Studies on the mechanisms of biliary excretion of circulating glycoproteins. The carcinoembryonic antigen.
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ABSTRACT:
SUBMITTER: Thomas P
PROVIDER: S-EPMC1162407 | biostudies-other | 1980 Dec
REPOSITORIES: biostudies-other
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Project description:1. The biliary excretion of injected [(14)C]aniline, [(14)C]benzoic acid, 4-amino-hippuric acid and 4-acetamidohippuric acid in six or eight species of animal (rat, dog, hen, cat, rabbit, guinea pig, rhesus monkey and sheep) was studied. 2. These compounds, with molecular weights in the range 93-236, are poorly excreted in the bile in all the species examined and, in effect, there is little significant species difference in the extent of their biliary excretion. 3. Compounds of higher molecular weight (355-495) were also studied, namely succinylsulphathiazole, [(14)C]stilboestrol glucuronide, sulphadimethoxine N(1)-glucuronide and phenolphthalein glucuronide. 4. With these compounds a clear species difference in the extent of biliary excretion was found, the rat, dog and hen being good excretors, the rabbit, guinea pig and monkey poor excretors, and the cat and sheep taking an intermediary position. 5. There was a general trend for biliary excretion to be higher in all species when the compounds were of higher molecular weight. 6. These results are discussed in their relation to species differences in drug metabolism.
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Project description:ObjectiveThe aim of the present study is to determine if CEACAM6 can be detected in the bile of patients with biliary cancer and can serve as a diagnostic biomarker for cholangiocarcinoma.Summary background dataDistinguishing bile duct carcinoma from other diagnoses is often difficult using endoscopic or percutaneous techniques. The cell surface protein CEACAM6 is over-expressed in many gastrointestinal cancers and may be selectively elevated in biliary adenocarcinoma.MethodsBile from patients with benign biliary disease and cholangiocarcinoma (hilar, intrahepatic and distal) was collected at the time of index operation. The concentration of CEACAM6 was quantified by sandwich enzyme-linked immunosorbent assay (ELISA) and correlated to pathologic diagnosis. Diagnostic capability of CEACAM6 was evaluated by Wilcoxon rank-sum, linear regression, multiple regression, and receiver operating characteristic (ROC) curve analysis.ResultsBile from 83 patients was analyzed: 42 with benign disease and 41 with cholangiocarcinoma. Patients in the benign cohort were younger, predominantly female, and had lower median biliary CEACAM6 levels than patients in the malignant cohort (7.5 ng/ml vs. 40 ng/ml; p = <.001). ROC curve analysis determined CEACAM6 to be a positive predictor cholangiocarcinoma with a CEACAM6 level >14 ng/ml associated with 87.5% sensitivity, 69.1% specificity, and a likelihood ratio of 2.8 (AUC 0.74). Multiple regression analysis suggested elevated alkaline phosphatase and the presence of biliary endoprostheses may influence CEACAM6 levels.ConclusionBiliary CEACAM6 can identify patients with extrahepatic cholangiocarcinoma with a high degree of sensitivity and should be investigated further as a potential screening tool.
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Project description:The kidneys integrate information from continuous systemic processes related to the absorption, distribution, metabolism and excretion (ADME) of metabolites. To identify underlying molecular mechanisms, we performed genome-wide association studies of the urinary concentrations of 1,172 metabolites among 1,627 patients with reduced kidney function. The 240 unique metabolite-locus associations (metabolite quantitative trait loci, mQTLs) that were identified and replicated highlight novel candidate substrates for transport proteins. The identified genes are enriched in ADME-relevant tissues and cell types, and they reveal novel candidates for biotransformation and detoxification reactions. Fine mapping of mQTLs and integration with single-cell gene expression permitted the prioritization of causal genes, functional variants and target cell types. The combination of mQTLs with genetic and health information from 450,000 UK Biobank participants illuminated metabolic mediators, and hence, novel urinary biomarkers of disease risk. This comprehensive resource of genetic targets and their substrates is informative for ADME processes in humans and is relevant to basic science, clinical medicine and pharmaceutical research.
| S-EPMC7484970 | biostudies-literature
Project description:PurposePrevious studies have shown that serum carcinoembryonic antigen (CEA) is independently associated with metabolic syndrome (MetS). However, these studies were mainly cross-sectional analyses, and cause was not clarified. In the present study, two bidirectional cohort studies were conducted to investigate the bidirectional associations between CEA and MetS using a Chinese male sample cohort.MethodsThe initial longitudinal cohort included 9629 Chinese males enrolled from January 2010 to December 2015. Two bidirectional cohorts were conducted in the study: subcohort A (from CEA to MetS, n = 6439) included participants without MetS at baseline to estimate the risk of developing incident MetS; subcohort B (from MetS to CEA, n = 8533) included participants without an elevated CEA level (Hyper-CEA) at baseline to examine the risk of developing incident Hyper-CEA. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.ResultsIn subcohort A, the incidence densities of MetS among participants with and without Hyper-CEA were 84.56 and 99.28 per 1000 person-years, respectively. No significant effects of Hyper-CEA on incident MetS were observed in subcohort A (HR, 0.89; 95% CI, 0.71 to 1.12; P = 0.326). In subcohort B, a higher incidence density of Hyper-CEA was found among participants with MetS (33.42 and 29.13 per 1000 person-years for those with and without MetS, respectively). For nonsmoking participants aged > 65 years, MetS increased the risk of incident Hyper-CEA (HR, 1.87; 95% CI, 1.09 to 3.20; P = 0.022).ConclusionFor the direction of CEA on incident MetS, no significant association was observed. For the direction of MetS on incident Hyper-CEA, MetS in nonsmoking elderly men could increase the risk of incident Hyper-CEA, while this association was not found in other stratified participants. The clinical implications of the association between CEA and MetS should be interpreted with caution.
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Project description:Iron is an essential nutrient yet toxic in excess. Our understanding of mammalian mechanisms of dietary iron absorption exceeds our understanding of mechanisms of iron excretion. Here we demonstrate that biliary excretion of excess iron in mice requires the metal transporter SLC39A14 and that excess Fe is excreted into bile as ferritin and heme. The identification of a molecular determinant of iron excretion and the biochemical form of bile iron could lead to development of novel therapeutics for human diseases of iron excess
2021-02-10 | MSV000086836 | MassIVE
Project description:Carcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94-3.73, p < 0.001). Pulmonary tuberculosis (7/1311, 0.53%) had the lowest positive rate of CEA elevations while pulmonary alveolar proteinosis (6/27, 22.22%) had the highest positive rate. The majority of patients with abnormally elevated CEA levels had multiple underlying diseases, mainly diseases of the circulatory system (42.28% [63/149]), endocrine diseases (26.85% [40/149]), and respiratory or heart failure (24.16% [36/149]. In endocrine diseases, 87.5% (35/40) of patients had diabetes. In conclusion, CEA is present at a low positive rate in the serum of patients with BLD, but few exceed 20 ng/mL. For lung disease patients, if CEA levels rise, we should carry out comprehensive analysis of types of lung diseases, age of patients, and comorbid diseases.
| S-EPMC8463604 | biostudies-literature
Project description:ImportanceA circulating tumor DNA (ctDNA) assay (Signatera; Natera) has been marketed for use in the surveillance of resected colorectal cancer despite limited data supporting such practice.ObjectiveTo compare a ctDNA assay with standard radiographic imaging and measurement of carcinoembryonic antigen (CEA) levels, per National Comprehensive Cancer Network guidelines, in the surveillance of resected colorectal cancer.Design, setting, and participantsThis retrospective, single-center cohort study evaluated surveillance strategies of ctDNA, imaging, and measurement of CEA levels in patients with resected colorectal cancer from September 1, 2019, to November 30, 2021.Main outcomes and measuresThe sensitivity and specificity of ctDNA, imaging, measurement of CEA levels, and combination of imaging plus measurement of CEA levels in detecting a confirmed recurrence of colorectal disease. A confirmed recurrence was defined as a positive ctDNA finding or a finding on imaging confirmed by biopsy, CEA level elevation, or subsequent tumor radiographic dynamics.ResultsA total of 48 patients with curatively resected colorectal cancer satisfied the inclusion criteria for this study (28 men [58.3%]; median age, 60 [IQR, 34-85] years) and underwent surveillance by ctDNA, imaging, and measurement of CEA levels. Fifteen patients had disease recurrence during surveillance. Positive ctDNA findings confirmed disease recurrence in 8 patients; imaging, in 9 patients; CEA levels, in 3 patients; and combined imaging plus CEA levels, in 11 patients. Numerically, ctDNA did not perform better than imaging in detecting recurrence, with sensitivities of 53.3% (95% CI, 27.4%-77.7%) and 60.0% (95% CI, 32.9%-82.5%), respectively (P > .99). The combination of imaging plus measurement of CEA levels (sensitivity, 73.3% [95% CI, 44.8%-91.1%]) had a numerical advantage compared with ctDNA in identifying recurrence (P = .55). In addition, no significant difference was noted among ctDNA (median, 14.3 months), imaging (median, 15.0 months), or imaging plus measurement of CEA levels (median, 15.0 months) in the time to identify disease recurrence.Conclusions and relevanceThe findings of this cohort study suggest that ctDNA assay may not provide advantages as a surveillance strategy compared with standard imaging combined with CEA levels when performed per National Comprehensive Cancer Network guidelines.
| S-EPMC8905389 | biostudies-literature
Project description:1. The biliary and urinary excretion of (+)-[U-(14)C]catechin was studied in normal male rats after a single injection of the flavonoid. 2. In rats large amounts of radioactivity (33.6-44.3% of the dose in 24h) were excreted in the bile as two glucuronide conjugates [one of which was a (+)-catechin conjugate] and three other unconjugated metabolites. 3. Excretion of radioactivity in the urine when the bile duct was not cannulated amounted to 44.5% of the dose. 4. In both the urine and bile the new metabolites showed maximum excretion in the (1/2)-1(1/2)h after intravenous injection of [(14)C]catechin. 5. The metabolites m-hydroxyphenylpropionic acid, p-hydroxyphenylpropionic acid, delta-(3-hydroxyphenyl)-gamma-valerolactone and delta-(3,4-dihydroxyphenyl)-gamma-valerolactione originate from the action of the intestinal micro-organisms on the biliary-excreted metabolites of (+)-catechin. These phenolic acid and lactone metabolites are then reabsorped and excreted in the urine. 6. It is proposed that, depending on the route of administration of (+)-catechin, there exists an alternative pathway, involving biliary excretion, for the metabolism of (+)-catechin.
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Project description:BACKGROUND:In colorectal cancer, survival of patients is drastically reduced when complete resection is hampered by involvement of critical structures. Targeted photodynamic therapy (tPDT) is a local and targeted therapy which could play a role in eradicating residual tumor cells after incomplete resection. Since carcinoembryonic antigen (CEA; CEACAM5) is abundantly overexpressed in colorectal cancer, it is a potential target for tPDT of colorectal cancer. METHODS:To address the potential of CEA-targeted PDT, we compared colorectal cancer cell lines with different CEA-expression levels (SW-48, SW-480, SW-620, SW-1222, WiDr, HT-29, DLD-1, LS174T, and LoVo) under identical experimental conditions. We evaluated the susceptibility to tPDT by varying radiant exposure and concentration of our antibody conjugate (DTPA-hMN-14-IRDye700DX). Finally, we assessed the efficacy of tPDT in vivo in 18 mice (BALB/cAnNRj-Foxn1nu/nu) with subcutaneously xenografted LoVo tumors. RESULTS:In vitro, the treatment effect of tPDT varied per cell line and was dependent on both radiant exposure and antibody concentration. Under standardized conditions (94.5 J/cm2 and 0.5 μg/μL antibody conjugate concentration), the effect of tPDT was higher in cells with higher CEA availability: SW-1222, LS174T, LoVo, and SW-48 (22.8%, 52.8%, 49.9%, and 51.9% reduction of viable cells, respectively) compared to cells with lower CEA availability. Compared to control groups (light or antibody conjugate only), tumor growth rate was reduced in mice with s.c. LoVo tumors receiving tPDT. CONCLUSION:Our findings suggest cells (and tumors) have different levels of susceptibility for tPDT even though they all express CEA. Furthermore, tPDT can effectively reduce tumor growth in vivo.
| S-EPMC6906275 | biostudies-literature
Project description:Uptake of carcinoembryonic antigen from the circulation of the mouse is inhibited by treatment of the animal with Triton WR1339, but not by asialo-fetuin. Uptake of asialo-carcinoembryonic antigen is inhibited by asialo-fetuin, but not by Triton WR1339. These results reflect the different mechanisms of uptake of the glycoproteins. The presence or absence of sialic acid does not seem to be important in governing Kupffer-cell uptake, but when terminal galactoses are exposed on a glycoprotein, uptake by hepatocytes is preferred. Kupffer-cell uptake of carcinoembryonic antigen is not due to the formation of high-molecular-weight complexes in the blood stream. The effect of asialo-fetuin and Triton WR1339 on the biliary excretion of carcinoembryonic antigen and asialo-carcinoembryonic antigen is discussed.
| S-EPMC1185867 | biostudies-other