RESUMEN
The sensitive detection of cancer biomarkers is crucial for early accurate diagnostics and therapy of cancer patients. Carcinoembryonic antigen (CEA) is a tumor-associated antigen derived from colon cancer and embryonic tissues. In this study, we have developed a label-free fluorescence biosensing platform for the quantification of CEA with the "turn-on" signal output. This platform employs a label-free strategy that incorporates an aptamer-modified gold nanoparticle (Apt@AuNP) probe for the recognition of CEA, in combination with hybridization chain reaction (HCR) amplification. In the presence of target CEA, Apt@AuNPs selectively capture CEA, resulting in a reduction of subsequent complementary chains (CP) binding on Apt@AuNPs. The remaining CP, acting as the initiator sequence for HCR, triggers the HCR, leading to the formation of abundant G-quadruplex structures. By employing Thioflavin T (ThT) for the formation of G-quadruplex/ThT complexes, the biosensor exhibits a significant enhancement of the fluorescence signal. Under optimized conditions, the biosensor platform demonstrates a limit of detection of 0.03 nM and a linear range from 0.1 to 2.5 nM. Additionally, the specificity investigation reveals the high selectivity of this fluorescent biosensor. Finally, the performance of this method has been validated by successfully detecting CEA in real-life samples, highlighting its potential for clinical applications.
Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Antígeno Carcinoembrionario , Oro , Nanopartículas del Metal , Hibridación de Ácido Nucleico , Oro/química , Antígeno Carcinoembrionario/análisis , Aptámeros de Nucleótidos/química , Nanopartículas del Metal/química , Humanos , Espectrometría de Fluorescencia , Límite de Detección , FluorescenciaRESUMEN
OBJECTIVE: This study assessed the diagnostic value of microRNA-200 (miR-200) expression in peripheral blood-derived extracellular vesicles (EVs) in early-stage non-small cell lung cancer (NSCLC). METHODS: This study retrospectively analyzed 100 healthy volunteers (the control group) receiving physical examinations, 168 early-stage NSCLC patients (the NSCLC group), and 128 patients with benign lung nodules (the benign group). The basic and clinical data of participants were obtained, including age, sex, smoking history, carbohydrate antigen 242 (CA242), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), forced expiratory volume in 1 s, maximal voluntary ventilation, forced vital capacity, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and miR-200 expression. The correlation of miR-200 expression in peripheral blood-derived EVs with CA242, CEA, and CA199 was analyzed, and the diagnostic value of peripheral blood-derived EV miR-200 for early-stage NSCLC was assessed. The risk factors of early-stage NSCLC development were also determined. RESULTS: Age, the percentage of patients with smoking history, CA242, CEA, CA199, IL-6, and TNF-α levels, and miR-200 expression in peripheral blood-derived EVs were significantly higher in the NSCLC group than in the benign and control groups. Lung disease patients with high miR-200 expression in peripheral blood-derived EVs comprised a higher percentage of patients with smoking history and mixed lesions and had higher CA242, CEA, CA199, and TNF-α levels than those with low miR-200 expression in peripheral blood-derived EVs. In lung diseases, miR-200 expression in peripheral blood-derived EVs was significantly and positively correlated with CA242, CEA, and CA199. Peripheral blood-derived EV miR-200 combined with CA242, CEA and CA199 had higher diagnostic value (area under the curve = 0.942) than single detection, along with higher specificity, and high expression of peripheral blood-derived EV miR-200 was an independent risk factor for early-stage NSCLC. CONCLUSION: Peripheral blood-derived EV miR-200 expression in patients with lung diseases is closely correlated with CA242, CEA, and CA199, and high expression of peripheral blood-derived EV miR-200 is an independent risk factor for early-stage NSCLC and is of high clinical diagnostic value for early-stage NSCLC.
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Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/sangre , Femenino , Masculino , Persona de Mediana Edad , MicroARNs/sangre , MicroARNs/genética , Vesículas Extracelulares/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/sangre , Estudios Retrospectivos , Biomarcadores de Tumor/sangre , Anciano , Adulto , Estadificación de Neoplasias , Detección Precoz del Cáncer/métodos , Antígeno Carcinoembrionario/sangreRESUMEN
Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of diarrheal illnesses annually ranging from mildly symptomatic cases to severe, life-threatening cholera-like diarrhea. Although ETEC are associated with long-term sequelae including malnutrition, the acute diarrheal illness is largely self-limited. Recent studies indicate that in addition to causing diarrhea, the ETEC heat-labile toxin (LT) modulates the expression of many genes in intestinal epithelia, including carcinoembryonic cell adhesion molecules (CEACAMs) which ETEC exploit as receptors, enabling toxin delivery. Here, however, we demonstrate that LT also enhances the expression of CEACAMs on extracellular vesicles (EV) shed by intestinal epithelia and that CEACAM-laden EV increase in abundance during human infections, mitigate pathogen-host interactions, scavenge free ETEC toxins, and accelerate ETEC clearance from the gastrointestinal tract. Collectively, these findings indicate that CEACAMs play a multifaceted role in ETEC pathogen-host interactions, transiently favoring the pathogen, but ultimately contributing to innate responses that extinguish these common infections.
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Toxinas Bacterianas , Escherichia coli Enterotoxigénica , Enterotoxinas , Infecciones por Escherichia coli , Proteínas de Escherichia coli , Interacciones Huésped-Patógeno , Escherichia coli Enterotoxigénica/metabolismo , Humanos , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Enterotoxinas/metabolismo , Toxinas Bacterianas/metabolismo , Vesículas Extracelulares/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Animales , Ratones , Antígenos CD/metabolismo , Antígenos CD/genética , Antígeno Carcinoembrionario/metabolismo , Antígeno Carcinoembrionario/genética , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Diarrea/microbiología , Diarrea/metabolismoRESUMEN
In this work, SiO2/CNTs photonic crystal beads were constructed by doping CNTs into SiO2 photonic crystals, which have an angle-independent responsive structural color and can be used as bipolar electrodes due to their good electrical conductivity. In addition, the bipolar electrode-electrochemiluminescence (BPE-ECL) experiments and finite element simulation prove that the low driving voltage can trigger the bipolar electrode electrochemical reactions by confinement effect. Inspired by this, it is the first to combine the SiO2/CNTs structural color coding scheme with low-drive voltage induced wireless BPE-ECL imaging based on the confinement effect of microchannels to achieve simultaneous immune detection of ovarian cancer biomarkers (CA125, CEA, AFP). The detection limits of successfully constructed high-throughput BPE-ECL biosensor for AFP, CEA, and CA125 are 0.72 ng/mL, 0.95 ng/mL, and 1.03 U/mL, respectively, and have good stability and specificity, which expands the application of electrochemiluminescence and lays a foundation for the development of electrochemiluminescence coding technology.
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Antígeno Ca-125 , Técnicas Electroquímicas , Mediciones Luminiscentes , Humanos , Antígeno Ca-125/análisis , Técnicas Biosensibles , Antígeno Carcinoembrionario/análisis , Dióxido de Silicio/química , Biomarcadores de Tumor/análisis , Tecnología Inalámbrica , Neoplasias Ováricas/diagnóstico por imagen , alfa-Fetoproteínas/análisis , Femenino , Color , Electrodos , Límite de DetecciónRESUMEN
PURPOSE: Systemic inflammation and nutrition are vital for tumor progression. This study aimed to identify prognostic inflammation nutrition markers and develop a predictive nomogram for gallbladder cancer (GBC). METHODS: A total of 123 patients with GBC who underwent surgical resection at the First Affiliated Hospital of Soochow University and Suzhou Kowloon Hospital were included in our study. The final prognostic variables were identified using univariate and multivariate analyses. A nomogram model was then established, and the consistency index (C-index), calibration curves, and Kaplan-Meier analysis were performed to evaluate the accuracy and discrimination of the nomogram. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) suggested that our nomogram had better predictive ability and clinical feasibility than a published model. RESULTS: The cox regression analysis showed that carcinoembryonic antigen (CEA) > 4.580, albumin-bilirubin (ALBI) > -2.091, geriatric nutritional risk index (GNRI) < 90.83, T3-T4, and N2 are independent prognostic factors. A predictive nomogram was constructed with a C-index of 0.793. In the calibration curves, the nomogram-predicted 1-, 3-, and 5-year survival matched well with the actual survival. Kaplan-Meier analysis showed that the high-risk group had worse survival than the low-risk group (P < 0.001). Finally, our nomogram achieved better 1-, 3- and 5-year AUCs than an established model (0.871, 0.844, and 0.781 vs. 0.753, 0.750, and 0.693). DCA also confirmed that our model outperformed the established model. CONCLUSIONS: In conclusion, our study revealed that CEA > 4.580, GNRI < 90.83, ALBI > -2.091, T3-T4 stage, and N2 were related to clinical outcomes of patients with GBC after surgical resection. The constructed nomogram has superior predictive ability and clinical practicality.
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Neoplasias de la Vesícula Biliar , Nomogramas , Humanos , Neoplasias de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/sangre , Neoplasias de la Vesícula Biliar/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Anciano , Antígeno Carcinoembrionario/sangre , Estimación de Kaplan-Meier , Evaluación Nutricional , Curva ROC , Estado Nutricional , Inflamación/sangre , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Biomarcadores de Tumor/sangre , Bilirrubina/sangre , Modelos de Riesgos Proporcionales , Biomarcadores/sangreRESUMEN
BACKGROUND: Tuberculosis often presents on imaging in the form of a solitary nodule, sometimes accompanied by elevated CEA, which is clinically difficult to differentiate from lung cancer and prone to misdiagnosis. METHODS: Lung tissue taken by lung biopsy and sent for NGS and Xpert MTB/RIF finally led to the definitive diag-nosis of nodular foci in the upper lobe of the left lung caused by tuberculosis. RESULTS: Enhanced CT of the chest showed nodular foci in the upper lobe of the left lung. Initially the nodules were thought to be malignant, but after a series of tests, were finally confirmed to be tuberculosis. CONCLUSIONS: In patients with lung disease, when chest imaging reveals a space-occupying lesion accompanied by an elevated CEA level, a comprehensive analysis of the type of lung disease, the patient's age, and comorbidities should be performed before final diagnosis to avoid misdiagnosis and delay in appropriate treatment.
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Antígeno Carcinoembrionario , Errores Diagnósticos , Neoplasias Pulmonares , Humanos , Antígeno Carcinoembrionario/sangre , Neoplasias Pulmonares/diagnóstico , Masculino , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/sangre , Diagnóstico Diferencial , Tomografía Computarizada por Rayos X , Persona de Mediana Edad , Pulmón/patología , Pulmón/diagnóstico por imagen , FemeninoRESUMEN
Specific markers for colorectal cancer (CRC), preceded by colorectal adenoma (pre-CRC), are lacking. This study aimed to investigate whether microRNAs (miR-19a-3p, miR-92a-3p, miR-193a-3p, and miR-210-3p) from tissues and exosomes are potential CRC biomarkers and compare them to existing biomarkers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. MiRNA was isolated in the samples of 52 CRC and 76 pre-CRC patients. Expression levels were analyzed by RT-qPCR. When comparing pre-CRC and CRC tissue expression levels, only miR-193a-3p showed statistically significant result (p < 0.0001). When comparing the tissues and exosomes of CRC samples, a statistically significant difference was found for miR-193a-3p (p < 0.0001), miR-19a-3p (p < 0.0001), miR-92a-3p (p = 0.0212), and miR-210-3p (p < 0.0001). A receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of CEA, CA 19-9, and miRNAs. CEA and CA 19-9 had good diagnostic values (AUCs of 0.798 and 0.668). The diagnostic value only of miR-193a-3p was highlighted (AUC = 0.725). The final logistic regression model, in which we put a combination of CEA concentration and the miR-193a-3p expression level in tissues, showed that using these two markers can distinguish CRC and pre-CRC in 71.3% of cases (AUC = 0.823). MiR-193a-3p from tissues could be a potential CRC biomarker.
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Adenoma , Biomarcadores de Tumor , Neoplasias Colorrectales , MicroARNs , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/metabolismo , MicroARNs/genética , Biomarcadores de Tumor/genética , Masculino , Femenino , Adenoma/genética , Adenoma/diagnóstico , Adenoma/metabolismo , Persona de Mediana Edad , Anciano , Curva ROC , Antígeno Carcinoembrionario/metabolismo , Antígeno Carcinoembrionario/genética , Diagnóstico Diferencial , Regulación Neoplásica de la Expresión Génica , Exosomas/genética , Exosomas/metabolismo , Adulto , Antígeno CA-19-9 , Anciano de 80 o más AñosRESUMEN
In this paper, we designed a novel shared cathode bipolar electrode chip based on Ohm 's law and successfully constructed a dual-mode dual-signal biosensor platform (DD-cBPE). The device integrates ELISA, ECL, and ECL imaging to achieve highly sensitive detection and visual imaging of carcinoembryonic antigen (CEA). The unique circuit structure of the device not only realizes the dual signal detection of the target, but also breaks the traditional signal amplification concept. The total resistance of the system is reduced by series-parallel connection of BPE, and the total current in the circuit is increased. In addition, Au@NiCo2O4@MnO2 nanozyme activity probe was introduced into the common cathode to enhance the conductivity of the material. At the same time, due to the excellent peroxidase (POD) activity of NiCo2O4@MnO2, the decomposition of H2O2 was accelerated, so that more electrons flowed to the BPE anode, and finally the dual amplification of the ECL signal was realized. The device affects the current in the circuit by regulating the concentration of the co-reactant TPrA, thereby affecting the resistance of the system. Finally, different luminescent reagents emit light at the same potential and the luminous efficiency is similar. In addition, the chip does not need external resistance regulation, which improves the sensitivity of the immunosensor and meets the needs of timely detection. It provides a new idea for the deviceization of bipolar electrodes and has broad application prospects in biosensors, clinical detection, and environmental monitoring.
Asunto(s)
Técnicas Biosensibles , Antígeno Carcinoembrionario , Electrodos , Oro , Técnicas Biosensibles/instrumentación , Antígeno Carcinoembrionario/análisis , Humanos , Oro/química , Diseño de Equipo , Compuestos de Manganeso/química , Óxidos/química , Límite de Detección , Técnicas Electroquímicas/instrumentación , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/química , Ensayo de Inmunoadsorción Enzimática , Mediciones Luminiscentes/instrumentaciónRESUMEN
BRCA1 gene and carcinoembryonic antigen (CEA) are important markers of breast cancer, so accurate detection of them is significant for early detection and diagnosis of breast cancer. In this study, a potential-resolved ratio electrochemiluminescence (ECL) biosensor using perylene diimide (PDI)-metal-organic framework and DNA nanoflowers (NFs)-CdS quantum dots (QDs) was constructed for detection of BRCA1 and CEA. Specifically, PDI-MOF and CdS QDs can generate potential-resolved intense ECL signals only using one coreactant, so the detection procedure can be effectively simplified. PDI-MOF was first attached to the electrode by graphene oxide, and the dopamine (DA) probe was linked to quench the ECL signal by DNA hybridization. In the presence of target BRCA1, it can form a bipedal DNA walker, so the quenching molecules (DA) were detached from the electrode via the walker amplification process aided by Mg2+, so that the PDI signal at -0.25 V was restored for the BRCA1 assay. Moreover, CdS QDs@DNA NFs as amplified signal probes were formed by self-assembly, and the target CEA-amplified product introduced the CdS QDs@DNA NFs to the electrode, so the QD ECL signal at -1.42 V was enhanced, while the ECL signal of PDI is unchanged; thus, CEA detection was achieved by the ratio value between them. Therefore, the detection accuracy is guaranteed by detection of two cancer markers and a ratio value. This biosensor has a great contribution to the development of new ECL materials and a novel ECL technique for fast and efficient multitarget assays, showing great significance for the early monitoring and diagnosis of breast cancer.
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Proteína BRCA1 , Técnicas Biosensibles , Compuestos de Cadmio , Antígeno Carcinoembrionario , ADN , Técnicas Electroquímicas , Imidas , Mediciones Luminiscentes , Perileno , Puntos Cuánticos , Sulfuros , Perileno/química , Perileno/análogos & derivados , Puntos Cuánticos/química , Compuestos de Cadmio/química , Técnicas Biosensibles/métodos , Sulfuros/química , Técnicas Electroquímicas/métodos , Imidas/química , ADN/química , Humanos , Proteína BRCA1/genética , Proteína BRCA1/análisis , Antígeno Carcinoembrionario/análisis , Antígeno Carcinoembrionario/sangre , Estructuras Metalorgánicas/químicaRESUMEN
Photothermal therapy (PTT) is a method for eradicating tumor tissues through the use of photothermal materials and photosensitizing agents that absorb light energy from laser sources and convert it into heat, which selectively targets and destroys cancer cells while sparing healthy tissue. MXenes have been intensively investigated as photosensitizing agents for PTT. However, achieving the selectivity of MXenes to the tumor cells remains a challenge. Specific antibodies (Ab) against tumor antigens can achieve homing of the photosensitizing agents toward tumor cells, but their immobilization on MXene received little attention. Here, we offer a strategy for the selective ablation of melanoma cells using MXene-polydopamine-antiCEACAM1 Ab complexes. We coated Ti3C2Tx MXene with polydopamine (PDA), a natural compound that attaches Ab to the MXene surface, followed by conjugation with an anti-CEACAM1 Ab. Our experiments confirm the biocompatibility of the Ti3C2Tx-PDA and Ti3C2Tx-PDA-antiCEACAM1 Ab complexes across various cell types. We also established a protocol for the selective ablation of CEACAM1-positive melanoma cells using near-infrared irradiation. The obtained complexes exhibit high selectivity and efficiency in targeting and eliminating CEACAM1-positive melanoma cells while sparing CEACAM1-negative cells. These results demonstrate the potential of MXene-PDA-Ab complexes for cancer therapy. They underline the critical role of targeted therapies in oncology, offering a promising avenue for the precise and safe treatment of melanoma and possibly other cancers characterized by specific biomarkers. Future research will aim to refine these complexes for clinical use, paving the way for new strategies for cancer treatment.
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Indoles , Melanoma , Polímeros , Polímeros/química , Indoles/química , Indoles/farmacología , Humanos , Melanoma/patología , Melanoma/tratamiento farmacológico , Melanoma/terapia , Línea Celular Tumoral , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Titanio/química , Animales , Ratones , Antígeno Carcinoembrionario/inmunología , Terapia FototérmicaRESUMEN
OBJECTIVES: Hepatic CEACAM1 expression declines with advanced hepatic fibrosis stage in patients with metabolic dysfunction-associated steatohepatitis (MASH). Global and hepatocyte-specific deletions of Ceacam1 impair insulin clearance to cause hepatic insulin resistance and steatosis. They also cause hepatic inflammation and fibrosis, a condition characterized by excessive collagen production from activated hepatic stellate cells (HSCs). Given the positive effect of PPARγ on CEACAM1 transcription and on HSCs quiescence, the current studies investigated whether CEACAM1 loss from HSCs causes their activation. METHODS: We examined whether lentiviral shRNA-mediated CEACAM1 donwregulation (KD-LX2) activates cultured human LX2 stellate cells. We also generated LratCre + Cc1fl/fl mutants with conditional Ceacam1 deletion in HSCs and characterized their MASH phenotype. Media transfer experiments were employed to examine whether media from mutant human and murine HSCs activate their wild-type counterparts. RESULTS: LratCre + Cc1fl/fl mutants displayed hepatic inflammation and fibrosis but without insulin resistance or hepatic steatosis. Their HSCs, like KD-LX2 cells, underwent myofibroblastic transformation and their media activated wild-type HSCs. This was inhibited by nicotinic acid treatment which blunted the release of IL-6 and fatty acids, both of which activate the epidermal growth factor receptor (EGFR) tyrosine kinase. Gefitinib inhibition of EGFR and its downstream NF-κB/IL-6/STAT3 inflammatory and MAPK-proliferation pathways also blunted HSCs activation in the absence of CEACAM1. CONCLUSIONS: Loss of CEACAM1 in HSCs provoked their myofibroblastic transformation in the absence of insulin resistance and hepatic steatosis. This response is mediated by autocrine HSCs activation of the EGFR pathway that amplifies inflammation and proliferation.
Asunto(s)
Antígenos CD , Células Estrelladas Hepáticas , Células Estrelladas Hepáticas/metabolismo , Animales , Ratones , Humanos , Antígenos CD/metabolismo , Antígenos CD/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Ratones Endogámicos C57BL , Antígeno Carcinoembrionario/metabolismo , Antígeno Carcinoembrionario/genética , Masculino , Eliminación de Gen , Transducción de SeñalRESUMEN
An intense cathodic electrochemiluminescence (ECL) is reported from a polarized glassy carbon electrode (GCE) in peroxydisulfate solution. After the polarization in 1 M Na2SO4 at the potential of - 3.7 V for 3 s, carbon nanosheets (C-NSs) were in situ grown on the surface of the GCE. Measured in 100 mM K2S2O8 solution, the ECL intensity of the GCE/C-NSs is 112-fold that of a bare GCE. The ECL spectrum revealed that the true ECL luminophore in the GCE/C-NSs-peroxydisulfate system is O2/S2O82- which is promoted by C-NSs. When Cu2+ was electrochemically enriched and reduced to Cu(0) on the catalytic sites of C-NSs, the ECL from GCE/C-NSs/Cu in K2S2O8 solution was decreased with increasing logarithmic concentration of Cu2+ in the range from 10 pM to 1 µM, with a limit of detection (LOD) of 3 pM. An immunoanalysis method is proposed via a biometallization strategy using CuS nanoparticles as the tags and carcinoembryonic antigen (CEA) as the model analyte. After the immune recognition in the microplate, the CuS tags in the immunocomplex were dissolved and the resultant Cu2+ was electrochemically enriched and reduced on the catalytic sites of C-NSs, quenching the ECL intensity of GCE/C-NSs-O2/S2O82- system. The proposed ECL immunoanalysis method was used to quantify CEA in actual serum samples with an LOD of 1.0 fg mL-1, possessing the advantages of simple electrode modification, high sensitivity and good reproducibility.
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Carbono , Antígeno Carcinoembrionario , Cobre , Técnicas Electroquímicas , Electrodos , Mediciones Luminiscentes , Carbono/química , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/inmunología , Antígeno Carcinoembrionario/análisis , Cobre/química , Límite de Detección , Humanos , Nanoestructuras/química , Inmunoensayo/métodos , Sulfato de Cobre/química , Nanopartículas del Metal/química , Vidrio/química , Sulfatos/químicaRESUMEN
A novel signal amplification strategy was developed by combining near-infrared light with MoS2/CuO/Au nanocomposite for building a colorimetric immunoassay. First, MoS2/CuO/Au nanocomposite was synthesized by precipitation and photoreduction methods and characterized by scanning electron microscopy (SEM) and X-ray powder diffraction (XRD). MoS2/CuO/Au nanocomposite has oxidase-like activity and can oxidize TMB to form a blue product (TMBox). Further, the catalytic oxidation of TMB was accelerated under near-infrared (NIR) laser radiation. The sandwich-type colorimetric immunoassay was constructed using MoS2/CuO/Au nanocomposite. Under the enhancement of near-infrared light, carcinoembryonic antigen (CEA) was sensitively detected in the range 0.1 to 40 ng/mL with the limit of detection of 0.03 ng/mL. Moreover, the immunosensor has excellent selectivity and anti-interference, good repeatability, and stability.
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Biomarcadores de Tumor , Antígeno Carcinoembrionario , Colorimetría , Cobre , Disulfuros , Oro , Rayos Infrarrojos , Límite de Detección , Molibdeno , Nanocompuestos , Molibdeno/química , Nanocompuestos/química , Cobre/química , Disulfuros/química , Colorimetría/métodos , Oro/química , Humanos , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/análisis , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/análisis , Inmunoensayo/métodos , Técnicas Biosensibles/métodos , Anticuerpos Inmovilizados/inmunologíaRESUMEN
An ultrasensitive photothermal assay was designed for point-of-care testing (POCT) of tumor markers based on a filter membrane. Firstly, Cu2-xSe was successfully encapsulated in liposome spheres with biotin on the surface and connected to carcinoembryonic antigen (CEA) aptamer with 3'end modified biotin by streptavidin. Secondly, the CEA antibody was successfully modified on the surface of the nitrocellulose membrane through simple incubation. Finally, the assay process was completed using a disposable syringe, and the temperature was recorded using a handheld infrared temperature detector. In the range 0-50 ng mL-1, the temperature change of the nitrocellulose membrane has a strong linear relationship with CEA concentration, and the detection limit is 0.097 ng mL-1. It is worth noting that the entire testing process can be easily performed in 10 min, much shorter than traditional clinical methods. In addition, this method was successfully applied to the quantitative determination of CEA levels in human serum samples with a recovery of 96.2-103.3%. This rapid assay can be performed by "one suction and one push" through a disposable syringe, which is simple to operate, and the excellent sensitivity reveals the great potential of the proposed strategy in the POCT of tumor biomarkers.
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Aptámeros de Nucleótidos , Biomarcadores de Tumor , Antígeno Carcinoembrionario , Cobre , Límite de Detección , Humanos , Antígeno Carcinoembrionario/sangre , Cobre/química , Aptámeros de Nucleótidos/química , Biomarcadores de Tumor/sangre , Liposomas/química , Técnicas Biosensibles/métodos , Sistemas de Atención de Punto , Temperatura , Biotina/química , Pruebas en el Punto de Atención , Colodión/químicaRESUMEN
Tumor markers should be measured regularly and accurately to prevent, diagnose, and monitor cancers efficiently. We aimed to characterize the pre-analytical factors effecting on the analytical performance of point-of-care test (POCT) platform IchromaTM II (Boditech Med Inc., Gangwon-do, Korea) for alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate specific antigen (PSA) and evaluate their consequences in clinical practice. Based on comprehensive evaluation for the analytical performance of IchromaTM II including precision, linearity, and method comparison performed according to CLSI guidelines, pre-analytical factors of sample types and conditions were extensively analyzed. A total of five sample types [serum, plasma (PL) and whole blood (WB) from EDTA tube, PL and WB from sodium heparin tube] from 40 patients were used for comparing among specimen types. Additionally, stability was assessed up to 21 h at room temperature, refrigerated for 8 days, and frozen for 16 weeks by using 4 levels of pooled patient samples which were measured in triplicate. Precision, linearity and correlation with central laboratory analyzers observed in all three tumor markers were within acceptable criteria. However, variable degrees of percent deviations were observed according to sample type and storage conditions. Only EDTA PL samples presented clinically acceptable percentage biases for all three tumor markers when stored at room temperature or refrigerated condition. Positive bias of CEA and PSA in storage duration until 16 weeks were observed when stored in frozen condition. While IchromaTM II showed an adequate analytical performance as a POCT platform with simple operating procedures for the measurement of tumor markers, clinical laboratories should be aware of stability issues when different types of blood specimens are practically utilized.
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Biomarcadores de Tumor , Humanos , Biomarcadores de Tumor/sangre , Antígeno Prostático Específico/sangre , Antígeno Prostático Específico/análisis , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/análisis , Sistemas de Atención de Punto/normas , alfa-Fetoproteínas/análisis , Manejo de Especímenes , Fase PreanalíticaRESUMEN
BACKGROUND/AIM: No clear treatment strategy for simultaneously detected liver and lung metastases (SLLM) of colorectal carcinoma has been established, to date. We aimed to identify the prognostic factors for SLLM and propose an appropriate treatment option. PATIENTS AND METHODS: This retrospective study included 64 patients with SLLM: 32 underwent pulmonary resection after hepatectomy in 32, while the other 32 underwent hepatectomy alone in 32. Poor prognostic factors and a suitable strategy for SLLM were assessed. RESULTS: Multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) level ≥20 ng/ml (p=0.001) and unresected lung metastases (p=0.001) were independent prognostic factors for poor overall survival. Compared with the non-pulmonary resection group, the rate of R1 resection of liver tumors (46.8% vs. 15.6%; p=0.007), incidence of complications after hepatectomy (Clavien-Dindo grade ≥III: 21.8% vs. 0%; p=0.005) and having four or more metastatic lung nodules (40.6% vs. 3.2%; p=0.001) were significantly higher in the group that underwent hepatectomy only. CONCLUSION: Preoperative CEA ≥20 ng/ml and unresectable pulmonary nodules were prognostic factors for poor survival of patients with SLLM. Furthermore, the presence of more than four pulmonary nodules was a preoperative predictive factor for unresectable pulmonary nodules. R1 resection and the occurrence of complications after hepatectomy should be avoided; a smooth transition from hepatectomy to pulmonary resection is important.
Asunto(s)
Neoplasias Colorrectales , Hepatectomía , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Masculino , Femenino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Pronóstico , Antígeno Carcinoembrionario/sangre , Adulto , Anciano de 80 o más AñosRESUMEN
PURPOSE: Colorectal cancer is the second leading cause of cancer death worldwide. Standard treatments for locally advanced rectal cancer include neoadjuvant chemoradiotherapy and total mesorectal excision (TME), which are associated with significant morbidity. After neoadjuvant therapy, one-third of patients achieve a pathological complete response (pCR) and are eligible for a watch-and-wait approach without TME. The purpose of this study was to determine the potential predictors of pCR before surgery. METHODS: The demographic, clinical, and endoscopic data of 119 patients with primary locally advanced rectal cancer without distant metastasis who underwent restaging endoscopy and TME 6-8 weeks after the end of neoadjuvant therapy were collected. The absence of tumor cells in the histological examination of the TME specimen after neoadjuvant therapy was considered pCR. Binary logistic regression and receiver operating characteristic curves were utilized for analysis. RESULTS: According to the multivariate logistic regression analysis, flattening of marginal tumor swelling (p value < 0.001, odds ratio = 100.605) emerged as an independent predictor of pCR in rectal cancer patients. Additionally, receiver operating characteristic curve analysis revealed that lower preoperative carcinoembryonic antigen and erythrocyte sedimentation rate levels predict pCR, with cutoffs of 2.15 ng/ml and 19.0 mm/h, respectively. CONCLUSION: Carcinoembryonic antigen and erythrocyte sedimentation rate, along with the presence of flattening of marginal tumor swelling, can predict pCR after neoadjuvant chemoradiotherapy in patients with primary rectal cancer. These factors offer a potential method for selecting candidates for conservative treatment based on endoscopic and laboratory findings.
Asunto(s)
Quimioradioterapia , Terapia Neoadyuvante , Curva ROC , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Proctoscopía , Adulto , Valor Predictivo de las Pruebas , Estadificación de Neoplasias , Antígeno Carcinoembrionario/sangre , Análisis Multivariante , Modelos LogísticosRESUMEN
Developing non-passivating and fully integrated electrode arrays for point-of-care testing of carcinoembryonic antigen (CEA) is crucial, as the serum level of CEA is closely associated with colorectal cancer. Herein, we propose a simple, low-cost, and eco-friendly template-assisted filtration method for the scalable preparation of carbon nanotube-bridged Ti3C2Tx MXene (MX@CNT) electrode arrays with a conductive network. Furthermore, we fabricate a homogeneous electrochemical (HEC) sensor for CEA detection by integrating a magnetic-bead-based alkaline phosphatase-linked immunoassay (MB-aElisa), which enables the in-situ generation of the electroactive substance 1-naphthol (1-NP). Benefiting from the unique electrochemical characteristics of a MX@CNT electrode array, such as ultra-low background signal and superior electrocatalytic activity towards the hydrolyzed 1-NP, the MB-aElisa-based HEC sensor specifically measures CEA within a detection range spanning from 0.005 to 1.0 ng mL-1, achieving a detection limit of 1.6 pg mL-1. Subsequently, this biosensing prototype is successfully utilized for the detection of CEA in serum specimens obtained from colorectal cancer patients. More importantly, the integration of MB-aElisa with a MX@CNT electrode array not only marks a significant advancement but also enables the creation of a one-step homogeneous electrochemical immunosensing platform, serving as a paradigm for the highly sensitive and selective measurement of trace tumor markers in complex biological samples.
Asunto(s)
Biomarcadores de Tumor , Técnicas Biosensibles , Antígeno Carcinoembrionario , Técnicas Electroquímicas , Límite de Detección , Nanotubos de Carbono , Nanotubos de Carbono/química , Humanos , Técnicas Biosensibles/instrumentación , Antígeno Carcinoembrionario/sangre , Técnicas Electroquímicas/métodos , Biomarcadores de Tumor/sangre , Inmunoensayo/métodos , Inmunoensayo/instrumentación , Anticuerpos Inmovilizados/química , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/sangre , ElectrodosRESUMEN
Biomarkers screening is a benefit approach for early diagnosis of major diseases. In this study, magnetic nanoparticles (MNPs) have been utilized as labels to establish a multi-line immunochromatography (MNP-MLIC) for simultaneous detection of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA 19-9), and alpha-fetoprotein (AFP) in a single serum sample. Under the optimal parameters, the three biomarkers can be rapidly and simultaneously qualitative screening within 15 min by naked eye. As for quantitative detection, the MNP-MLIC test strips were precisely positioned and captured by a smartphone, and signals on the test and control lines were extracted by ImageJ software. The signal ratio of test and control lines has been calculated and used to plot quantitative standard curves with the logarithmic concentration, of which the correlation coefficients are more than 0.99, and the limit of detection for CEA, CA 19-9, and AFP were 0.60 ng/mL, 1.21 U/mL, and 0.93 ng/mL, respectively. The recoveries of blank serum were 75.0 ~ 112.5% with the relative standard deviation ranging from 2.5 to 15.3%, and the specificity investigation demonstrated that the MNP-MLIC is highly specific to the three biomarkers. In conclusion, the developed MNP-MLIC offers a rapid, simple, accurate, and highly specific method for simultaneously detecting multiple biomarkers in serum samples, which provides an efficient and accurate approach for the early diagnosis of diseases.