Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five studies presented at the 1992 ASCO meeting are analysed. Kligerman's study was designed to determine if pre-treatment with WR-2721 could protect normal tissues from the toxicities induced by radiation therapy (in 100 patients with advanced rectal cancer). This pre-treatment resulted in a 13% reduction of moderate and severe acute toxicity. No WR-2721 patient experienced moderate or severe late toxicities compared to five in the group without pre-treatment. The complete response rate was higher in the WR-2721 group and there was no major WR-2721 related toxicity. Minski studied the acute toxicity (during treatment and two weeks after) of combined pelvic radiation therapy, 5-FU and leucovorin when delivered pre-operatively (16 patients) versus post-operatively (25 patients) in patients with rectal cancer. The toxicity criteria were fatigue, diarrhea, tenesmus, bowel movements, dysuria and erythema. Grade 3+ toxicity was more important in the post-operative therapy group (48% versus 13%). Given this high incidence of grade 3+ toxicity future randomized trials should explore the pre-operative approach. The final report of the inter group study of 5-FU plus levamisole as adjuvant therapy for stage C colon cancer was made by Moertel. With a median follow-up time of 5.5 years, the 5-FU plus levamisole treatment has reduced the recurrence rate by 39%, the cancer related death rate by 32% and the overall death rate by 31%. Most of the recurrences occurred during the first two years. There was a decrease in the liver, great omentum, peritoneum and lung metastases, but there was no modification in loco-regional recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Pathol Biol (Paris) 1992 Dec
PMID:[Cancers of the colon and the rectum: news in 1992]. 133 19

Cytoplasmic alkalinization induced by activation of the Na+/H+ antiport plays an essential role in the initiation of cell proliferation. In the present study we examined the effects of amiloride, a specific and reversible inhibitor of Na+/H+ antiporter, on the growth of human colon cancer cells (HT-29). Amiloride (50-800 microM) inhibited the growth of HT-29 cells in a dose-dependent fashion. Forty-three percent inhibition of growth was found at an amiloride concentration of 400 microM after 4 days of treatment. The inhibitory effect of amiloride on growth of HT-29 cells was reversible since removal of amiloride by a media change after 48 h treatment lead to rapid regrowth to control levels. The reversibility of growth inhibition suggests that amiloride is not a non-specific cytotoxin for HT-29 cells. We examined the possible mechanisms for the inhibitory effects of amiloride. Amiloride (400 microM) completely abolished serum-stimulated ODC activity and inhibited difluoromethylornithine (DMFO)-stimulated putrescine uptake by 56%. We conclude that amiloride inhibits the in vitro growth of human colon cancer cells; since ODC-activity and polyamine transport were both inhibited, the inhibitory effects may be mediated in part by polyamine-dependent processes. Amiloride may be a useful agent in the treatment of colon cancer.
Surg Oncol 1992 Dec
PMID:Amiloride inhibits the growth of human colon cancer cells in vitro. 134 Dec 75

The human colon cancer cell line Caco-2 undergoes spontaneous enterocytic differentiation during growth, and expresses a number of brush-border-membrane-associated hydrolases typical of a differentiated phenotype. Among these are alkaline phosphatase, dipeptidyl peptidase IV and sucrase-isomaltase (sucrase, EC 3.2.1.48). Neutral endopeptidase 24.11 [EC 3.4.24.11, neprilysin (NEP)] is another abundant protease of normal enterocytes but its presence in Caco-2 cells has not been fully documented yet. In this paper, we show that Caco-2 cell extracts hydrolyse tritiated [D-Ala2Leu5]enkephalin with a Km of 180 microM, very close to the value obtained for the NEP present in the rabbit kidney (118 microM). Western-blot analysis of brush-border membranes purified from post-confluent cells revealed a protein with an apparent molecular mass of 94000 Da similar to that of the rabbit kidney NEP. The amount of enzyme in cell extracts increased as a function of the age of the culture, indicating that NEP expression is correlated with the degree of cell differentiation as is also the case for sucrase and dipeptidylpeptidase IV (DPP-IV). Binding of a radiolabelled antibody to Caco-2 cell monolayers grown on semi-permeable filters indicated that 95% of NEP molecules present at the cell surface are on the apical side. Immunocytochemical and flow cytometric analysis of intact and permeabilized cells were also used to investigate the presence of NEP and DPP-IV at the surface of Caco-2 cells. Whereas DPP-IV staining appeared to be homogeneous throughout the entire cell population, NEP-related fluorescence exhibited a bimodal distribution which indicates an uneven expression of the protein at the cell surface. Permeabilization of monolayers with saponin before staining restored a labelling pattern for NEP similar to the one obtained for DPP-IV. This suggests that although DPP-IV and NEP follow similar patterns of expression when enzymic activities are measured on whole-cell extracts, targeting of these brush-border proteins to the cell surface appears to be regulated in different ways.
Biochem J 1992 Dec 15
PMID:Polarized distribution of neutral endopeptidase 24.11 at the cell surface of cultured human intestinal epithelial Caco-2 cells. 136 26

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface adhesion glycoprotein that mediates leukocyte adhesion through interaction with the leukocyte CD11/CD18 adhesion complex. The aim of this study was to determine whether ICAM-1 is expressed by normal or neoplastic colonic epithelial cells. Immunohistochemical studies on human colonic tissue demonstrated focal ICAM-1 expression by colonic carcinomas but not by normal colonic epithelium. ICAM-1 expression by colonic carcinomas showed a positive correlation with the presence of a peritumoral inflammatory infiltrate. Surface expression of ICAM-1 was also observed in HT-29 cultured human colon cancer cells by both immunohistochemistry and enzyme immunoassay. Interferon-gamma and interleukin-1 beta significantly increased ICAM-1 surface expression by HT-29 cells in a dose-dependent manner. Upregulation of ICAM-1 surface expression became evident some hours after cytokine stimulation and was inhibited by both actinomycin D and cycloheximide, indicating a requirement for de novo RNA and protein synthesis. HT-29 monolayers supported adhesion of human lymphocytes as determined by a quantitative 111In-labeled leukocyte adhesion assay. Adhesion was mediated in part via interaction of ICAM-1 on HT-29 cells with lymphocyte function-associated antigen-1 (CD11a/CD18) on lymphocytes, as defined by using blocking monoclonal antibodies. Expression of ICAM-1 and/or other leukocyte adhesion receptors by neoplastic epithelial cells may play a role in directing leukocyte trafficking and leukocyte-epithelial cell interactions in colonic carcinoma.
Am J Physiol 1992 Dec
PMID:Human colon cancer cells express ICAM-1 in vivo and support LFA-1-dependent lymphocyte adhesion in vitro. 136 41

Tumorigenesis is a heterogeneous process that occurs over a relatively long time span, progressing from a single cell through intermediate stages to give rise to a tumour that becomes more aggressive over time. Recent discoveries have begun to define the molecular events that underlie this progression in breast and colon cancer.
Curr Opin Biotechnol 1991 Dec
PMID:Genetic basis of cancer. 136 53

The mitogenic role of estradiol on the growth of colon cancer was examined in mice. Sham-operated or ovariectomized mice were injected with cancer cells and received estradiol treatment. Tumor growth was noted: tumor weights were higher in female than male mice. The growth of the tumors was least in ovariectomized mice and highest in estradiol-treated ovariectomized mice. Tumor messenger RNA (mRNA) levels for ornithine decarboxylase (ODC) and proto-oncogenes c-myc, c-fos, and H-ras were examined. Two transcripts (2.2 and 2.7 kilobase pairs) of ODC were observed. The steady-state mRNA levels for ODC paralleled the changes observed in the weight of the tumors in all groups of animals. Less dramatic changes were observed in c-myc mRNA levels. No significant differences were observed in the mRNA levels for H-ras and c-fos. It thus appears likely that an increase in the ODC mRNA levels and, to a lesser extent, an increase in c-myc mRNA levels may be some of the important mechanisms by which estradiol mediates its growth effects on colon cancer cells in vivo.
Gastroenterology 1992 Dec
PMID:Estradiol is trophic for colon cancer in mice: effect on ornithine decarboxylase and c-myc messenger RNA. 145 76

We found that the human colon cancer cell line SW480 consists of two distinct subpopulations which we have designated E-type (epithelial) and R-type (round). Pure cultures of each type were obtained by subcloning, and both have maintained their characteristic phenotypes for at least 1 year (40 passages). E-type cells are the major (> 98%) type in the parental SW480 cell line. They form flat epithelial-like colonies. In contrast, R-type cells, which constitute a minor fraction (< 2%) of the parental cell line, have a rounded shape and grow in clusters of piled-up cells. Compared to E-type cells or the parental SW480 cells, isolated R-type cells display decreased doubling time, loss of contact inhibition, less adhesiveness to culture plates, higher anchorage-independent growth in soft agar, and a much more aneuploid karyotype. When injected s.c. into nude mice, R-type cells produce much larger tumors within the same period of time than E-type cells, and the tumors are less differentiated than those produced by the E-type cells. Cell fusion experiments between R-type and E-type cells revealed that the R-type phenotype is dominant, and the results suggest that this is due to one or a few genetic changes. Taken together, these findings suggest that the R-type cells represent a more malignant variant of the E-type cells. They may be useful, therefore, for studying mechanisms involved in tumor progression.
Cancer Res 1992 Dec 15
PMID:Isolation and characterization of a highly malignant variant of the SW480 human colon cancer cell line. 145 72

The 3T3-L1 cell line is a preadipocyte cell line derived from the Swiss 3T3 mouse fibroblast cell line. We have compared the effect of 3T3-L1 conditioned medium (3T3-L1 CM) and Swiss 3T3 conditioned medium (3T3 CM) on the growth of normal mouse mammary cells (NMMG) and the human MCF-7 breast carcinoma cell line. 3T3 CM increased the growth of both NMMG and MCF-7 cells by 19 +/- 2% (SD) and 24 +/- 3%, respectively, and increased thymidine incorporation by 74 +/- 4% and 104 +/- 8%, respectively. Conditioned medium from 3T3-L1 cells stimulated the growth of NMMG cells by 64 +/- 2%; in contrast, 3T3-L1 CM inhibited the growth of MCF-7 cells by 36 +/- 1%. In parallel with these growth studies, thymidine incorporation increased by 20 +/- 4% in NMMG cells and decreased by 72 +/- 5% in the MCF-7 cells. Moreover, a similar effect was also noted in NCI H630 colon cancer cells, where 3T3-L1 CM produced a 58 +/- 4% decrease in growth and a 82 +/- 6% decrease in thymidine incorporation. Heating the 3T3-L1 CM at 100 degrees C for 30 min destroyed all inhibitory activity. Several known inhibitory growth factors (fibroblast growth factor, 20 ng/ml; interleukin 6, 1000 units/ml; tumor necrosis factor alpha, 15 ng/ml; transforming growth factor beta, 1 ng/ml) were tested for activity in the MCF-7 cells. Tumor necrosis factor alpha and transforming growth factor beta produced a 97% and 67% inhibition of thymidine uptake, respectively, whereas interleukin 6 and fibroblast growth factor had no effect. Neither transforming growth factor beta nor tumor necrosis factor alpha activity was detectable in 3T3-L1 CM using an enzyme-linked immunosorbent assay. High-performance liquid chromatography fractionation of the 3T3-L1 CM revealed that the inhibitory activity eluted at a molecular weight of 67,000; moreover, silver staining of these eluates on a denaturing polyacrylamide gel revealed that M(r) 69,000 peptide was the predominant protein band in the inhibitory fractions. Thus 3T3-L1 CM stimulates the growth of normal breast epithelial cells and inhibits the growth of MCF-7 breast cancer cells. This inhibitory activity appears to be due to a protein secreted by 3T3-L1 preadipocytes.
Cancer Res 1992 Dec 15
PMID:Identification of a protein factor secreted by 3T3-L1 preadipocytes inhibitory for the human MCF-7 breast cancer cell line. 145 74

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.
Int J Cancer 1992 Dec 02
PMID:Proliferation of human colon cancer cells: role of epidermal growth factor and transforming growth factor alpha. 145 40

The anthracyclines are the class of antitumor drugs with the widest spectrum of activity in human cancers, and only a few cancers (eg, colon cancer) are unresponsive to them. The first two anthracyclines were developed in the 1960s. Doxorubicin (DOX) differs from daunorubicin (DNR) only by a single hydroxyl group. This fact has spurred researchers worldwide to find analogs of DOX that have less acute toxicity, cause less cardiomyopathy, can be administered orally, and/or have different, or greater, antitumor efficacy. Five DOX/DNR analogs are marketed in other countries, and one (idarubicin) is available in the United States. None of these analogs have stronger antitumor efficacy than the original two anthracyclines, but there are some differences in toxicity. Methods have been fashioned to keep the peak plasma level of DOX muted to minimize cardiotoxicity, but the only apparently effective method available so far (prolonged drug infusion) is cumbersome. The bisoxopiperazine class of drugs (especially dexrazoxane) provides protection against anthracycline-induced cardiomyopathy and has much promise for helping mitigate this major obstacle to prolonged use of the anthracyclines. The DOX analogs being evaluated in the 1990s have been selected for their ability to overcome multidrug resistance in cancer cells. Thirty years after discovery of the anticancer activity of the first anthracycline, some means of reducing anthracycline toxicity have been devised. Current studies are evaluating increased doses of epirubicin to improve anthracycline cytotoxicity, while limiting cardiotoxicity, but at present DOX still reigns in this drug class as the one having the most proven cancerocidal effect.
Semin Oncol 1992 Dec
PMID:The anthracyclines: will we ever find a better doxorubicin? 146 66


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