap at the posterior wall of the vagina was reversed to become the anterior wall of the distal vagina. The urogenital sinus (UGS) was preserved to serve as the urethra. The colon distal to the colostomy was divided into two loops; a segment of the distal loop was opened and trimmed to form a flap, and served as the posterior wall of the distal vagina. The proximal segment was pulled down to become the rectum. To construct the vestibule, a vertical midline incision was made from the fused labia minora to the perineum, cutting back the UGS. The anterior wall of the vagina, which was pulled through just behind the UGS, was divided vertically and sutured around the opened UGS and the suitably prepared labia minora. The posterior wall, which consisted of the colonic flap, was sutured to the incised perineal skin, creating a posterior commissure. At present, 2 1/2 years after the repair, the patient is dry between completely continent urinations and has little vaginal discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1987

Changes in phase I and phase II biotransformation with age in male Fischer 344 rat colon: relationship to colon carcinogenesis.

Using male Fischer 344 rats classified as young (2-4 months), middle aged (12-14 months), and old (22-25 months), the activities of several Phase I and Phase II biotransformation pathways in the large intestine were investigated, including benzo[a]pyrene hydroxylase (BPOH), alcohol dehydrogenase (ADH), glutathione S-transferase (GST), glutathione peroxidase (GSH-PX), beta-glucuronidase (BG), and microsomal and nuclear glucuronyltransferase (UDPGT). Levels of oxidized (GSSG) and reduced (GSH) glutathione and uridine 5'-diphosphoglucuronic acid (UDPGA) were also measured. BPOH increased 33% in old rats, while ADH and BG activity remained unchanged with age. Nuclear UDPGT remained unchanged with age, whereas form I of GSH-PX declined slightly in old rats. GST, microsomal UDPGT, and form II of GSH-PX declined by 38, 37 and 44%, respectively, in old rats. The decrease in GST and microsomal UDPGT was also significant in middle aged rats. Levels of colonic GSH, GSSG and UDPGA were found to be unchanged with age. These in vitro data suggest the possibility that if reactive intermediates are generated to the same extent in old rats as in young rats, decreased detoxification mechanisms in the old rat may increase susceptibility of the colon to actions of chemical carcinogens.

Aging↗
PubMed2004

Amylose formulations for drug delivery to the colon: a comparison of two fermentation models to assess colonic targeting performance in vitro.

The purpose of this study was to develop an enzyme-based fermentation system for the in vitro assessment of colonic digestion of amylose films and coatings, and to compare its performance with a conventional fermentation model inoculated with human faecal bacteria. Amylose and ethylcellulose were mixed in different ratios and cast as isolated films, as well as spray coated onto drug-(5-aminosalicylic acid) loaded pellets. Four commercial amylase enzymes were individually screened for their ability to digest amylose cast films. The enzyme from the bacterium Bacillus licheniformis was found to be the most active against this substrate. Digestion of mixed amylose and ethylcellulose films was also observed, with the extent of digestion being proportional to the quantity of amylose present in the film. In terms of product performance, drug release from coated pellets was accelerated in the presence of the enzyme. The results with the enzyme system were comparable to those obtained from a faecal-based fermentation model, thereby suggesting that such a system has practical potential for in vitro screening of putative amylose formulations for colonic drug delivery.

Amylases↗
PubMed1981

Parasternal intrapleural colon interposition: an alternative pathway for the colon graft.

A new pathway for the placement of the interposed colon in esophagocolonoplasty is described. In a patient with a peptic stricture and a history of previous coronary artery bypass operation and multiple thoracotomies, the interposed colon was placed in the parasternal right intrapleural space successfully. This avoided a thoracotomy as well as the areas of adhesion. Technical details are described.

Colon↗
PubMed1998

Gastric duplication-colonic fistula with colonic ulceration and bleeding.

An 11-month-old girl had massive rectal bleeding. A midabdominal mass was palpated. Ultrasound scan showed a large cystic mass with diffusely echogenic contents; Tc-99M radionuclide scan confirmed a duplication. Exploratory surgery and pathology examination showed a gastric duplication with formation of a fistula into the transverse colon with a colonic ulcer and hemorrhage. This combination of findings is presented as a rare cause of lower gastrointestinal hemorrhage in infancy.

Colonic Diseases↗
PubMed2000

Chronotropic action of 5-hydroxytryptamine (5-HT) on colonic migrating motor complexes (CMMCs) in the isolated mouse colon.

The effects of 5-hydroxytryptamine (5-HT) and related drugs on colonic migrating motor complexes (CMMCs) were evaluated in isolated colons from the heterozygotes of pie-bald lethal mice. 5-HT produced a dose-related increase in the frequency of CMMCs without any change in the amplitude or duration of the CMMC contractions themselves. The 5-HT(2) agonist, alpha-methyl 5-HT, (100 nM-1 microM) increased the frequency of CMMCs whilst the 5-HT(3) agonist, 2-methyl 5-HT, did so at 10 microM. The 5-HT(4) agonist, 5-methoxy dimethyl tryptamine oxalate did not alter the frequency of CMMCs in the concentration range 1 nM-10 microM. The 5-HT(3) receptor antagonist, ondansetron, increased the interval between CMMCs in the concentration range 100 nM-1 microM, whilst the 5-HT(1) receptor antagonist, methiothepin, the 5-HT(2) receptor antagonist, cyproheptadine and the 5-HT(4) receptor antagonist, SDZ 205 557, had no significant effects on the interval between CMMCs in the concentration range 1 nM-10 microM. The effects of 5-HT did not appear to be altered by the presence of ondansetron (1 microM) or cyproheptadine (1 microM). However, in the presence of ondansetron (1 microM), the further addition of cyproheptadine (1 microM) effectively abolished CMMCs. Furthermore, in the combined presence of these antagonists the effects of 5-HT were severely diminished. It is suggested that the frequency of CMMCs may be under the influence of endogenously released 5-HT in this preparation

4-Aminobenzoic Acid↗
PubMed1997

Decreased Stability of Transforming Growth Factor beta Type II Receptor mRNA in RER+ Human Colon Carcinoma Cells

Transforming growth factor beta (TGF-beta) is a potent inhibitor of cell growth and tumor progression. Previous work has shown that loss of functional TGF-beta type II receptor (RII) due to a frameshift mutation in the 5' half of the RII gene leads to TGF-beta resistance in a highly progressed, RER+ human colon carcinoma cell line designated HCT116. Expression of this mutated RII gene was highly repressed in RER+ cell lines such as HCT116 and RKO, as analyzed by RNase protection assays. Nuclear run-on and RII promoter-reporter (CAT) assays showed that the transcriptional levels of the RII gene in these RER+ cells were not reduced, compared to RII-expressing cells. However, the half-lives of the RII mRNA, as analyzed by RNase protection assays following actinomycin D treatment, were significantly decreased. This suggested that the decreased expression of the RII gene mutant was due to decreased mRNA stability. Furthermore, RII mRNA from HCT116 transfected with wild-type RII had a longer half-life than the endogenous mutated RII mRNA. A dominant negative RII mutant, which encodes a similarly truncated RII protein as HCT116 but lacks the extensive 3' untranslated region of RII mRNA, gave the same half-life as endogenous wild-type RII mRNA. We conclude that the frameshift mutation which results in a premature stop codon in the 5' half of the mRNA transcript accounts for the reduced RII mRNA levels in RER+ cells.

Journal Article↗
PubMed1998

Fibronectin is chemotactic for CT 26 colon carcinoma cells: sub-lines selected for increased chemotaxis to fibronectin display decreased tumorigenicity and lung colonization.

CT 26 murine colon carcinoma cells demonstrated directional migration (chemotaxis) in response to fibronectin (FN). Sub-lines were derived by positive and negative selection to FN across Transwell filters of 8 microm pore size. The FL6 sub-line (positively selected) demonstrated a significantly increased chemotactic response (P<0.01) to FN compared with parental CT 26 cells, while the FU7 sub-line (negatively selected) showed a reduced chemotactic response to FN (P<0.01). Comparable levels of alpha4, alpha5, alphav and beta1 integrins, which mediate FN attachment, were expressed on positively and negatively selected sub-lines and parental CT 26 cells. Activation of integrins with Mn2+ suggested that the integrins expressed on FL6 cells were in the fully activated state; in contrast FU7 cells displayed only partially activated integrins. Cell attachment and integrin activation status of the sub-lines correlated with their chemotactic response to FN. In vivo FL6 cells showed a significantly reduced tumour growth rate s.c. and a reduction in the number of lung colonies formed following i.v. injection compared with parental CT 26 and FU7 cells. In contrast FU7 cells displayed a significant increase in s.c. tumour growth and the number of lung colonies when compared with the parental line and FL6 sub-line. The results indicate that interaction between integrin receptors expressed on cancer cells and FN plays a central role in the chemotactic response of CT 26 colon carcinoma cells, and that in this model cells selected for chemotaxis to FN displayed a reduced malignant potential.

Adenocarcinoma↗
PubMed2004

Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer.

BACKGROUND: Colorectal cancers resulting from defective DNA mismatch repair can occur in both hereditary non-polyposis colon cancer (HNPCC) and in the sporadic setting. They are characterised by a high level of microsatellite instability (MSI-H) and superficially resemble each other in that they are frequently located in the proximal colon and share features such as circumscribed tumour margins and tumour-infiltrating lymphocytes. However, significant differences can be demonstrated at the molecular level including widespread promoter hypermethylation and BRAF -activating mutations which occur significantly less often in HNPCC. AIMS: In this study, we sought to determine whether the presence of widespread promoter hypermethylation and BRAF mutations would exclude HNPCC. MATERIALS AND METHODS: We investigated the methylation status of four methylated in tumour markers (MINTs 1,2,12 and 31), and the promoter regions of 5 genes hMLH1, HPP1, MGMT, p16INK4A and p14ARF, in 21 sporadic MSI-H colorectal cancers and compared these with 18 cancers from HNPCC patients. The methylation status of CpG islands were determined by either methylation specific PCR (MSP) or combined bisulfite restricton analysis (COBRA). In addition we considered the BRAF mutation status of 18 HNPCC tumours and 19 sporadic MSI-H cancers which had been previously determined by RFLP analysis and confirmatory sequencing. RESULTS: Methylation of the promoter regions in target genes occurred less frequently within the HNPCC tumours (27% of analyses), compared with the sporadic MSI-H tumours (59% of analyses) (P < 0.001). Methylation of MINTs 1, 2, 12 and 31 occurred in 4% of analyses for HNPCC tumours contrasted with 73% for sporadic MSI-H tumours (P < 0.001). BRAF mutations were detected in 74% of sporadic tumours but none of the HNPCC cancers tested. CONCLUSIONS: The total number of genes and MINTs methylated in HNPCC was lower than in MSI-H colorectal tumours. No HNPCC tumour showed evidence of widespread promoter hypermethylation or BRAF mutation suggesting this feature could be used as a discriminator between familial and sporadic cases.

Aged↗
PubMed2001

Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igkappa leader sequence.

IL-18 is a novel cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature IL-18 cDNA linked with the Igkappa leader sequence and the pro-IL-18 cDNA to estimate the efficacy of the mature IL- 18 vector and to evaluate IL-18--producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the abovementioned vectors or with vector alone (mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of murine IL-18 cDNA in both mature IL-18 and pro-IL-18 transfectants in comparison to that in mock transfected cells. The ability of the culture supernatants of mature IL-18 transfectants to induce IFN-gamma secretion was extremely high (40-140 pg/10(6) cells) in comparison to that of pro-IL-18 transfectants (4-18 pg/10(6) cells). When injected into syngeneic BALB/c mice, the growth of mature IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells ( P< .01, by ANOVA and analysis of covariance). In addition, injection of colon 26 or Meth-A cells into mice immunized with a mature IL-18 transfectant revealed acquired immunity. Depletion of natural killer cells did not affect the growth of transfectants. However, the growth inhibitory effects were partially abrogated following treatment with anti-CD4+ and anti-CD8+ antibodies. These data suggest that the rejection of mature IL-18/colon 26 cells was mediated through T-cell activation. Gene therapy using mature IL-18 transfectants containing a plasmid vector and the Igkappa leader sequence may be a useful tumor vaccine.

Adenoviridae↗
PubMed2006

Identifying candidate colon cancer tumor suppressor genes using inhibition of nonsense-mediated mRNA decay in colon cancer cells.

Inhibition of the nonsense-mediated decay (NMD) mechanism in cells results in stabilization of transcripts carrying premature translation termination codons. A strategy referred to as gene identification by NMD inhibition (GINI) has been proposed to identify genes carrying nonsense mutations. Genes containing frameshift mutations in colon cancer cell line have been identified using a modified version of GINI. To increase the efficiency of identifying mutant genes using GINI, we have now further improved the strategy. In this approach, inhibition of NMD with emetine is complemented with inhibiting NMD by blocking the phosphorylation of the hUpf1 protein with caffeine. In addition, to enhance the GINI strategy, comparing mRNA level alterations produced by inhibiting transcription alone or inhibiting transcription together with NMD following caffeine pretreatment were used for the efficient identification of false positives produced as a result of stress response to NMD inhibition. To demonstrate the improved efficiency of this approach, we analysed colon cancer cell lines showing microsatellite instability. Bi-allelic inactivating mutations were found in the FXR1, SEC31L1, NCOR1, BAT3, PHF14, ZNF294, C19ORF5 genes as well as genes coding for proteins with yet unknown functions.

Caffeine↗
PubMed2000

Optimization of orthotopic colonic bladder: implantation of tubularized mucosal flap from colonic segment into demucosalized urethra.

If the urethral mucosa of a female could be replaced by another mucosa, one could augment the indication for orthotopic reconstruction of the bladder. A mucosal replacement technique for the female urethra is reported. A colonic mucosal flap formed from a colonic bladder was used in a patient with bladder cancer for whom cystectomy was indicated. For 3 years after the surgery, the patient has maintained satisfactory voiding and urethral function. There has been no evidence of a recurrence. The orthotopic bladder with the mucosal replacement technique can be applied to female patients who have a bladder cancer with a high risk of urethral recurrence.

Adult↗
PubMed1998

The alpha-subunit of the colonic H+,K+-ATPase assembles with beta1-Na+,K+-ATPase in kidney and distal colon.

Previous experiments from our laboratory (Codina, J., Kone, B. C., Delmas-Mata, J. T., and DuBose, T. D., Jr. (1996) J. Biol. Chem. 271, 29759-29763) demonstrated that the alpha-subunit of the colonic H+, K+-ATPase (HKalpha2) requires coexpression with a beta-subunit to support H+/K+ transport in a heterologous expression system (Xenopus laevis oocytes). In these studies, HKalpha2 formed stable and functional alpha.beta complexes when coexpressed with either the rat beta1-subunit of the Na+,K+-ATPase or the beta-subunit of the gastric H+,K+-ATPase, suggesting that different beta-subunits may interact with HKalpha2. The present studies tested this hypothesis by development and application of a specific antibody against HKalpha2 peptide. Subsequently, immunoprecipitation experiments were performed to determine if HKalpha2 co-precipitates with the same beta-subunit in organs known to express HKalpha2 protein. The data demonstrate that HKalpha2 assembles with beta1-Na+,K+-ATPase in the renal medulla and in distal colon.

Animals↗