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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence in tumors of numerous cytokines suggests that they potentially modulate tumor cell activities and host tissue remodelling. To investigate the possible involvement of transforming growth factor type beta (TGF beta) in the metastatic process of cancer development, we have studied the effect of this factor on two rat colon carcinoma cell lines. These cell clones had been previously tested and selected for their ability to develop metastases in syngenic animals or lack of it. The two cell lines were characterized for their production of TGF beta. Production of active and latent forms of TGF beta 1 in the medium conditioned by the rat colon cancer cells were quantified using a bioassay. The presence of active TGF beta 1 was demonstrated in conditioned medium from the progressive tumor (PROb) cells and significant expression of latent forms of TGF beta 1 were found in the conditioned media from both cell clones. TGF beta 1 slightly inhibited proliferation of PROb cells which had been previously described as moderately differentiated, and significantly stimulated proliferation of the regressive (REGb) cells, described as poorly differentiated. On the basis of our observations, we suggest that this endogenous factor could be involved in autocrine regulation of tumor cell activities and in paracrine regulation of stroma cell and immune responses. Active and/or latent expression of TGF beta 1 by the two rat colon carcinoma cell lines, and their variable responses to the growth factor, strongly suggest that this polypeptide is involved in the regulation of tumorigenic expression of adenocarcinoma cells.
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PMID:Possible involvement of TGF beta 1 in the distinct tumorigenic properties of two rat colon carcinoma clones. 133 1

A cDNA (DPCR1) specific for human intestinal dipeptidyl peptidase IV (DPP IV) has been isolated. This 1.7-kilobase cDNA, together with a previously published partial sequence, covers the entire open reading frame of human DPP IV plus 67 base pairs of the 3'-untranslated end. Human DPP IV is a 766-amino acid polypeptide with a high degree of homology with the rat liver protein. The characterization of this molecular probe allowed us to definitively confirm the identity of DPP IV with CD 26, a mouse thymocyte activation antigen, a conclusion strengthened by the fact that we observed identical patterns on Southern blot of human genomic DNA hybridized either with human DPP IV or mouse CD 26 cDNA probe. Using this new tool, we have investigated the expression of DPP IV during the onset of enterocytic differentiation of two cultured human colon cancer cell lines, HT-29 and Caco-2. Whatever the cell line and the culture conditions, DPP IV expression strictly correlates with the presence of a differentiated phenotype, as shown by enzyme activity and the steady state amount of the protein measured by indirect immunofluorescence and Western blot. Accordingly, DPP IV biosynthesis exclusively increases in cells that display an enterocytic differentiation. Neither the glycosylation nor the stability of the protein appear to be dependent on the state of enterocytic differentiation. The DPP IV mRNA level remains very low in undifferentiated cell populations and specifically increases in cells that undergo an enterocytic differentiation. These results strongly suggest that DPP IV gene expression is controlled at the transcriptional or posttranscriptional level during intestinal differentiation.
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PMID:Dipeptidyl peptidase IV (CD 26) gene expression in enterocyte-like colon cancer cell lines HT-29 and Caco-2. Cloning of the complete human coding sequence and changes of dipeptidyl peptidase IV mRNA levels during cell differentiation. 134 43

Specimens of the sigmoid colon were obtained from male and female patients (n = 11) with carcinoma of the colon or rectum and studied immunohistochemically for vasoactive intestinal polypeptide-, somatostatin-, substance P-, neuropeptide Y-, calcitonin gene-related peptide-, met- and leu-enkephalin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-containing nerves. In the subdivisions of the submucous plexus (namely, Schabadasch's, Meissner's, and the intermediate plexuses), substance P- and vasoactive intestinal polypeptide-immunoreactive nerve fibers were the most numerous, and equal densities of these nerves were found in all three layers. In contrast, few neuropeptide Y-, met-enkephalin-, leu-enkephalin-, calcitonin gene-related peptide-, somatostatin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-immunoreactive nerves were found in these regions. The nerve cell bodies of the submucous plexus contained vasoactive intestinal polypeptide, substance P, leu-enkephalin, somatostatin, and 5-hydroxytryptamine but not neuropeptide Y, met-enkephalin, calcitonin gene-related peptide, and dopamine beta-hydroxylase. Vasoactive intestinal polypeptide-containing nerve cell bodies were found in all three subdivisions. Substance P-, leu-enkephalin-, and somatostatin-immunoreactive nerve cell bodies were found in Schabadasch's plexus and the intermediate region of the submucous plexus, but they were absent from Meissner's plexus; 5-hydroxytryptamine-containing nerve cell bodies were only observed in Schabadasch's plexus. The possible function of the neuropeptide-, dopamine beta-hydroxylase-, and 5-hydroxytryptamine-containing neurons in the different layers of the submucous plexus is discussed.
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PMID:Peptide-containing neurons in different regions of the submucous plexus of human sigmoid colon. 848 77

Methods of morphological, histochemical and immunohistochemical analyses were used to further characterize differences between tumourous and adjacent grossly normal tissues in chemically-induced colon cancer in rats. Colon tumors were induced by the treatment of rats with 1,2-dimethylhydrazine or with N-methyl-N'-nitro-N-nitrosoguanidine alone or with subsequent treatment with deoxycholic bile acid. Tissues were studied morphologically (for the presence of goblet cells in the colon crypts, and the extent of infiltration of lymphocytes into the crypts and between them), histochemically (for the presence of positive reaction to neutral and acid mucopolysaccharides) and immunohistochemically (for the presence of tissue polypeptide antigen). All data were evaluated quantitatively, and index of tissue damage was calculated for both tumorous and non-tumorous tissues. Significant morphological differences were found between tumorous and adjacent apparently normal tissue. Histochemically and immunohistochemically, both types of tissue reacted very similarly to exposure to the carcinogens. Index of damage was significantly different from normal untreated colon in both kinds of tissue. It was suggested that precancerous state in tissue adjacent-to-tumor could be detected using the combination of these methods.
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PMID:Morphological, histochemical and immunohistochemical differences between tumorous and adjacent tissues in chemically induced colon cancer in rats. 141 10

Human colon cancer cells produce and secrete a variety of polypeptide growth factors. The functional role of these growth factors, however, is poorly understood. Though the secretion of epidermal growth factor (EGF)-like activity and EGF-related molecules by human colon cancer cells in culture has been reported, it is not known whether colon cancer cells produce and secrete EGF, and the functional role of EGF in the growth control of these cells is also unknown. We have shown that EGF acts as a potent growth stimulator on the moderately differentiated Moser colon cancer cell line and as an inhibitor on the highly metastatic KM12SM cell line. In the present study, we show that EGF is produced by human colon cancer cells and characterize the levels of EGF mRNA expression and EGF protein secretion from 8 human colon cancer cell lines. The cell-surface EGF receptors on these cell lines were also characterized by radiolabeled ligand binding and Scatchard analyses. All the cell lines expressed EGF mRNA and secreted EGF. Both high- and low-affinity subtypes of EGF receptor were detected on 7 of the cell lines. These lines also secreted transforming growth factor (TGF)alpha. Some cell lines exhibited a proliferative response to treatment with either exogenous EGF or TGF alpha, while others did not respond to treatment with these growth factors. Antibody-blocking experiments, using anti-EGF or anti-EGF receptor antibody, suggested that these cell lines could be broadly classified into 2 groups in terms of their autocrine or paracrine growth regulation via the cell-surface EGF receptor: (1) cells that utilized EGF and/or TGF alpha; and (2) cells that did not utilize EGF or TGF alpha (via the cell-surface receptor), even though they secreted abundant amounts of these growth factors.
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PMID:Proliferation of human colon cancer cells: role of epidermal growth factor and transforming growth factor alpha. 145 40

Ruthenium red (RR) is an inorganic dye that has shown to block the actions of capsaicin on primary sensory neurons in different animal models. The aim of this study was to assess whether RR is able to antagonize the release of vasoactive intestinal polypeptide (VIP) evoked by capsaicin in the human colon. Samples of descending colon were collected from patients undergoing colectomy for carcinoma of the colon. Tissue slices from the muscle of human colon were exposed to either 10 microM capsaicin or an isotonic high K+ medium (KCl 80 mM), in the absence or presence of 10 microM RR. Either capsaicin or high K+ produced a prompt release of VIP. RR (10 microM) completely antagonized the capsaicin-induced release of VIP from muscle of human colon. This effect was elective, since VIP release evoked by high K+ was unaffected by the presence of RR. These findings indicate that RR acts as a selective antagonist of capsaicin in human tissue and that the mechanism underlying peptide release by capsaicin is preserved across species. Multiple mechanisms leading to VIP release exist in the human colon.
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PMID:Ruthenium red selectively antagonizes capsaicin-induced release of vasoactive intestinal polypeptide (VIP) from the human colon. 171 94

The role of selected histopathological methods was evaluated for the characterization of tumourous tissues resulting from chemically induced carcinogenesis in rats. Colon cancer was induced by treating rats with a direct carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), alone or with subsequent treatments with secondary bile acids. Morphological studies showed that the tumorigenic effect of MNNG resulted in changes in the shape of the crypts, disappearance of mucous (goblet) cells, and marked increases in the mitotic index, the size of nuclei and the number of aberrant nuclei. A significant number of lymphocytes infiltrated between the crypts and into their lumens. A sharp decrease in concentrations of neutral mucopolysaccharides and sulfomucins and an increase in the amount of vic-glycol groups and nonsulfated mucosubstances were demonstrated in tumourous epithelial cells. A moderate positive reaction to tissue polypeptide antibody was observed in these cells. The tumor-promoting effects of secondary bile acids were detected morphologically by an increase in the amount of connective tissue that infiltrated newly formed tumors. The increased number of micronuclei in otherwise histologically unaltered colon tissues adjacent to a tumor suggests that these regions represent a precancerous stage in the development of tumors. The important role of morphological methods in the evaluation of the effects of carcinogen and tumor promoters and in the detection of various phases in experimental carcinogenesis was discussed.
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PMID:Role of morphological methods in the analysis of chemically induced colon cancer in rats. 183 46

Mouse monoclonal antibody A 7, which was raised against human colon cancer, was used for preparing the conjugates with neocarzinostatin, mitomycin C and adriamycin. The tissue distribution of these three conjugates were examined in athymic nude mice transplanted with human colon cancer. The distribution in tumor was different in these three conjugates. The route of administration of the conjugate affected its distribution in tumor tissues. In the case of tumor transplanted in the back of mice, intravenous administration seemed to superior to intraperitoneal one. In clinical trials of immunoconjugate composed of A 7 and polypeptide anticancer drug neocarzinostatin (A 7-NCS), human anti-mouse antibody (HAMA) was observed in most cases without serious immune response such as anaphylactic shock. Human antibody against neocarzinostatin could not be detected in any case receiving A 7-NCS.
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PMID:[Host factors that changes the distribution of immunotoxin]. 213 73

Human cancers express organ-specific neoantigens (OSNs) that elicit immune responses in the tumor host. Leukocyte adherence inhibition, an in vitro assay that detects the antitumor immunity, was used to monitor the purification of the OSN from serum-free spent medium of tissue-cultured colon cancer cell lines (HCT-15 and SW-620). A monoclonal antibody (anti-p40) directed to a cross-reactive framework determinant of Mr 40,000 (p40) cell surface polypeptide, which was a principal component of the enriched isolate with OSN activity, was used to monitor the purification of p40 by enzyme-linked immunosorbant assay. About 50 liters of spent medium were generated from 20 m2 of cells, collected, concentrated, and then separated by anion exchange, molecular-sieve, and blue-Sepharose affinity chromatography. OSN and p40 activity coisolated. p40 was then purified by monoclonal antibody anti-p40 affinity chromatography. The affinity-purified fraction was enriched for both p40 and leukocyte adherence inhibition activity that was specific for leukocytes from colon cancer patients in blind leukocyte adherence inhibition assays. When affinity-purified p40 from colon and lung cancers was tested blind in a criss-cross fashion with leukocytes from colon and lung cancer patients, the positive responses were to the appropriate p40. The homologous colon cancer p40 molecule showed size and considerable charge microheterogeneity (pI 6.3 to 7.6). Affinity-purified p40 and OSN coisolated on hydrophobic interaction and hydroxylapatite high-pressure liquid chromatography. Note that not all colon cancer OSN activity was bound by the anti-p40 affinity column. However, unbound OSN activity also eluted from hydrophobic interaction high-pressure liquid chromatography at the same time as affinity-purified p40, and residual p40 activity was detected by enzyme-linked immunosorbant assay. The results indicate that a p40 glycoprotein from the cell membrane of colon cancer cells coisolates with fractions having OSN activity. Impurities do not seem to account for the OSN activity. The OSN epitope on the Mr 40,000 molecule is recognized by leukocytes from colon cancer patients and is distinct from the cross-reactive framework determinant recognized by mouse monoclonal antibody anti-p40.
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PMID:Identification of a Mr 40,000 polypeptide from colorectal cancer which expresses organ-specific cancer neoantigen activity as determined by leukocyte adherence inhibition. 241 55

The effects of vasoactive intestinal polypeptide (VIP) and dibutyryl cyclic adenosine 3':5'monophosphate (dbcAMP) on two human colon carcinoma cell lines, HCT 116 and GEO, were investigated. VIP and dbcAMP inhibited the growth of both cell lines in monolayer culture in a dose-dependent manner. Within 6 h of treatment with 1 mM dbcAMP or 0.3 microM VIP, numerous mucin-like droplets were secreted by GEO cells. VIP and dbcAMP also increased carcinoembryonic antigen (CEA) secretion. In both cell lines, a 9-fold increase in conditioned medium CEA levels was observed at 1 mM dbcAMP and a 2.6-fold increase at 1.5 microM VIP. Time- and concentration-dependent evaluation in cAMP levels were elicited by VIP in the two cell lines. Immunocytochemical studies for cell-surface glycoprotein detection in GEO cells showed that VIP induced a morphological and functional organization of mucin-secreting cells. These results indicate that VIP and dbcAMP have antiproliferative and strong differentiation-promoting effects in colon cancer cells. This is the first report of VIP-induced mucin secretion in colon tumor cells.
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PMID:Promotion of differentiation in human colon carcinoma cells by vasoactive intestinal polypeptide. 254 28


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