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)

Fifty-two patients with resectable carcinoma of the colon and rectum have been monitored by three monthly serial estimations of three APRP (serum protein hexose, transferrin and ceruloplasmin) together with CEA. In 36 patients, subsequent clinical evidence of a recurrence of the disease developed during the study period. Monitoring with APRP can detect a recurrence of the disease at the subclinical stage in the majority of patients and appears to be complimentary to monitoring with CEA. However, due to the low incidence of surgical removal of recurrent carcinoma, this does not give real benefit for patients.
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PMID:Monitoring of patients with carcinoma of the large intestine by use of acute phase proteins and carcinoembryonic antigen. 685 57

We examined the alterations of proliferative activity and c-myc expression of a colon cancer cell line (Caco-2) during its spontaneous differentiation. Caco-2 cells were cultured in various types of media and the degree of differentiation was monitored in terms of dome formation in cell monolayers and expression of alkaline phosphatase (ALP) activity. In Caco-2 cells cultured with Eagle's minimum essential medium (EMEM) containing 10% fetal calf serum (FCS), dome formation was demonstrated and ALP activity was markedly increased after the cells reached confluence. Five-fold reduction of c-myc mRNA and a marked decrease in S-phase cells were observed in the differentiated cells. These changes were not induced in FCS-free EMEM. The addition of insulin and transferrin to FCS-free EMEM did not induce cell differentiation or reduction of c-myc mRNA expression. When Caco-2 cells were cultured with three different serum-free media, the induction of dome formation and the increase of ALP activity were observed to varying degrees. Expression of c-myc mRNA in the cells cultured with one serum-free medium decreased to a level similar to that in fully differentiated cells cultured with EMEM containing 10% FCS. These results suggest that a spontaneous switch from a proliferative state with high c-myc expression to differentiated phenotype occurs after cells reach confluence and depends on the culture conditions.
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PMID:Changes of proliferative activity and phenotypes in spontaneous differentiation of a colon cancer cell line. 839 33

Prospectively gathered data from the National Health and Nutrition Examination Survey I and the National Health Evaluation Follow-Up Study were analyzed to evaluate the risk of colorectal cancer due to consumption of iron. Morbidity and mortality data due to colorectal cancer were available on 14,407 persons first interviewed in 1971 and followed through 1986. A total of 194 possible colorectal cancers occurred in this group over the 15-year period. Subsite analysis showed that the risk of colon cancer due to iron intake was elevated throughout the colon for both men and women, with the highest adjusted risks for the interquartile range seen in the proximal colon for females (relative risk, 1.51; 95% confidence interval, 1.41-1.60). The risk of rectal cancer was not significantly elevated for men or women. Elevated serum iron was also associated with increased risk; however, this effect was strongest in the distal (rather than proximal) colon and was significant only among females (adjusted relative risk, 1.73; 95% confidence interval, 1.03-2.92). The mean transferrin saturation was higher among cases than controls (30.7 versus 28.7%), but total iron-binding capacity did not seem to predict the occurrence of colorectal cancer. Proportional hazards models confirmed that the effects of iron and serum iron were not confounded by age, gender, energy consumption, fat intake, or other known risk factors for colorectal cancer. These data suggest that iron may confer an increased risk for colorectal cancer, and that the localization of risk may be attributable to the mode of epithelial exposure. It seems that luminal exposure to iron increases risk proximally, whereas humoral exposure increases risk distally. These differences may be due to such factors as oxidation state, binding proteins and the presence of other cofactors such as bile acids, products of bacterial metabolism.
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PMID:Iron intake and the risk of colorectal cancer. 882 53

Macromolecules accumulate in solid tumors and can thus be used as carriers for the delivery of attached contrast agents to tumors. We report the synthesis and use of serum protein-dye conjugates consisting of transferrin (Tf) or human serum albumin (HSA) and an indotricarbocyanine (ITCC) derivative as contrast agents for the optical imaging of tumors. The compounds were characterized with respect to their photophysical properties and tested in vitro for their ability to bind to tumor cells and in vivo for their potential to delineate experimental tumors. In contrast to HAS-ITTC, Tf-ITCC showed receptor-mediated uptake by HT29 human colon cancer cells in vitro. After intravenous injection into HT29 tumor-bearing nude mice both compounds induced increased fluorescence contrast of tumors in vivo. After 24 h the contrast between tumor and normal tissue was significantly higher for Tf-ITCC than for HAS-ITCC. Dye-induced fluorescence was found to be predominantly located in perinecrotic areas of the tumor. Furthermore, Tf-ITCC produced fluorescence of viable tumor cells, whereas HAS-ITCC fluorescence was recorded along connective tissue. We conclude that ITCC-labeled Tf and HSA can serve as macromolecular contrast agents for the optical imaging of tumors, with Tf-ITCC showing higher efficiency.
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PMID:Macromolecular contrast agents for optical imaging of tumors: comparison of indotricarbocyanine-labeled human serum albumin and transferrin. 1094 78

Benzamide riboside, a recently discovered inhibitor of IMP dehydrogenase (IMPDH) exhibits oncolytic activity. IMPDH is the key enzyme of de novo guanylate biosynthesis and was shown to be linked with proliferation. Therefore, IMPDH is a very good target for antitumor therapy. In order to be active, benzamide riboside has to be converted to BAD, an NAD analogue that binds to the NAD site on IMPDH. Inhibition of the enzyme by benzamide riboside selectively inhibits tumor cell growth and induces apoptosis in various human tumor cell lines. In this manuscript we describe the induction of the CD71 transferrin receptor in human promyelocytic leukemia HL-60 cells following treatment with benzamide riboside. The results indicate a possible involvement of the iron metabolism in the action of this new compound. Benzamide riboside might be clinically used in the treatment of leukemia and solid tumors, alone or as part of combination therapy. Since transferrin receptors are overexpressed in certain cancers, such as glioma and colon cancer, a combination therapy that includes benzamide riboside in transferrin-coupled liposomes will not only target cancer cells but also leads to suicidal action because benzamide riboside will upregulate transferrin receptors on cancer cells thereby make it accessible to dose-intensive chemotherapy. We therefore believe that benzamide riboside itself or derivatives of benzamide riboside might become an important addition for the treatment to diseases that are otherwise fatal.
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PMID:Benzamide riboside, a recent inhibitor of inosine 5'-monophosphate dehydrogenase induces transferrin receptors in cancer cells. 1196 39

Recent reports have demonstrated that hypoxia induces the up-regulation of transferrin receptor expression in tumour cells. Tumour cells take up 67Ga in the form of a 67Ga-transferrin complex via transferrin receptors. As a result, we attempted to determine the influence of hypoxic conditions on 67Ga uptake in tumour cells. B16 melanoma cells and LS180 colon cancer cells were incubated in 95% air/5% CO2 or 95% N2/5% CO2 for 1 h at 37 degrees C. Cellular uptake of 67Ga citrate was subsequently determined at 20, 40, 60 and 90 min. Uptake of the 67Ga-transferrin complex pre-chelated in vitro was similarly assessed. The effect of hypoxia on 67Ga binding to serum proteins was also investigated. Both B16 and LS180 cells displayed increased cellular uptake of 67Ga citrate in N2 gas in comparison to that in air (P < 0.0001). Hypoxia more prominently influenced cellular uptake of Ga-transferrin relative to that of 67Ga citrate (P < 0.0001). Hypoxia did not affect the percentages of 67Ga radioactivity bound to protein in medium supplemented with fetal calf serum, indicating that the results were not caused by the alteration of 67Ga-transferrin formation. These findings suggest the role of tissue hypoxia with respect to accumulation of 67Ga in tumours, which is likely mediated by transferrin receptors.
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PMID:Hypoxia as a factor for 67Ga accumulation in tumour cells. 1506 Dec 64

Type 2 hereditary hemochromatosis (HH) or juvenile hemochromatosis is an early onset, genetically heterogeneous, autosomal recessive disorder of iron overload. Type 2A HH is caused by mutations in the recently cloned hemojuvelin gene (HJV; also called HFE2) (Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M. L., Franchini, P. L., Dube, M. P., Andres, L., MacFarlane, J., Sakellaropoulos, N., Politou, M., Nemeth, E., Thompson, J., Risler, J. K., Zaborowska, C., Babakaiff, R., Radomski, C. C., Pape, T. D., Davidas, O., Christakis, J., Brissot, P., Lockitch, G., Ganz, T., Hayden, M. R., and Goldberg, Y. P. (2004) Nat. Genet. 36, 77-82), whereas Type 2B HH is caused by mutations in hepcidin. HJV is highly expressed in both skeletal muscle and liver. Mutations in HJV are implicated in the majority of diagnosed juvenile hemochromatosis patients. In this study, we stably transfected HJV cDNA into human embryonic kidney 293 cells and characterized the processing of HJV and its effect on iron homeostasis. Our results indicate that HJV is a glycosylphosphatidylinositol-linked protein and undergoes a partial autocatalytic cleavage during its intracellular processing. HJV co-immunoprecipitated with neogenin, a receptor involved in a variety of cellular signaling processes. It did not interact with the closely related receptor DCC (deleted in Colon Cancer). In addition, the HJV G320V mutant implicated in Type 2A HH did not co-immunoprecipitate with neogenin. Immunoblot analysis of ferritin levels and transferrin-55Fe accumulation studies indicated that the HJV-induced increase in intracellular iron levels in human embryonic kidney 293 cells is dependent on the presence of neogenin in the cells, thus linking these two proteins to intracellular iron homeostasis.
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PMID:Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells. 1610 17

Titanocene dichloride exhibits anti-proliferative activity in a wide spectrum of murine and human tumors. Although it is still unclear as to which species are active in biological media, they all readily deliver Ti(IV) to transferrin, the protein that transports iron in the blood. In this article, we report that aging of the complex in alcohols (namely methanol and ethanol) or dimethyl sulfoxide, the co-solvents used to prepare mother solution of the drug, leads to increased cytotoxic activity (i.e. lower IC(50) values) in HCT116 colon cancer cell lines, to a different extent. The TiCp(2)Cl(2) solvolysis was followed by (1)H NMR, ESI-MS, electrochemical and conductivity measurements, and the intracellular Ti(IV) uptake was evaluated.
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PMID:Enhancement of the cytotoxicity of titanocene dichloride by aging in organic co-solvent. 1620 87

In vitro and in vivo studies have associated iron with both the initiation and promotional stages of carcinogenesis. We investigated whether iron was associated with colorectal cancer in a nested case-control study within the alpha-tocopherol, beta-carotene cancer prevention study cohort. Exposure was assessed at baseline, using a 276-item food frequency questionnaire and a fasting serum sample. The study included 130 colorectal cancer cases (73 colon cancers and 57 rectal cancers) and 260 controls. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Supplemental iron intake was only reported for 4 cases and 18 controls; therefore, we were unable to obtain meaningful results for this variable. Comparing the highest to the lowest quartiles, there was an inverse association between serum ferritin and colorectal cancer risk (OR = 0.4, 95% CI = 0.2-0.9) and a suggestion of an inverse association between dietary iron and colorectal cancer risk (OR = 0.4, 95% CI = 0.1-1.1). In addition, serum ferritin, serum iron and transferrin saturation were all inversely associated with colon cancer risk specifically (OR = 0.2, 95% CI = 0.1-0.7, p trend = 0.02; OR = 0.2, 95% CI = 0.1-0.9, p trend = 0.05; OR = 0.1, 95% CI = 0.02-0.5, p trend = 0.003, respectively), whereas serum unsaturated iron binding capacity was positively associated with colon cancer risk (OR = 4.7, 95% CI = 1.4-15.1, p trend = 0.009). In summary, we found a significant inverse association between several serum iron indices and colon cancer risk.
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PMID:Iron and colorectal cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study. 1642 87

Malignant transformation is often accompanied by an aberrant glycosylation profile of the cell surface-in particular, the production of GlcNAcbeta1-6Manalpha1 branches in N-linked glycoproteins. To identify the target glycoproteins, we show a method using recombinant chicken N-acetylglucosaminyltransferase VI (GnT VI) and radiolabeled uridine (5'-)diphosphate-GlcNAc. The assay exploits the fact that GnT VI has a strict requirement for the GlcNAcbeta1-6Manalpha1 structure for activity, when a pyridylaminated free N-glycan is used as the acceptor substrate. Human asialo-agalacto alpha1-acid glycoprotein (AGP), which is known to contain GlcNAcbeta1-6Manalpha1 branches in its N-linked glycan chains, was radiolabeled when reacted with GnT VI, whereas human asialo-agalacto transferrin and bovine fetuin, neither of which contains a GlcNAcbeta1-6Manalpha1 structure were not, thus corroborating the specificity of the assay. Several proteins from human serum after pretreatment with sialidase and beta-galactosidase could be detected using the assay. One was identified as AGP from its mobility on SDS-PAGE, demonstrating the potential of this assay even with crude materials. Furthermore, this method could detect a protein that was also positively stained with leukoagglutinating phytohemagglutinin (L(4)-PHA) using glycoproteins prepared from WiDr human colon cancer cells. This method should provide a useful complement to the current method, which relies on the specificity of L(4)-PHA.
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PMID:A specific detection of GlcNAcbeta1-6Manalpha1 branches in N-linked glycoproteins based on the specificity of N-acetylglucosaminyltransferase VI. 1642 2


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