UMLS:C0699790 - FACTA Search

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

The counterattack hypothesis, suggesting that cancer cells express Fas ligand (FasL) and are able to kill Fas-expressing tumor-infiltrating activated T cells, was supported by reports of the killing of Jurkat cells by FasL-expressing human colon cancer cell lines. Through the use of an improved cytotoxic assay in which soluble FasL and FasL-transfected KFL9 cells were used as positive controls, we show that none of seven human colon cancer cell lines induce apoptosis of two Fas-expressing target cell lines, Jurkat and L1210-Fas cells. Moreover, in coculture experiments, cancer cell monolayers do not inhibit the growth of Fas-expressing lymphoid cells. Although FasL mRNA and protein were detected in the extracts of the colon cancer cell lines, flow cytometry and confocal microscopy failed to detect the protein on the surface of tumor cells. These results suggest that the counterattack of tumor-infiltrating T lymphocytes by cancer cells may not account for immune tolerance toward tumor cells.
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PMID:Cutting edge: the tumor counterattack hypothesis revisited: colon cancer cells do not induce T cell apoptosis via the Fas (CD95, APO-1) pathway. 1079 56

A defective function of the antigen-presenting cells may represent one of the ways used by cancer cells to escape the immune response. We have previously shown that human and rat colon carcinomas were infiltrated by dendritic cells that did not express the B7 co-stimulatory molecules required for inducing an efficient T-cell response. Flt3 ligand is a cloned hematopoietic growth factor that markedly augments the number of functional dendritic and NK cells in lymphoid and non-lymphoid tissues and exerts anti-tumor activity in various experimental models. We show here that repeated Flt3 ligand administration delays the s.c. growth of rat colon cancer cells in syngeneic animals without inducing tumor regression. In tumor-bearing animals, Flt3 ligand has a limited stimulatory effect on the antigen-presenting capacity of intra-tumoral and splenic dendritic cells, without restoring the high functional level of dendritic cells from tumor-free animals. Moreover, Flt3 ligand-mediated activation of NK cell cytotoxicity decreases when the tumor mass increases. Our results indicate that Flt3 ligand treatment of tumor-bearing animals does not sufficiently overcome tumor-induced immunosuppression to restore the inhibited functions of dendritic and NK cells and allow complete tumor regression.
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PMID:Flt3 ligand lessens the growth of tumors obtained after colon cancer cell injection in rats but does not restore tumor-suppressed dendritic cell function. 1084 97

Increased cytoplasmic beta-catenin levels and the associated nuclear beta-catenin/T-cell factor (Tcf)-lymphoid enhancer factor (LEF) complex formation have been frequently found in colon cancer. In this context, overproduction of nitric oxide (NO) attributable to inflammatory stimuli in diseases such as ulcerative colitis and Crohn's disease may-contribute to colonic carcinogenesis. Therefore, we examined the modulation by NO of cytoplasmic beta-catenin levels and the formation of the nuclear beta-catenin/LEF-1 DNA binding complex in conditionally immortalized mouse colonic epithelial cells that differed in adenomatous polyposis coli (Apc) genotype, namely young adult mouse colon (YAMC; Apc+/+) and immortal mouse colon epithelium (IMCE; ApcMin/+). Unlike most colon cancer cell lines, this pair of cell lines has either nondetectable or low basal level of beta-catenin when they are cultured under nonpermissive and nonproliferative conditions. Using electrophoretic mobility shift assays, we found that NO-releasing agents (E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide and S-nitroso-N-acetylpenicillamine greatly enhanced the formation of beta-catenin/LEF-1 DNA binding complex in a concentration- and time-dependent fashion in YAMC and IMCE cells. Significantly, IMCE cells showed a markedly greater amount of nuclear beta-catenin/LEF-1 DNA binding complex in response to NO. Super shift by anti-beta-catenin antibody confirmed the presence of beta-catenin in the complex. Western blot analysis of the soluble cytoplasmic fractions demonstrated that these NO donors caused differential accumulation of cytoplasmic beta-catenin in YAMC and IMCE. In conclusion, this study indicates that the defective beta-catenin degradation machinery attributable to ApcMin/+ mutation in IMCE cells not only affects basal levels but also contributes to NO-induced dysregulation of cytoplasmic beta-catenin and nuclear beta-catenin/LEF-1 DNA binding complex formation.
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PMID:Differential formation of beta-catenin/lymphoid enhancer factor-1 DNA binding complex induced by nitric oxide in mouse colonic epithelial cells differing in adenomatous polyposis coli (Apc) genotype. 1091 42

Epidemiological studies on the relation between coffee consumption and cancer risk have been mainly focused on cancers of the urinary bladder, pancreas and colorectum. The relation between coffee and bladder cancer is controversial, despite a large number of studies published over the last three decades. In most studies, the risk tends to be higher in coffee drinkers than in those who do not drink coffee, but the excess risk is generally moderate and is neither dose- nor duration-related. Thus, a strong association between coffee drinking and bladder cancer can be excluded, although it is still unclear whether the weak association is causal or nonspecific and due to some bias or confounding. For pancreatic cancer, a possible association with coffee consumption has been postulated in a large case-control study published in 1981; since then, however, most studies have shown no substantial association, and overall evidence suggests that coffee is not materially related to pancreatic cancer risk. Overall evidence on the coffee-colorectal cancer relation suggests an inverse association, since most case-control studies found odds ratios below unity, particularly for colon cancer. The pattern of risk is less clear for cohort studies. A plausible biological explanation has been given in terms of coffee-related reduction of bile acids and neutral sterol secretion in the colon. For other cancer sites, including oral cavity, oesophagus, stomach, liver, breast, ovary, kidney and lymphoid neoplasms, the relation of coffee drinking with cancer risk has been less extensively investigated, but the evidence is largely reassuring.
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PMID:Coffee and cancer: a review of epidemiological studies, 1990-1999. 1095 27

Constitutive activation of the Wnt signaling pathway is a root cause of many colon cancers. Activation of this pathway is caused by genetic mutations that stabilize the beta-catenin protein, allowing it to accumulate in the nucleus and form complexes with any member of the lymphoid enhancer factor (LEF1) and T-cell factor (TCF1, TCF3, TCF4) family of transcription factors (referred to collectively as LEF/TCFs) to activate transcription of target genes. Target genes such as MYC, CCND1, MMP7 and TCF7 (refs. 5-9) are normally expressed in colon tissue, so it has been proposed that abnormal expression levels or patterns imposed by beta-catenin/TCF complexes have a role in tumor progression. We report here that LEF1 is a new type of target gene ectopically activated in colon cancer. The pattern of this ectopic expression is unusual because it derives from selective activation of a promoter for a full-length LEF1 isoform that binds beta-catenin, but not a second, intronic promoter that drives expression of a dominant-negative isoform. beta-catenin/TCF complexes can activate the promoter for full-length LEF1, indicating that in cancer high levels of these complexes misregulate transcription to favor a positive feedback loop for Wnt signaling by inducing selective expression of full-length, beta-catenin-sensitive forms of LEF/TCFs.
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PMID:Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. 1132 60

The DCC (deleted in colon cancer) gene has a brain restricted high expression pattern. It encodes a transmembrane protein of the immunoglobulin superfamily identified as the netrin-1 receptor. It might be a member of the so called "brain-lymphoid" molecules, which control key cell surface events. To test this hypothesis we have assessed the DCC mRNA level in human normal and malignant myeloid and lymphoid cells. A high mRNA content has been observed only in mature B cells at the secreting or presecreting stage. Expression of DCC was also assessed in the anti-CD40 model of immunopoiesis. Activation of purified tonsillar B cells by anti-CD 40 antibody strongly increased the DCC mRNA level and this effect was dramatically enhanced by the association of IL-2 + IL-10, which is a potent and selective in vitro inducer of the B cell memory phenotype. In contrast no effect has been detected after activation of T cells by anti-CD3. These data suggest that the DCC encoded netrin receptor is involved in B cell immunopoiesis.
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PMID:Upregulation of the netrin receptor (DCC) gene during activation of b lymphocytes and modulation by interleukins. 1135 76

Microsatellite instability (MSI), characterized by contraction or expansion in microsatellite length or short tandem repeats compared with germline lengths, is found in 85% to 90% of colon cancer arising in hereditary nonpolyposis colorectal cancer families. These cancers commonly have characteristic histologic appearances, including medullary features with intense lymphoid infiltrates. In pancreatic cancer, a rare medullary histologic subtype more often demonstrates MSI than the more common adenocarcinoma subtype. We hypothesized that the medullary histologic pattern might correlate with MSI in additional tumor types and analyzed 8 cases of typical and atypical medullary carcinoma of the breast. Tumor and normal DNA was extracted from paraffinized tissue blocks of tumor and histologically uninvolved axillary lymph nodes, respectively. We analyzed the tumors for instability in 5 primary (BAT25, BAT26, D17S250, D5S346, D2S123) and 3 alternative (BAT40, D18S55, D18S58) microsatellites recommended at the National Cancer Institute--sponsored conference for diagnosis of MSI in colorectal cancer. All 8 tumors were microsatellite stable at the 8 loci, suggesting that MSI is not commonly associated with medullary or atypical medullary breast carcinoma, in contrast with the reported association with medullary tumors of the colon and pancreas.
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PMID:Microsatellite instability is infrequent in medullary breast cancer. 1139 77

Previous studies on the distribution of positive lymph nodes have revealed that the colon should be resected 10 cm from the tumor on both sides and that the intermediate nodes along the main vessel should be dissected in patients with colon cancer. In rectal cancer, superior lymphatic spread along the inferior mesenteric artery (IMA) is the main metastatic route. The IMA should be dissected immediately after the bifurcation of the left colic artery, and the intermediate lymph nodes should be removed. The positive rate of the lateral lymph nodes is about 10%. The rate of local failure is high and the prognosis is poor in patients with positive lateral lymph nodes, even if the lateral lymph nodes have been dissected. However, it has been reported that lateral lymph node dissection combined with excision of the internal iliac vessels results in good disease-free survival in patients with positive lateral nodes. Therefore the indications for lateral node dissection remain controversial. Lymphatic spread into the mesorectum on the anal side has been shown to be an important factor in local failure. The mesorectum should be resected for up to 4 or 5 cm from the inferior tumor margin in middle rectal cancer, and the entire mesorectum should be removed in lower rectal cancer. Nerve tissue preserved in pelvic autonomic nerve-preserving surgery contains a small amount of lymphoid tissue and lymph nodes. Therefore the extent of lymph node dissection and the area of autonomic nerves to be preserved based on tumor site or tumor penetration remain controversial.
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PMID:[Optimal lymph node dissection for colorectal cancer]. 1143 14

We studied whether feeding pregnant female rats a 15% olive-oil diet affects the activity of lymph cells in the spleen and tumors in offspring with chemically-induced colon tumors. Rat mothers were fed either a 7% corn-oil or a 15% olive-oil diet. Five-week-old male offspring were divided into 3 groups. A control group was fed the 7% corn-oil diet similar to their mothers. The experimental group I was fed the 7% corn-oil diet whereas their mothers were fed the 15% olive-oil diet. The experimental group II was fed the same 15% olive-oil diet as their mothers. Experimental rats were injected weekly for 8 weeks with the carcinogen, 1,2-dimethylhydrazine (DMH), 20 mg/kg b.w. Results of experiments were studied 6 months later. The area of zones in the spleen responsible for producing B and T lymphocytes were measured and the number of cells counted. The activity of lymphoid elements of the spleen and of tumors were studied using immunohistochemical methods for evaluating the synthesis of CD8(+) lymphocytes and proliferative activity of lymphocytes in spleens and tumors. Feeding pregnant or lactating mothers with the 15% olive-oil diet had no marked tumor-protective effect on chemically-induced colon cancer in offspring. Diet-dependent changes were found at the cellular level. In the spleen of control offspring, the presence of a tumor was accompanied by an increase in the number of Ki-67(+) cells and CD8(+) lymphocytes in the red pulp. In experimental group I, DMH significantly increased the total cell number and the number of CD8(+) lymphocytes in the red pulp of the spleen in both tumor-bearing and tumor-free rats. In experimental group II, the total number of lymph cells and the number of CD8(+) lymphocytes increased compared to offspring fed a control diet. Tumor formation activated the proliferative activity of lymph elements. The total number of cells in infiltrates of the colon mucosa decreased in tumor-bearing rats compared to tumor-free counterparts, and this was seen in all three dietary groups of rats. In tumors from offspring of experimental group II, only the number of CD8(+) lymphocytes increased compared to those in offspring of experimental group I. The findings indicate that feeding mothers the 15% olive-oil diet had a cancer-inhibiting role in offspring, predominantly changes at the cellular level.
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PMID:Transplacental effect of a 15% olive-oil diet on functional activity of immune components in the spleen and colon tumors of rat offspring. 1149 14

About 5% of colon cancer cases correspond to classic hereditary monogenic mendelian transmission involving at least 8 major genes of predisposition to this tumor. Genes with more moderate effects, in association with other genes can contribute to the occurrence of sporadic polygenic forms. These genes confer susceptibility to environmental factors and can play the role of aggravating or protective modifier genes in the different hereditary forms. Foods can interact with these genes and modulate their expression. Moreover sequence variations (polymorphisms) in these genes may also be responsible for slower or more rapid metabolism of nutrients leading to toxic or carcinogenic compounds. If some foods, or "pharmafoods" can have beneficial effects in some individuals with a particular subtype of the disease, others can be inefficient or even detrimental in patients with the same disease but with a different genetic origin or if the genetic background is different. Moreover tumorigenic processes are diverse. Tumor progression depends on genetic and environmental factors different from tumor initiation and on the site of the tumor along the colon tract. Interactions with the gut flora, the lymphoid system and specific features of growth of the colon mucosa are also important parameters. Today with a formidable genetic knowledge arising from the genome project, new epidemiological data integrating the genetic data for multiple markers and a better knowledge of the tumorigenic processes involved, a new discipline is emerging. "Nutrigenetics" which is the study of hereditary basis of individual variations in response to foods opens for the oncoming decade the era of a personalised predictive medecine based on a nutrition adapted to the genetic make up of each of us.
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PMID:[Colon cancer and nutritional genetics: modifier genes]. 1159 47

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