ABSTRACT
Immunotherapy has shown great potential in cancer therapeutics but has limitations of the insufficient activation of dendritic cells (DCs) and immune-suppressive microenvironment. To overcome these obstacles, a cascade synergistic immunotherapy nanosystem (denoted as CpG@PDA-FA) was designed to elevate anticancer immune response. The combination nanosystem including a photothermal agent polydopamine (PDA) and immunomodulator CpG oligodeoxynucleotides (CpG ODNs). On the one hand, polydopamine (PDA) acts as a photothermal agent to induce low-temperature PTT. It leads to immunogenic cell death (ICD), a programmed cell death pathway, which can activate DCs and enhance the antitumor immune response of T cells. On the other hand, CpG ODNs further promote maturation and migration of DCs as well as ameliorates the immunosuppression microenvironment of the tumor (TME). This paper focuses on a cancer synergistic treatment of ICD-induced immunotherapy by low-temperature PTT and ameliorates TME by immunomodulator CpG ODNs. We proved that CpG@PDA-FA NPs realized a remarkable synergistic treatment effect compared with respective single PTT or CpG therapy in the maturation of DCs and activation of T cells. In addition, CpG@PDA-FA NPs also reduced myeloid-derived suppressor cells and regulatory T cells to relieve immunosuppression. Hence, CpG@PDA-FA NPs provide a bidirectional immunotherapy strategy for tumor inhibition and highlight the cascade effects of low-temperature PTT and immunotherapy.
Subject(s)
Immunologic Factors/therapeutic use , Immunotherapy/methods , Neoplasms/immunology , Tropanes/immunology , Cell Line, Tumor , Humans , Immunologic Factors/pharmacology , TemperatureABSTRACT
In this study, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) based on a broad-spectrum monoclonal antibody for tropane alkaloids (TAs) was established for the rapid screening of atropine, scopolamine, homatropine, apoatropine, anisodamine, anisodine and L-hyoscyamine residues in pig urine, pork and cereal flour samples through a simple sample preparation procedure. The half inhibitory concentrations of atropine, homatropine, L-hyoscyamine, apoatropine, scopolamine, anisodamine and anisodine were 0.05, 0.07, 0.14, 0.14, 0.24, 5.30 and 10.15 ng mL-1, respectivelyThe detection and quantitative limits of this method for TAs in samples were 0.18-73.18 and 0.44-74.77 µg kg-1. The spiked recoveries ranged from 69.88% to 147.93%, and the coefficient of variations were less than 14%. Good correlation (R2 = 0.9929) between the results of the ic-ELISA and the high performance liquid chromatography-tandem mass spectrometry support the reliability of the developed ic-ELISA method.
Subject(s)
Antibodies, Monoclonal , Enzyme-Linked Immunosorbent Assay/methods , Flour/analysis , Pork Meat/analysis , Tropanes/analysis , Animals , Antibodies, Monoclonal/immunology , Atropine/analysis , Atropine/urine , Chromatography, High Pressure Liquid/methods , Female , Food Analysis/methods , Mice, Inbred BALB C , Reproducibility of Results , Scopolamine/analysis , Scopolamine/urine , Solanaceous Alkaloids/analysis , Solanaceous Alkaloids/urine , Swine , Tandem Mass Spectrometry , Tropanes/immunology , Tropanes/urineABSTRACT
Early warning systems for monitoring toxic events may benefit from the availability of monoclonal antibodies enabling the sensitive and specific detection of anatoxin-a, a cyanotoxin involved in numerous cases of animal poisoning resulting from toxic algal blooms in freshwaters. Through the synthesis of three functionalized derivatives of anatoxin-a, we have succeeded in generating the first-ever reported immunoreagents (bioconjugates and antibodies) suitable for the development of immunoanalytical approaches aimed at rapid and onsite detection of this harmful cyanotoxin.
Subject(s)
Antibodies, Monoclonal/immunology , Enzyme-Linked Immunosorbent Assay , Haptens/immunology , Tropanes/analysis , Animals , Antibodies, Monoclonal/chemistry , Cattle , Cyanobacteria Toxins , Haptens/chemistry , Harmful Algal Bloom , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/immunology , Stereoisomerism , Tropanes/immunologyABSTRACT
Hepatic angiomyolipoma (HAML) is a rare, benign mesenchymal neoplasm composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. Its morphological diversity often poses diagnostic problems. In this paper, the authors report a peculiar case of epithelioid HAML mimicking histologically hepatocellular carcinoma with focal areas resembling inflammatory pseudotumour. A 57 year-old male patient presented with abdominal pain and discomfort. Non enhanced CT scan demonstrated a heterogeneous hypodense mass located in segment II and IV of the liver. Hepatocellular carcinoma was suspected and the patient underwent left lobectomy. Histologically, the tumour was mainly composed of epithelioid cells arranged in trabeculae and sheets (50% of the tumour surface) admixed with mature fat cells (20%) and thick-walled blood vessels. Lymphocytic aggregates and clusters of foamy histiocytes were focally found in the stroma (30%). Most of the epithelioid tumour cells were immunoreactive to homatropine methylbromide 45 (HMB-45) and smooth muscle actin. Morphological pattern and immunophenotype were consistent with epithelioid HAML.
Subject(s)
Angiomyolipoma/diagnosis , Carcinoma, Hepatocellular/diagnosis , Granuloma, Plasma Cell/diagnosis , Hepatectomy/methods , Liver Neoplasms/diagnosis , Liver/pathology , Diagnosis, Differential , Epithelioid Cells/immunology , Epithelioid Cells/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Postoperative Care/methods , Tomography, X-Ray Computed , Treatment Outcome , Tropanes/immunologyABSTRACT
Potential medications for cocaine abusers include: anticocaine catalytic antibodies, which could serve as circulating peripheral blockers of cocaine that prevents its action in the brain; and 3-phenyltropane cocaine analogs, which could serve as potent, selective, and long-lasting substitutes that reduce drug-seeking. In order to evaluate the compatibility of these agents, we measured if a catalytic antibody would bind and interact with some cocaine analogs. Anticocaine catalytic antibody 15A10 had no significant affinity for RTI-51, RTI-112, or RTI-177 as examined by ELISA. They exhibited high affinity for the immunogen TSA1 in the same experiment, as expected. Because the antibody and the RTI compounds do not interact, they are candidates for simultaneous use.