RESUMO
The advent of immune checkpoint inhibitors (ICIs) has greatly improved the prognosis of advanced lung cancer patients, but can lead to pseudoprogression (PsP), which complicates clinical evaluation and management. PsP is manifested as temporary enlargement of the tumour or the appearance of new lesions, etc., and improvement in imaging occurs with continued treatment, mostly without worsening of clinical symptoms. Currently, there are still difficulties in the early diagnosis of PsP, and its occurrence mechanism is not yet clear, lacking good predictive factors and related biomarkers. This article reviews the current research status of PsP of ICIs in non-small cell lung cancer in order to provide helpful clinical strategies for oncologists using these drugs.â©.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Progressão da DoençaRESUMO
INTRODUCTION: Bimetallic nanoparticles, specifically Zinc oxide (ZnO) and Silver (Ag), continue to much outperform other nanoparticles investigated for a variety of biological uses in the field of cancer therapy. This study introduces biosynthesis of bimetallic silver/zinc oxide nanocomposites (Ag@ZnO NCs) using the Crocus sativus extract and evaluates their anti-cancer properties against cervical cancer. METHODS: The process of generating bimetallic nanoparticles (NPs), namely Ag@ZnO NCs, through the utilization of Crocus sativus extract proved to be uncomplicated and eco-friendly. Various methods, such as UV-vis, DLS, FTIR, EDX, and SEM analyses, were utilized to characterize the generated Ag@ZnO NCs. The MTT assay was employed to assess the cytotoxic properties of biosynthesized bimetallic Ag@ZnO NCs against the HeLa cervical cancer cell line. Moreover, the impact of Ag@ZnO NCs on HeLa cells was assessed by examining cell survival, ROS production, MMP levels, and induced apoptosis. Through western blot analysis, the expression levels of the PI3K, AKT, mTOR, Cyclin D, and CDK proteins seemed to be ascertained. Using flow cytometry, the cancer cells' progression through necrosis and apoptosis, in addition to the cell cycle analysis, were investigated. RESULTS: Bimetallic Ag@ZnO NCs that were biosynthesized showed a high degree of stability, as demonstrated by the physicochemical assessments. The median size of the particles in these NCs was approximately 80-90â¯nm, and their zeta potential was -14.70â¯mV. AgNPs and ZnO were found, according to EDX data. Further, Ag@ZnO NCs hold promise as a potential treatment for cervical cancer. After 24â¯hours of treatment, a dosage of 5⯵g/mL or higher resulted in a maximum inhibitory effect of 58 ± 2.9. The concurrent application of Ag/ZnO NPs to HeLa cells resulted in elevated apoptotic signals and a significant generation of reactive oxygen species (ROS). As a result, the bimettalic Ag@ZnO NCs treatment has been recognized as a chemotherapeutic intervention by inhibiting the production of PI3K, AKT, and mTOR-mediated regulation of propagation and cell cycle-regulating proteins. CONCLUSIONS: The research yielded important insights into the cytotoxic etiology of biosynthesized bimetallic Ag@ZnO NCs against HeLa cells. The biosynthesized bimetallic Ag@ZnO NCs have a significant antitumor potential, which appears to be associated with the development of oxidative stress, which inhibits the development of the cell cycle and the proliferation of cells. Therefore, in the future, biosynthesized bimetallic Ag@ZnO NCs may be used as a powerful anticancer drug to treat cervical cancer.
Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Nanocompostos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Prata , Serina-Treonina Quinases TOR , Neoplasias do Colo do Útero , Óxido de Zinco , Humanos , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Prata/química , Prata/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Feminino , Células HeLa , Fosfatidilinositol 3-Quinases/metabolismo , Nanocompostos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Nanopartículas Metálicas/química , Ensaios de Seleção de Medicamentos Antitumorais , Transdução de Sinais/efeitos dos fármacosRESUMO
The Shanghai Soft X-ray Free-Electron Laser (SXFEL) is the first X-ray free-electron laser facility in China. The SASE beamline, which consists of a pink-beam branch and a mono-beam branch, is one of the two beamlines in the Phase-I construction. The pink-beam branch opened for users in 2023 after successful first-round beamline commissioning. In this paper, the design of the beamline is presented and the performance of the pink-beam branch is reported. The measured energy-resolving power of the online spectrometer is over 6000 @ 400â eV. The focusing spot size of the pink beam is less than 3â µm in both the horizontal and vertical at the endstation.