Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to improve the non aggressive diagnosis of hepatic metastasis from digestive neoplasm, the authors analyzed the following biological parameters: aminotransferases, alkaline phosphatase and lacticodehydrogenase isoenzymes, gammaglutamyl-transpeptidase, conjugated and total bilirubin, C-reactive protein, type A, G, M immunoglobulins, C3 complement factor, alpha-1 acidic glycoprotein (orosomucoid), haptoglobin, ceruloplasmin, transferrin, albumin, prealbumin, ferritin. This work included 54 patients with digestive tract cancer (esophageal, gastric, colic, rectal, anal localizations), divided in two groups: M- (n = 27), without hepatic metastasis), and M+ (n = 27, with histological confirmed hepatic metastasis). The Mann-Whitney test showed significant differences for 12 parameters between the 2 groups. With more than 60% sensitivity (Se) and specificity (Sp), according to the ROC curves, the following parameters can be selected: Total alkaline phosphatase (Se 89%, Sp 70%) and their macromolecular H2 fraction, lacticodehydrogenase fraction 4 (Se 63%, Sp 63%), gammaglutamyl-transpeptidase (Se 85%, Sp 82%), ceruloplasmin (Se 64%, Sp 65%), aspartate-aminotransferase determination (Se 63%, Sp 65%).
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PMID:[Detection of liver metastases from digestive cancer. Value of alkaline phosphatases, their macromolecular isoenzyme and of ceruloplasmin]. 923 22

This study examined the effect of an acute-phase response on plasma trace element concentrations of non-small cell lung cancer (NSCLC) patients. In normal subjects (n = 13) and NSCLC patients (n = 22), fasting concentrations of albumin, C-reactive protein, the trace elements iron, zinc, copper, and selenium, and their associated proteins transferrin, albumin, ceruloplasmin, and glutathione peroxidase were measured. The NSCLC patients were subdivided into two equal groups depending on whether they had a C-reactive protein concentration < 35 mg/l (Group 1) or > 35 mg/l (Group 2). Circulating zinc, iron, and transferrin concentrations were significantly lower in NSCLC Group 1 than in the control group (p < 0.05). Circulating concentrations of iron, zinc, and the binding proteins transferrin and albumin were significantly lower in NSCLC Group 2 than in the control group and NSCLC Group 1 (zinc not significantly different) (p < 0.01). In contrast circulating concentrations of copper and its binding protein ceruloplasmin were significantly increased in NSCLC Group 2 compared with NSCLC Group 1 and the control group (p < 0.01). Additionally, plasma selenium and glutathione peroxidase concentrations were significantly lower (p < 0.05) in NSCLC Group 2 than in NSCLC Group 1 and the control group. In the NSCLC patients there were significant negative correlations between concentrations of C-reactive protein and iron, transferrin, zinc, albumin, and selenium (p < 0.05). Furthermore, there were also significant positive correlations between C-reactive protein and copper (r = 0.788, p < 0.001) and ceruloplasmin (r = 0.831, p < 0.001) concentrations. The presence of an acute-phase response has implications for the interpretation of circulating trace element concentrations, the status of patients with NSCLC, and supplementation with trace elements in patients with NSCLC.
Nutr Cancer 1997
PMID:Acute-phase reactants and plasma trace element concentrations in non-small cell lung cancer patients and controls. 934 41

Trace elements have been extensively studied in recent years to assess whether they have any modifying effects in the etiology of cancer. In the present study serum levels of copper, zinc, ceruloplasmin, total iron and total protein were estimated in 92 patients with oral leukoplakia and squamous cell carcinoma and 45 age and sex matched controls. Copper was significantly increased in oral leukoplakia and cancer in both sexes. The level of zinc decreased significantly only in male patients with leukoplakia and cancer. Copper zinc ratio was found significantly elevated in oral leukoplakia and cancer. A marked increase in serum ceruloplasmin was seen in oral leukoplakia and cancer in both sexes. A significant decrease of serum total iron and proteins were observed only in carcinomas. These findings suggest that reduction in the serum total iron and total protein may be due to malnutrition caused, on its turn, by tumour burden. Serum ceruloplasmin level and copper-zinc ratio demonstrated significant differences in the patients of both sexes from those of controls, while, comparing leukoplakia with cancer, a significant difference is only observed in male patients. Thus, the present study shows that these factors have diagnostic value only in differentiating malignancies from normal and a little value as biomarkers of disease progression. However, the exact mechanism responsible for the alteration of these factors in oral lesions is still not clear and a detailed study on large sample size is therefore needed.
J Exp Clin Cancer Res 1997 Sep
PMID:Serum levels of copper, zinc, iron and ceruplasmin in oral leukoplakia and squamous cell carcinoma. 938 4

We investigated the generation of nitric oxide (NO) by H2O2-dependent peroxidation of hydroxyurea in the presence of copper-containing proteins such as Cu,Zn-superoxide dismutase (Cu,Zn-SOD) or ceruloplasmin as a catalyst. In the reaction mixture of hydroxyurea, CuZn-SOD, and H2O2, NO generation was identified by measuring the specific electron spin resonance (ESR) signal of 2-phenyl-4, 4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO). The ESR signal of the NO-hemoglobin adduct was also detected in human red blood cells during copper-catalyzed peroxidation of hydroxyurea. The NO production during peroxidation of hydroxyurea was quantified as NO2- formation, measured by using the Griess assay, the amount of NO2- was dependent on the concentrating of hydroxyurea of the reaction mixture. ESR spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) showed hydroxy radical (OH) generation in the reaction of H2O2 with either Cu,Zn-SOD or ceruloplasmin. Several OH scavengers, such as ethanol, thiourea, DMPO, and dimethylsulfoxide, and the metalchelating agent diethylenetriaminepentaacetic acid significantly inhibited NO generation from hydroxyurea. This indicates that NO release from hydroxyurea may be mediated by OH derived from the copper-catalyzed Fenton-like reaction. Incubation of hydroxyurea and Cu,Zn-SOD with xanthine oxidase and hypoxanthine in a system forming O2- -->H2O2 also resulted in appreciable NO production. These results suggest that NO production from hydroxyurea catalyzed by copper-containing proteins may be the molecular basis of the pharmacological and antitumor action of hydroxyurea.
Jpn J Cancer Res 1997 Dec
PMID:Nitric oxide generation from hydroxyurea via copper-catalyzed peroxidation and implications for pharmacological actions of hydroxyurea. 947 38

The pursuit of the ideal tumor marker has generated many tests for use in the diagnosis and management of cancer, several of which are now widely available. The objective of this study was to evaluate the diagnostic utility as a cancer marker of plasmatic levels of ceruloplasmin. Ceruloplasmin is a glucoprotein that transports serum copper. A case-control design was used. Serum values were evaluated in 144 patients and 103 normal controls by receiver operating characteristic (ROC) curve analysis to define the optimal cut-off levels for the serum values of ceruloplasmin in the diagnosis of cancer. The ROC analysis showed that ceruloplasmin is considerably sensitive in men (80%) at the specificity level of 80.3% and in women the sensitivity (Se) was (63.2%) and the specificity (Sp) was (63.3%). According to this study, it would seem optimal to use the cut-off level of 358 mg/l in men and 383 mg/l in women. In conclusion, serum ceruloplasmin was significantly elevated in advanced stages of solid malignant tumors, however, locally advanced or locoregionally spreading tumors did lead to significant increases (P < 0.01). Finally, the results of ROC curve analysis suggest that the ceruloplasmin is characteristic of good diagnostic markers.
Cancer Lett 1997 Dec 23
PMID:Serum ceruloplasmin as a diagnostic marker of cancer. 957 Mar 51

Variations in copper-containing superoxide dismutase (SOD) 1 are hypothesized to produce variations in resistance to carcinogenesis, particularly in mammary tissue. Therefore, it is reasonable to speculate that low copper intake, which causes low SOD 1 activities in various tissues, would cause poor resistance to mammary carcinogenesis. This idea was tested using female rats fed diets either low or adequate in copper (< 0.5 or 8 mg copper/kg diet) plus or minus oral gavage with the mammary carcinogen 7,12-dimethylbenz[a]anthracene (5 mg/kg, given 5 wk after dietary modification, 28 wk before sacrifice). Low copper intake produced low activities of two serum copper enzymes: ceruloplasmin and extracellular SOD. In contrast, low copper intake did not affect mammary tissue SOD 1 activities, nor did it statistically influence any of several parameters of 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis.
Nutr Cancer 1998
PMID:No effects of low copper intake on rat mammary tissue superoxide dismutase 1 activity and mammary chemical carcinogenesis. 979 75

40 cases of breast malignancy constituted the study group and 10 sex matched formed the control grp. Serum level of copper was estimated by atomic absorption photometry and ceruloplasmin was done by Houchin's method. The study group showed significant hypercupremia and increased level of serum ceruloplosmin. It was postulated that levels copper and ceruloplasmin may help in prognosis & diagnosis of disease.
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PMID:Copper and ceruloplasmin levels in serum of women with breast cancer. 980 8

The levels of 21 protein components of the sera of 45 patients with cancer of the larynx undergoing radiation therapy were determined by a single radial immunodiffusion method before and after radiation therapy. We examined the correlation between changes in serum protein fractions and the prognosis of the patients. The patients with cancer of the larynx were treated with external irradiation of 60Co gammer-rays. Total target doses were 60 Gy. The levels of the same protein components were also measured in 43 normal adult individuals as a control. All patients were observed for 5 years and 12 years following radiation therapy. In the pretreatment sera obtained from patients with cancer of the larynx, the concentrations of prealbumin (Prealb), antithrombin III (ATIII) and plasminogen (Pmg) were significantly lower than controls. However the concentrations of alpha 1-acid glycoprotein (alpha 1AG), alpha 1-antitrypsin (alpha 1AT), alpha 1-antichymotrypsin (alpha 1X), haptoglobin (Hp), fibrinogen (Fib) and hemopexin (Hx) were elevated. At the completion of radiation therapy, the alpha 1AG, alpha 1AT, alpha 1X, Hp, Fib and inter alpha trypsin inhibitor (I alpha I) were significantly elevated than those normal controls. In patients without recurrent cancer after radiation therapy, the alpha 1AT, ceruloplasmin (Cp), Fib, IgA and Hx levels measured before radiation therapy were significantly lower than those patients with recurrent cancer. In patients without recurrent cancer after radiation therapy, the alpha 1AT, Hp, Cp, IgG, and IgA levels measured after radiation therapy were reduced compared with those patients with recurrent cancer. In patients who had lived more than 5 years after radiation therapy, the alpha 1AT, Cp and Fib levels measured before radiation therapy reduced significantly compared with those who had died within 5 years. In those who had lived more than 5 years, the alpha 1AG, alpha 1AT, Hp, Fib, IgG, and IgA levels measured after radiation therapy were reduced significantly compared with those who died within 5 years. In cases of laryngeal cancer following a period of 5 to 12 years after radiation therapy, multiple regression analysis was used to determine whether increased concentrations of serum protein fractions were associated with good prognosis for the original disease. AT III, Prealb, alpha 1AG, albumin (Alb) and I alpha I before radiation therapy were positively correlated with survival, whereas Hx, Pmg, Cp, IgM, Cl inhibitor (ClInh), alpha 1AT and Fib showed negative correlations. After radiation therapy, transferrin (Tf), Cp, Prealb, AT III and I alpha I were found to be positively associated with survival, whereas IgA, IgM, Pmg, alpha 1X and alpha 1AG were negative factors. From the elevation levels of acute phase proteins (alpha 1AT, Cp) and Fib and immunoglobulins (IgA, IgM) in the serum and lower levels of Prealb and AT III before and after radiation therapy, we may predict a relatively poor prognosis in these patients of laryngeal cancer.
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PMID:[Serum protein fractions in patients with laryngeal cancer undergoing radiation therapy. Possibility as a prognostic factor]. 1019 63

The presence of an acute-phase protein response (APPR) has been suggested to shorten survival and contribute to weight loss in patients with pancreatic cancer. Fatty acids derived from fish oil have been shown to alter proinflammatory cytokine production and acute-phase protein synthesis in vitro. The present study was designed to determine the effects of a fish oil-enriched nutritional supplement on the concentrations of a range of individual acute-phase proteins (APP) in patients with advanced pancreatic cancer. In a sequential series, 18 patients with pancreatic cancer received the supplement (providing 2 g eicosapentaenoic acid and 1 g docosahexaenoic acid/d) for 3 wk while another 18 received full supportive care alone. Six healthy subjects served as additional controls. Acute-phase proteins were measured before and after the 3-wk intervention period in cancer patients. At baseline, albumin, transferrin and pre-albumin were significantly reduced and fibrinogen, haptoglobin, alpha-1-acid glycoprotein, alpha-1-antitrypsin, ceruloplasmin and C-reactive protein (CRP) were significantly elevated in the cancer patients compared with healthy controls, reflecting their roles as negative and positive acute phase proteins, respectively. In the supplemented cancer group, the only significant change in APP concentrations over the 4-wk study period was an increase in transferrin. In the control cancer group there were further significant reductions in albumin, transferrin and pre-albumin, and a significant increase in CRP concentration. These results suggest that many positive and negative APP are altered in advanced pancreatic cancer. The APPR tends to progress in untreated patients but may be stabilized by the administration of a fish oil-enriched nutritional supplement. This may have implications for reducing wasting in such patients.
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PMID:Fish oil-enriched nutritional supplement attenuates progression of the acute-phase response in weight-losing patients with advanced pancreatic cancer. 1035 75

Preclinical and in vitro studies have determined that copper is an important cofactor for angiogenesis. Tetrathiomolybdate (TM) was developed as an effective anticopper therapy for the initial treatment of Wilson's disease, an autosomal recessive disorder that leads to abnormal copper accumulation. Given the potency and uniqueness of the anticopper action of TM and its lack of toxicity, we hypothesized that TM would be a suitable agent to achieve and maintain mild copper deficiency to impair neovascularization in metastatic solid tumors. Following preclinical work that showed efficacy for this anticopper approach in mouse tumor models, we carried out a Phase I clinical trial in 18 patients with metastatic cancer who were enrolled at three dose levels of oral TM (90, 105, and 120 mg/day) administered in six divided doses with and in-between meals. Serum ceruloplasmin (Cp) was used as a surrogate marker for total body copper. Because anemia is the first clinical sign of copper deficiency, the goal of the study was to reduce Cp to 20% of baseline value without reducing hematocrit below 80% of baseline. Cp is a reliable and sensitive measure of copper status, and TM was nontoxic when Cp was reduced to 15-20% of baseline. The level III dose of TM (120 mg/ day) was effective in reaching the target Cp without added toxicity. TM-induced mild copper deficiency achieved stable disease in five of six patients who were copper deficient at the target range for at least 90 days.
Clin Cancer Res 2000 Jan
PMID:Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: Phase I study. 1065 25


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