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)

Ferritin from malignant tissue differs electrophoretically from normal ferritin. The molecular basis of this difference has not yet been defined. Malignant tissue contains a mixture of ferritins from normal cells, inflammatory cells as well as cancer cells. GW-39 is a pure colon carcinoma cell system that synthesizes human carcinoembryonic antigen. Therefore, ferritin was isolated from normal colon mucosa and colon cancer tissues, as well as from the colon carcinoma cell line, to clarify the molecular relationship between normal and malignant ferritins. Colon carcinoma ferritin differs in primary structure from normal colon mucosal ferritin and contains at least six additional different tryptic peptides. These six peptides were also found in the ferritin from the colon carcinoma cell line. These data suggest that the alteration in ferritin structure occurs at the cellular level and is associated with the malignant state.
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PMID:Alteration in tryptic peptide patterns of ferritins purified from human colon carcinoma. 50 93

Monoclonal antibody F30 was produced by the fusion of murine myeloma cell line P3-X63-Ag8-653 with spleen cells from a BALB/C mouse immunized with established human pancreatic cancer cell line (PK-1) and the reaction specificity was analyzed. The antigen recognized by monoclonal antibody F30 was different from HLA-associated antigen, beta 2-microglobulin, fetal bovine serum components, ferritin, AFP, or CEA. Monoclonal antibody F30 reacted with all of six pancreatic cancer cell lines established in our laboratory. Cross-reactivity was detected with a colon cancer cell line or an esophagus cancer cell line among various tumor cell lines tested. No reaction was detected with red blood cells, lymphocytes, or lymphoid and myeloid cell lines. By immunoperoxidase staining of frozen sections, the F30-defined antigen was detected not only on pancreatic cancer cell membrane but also on other adenocarcinomas. In addition, the monoclonal antibody F30 had a more wide-spread distribution on normal epithelial cells in the gastrointestinal organs, respiratory system, and urinary system. F30-defined antigen was composed of two protein components with molecular weight of 190 and 160 K. It was indicated that the antigen was an integral protein in the cell membrane since the antigen was not detected in the spent culture medium of antigen-positive cells.
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PMID:Human pancreatic cancer associated antigen detected by monoclonal antibody. 351 31

Studies on the purification, characterization and clinical application of pancreatic oncofetal antigen were reported. This antigen was purified from fetal pancreas, and migrated in the beta-region on electrophoresis. Its molecular weight was about 80 x 10(4) daltons on gel filtration with a Sephacryl S-300. This antigen is clearly different from other oncofetal antigens such as alfafetoprotein, carcinoembryonic antigen or ferritin. Clinically, this pancreatic oncofetal antigen was positive in sera of 68.4% of the patients with pancreatic cancer. However, elevated level of this antigen was also observed in the sera of some patients with biliary tract cancer, colon cancer or gastric cancer. The antigen was also found in pancreatic juice obtained from patients with pancreatic cancer in almost the same incidence as in their sera. It is suggested that a pancreatic oncofetal antigen assay of sera and pancreatic juice in combination with other oncofetal antigens is valuable for the diagnosis and monitoring the clinical course of pancreatic cancer.
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PMID:A pancreatic oncofetal antigen: its partial purification and clinical application. 726 7

Neovascularization and hemorrhage are common features of malignant tumors. We wondered whether hemoglobin derived from extravasated RBC deposits heme-derived iron into the tumor, which could modulate the sensitivity of cancer cells to oxidant-mediated injury. A brief exposure (1 h) of 51Cr-radiolabeled breast cancer cells (BT-20) but not colon cancer cells (Caco-2) to hemin (10 microM) or FeSO4 (10 microM) significantly enhances cytotoxicity mediated by 0.5 mM hydrogen peroxide (H2O2). Associated with Caco-2 resistance, these cells were found to be enriched in the endogenous iron chelator, ferritin. If cellular ferritin is even further increased through 1 h incubation (24 h prior to H2O2 exposure) of both cell types with hemin, FeSO4, or exogenous spleen apoferritin itself (24 h), marked resistance to H2O2-mediated cytotoxicity is manifest. Under several conditions, the sensitivity of tumor cells to oxidant-mediated lysis is inversely proportional to their ferritin content. Pretreatment of BT-20 and Caco-2 cells with hemin or FeSO4 rapidly increases H-ferritin mRNA but only slightly increases L-ferritin mRNA; nevertheless, large increases in overall ferritin content of iron-exposed cells result. Data analogous to those with H2O2-mediated cytotoxicity were obtained in studies of bleomycin-engendered DNA strand breakage and cell damage, i.e., brief treatment of BT-20 cells with both hemin or FeSO4 significantly increases their sensitivity to bleomycin (100 micrograms/ml), whereas treatment followed by 24 h incubation with media alone significantly protects against bleomycin toxicity. We speculate that acute exposure of tumors to iron (e.g., derived from heme-proteins in hemorrhagic cancerous lesions) may increase sensitivity of some cancer cells, particularly those relatively low in endogenous ferritin, to oxidant-mediated lysis. In contrast, repeated, more chronic, exposure effector cells or chemotherapeutic agents, an effect derived from their increased synthesis and accumulation of the intracellular iron scavenger, ferritin.
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PMID:Tumor cell heme uptake induces ferritin synthesis resulting in altered oxidant sensitivity: possible role in chemotherapy efficacy. 822 66

We investigated blood loss from colorectal cancer in 92 men seen between January 1990 and June 1997, in relation to the size and site of the tumor, Dukes stage, pathologic type of cancer, and serum carcinoembryonic antigen (CEA) positivity. We used indirect methods, measuring serum hemoglobin, iron, and ferritin concentrations. The means of these three concentrations were significantly lower in patients with a tumor >3cm than in those with a tumor < or =3cm in largest diameter. The means of the three values were lower in patients with proximal colon cancer than in those with distal colon cancer, but only the difference in serum hemoglobin concentration was significant. Cancers of the ulcerative type were found more often in the proximal colon. The proportion of patients with Dukes stage C or D was not different between those with proximal colon cancer and those with distal colon cancer. There was a positive correlation between tumor size and Dukes stage. There were no differences in serum hemoglobin, iron, and ferritin concentrations with respect to the pathologic type of cancer and CEA positivity. These findings show that blood loss from colorectal cancer is closely related to the size and site of the tumor.
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PMID:Serum iron and ferritin levels in patients with colorectal cancer in relation to the size, site, and disease stage of cancer. 1021 18

In a retrospective study of 79 consecutive patients, we evaluated characteristics of polymyositis (PM) and dermatomyositis (DM) and compared clinical presentation, biochemical findings, histologic changes, evolution, complications, and mortality rate of elderly patients (aged > or = 65 yr) and younger patients (aged < or = 64 yr) at the onset of PM/DM. We found a high prevalence of PM/DM in elderly patients: 23 patients (29%) were aged 65 years or over. We also found that esophageal involvement (34.8% versus 16.1%, respectively) and bacterial pneumonia related to both ventilatory insufficiency and esophageal impairment (21.7% versus 5.4%, respectively) were more common in elderly patients compared with younger patients, resulting in increased morbidity and mortality rates. Moreover, malignancy frequency was higher in elderly patients compared with younger patients (47.8% versus 9.1%, respectively, p = 0.0001), particularly patients with DM (10/11). Fifty percent of malignancies were colon malignancies in elderly patients. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and ferritin levels were also higher in the elderly patient group compared with the younger group, and the presence of serum hypoprotidemia, hypoalbuminemia, and anemia was more frequent. Finally, PM/DM complete remission was less frequent (13.6% versus 41.1%) and the mortality rate (47.8% versus 7.3%) was higher in elderly patients than in younger patients. The main causes of death in elderly patients were bacterial pneumonia, due to ventilatory insufficiency and esophageal impairment, and malignancies. Our findings therefore indicate that PM/DM-related esophageal and lung involvement should be systematically searched for in elderly patients. Esophageal manometry and pulmonary function tests should become an integral part of initial evaluation in elderly patients for early detection of impairment. Moreover, as we observed a marked overrepresentation of colon cancer in elderly patients with DM, we suggest that the search for malignancies in elderly patients with DM should include lower gastrointestinal tract investigations.
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PMID:Influence of age on characteristics of polymyositis and dermatomyositis in adults. 1035 46

To study the mechanisms that control epithelial commitment and differentiation we have used undifferentiated HT-29 colon cancer cells and a subpopulation of mucus secreting cells obtained by selection of HT-29 cells in 10-6 M methotrexate (M6 cells) as experimental models. We isolated cDNAs encoding transcripts overexpressed in early confluent M6 cells regarding steady-state levels in HT-29 cells by subtractive hybridisation. Fifty-one cDNA clones, corresponding to 34 independent transcripts, were isolated, partially sequenced by their 5' end, and classified into four groups according to their identity: transcripts that included a repeated sequence of the Alu family (10 clones, among them those encoding ribonucleoprotein RNP-L and E-cadherin), transcripts encoded by the mitochondrial genome (nine clones), transcripts encoding components of the protein synthesis machinery (23 clones, including the human ribosomal protein L38 not previously cloned in humans) and nine additional cDNAs that could not be classified in the previous groups. These last included ferritin, cytokeratin 18, translationally controlled human tumour protein (TCHTP), mt-aldehyde dehydrogenase, as well as unknown transcripts (three clones), and the human homologues of the molecular motor kinesin KIF3B and of the ser/thr protein kinase EMK1. Spot dot and Northern blot analyses showed that ser/thr protein kinase EMK1 was differentially expressed in M6 cells when compared with parental HT-29 cells. Steady-state levels of EMK1 were higher in proliferating, preconfluent, M6 and HT-29 cells than in 2 days post confluence (dpc) and 8dpc M6 and HT-29 cells. Transcripts that included an Alu repeat were also shown to be differentially expressed and accumulated in differentiating M6 cells when analysed by Northern blot. The significance of the transcripts cloned is discussed in the context of the commitment and differentiation of the M6 cells to the mucus secreting lineage of epithelial cells.
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PMID:Expressed sequence tag (EST) phenotyping of HT-29 cells: cloning of ser/thr protein kinase EMK1, kinesin KIF3B, and of transcripts that include Alu repeated elements. 1039 37

We described before that iron-containing, anti-anaemic drug, ferric-sorbitol-citrate complex (FSC) inhibited proliferation of various murine cancer cells in vitro and caused tumour regression in vivo, but did not affect proliferation of the non-malignant cells. The aim of this study was to evaluate further the anticancer activity mechanism of FSC using human colon cancer cell line CaCo2. After treatment with FSC for 72 hours impaired proliferative ability and viability of CaCo2 cells as observed. Growth modification caused by FSC involved diminished expression of Bcl-2, and over-expression of mp53 proto-oncogenes, accompanied by increased incidence of apoptosis. Immunostaining the cells applying monoclonal antibodies for lipid peroxidation product 4-hydroxynonenal (HNE) showed that FSC-iron increased intracellular HNE, but did not induce severe HNE-mediated oxidative stress. Thus, antitumorous mechanism of FSC involves modulation of oncogene expression and induction of apoptosis apparently not triggered by lipid peroxidation-mediated oxidative stress, although FSC might restore endogenous HNE production in the CaCo2 cells to level resembling physiological for various non-malignant cells and tissues. Higher dose of FSC increased also number of intracellular ferritin positive CaCo2 cells.
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PMID:Involvement of lipid peroxidation, oncogene expression and induction of apoptosis in the antitumorous activity of ferric-sorbitol-citrate. 1094 36

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

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


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