Carcinoembryonic Antigen Concentration Research Articles

Ultrasensitive Electrochemical Detection of Carcinoembryonic Antigen with a Label‐Free Immunosensor Using Gold Nanoparticle‐Decorated Poly(pyrrole‐co‐3,4‐ethylenedioxythiophene)

AbstractIn this study, an electrochemical immunosensor was developed using gold nanoparticles (AuNPs), 3,4‐ethylenedioxythiophene (EDOT), and pyrrole (Py) to detect carcinoembryonic antigen (CEA) sensitively. Firstly, the electrocopolymerization of PPy and EDOT was carried out on a pencil graphite electrode (PGE) by the chronoamperometry method (p(Py‐co‐EDOT)/PGE). Then, gold nanoparticles were electrochemically deposited on the prepared p(Py‐co‐EDOT)/PGEs by the chronoamperometry method. The characterizations of the developed label‐free immunosensor (AuNPs/p(Py‐co‐EDOT)/PGE) were carried out using CV, EIS, XPS, SEM, EDX, and FTIR methods. Antibody concentration, antibody immobilization time, and immunocomplex time were optimized using differential pulse voltammetry (DPV). After optimal conditions are determined, the DPV peak current of the immunosensor decreases linearly with increasing CEA concentration of 0.001–100 ng mL−1. The detection limit was calculated as 0.741 pg mL−1 from the calibration graph (S/N=3). The developed sensor showed excellent anti‐interference ability against ascorbic acid, bovine serum albumin, dopamine, and glucose. The applicability of the developed sensor to real samples was investigated, and good recovery values were obtained. As a result, the AuNPs/p(Py‐EDOT)/PGE provides low‐cost, selective, and rapid detection of CEA. Our findings suggest the present immunosensor is a good candidate for application in clinical screening.

Development of Carcinoembryonic Antigen Rapid Detection System Based on Platinum Microelectrode.

Rapid and highly sensitive detection of carcinoembryonic antigen (CEA) in blood could effectively improve the diagnostic sensitivity of colorectal cancer. In this work, a platinum microelectrode (PtμE) modified with gold nanoparticles was developed as a microsensor for the detection of CEA. As the recognition element, a CEA aptamer modified with sulfhydryl could be conjugated onto the surface of the PtμEs/Au. The quantitative analysis of the concentration of CEA [CEA] by the prepared PtμEs/Au aptasensor was carried out through square wave voltammetry. Under the optimized conditions, the PtμEs/Au aptasensor exhibits a linear response toward [CEA] in the range of 1.0 × 10–11—1.0 × 10–7 g/ml (S = 5.5 nA/dec, R 2 = 0.999), and the detection limit is 7.7 × 10–12 g/ml. The PtμEs/Au aptasensor also has good selectivity against other types of proteins existing in blood. The availability of the developed assay toward [CEA] in blood samples was investigated, and the results agreed well with those obtained through electrochemiluminescence provided by the hospital, and the volume of the blood sample for detection is only 20 μl. Herein, the proposed detection system could be used for the quantitative analysis of CEA in blood, with the advantages of high sensitivity, short time, and low cost. Moreover, the PtμEs/Au aptasensor has a potential application in clinical diagnosis.

Molybdenum blue mediated photothermal immunoassay for CEA detection based on Ag4P2O7@Ag nanocomposites

A photothermal immunoassay was built for tumor marker detection based on Ag4P2O7@Ag nanocomposites. Ag4P2O7@Ag nanomaterials were synthesized by precipitation-photoreduction reaction, and characterized by transmission electron microscope (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectra (XPS) and X-ray powder diffraction (XRD). Come about PO43− derived from Ag4P2O7@Ag under acidic conditions react with ammonium molybdate in the action of reductant generating molybdenum blue. The photothermal change is due to molybdenum blue solution depending on the concentration of carcinoembryonic antigen (CEA) in immunoassay. Under optimal conditions, there is a linear relation between ΔT and CEA concentration in the range of 1 pg mL−1–40 ng mL−1 with the detection limit of 0.33 pg mL−1. Meanwhile, the developed photothermal immunoassay displays preferable selectivity, repeatability, and stability.

Clinical value of combining serum tumor marker detection with fecal occult blood testing in diagnosing colorectal cancer.

This study aimed to investigate the value of combining the detection of serum tumor markers, namely, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 199, CA 242, and CA 50, with fecal occult blood (FOB) testing in the diagnosis of colorectal cancer (CRC). One hundred patients with CRC who were diagnosed and treated at the First Hospital of Jiaxing, Zhejiang Province, China, between January 2019 and April 2020 were enrolled as the case group, and 200 healthy people who underwent a physical examination at the hospital during the same period were recruited as the control group. The concentrations of CEA, CA199, CA242, and CA50 in serum were measured alongside FOB indicators. Compared with the control group, the concentrations of CEA, CA199, CA242, and CA50 in the case group were significantly higher, and they were related to age, tumor differentiation, tumor stage, and other clinicopathological features (P<0.05). The diagnostic performance of the combination of four tumor markers for CRC was significantly better than when using a single marker (four-combined test: AUC (area under the curve) AUC=0.80), and the diagnostic performance was further improved after adding the fecal occult blood test test (FOBT) results (five-combined test: AUC=0.90). The combined detection of the five indexes was found to be effective for the early diagnosis of CRC (AUC=0.87). We concluded that the detection of serum tumor markers CEA, CA199, CA242, and CA50 combined with an FOBT could significantly improve the sensitivity and accuracy of a CRC diagnosis and contributed to an early diagnosis and appropriate treatment.

Highly Sensitive Detection of Carcinoembryonic Antigen via an Electrochemical Platform Fabricated by AuNPs/Streptavidin/Reduced Graphene Oxide.

Tumor markers are one of the important indicators for early cancer diagnosis. As a new analytical method, electrochemical immunosensing analysis has the advantages of high sensitivity, good selectivity, and rapid detection, which is of great significance for the detection of tumor markers. In this work, an AuNP/reduced graphene oxide (AuNP/rGO) composite was synthesized. We used it for electrochemical sensor fabrication with the assistance of the biotin–streptavidin protein (SA) system to further amplify the signal to achieve sensitive detection of carcinoembryonic antigen (CEA). In addition, AuNPs have been incorporated due to their good electrical conductivity and biocompatibility, which can accelerate electron transfer at the electrode interface and improve the loading capacity to capture antibodies. The fabricated AuNPs/SA/rGO has a large working surface area and high material utilization ratio, which improves the catalytic capacity of H2O2 reduction and effectively amplifies the current signal. The linear range of the response current signal of the sensor toward the CEA concentration is 20 fg/ml to 200 ng/ml, and the limit of detection can achieve 6.2 fg/ml. In addition, the fabricated immunosensor has good reproducibility, selectivity, and stability.

Handheld pH‐Meter‐based Electrochemical Aptasensing of Carcinoembryonic Antigen on Multifuctional Magnetic Beads

AbstractMethods derived from immunoassays and aptasensors have been established for monitoring of carcinoembryonic antigen (CEA) in biological fluids, but most involved complex procedure and various reactions. We designed an uncomplicated and convenient electrochemical aptasensing platform for the quantitative monitoring of CEA on multifunctionalized magnetic beads with a handheld pH meter as the read‐out. Initially, CEA‐specific aptamers were covalently conjugated to magnetic beads, and then hybridized with glucose oxidase‐labeled complementary strands to construct multifunctional nanoprobes. After addition of target CEA, the analyte interacts with the corresponding aptamer and then release the complementary strand. After magnetic separation, the released glucose oxidase‐labeled complementary strands hydrolysed glucose, thereby leading to a change in pH of the detection solution, which was quantitatively monitored on a hand‐held pH meter. Under the optimum conditions, the aptasensor based on pH meter exhibited well responses relative to CEA concentrations inside the dynamic range between 0.01 and 100 ng mL−1 and detection limit at least 9.3 pg mL−1. Good duplicability, high specificity and ability for long‐term stable storage are obtained for the as‐prepared aptasensors. Additionally, human serum specimens were determined through pH‐meter‐based aptasensors, and the results closely matched the commercial enzyme‐linked immunosorbent assay (ELISA) of human CEA.

Assessment of carcinoembryonic antigen as a prognostic marker in ovarian malignancies treated in a rural hospital of West Bengal

Background: Ovarian neoplasms are the second most common cause of gynecological malignancy both worldwide as well as in India. Innocuous clinical presentation and late diagnosis contribute to the mortality toll of this neoplasm. Thus, early diagnosis remains the cornerstone to increase the survival rate of ovarian neoplasms. Though, cancer antigen 125 (CA-125) is a time-tested marker for ovarian neoplasm diagnosis yet its increment in benign gynecological conditions questions its own diagnostic specificity. Carcinoembryonic antigen (CEA), the conventional marker for colorectal cancer detection, is found to be associated with epithelial ovarian cancer. Aims and Objectives: This study was aimed to find the efficacy of CEA along with CA-125 in the early detection of ovarian neoplasm and predicting the outcome. Materials and Methods: This hospital-based longitudinal study was conducted in the Biochemistry department of Bankura Sammilani Medical College. Established cases of ovarian neoplasm were recruited as study population using pre-defined inclusion and exclusion criteria. Serum CEA and CA-125 were estimated at the time of diagnosis, 6 weeks, 6 months, and 12 months after surgery. Results: There was no significant difference between the median concentration of CEA among the four phases of treatment. Serum CEA was positively correlated to CA-125 during all phases of treatment (Ρ=0.653, P=0.000). The binary logistic regression revealed that CEA (odds ratio=1.2, 0.83–1.69) had higher chances to be associated with ovarian stages associated with cancers beyond Stage IC. CEA had a lower sensitivity and specificity in comparison to CA-125. Conclusion: This study suggested CEA, a theranostic marker, can supplement the present biochemical diagnostic modalities to improve diagnostic and prognostic efficacy cost-effectively.

Ratiometric electrochemical aptasensor for the sensitive detection of carcinoembryonic antigen based on a hairpin DNA probe and exonuclease I-assisted target recycling

A novel ratiometric electrochemical aptasensor was constructed for the detection of carcinoembryonic antigen (CEA) based on a hairpin DNA (hpDNA) probe and exonuclease Ⅰ (Exo Ⅰ)-assisted target recycling amplification strategy. A thiolated methylene blue (MB)-labeled hpDNA as the internal control element was fixed on the surface of the gold nanoparticles (AuNPs)-modified gold electrode (AuE) through Au–S bonds. A ferrocene (Fc)-modified aptamer DNA (Fc-Apt) was partially hybridized with hpDNA to form a Fc-Apt/hpDNA duplex. Due to the specific recognition of Fc-Apt to CEA, the presence of CEA caused dissociation of Fc-Apt from the duplex, and further triggered the degradation process of Exo Ⅰ and recycling of CEA. Hence, the Fc tags were released from the electrode surface and the oxidation peak current of Fc (IFc) decreased while that of MB (IMB) remained stable owing to the distance between MB tags and the electrode unchanged. A linear relationship was observed between IFc/IMB and the logarithm of CEA concentration from 10 pg mL−1 to 100 ng mL−1 with a detection limit of 1.9 pg mL−1. Moreover, the developed aptasensor had been applied to detect CEA in diluted human serum with satisfactory results, indicating its great potential in practical applications.

Ratiometric electrochemical immunosensor triggered by an advanced oxidation process for the ultrasensitive detection of carcinoembryonic antigen

Conventional electrochemical immunosensors often achieve detection purposes through a single signal output, but its electrical signal is susceptible to external environmental interference, which seriously interferes with the sensitivity and repeatability of the sensors. In this work, a novel ratiometric electrochemical immunosensor triggered by an advanced oxidation process (AOP) was developed for the ultrasensitive detection of carcinoembryonic antigen (CEA). The sensor uses gold nanoparticle-reduced graphene oxide/methylene blue adsorbed by sodium alginate (Au-rGO/MB-SA) as matrix to immobilize primary antibody (Ab1) and Ag nanoparticles-functionalized egg yolk structure Co3O4@SiO2 (Co3O4-Ag@SiO2) as a marker to label secondary antibody (Ab2). When the detection solution contains peroxymonosulfate (PMS), the signal probe Co3O4-Ag@SiO2 activates PMS to produce SO4•−/•OH radicals to degrade MB, thus generating two independent electrochemical signals with opposite directional changes (IAg and IMB). The sensitivity of the sensor is improved due to an enhanced response magnitude on account of the processing of the dual selective responsive signals to yield a response magnitude greater than that of the signal from a single sensor. Square wave voltammetry (SWV) analysis shows that the dual signal ratio (I = IAg/IMB) has a linear relationship with the logarithm of the CEA concentration in the range of 0.01 pg/mL to 40 ng/mL, and the detection limit is as low as 3.42 fg/mL. In addition, the sensor has good selectivity and reproducibility, showing great promise for applications in bioanalysis and disease diagnosis.

Magnetic antifouling material based ratiometric electrochemical biosensor for the accurate detection of CEA in clinical serum

A novel ratio electrochemical biosensor based on multi-functional nanocomposite was developed. Fe3O4 was synthesized in situ on carboxyl functionalized 2D nanomaterial MXene, and then covalently bonded with [Ru(NH3)6]3+ to obtain nanocomposites MXC-Fe3O4-Ru. Fe3O4 and [Ru(NH3)6]3+ can neutralize the electronegativity of the MXene to make the nanocomposites electrically neutral. Combine with the good hydrophilicity and conductivity of MXene, the nanocomposites can be utilized to construct antifouling electrochemical biosensors without modifying with specific antifouling materials. Moreover, Fe3O4 can endow the nanocomposites with magnetism, and [Ru(NH3)6]3+ is used as an internal standard molecule. The strong magnetic MXC-Fe3O4-Ru can be easily separated and firmly modified on the magnetic gold electrode (MGE). DNA double-stranded (dsDNA) containing an ferrocene (Fc)-modified carcinoembryonic antigen (CEA) aptamer can be specifically captured to the surface of the electrode by amido bond. In the presence of CEA, CEA binds to the aptamer and leaves the electrode surface, the electrochemical signal of Fc decreases, while the electrochemical signal of [Ru(NH3)6]3+ is fixed on the electrode surface remains basically unchanged. The ratio of the electrochemical signals of Fc and [Ru(NH3)6]3+ is proportional to the CEA concentration. The linear range of the sensor is 1 pg/mL to 1 μg/mL with a detection limit of 0.62 pg/mL. With the excellent antifouling performance, good conductivity of the nanocomposite, and the application of the ratiometric strategy, the biosensor can achieve high selectivity, accuracy, and sensitivity for the detection of targets even in complex samples, such as FBS and clinical serum.

The Association of Carcinoembryonic Antigen (CEA) and Air Pollutants—A Population-Based Study

Air pollutants are substances in the air that have harmful effects on humans and the ecological environment. Although slight elevations in carcinoembryonic antigen (CEA) are commonly observed in apparently healthy persons, potential associations between CEA levels and chronic low-grade inflammation induced by air pollution have yet to be documented. We conducted a community-based cross-sectional study to estimate the association between short-term exposure to ambient air pollution and the CEA. A total of 9728 participants from health examinations were enrolled for the analysis and linked with their residential air pollutant data including ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO), sulphur dioxide (SO2), and particulate matter (PM10). The results showed that every increase of 1 ppm O3 significantly increased the mean differences of the CEA blood concentration by 0.005 ng/mL. Each increase of 1 ppm CO significantly reduced the mean differences of the CEA blood concentration by 0.455 ng/mL. Although smoking and alcohol drinking also increased the CEA levels, with adjustment of these confounders we identified a significant association between serum CEA in the general population and levels of the air pollutants O3 and CO. In conclusion, the serum CEA concentrations and short-term air pollutants O3 and CO exposure were found to have a significant relationship; however, its mechanism is still unclear. Moreover, long-term air pollution exposure and changes in CEA concentration still need to be further evaluated.

Fast screening method for early diagnostic of gastric cancer based on utilization of a chitosan – S-doped graphene - based needle stochastic sensors

Needle stochastic sensors were developed for the assay of carbohydrate antigen 19–9 (CA 19–9) and carcinoembryonic antigen (CEA) in different biological samples (e.g., whole blood, tissues, urine, and saliva). Sulfur doped graphene powders were modified with chitosan; paraffin oil was added to form a homogeneous paste that was used as active side of the stochastic sensors. High sensitivities and low limits of determination were achieved for the assay of CA19-9 and CEA in biological samples. The validation of the proposed screening method (which is utilizing the stochastic sensors as screening tools) was made by using real biological samples obtained from confirmed patients with gastric cancer; very good correlations for the concentrations of CEA and CA19-9 were obtained using the needle stochastic sensors.

An electronic biosensor based on semiconducting tetrazine polymer immobilizing matrix coated on rGO for carcinoembryonic antigen

Point-of-care devices are expected to play very critical roles in early diagnosis and better treatment of cancer. Here, we report the end-to-end development of novel and portable biosensors for detecting carcinoembryonic antigen (CEA), a cancer biomarker, almost instantly at room temperature. The device uses reduced graphene oxide (rGO) as the base conducting layer and a novel poly[(1,4-phenylene)-alt-(3,6-(1,2,4,5-tetrazine)/3,6-(1,2,4,5-dihydrotetrazine))] (PhPTz) as an immobilizing matrix for the CEA antibodies. Judiciously introduced nitrogen-rich semiconducting PhPTz brings multiple advantages to the device—(1) efficiently immobilizes anti-CEA via synergistic H-bonding with peptide and N-glycal units and (2) transports the charge density variations, originated upon antibody-antigen interactions, to the rGO layer. The CEA was dropped onto the anti-CEA/PhPTz/rGO devices at ambient conditions, to facilitate binding and the change in current flowing through the sensors was measured. A response of 2.75–33.7 μA was observed when the devices were tested for a broad range of concentrations (0.25 pg/mL to 800 ng/mL) of CEA. A portable read-out circuit was assembled using Arduino UNO and a voltage divider circuit, and a simple algorithm was developed for the classification of the CEA concentrations. The prediction accuracy of the interfacing electronics along with the algorithm was found to be 100%.

Efficacy of active hexose correlated compound on survival of patients with resectable/borderline resectable pancreatic cancer: a study protocol for a double-blind randomized phase II study

BackgroundThe prognosis of pancreatic ductal adenocarcinoma remains very poor. One possible reason for the short survival of patients with this disease is malnutrition, which can be present at the initial diagnosis, and continue after pancreatectomy. Then, it is important to improve nutritional status and to decrease adverse events during neoadjuvant and adjuvant chemotherapy. Active hexose correlated compound (AHCC) is a standardized extract of cultured Lentinula edodes mycelia, and is considered a potent biological response modifier in the treatment of cancer. To evaluate the survival impact of AHCC on the patients with pancreatic ductal adenocarcinoma, we plan to perform this trial.MethodsThis is a prospective multicenter phase II trial in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma to investigate the efficacy of AHCC regarding survival. Patients will begin taking AHCC or placebo on the first day of neoadjuvant therapy. AHCC or placebo will be continued until 2 years after surgery. The primary endpoint will be 2-year disease-free survival. The secondary endpoints are the completion rate, dose intensity, and adverse event profile of preoperative chemotherapy; response rate to preoperative chemotherapy; rate of decrease in tumor marker (carbohydrate antigen 19-9, carcinoembryonic antigen) concentrations during preoperative chemotherapy; entry rate, completion rate, dose intensity, and adverse event profile of adjuvant chemotherapy; safety of the protocol therapy (adverse effect of AHCC); 2-year overall survival rate; and nutrition score before and after preoperative chemotherapy, and before and after adjuvant chemotherapy. We will enroll 230 patients, and the study involves eight leading Japanese institutions that are all high-volume centers in pancreatic surgery.DiscussionAHCC is expected to function as a supportive food in patients with pancreatic ductal adenocarcinoma, to reduce the proportion of severe adverse events related to neoadjuvant chemotherapy, and to increase the completion proportion of multimodal treatments, resulting in improved survival.Trial registrationThe trial protocol has been registered in the protocol registration system at the Japan Registry of Clinical Trials (Trial ID: jRCTs051200029). At the time of the submission of this paper (October 2020), the protocol version is 2.0. The completion date is estimated to be November 2024.

An all-in-one approach for self-powered sensing: A methanol fuel cell modified with a molecularly imprinted polymer for cancer biomarker detection

• A hybrid methanol fuel cell operating with a biosensor. • One electrode of the fuel cell is the biosensing element. • A molecularly-imprinted polymer tailored in situ for carcinoembryonic antigen. • The overall power of the hybrid cell is carcinoembryonic antigen concentration dependent. • This hybrid fuel cell pursues an application in point-of-care. This work describes the development of an innovative electrochemical biosensor comprehending a passive direct methanol fuel cell (DMFC) assembly, modified by a layer of a molecularly imprinted polymer (MIP) on a carbon fabric anode electrode containing Pt/Ru nanoparticles. This MIP film was prepared from poly(3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPy) obtained by in situ electropolymerization of the corresponding monomers on the anode electrode surface. This MIP film is designed to detect an important cancer biomarker- carcinoembryonic antigen (CEA). This innovative, all-in-one device works in a simple way. First, CEA is incubated on the anode container of the fuel cell, then methanol is added, followed by the response evaluation (polarization curves determination). As CEA selectively interacts with the MIP film, it blocks the methanol's access to the Pt catalyst, remains specific bonded, and interferes with the subsequent polarization curves of the DMFC. Polarization curves obtained in the presence of standard solutions prepared in buffer and human serum confirmed linear responses of log CEA concentration ranging from 30 to 30 000 ng/mL in both media. The biosensor DMFC showed a sensitive response with a detection limit of 4.41 ng/mL when an aqueous 0.05 M methanol solution was used as fuel. When methanol was replaced by an ethanol solution of the same concentration (using the same setup developed for the DMFC), the lower detection limit of 3.52 ng/mL was obtained. Overall, the obtained results show that methanol/ethanol fuel cells operating without flow-through can be successfully used for the fabrication of self-powered biosensors. The novel biosensor concept presented here is simple, inexpensive, and effective, and can be further developed to meet point-of-care requirements.

A Novel Label‐free Chronoamperometric Immunosensor Based on a Biocomposite Material for Rapid Detection of Carcinoembryonic Antigen

AbstractIn this research, poly(diallyldimethylammonium chloride)‐capped gold nanoparticles, nickel ferrite particles, and carbon nanotubes were combined to form a PANC metal composite. The prepared metal composite modified onto a glassy carbon electrode was electropolymerized with poly(o‐phenylenediamine) and immobilized with horseradish peroxidase, anti‐carcinoembryonic antigen antibody, and bovine serum albumin to create the label‐free immunosensors for rapid detection of carcinoembryonic antigen (CEA) using chronoamperometry. This developed biocomposite material modified onto a glassy carbon electrode presented an excellent electrocatalytic response to the redox reaction of hydrogen peroxide as a sensing probe, from which the kinetic parameters including of a charge transfer rate constant, a diffusion coefficient value, an electroactive surface area, and a surface concentration were calculated to be 1.85 s−1, 4.28×10−6 cm2 s−1, 0.14 cm2 and 1.87×10−8 mol cm−2, respectively. The developed immunosensors also exhibited a wide linear range of CEA concentration from 0.01 to 25 ng mL−1 with high sensitivity (96.21 μA cm−2 ng−1 mL) and low detection limit (0.72 pg mL−1), excellent selectivity without interfering effects from possible species (amoxicillin, ascorbic acid, aspirin, caffeine, cholesterol, dopamine, glucose, and uric acid), outstanding stability (n=100, %I&gt;50 %), repeatability (%RSD=0.34, n=10), reproducibility (%RSD=4.06, n=10), and rapid analysis (25 s each operation time). This proposed method was successfully applied for CEA detection in whole blood samples with satisfactory results, suggesting that this developed sensing platform may be considered to be exploited for fabrication of other label‐free electrochemical immunosensors for the real sample analysis.

A Colorimetric Immunoassay Based on g-C3N4@Fe3O4 Nanocomposite for Detection of Carcinoembryonic Antigen.

We proposed a colorimetric immunosensor based on g-C3N4@Fe3O4 nanocomposite-mediated transformation strategy for sensitive detection of carcinoembryonic antigen (CEA). The g-C3N4@Fe3O4 nanocomposite was synthesized and characterized by the scanning electron microscope (SEM), energy dispersive X-ray spectra (EDX), X-ray powder diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Fe3+ derived from g-C3N4@Fe3O4 nanocomposite could combine with sodium salicylate to form purple complex products. Based on this color development, the sandwich colorimetric immunoassay was built by utilizing g-C3N4@Fe3O4 nanocomposite as nanolabels on the microplate. With the increasement of CEA concentration, the purple color showed a gradient change. Under optimal conditions, the linearity range is 0.001–50 ng/mL with the detection limit of 0.35 pg/mL for CEA. More importantly, the colorimetric immunoassay has good selectivity, specificity, repeatability, and stability.

Assessment of the Antitumor Activity of Green Biosynthesized Zinc Nanoparticles as Therapeutic Agent Against Renal Cancer in Rats

Zinc nanoparticles (Zn-NPs) have garnered a great deal of attention as potential cancer therapy. The use of microorganisms in the synthesis of nanoparticles emerges as an eco-friendly and exciting approach. This study was designed to assess biosynthesized Zn-NPs as therapeutic agent against kidney cancer induced by ferric-nitrilotriacetate (Fe-NTA) in rats.Zn-NPs were synthesized from edible mushroom then characterized by transmission electron microscopy analysis, dynamic light scattering, and Fourier transform infrared spectroscopy. Rats were divided into 4 different groups: group I (control), group II (Fe-NTA group), group III (Zn-NPs group), and group IV (Fe-NTA + Zn-NPs group). Animals were sacrificed then kidney and liver function tests, MDA level, glutathione, glutathione peroxidase, and superoxide dismutase activities were measured by using colorimetric methods. Caspase-3 level and carcinoembryonic antigen concentration were measured by using ELISA. Finally, DNA fragmentation was visualized by using agarose gel electrophoresis.Treatment with Zn-NPs significantly suppressed renal oxidative stress by restoring glutathione level, glutathione peroxidase, and superoxide dismutase activities and ameliorated oxidative damage parameters of lipid peroxidation as well as renal toxicity markers. Molecular and tumor markers showed significant improvement with respect to induction group, and this was well appreciated with the histopathological alteration findings in the treated groups.Microbial synthesized Zn-NPs possess antitumor-promoting activity against Fe-NTA-induced toxicity and carcinogenesis, which should be evaluated in a clinical study.

Diagnostic, Prognostic, and Recurrence Monitoring Value of Plasma CYFRA21-1 and NSE Levels in Patients With Esophageal Squamous Cell Carcinoma.

This study was aimed to evaluate the clinical values of single markers and combination in the diagnosis, short-term efficacy and recurrence risk assessment of esophageal squamous cell carcinoma (ESCC).MethodsTotally 50 patients with I-IVa stage ESCC, 50 healthy controls and 11 patients with recurrent esophageal cancer after comprehensive treatment were enrolled. Serum biomarkers were collected and evaluated. Serum concentrations of carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and neuron specific enolase (NSE) were measured by enzyme-linked immunosorbent assay before and after treatment.ResultsThe diagnostic efficacy ROC curve area of CEA, CYFRA21-1 and NSE in esophageal cancer was 0.70, 0.71 and 0.64(all P <0.05), respectively, the sensitivity was 80%, 88.89% and 60% respectively, and the specificity was 53%, 58.5% and 58% respectively. The sensitivity and specificity of the combined detection were 68% and 78% respectively. The area under ROC curve was 0.75. CEA, CYFRA21-1 and NSE were significantly higher than the healthy control group and thus can be used as diagnostic markers of esophageal cancer (all P <0.05). After standard treatment, the clinical CR and PR rate of patients with positive CYFRA21-1 or NSE before treatment was significantly lower than that of patients with negative CYFRA21-1 or NSE (X2 = 4.52,P =0.03). A significant negative correlation was found between N stage and clinical efficacy (HR 2.48, 95%CI 1.07-5.73). After comprehensive treatment, the serum CYFRA21-1 and NSE levels in recurrent patients also increased significantly(all P<0.05), indicating these two markers play obvious roles in recurrence monitoring.ConclusionCYFRA21-1 and NSE may help to predict the response of ESCC to CRT, and play important roles in the diagnosis and recurrence monitoring of esophageal cancer. These markers have a diagnostic value of esophageal cancer when combined with CEA.

Reduced Graphene Oxide Based Electronic Sensors for Rapid and Label-Free Detection of CEA and CYFRA 21-1

Proper and early diagnosis of diseases is a key to efficient treatment and better prognosis. This paper reports a simple and label-free method of detection of two antigens – carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA 21-1) which are the biomarkers of many cancers including lung cancer. The sensor devices were fabricated by coating antibody/gold nanoparticles (AuNPs)/reduced graphene oxide (RGO) on indium tin oxide (ITO) coated glass. The sensors fabricated for detecting CEA had <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$6 ~\mu \text{L}$ </tex-math></inline-formula> of CEA antibodies and the ones developed for detecting CYFRA 21-1 were coated with <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$6 ~\mu \text{L}$ </tex-math></inline-formula> CYFRA 21-1 antibodies. The thickness of the graphene oxide was found to be ~1nm and the thickness of anti-CEA/AuNPs/RGO was found to be ~25 nm when observed using atomic force microscope. The sensing layers exhibited reflectance in the wavelength ranging from 248 to 300 nm when tested with UV-Visible spectrophotometer. A simple technique to capture the antibody-antigen binding has been developed in which the antigens are to be dropped onto the sensor devices and the change in the current across the sensors are to be measured. The biosensors were tested for 0.25 pg/mL to 20 ng/mL concentrations of CEA and CYFRA 21-1 at room temperature. The responses of the sensors ranged from 10.96 to 26.48% for 0.25 pg/mL to 20 ng/mL CEA and it varied from 17.66 to 26.68% for 0.25 pg/mL to 20 ng/mL CYFRA 21-1.