ABSTRACT
ZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a "nonself" label in tumor cells and then turn the tumor cells from the "self" state into the "nonself" state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.
Subject(s)
Adenoviridae/genetics , Immunotherapy/methods , Interleukins/metabolism , Melanoma/genetics , Animals , Disease Models, Animal , Female , Humans , Mice , Mice, NudeABSTRACT
As a promising generation of porous micro-materials, covalent organic frameworks (COFs) have great potentials for applications in separation and adsorption. In the present study, an advanced food-safety inspection method involving COFs as the adsorbents of solid phase extraction (SPE) is proposed for sensitive and accurate determination of target hazardous substances. Typical spherical TpBD COFs with large surface area and superior chemical stability were utilized as adsorbents for the preconcentration of phenolic endocrine disruptors (PEDs), followed by high performance liquid chromatography (HPLC) analysis. The well-prepared TpBD COFs were encapsulated in SPE cartridges and applied in food research, namely, for the separation and enrichment of four target endocrine disruptors in food samples. The possible factors influencing the SPE performance including the composition of the sample solvent, sample solution pH, sample flow rate, composition of the eluent, and the volume of the eluent were investigated and optimized. Due to the porous architecture and superior surface area of spherical TpBD, the enrichment of analytes via a COF-filled SPE column gave extremely low detection limits of 0.056-0.123 µg L-1 along with a wide linear range of 0.5-100 µg L-1 for all the analytes. Nine parallel determinations of the mixed standard with a concentration of 10 µg L-1 produced the relative standard deviations of 2.23-3.08%, indicating the excellent repeatability of the COF-SPE assay. This study can open up a new route for the employment of COFs as efficient SPE adsorbents for the enrichment and quantification of trace/ultra-trace hazardous materials in complex food samples.
ABSTRACT
Herein, for the first time, the typical porous Covalent Organic Frameworks (COFs) CTpBD with superior chemical stability and large surface area were applied as sorbents for solid phase extraction of trace ions via flow injection followed by inductively coupled plasma mass spectrometry (ICP-MS) detection. The well-prepared and fully-characterized CTpBD COFs were filled in solid phase extraction cartridge as novel and robust adsorbents for element analysis. Separation and enrichment of Cr (III), Mn (II), Co (II), Ni (II), Cd (II), V (V), Cu (II), As (III), Se (IV), and Mo (VI) was then carried out, and the contents were measured by ICP-MS. Owing to the large surface area and instinctive porous structure of CTpBD, preconcentration of the target trace elements via COF-filled on-line SPE column has achieved low detection limits of 2.1-21.6ngL-1 along with a wide linearity range at 0.05-25µgL-1 for all target ions. The relative standard deviations (RSD) of 1.2%-4.3% obtained via 11 parallel determinations at the sample concentration of 100ngL-1 revealed excellent repeatability of the developed methods Our proposed methods have been successfully utilized for trace element analysis in environmental and food samples.