In order to early screen and detect suspected biomarkers from pathogens and the human body itself, tracers or reaction strategies that can act as signal enhancers have been proposed forth at purpose. In this paper, we discussed the applicability of magnetic microparticles-assisted time-resolved fluoroimmunoassay (MMPs-TRFIA) for sensitive determination of potential analytes. Hepatitis B e antigen, antibody to hepatitis B surface antigen and free triiodothyronine were used as biomarker models to explore the reliability of the method. By coupling with bioprobes, MMPs were used as immunoassay carriers to capture target molecules. Under optimal condition, assay performance, including accuracy, precision and specificity, was outstanding and demonstrated satisfactory. To further evaluate the performance of the MMPs-TRFIA in patients, a total of 728 serum samples from hospital were analyzed for three biomarkers in parallel with the proposed method and chemiluminescence immunoassay kit commercially available. Fairly good agreements are obtained between the two methods via data analysis. Not only that but the reliability of MMPs-TRFIA has also been illustrated by three different reaction models. It is confirmed that the novel method modified with MMPs has been established and showed great potential applications in both biological detection and clinical diagnosis, including big molecule protein and low molecular weight haptens.
Luminescent oxygen channeling assay (LOCITM) is a homogeneous immunoassay method capable of rapid, quantitative determination of a wide range of analytes-including high and very low concentrations of large and small molecules , free (unbound) drugs, DNA, and specific 1gM. Assays have been carried out in serum and in lysed blood. Reliable detection of 1.25 tUfL thyrotropin (TSH) and 5 ngfL hepatitis B surface antigen (HBsAg) corresponds to detection limits-3-and-20-fold lower, respectively, than those of the best commercially available assays. An assay of chorionic gonadotropin is capable of quantification over a 106-fold range of concentrations without a biphasic response. Latex particle pairs are formed in the assay through specific binding interactions by sequentially combining the sample and two reagents. One particle contains a photosen-sitizer, the other a chemiluminescer. Irradiation causes photosensitized formation of singlet oxygen, which migrates to a bound particle and activates the chemilumi-nescer, thereby initiating a delayed luminescence emission. Assay times range from 1 to 25 mm. INDEXING TERMS: latexagglutination,singletoxygen #{149} chemi-luminescence. photosensitizers. biotin-streptavidin interaction #{149} digoxin #{149} cyclosporine#{149} thyrotropin#{149} hepatitis #{149} chorionic gonadotropin Development of a sensitive homogeneous immunoassay methodology has been the goal of numerous researchefforts [1, 2]. A method thatwould eliminatethe need to separatebound from free labeled analyte(and the associatedwash steps)would be particularly useful if it were suitable for both haptens and proteins and sufficiently sensitive to permit quantification of all common analytes. Chemiluminescence-based homogeneous im-munoassays provide the required sensitivity [3, 4], but the complex chemistry of chemical excitation and emission renders them highly susceptible to matrix effects. Latex agglutination techniques [5], in which detection is based on low-angle light scattering, also have the theoretical ability to provide exceptionally high sensitivity, but the measurements require rigorous exclusion of adventitious particles [6-8]. Enzyme channeling immunoassays are applicable to both small and large molecules but have limited sensitivity because of their susceptibility to matrix effects. In these assays, an immune reaction brings two enzymes into proximity on a surface; at that surface, one enzyme produces a product that serves as a chro-mogenic substrate for the second enzyme [9]. The product reaches higher concentrations near the surface than in the bulk solution, which leads to an increase in the rate of reaction with the proximate second enzyme. We report here on the development of an unusually robust and sensitive homogeneous chemiluminescent immunoassay that is based on a combination of the principles of latex agglutination and channeling. The luminescent oxygen channel-ing assay (LOCIm'M) principle, which has been described previously [10], uses two different ligand-or receptor-coated polystyrene p...
Janus-activated kinase-1 (JAK1) plays an important role in many signaling pathways, including the JAK–STAT and SOCS pathways.
Molecular targeting and immunotherapy provide durable responses for advanced lung cancer clinical therapy in many patients. However, the mechanisms of occurrence of progressive disease and resistance to targeted therapy and immunotherapy have not been elucidated. Herein, we report two cases of small cell transformation of non-small cell lung cancer (NSCLC) after targeted therapy or immunotherapy. The first case was a 63-year-old female patient presenting with cough and expectoration. Left lung invasive adenocarcinoma was diagnosed after left lung tumor biopsy. After epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapy for almost 2 years, disease progression and symptom aggravation were observed. Pathological and immunohistochemical staining results after biopsy revealed small cell lung cancer (SCLC). The second case was a 75-year-old male patient diagnosed with stage IV squamous cell carcinoma of the lung, who received carboplatin/paclitaxel adjuvant chemotherapy and pembrolizumab treatment with partial response. Disease progression and metastasis occurred within 15 cycles of immunotherapy. Computed tomography revealed a lower left lung tumor. Cytological examination of lung lavage fluid and biopsy under thoracoscope revealed SCLC. In conclusion, histological transformation to SCLC is a potential mechanism of NSCLC resistance to targeted therapy or immunotherapy. During treatment, clinicians should monitor serum tumor markers or genome sequencing, particularly in patients with disease progression, as this may be beneficial for early detection of SCLC transformation. Repeated biopsy can be performed if necessary, and the therapeutic regimen can be adjusted in a timely manner according to the results of molecular pathological tests for personalization and whole-process management.
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