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OBJECTIVE: We conducted a systematic review and meta-analysis aiming to assess the efficacy and safety of Nivolumab treatment in patients with newly diagnosed and recurrent glioblastoma multiforme (GBM). DATA SOURCES: Our study followed the guidelines outlined in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. The protocol for this review can be found in the International Prospective Register of Systematic Reviews Database (CRD42022340071). We performed searches on the Medline, PubMed, Embase, Scopus, and Web of Science databases. DATA SUMMARY: A total of 545 studies were identified through our comprehensive search across the five databases (PubMed: 78, Embase: 82, Medline: 173, Scopus: 138, Web of Science: 74). After conducting a thorough analysis, our meta-analysis indicated that treatment with Nivolumab led to improved overall survival (OS) outcomes in newly diagnosed glioblastoma patients, as evidenced by a prolonged median OS based on trial data. However, there was no significant beneficial effect observed in terms of median progression-free survival (PFS), as well as OS at 6, 12, and 24 months. Furthermore, our results demonstrated no efficacy of Nivolumab in the treatment of recurrent GBM patients. CONCLUSIONS: In conclusion, Nivolumab demonstrated promising results that warrant further investigation for its use in newly diagnosed glioblastoma patients. However, its effectiveness was not observed in the context of recurrent GBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Nivolumabe/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de ProgressãoRESUMO
Trichoderma reesei superoxide dismutase (TrSOD) is a well-characterized enzyme being stable between 30 and 90°C for 1 h with activity at pH between 2.6 and 9.0. This work aimed to clone, express, purify, and evaluate the protective effect antioxidant of this enzyme on skin cells when fused to transactivator of transcription (TAT) protein transduction domain of HIV-1 and abalone (Ab) peptides to allow cell penetration. TrSOD, TAT-TrSOD-Yfp (fused to yellow fluorescent protein), and Ab-TrSOD were expressed in E. coli and purified as soluble proteins. The cytotoxicity of the enzymes, at the concentrations of 1, 3, and 6 µmol/L, was evaluated for a period of 24 and 48 h of incubation, with no cytotoxic effect on 3T3 fibroblasts. The 3T3 cells were exposed to the oxidant agent tert-butyl hydroperoxide and evaluated for reactive oxygen species (ROS) generation, in the presence or not of the recombinant enzymes. TAT-TrSOD-Yfp was able to decrease the generation of ROS by 15% when used in the concentrations of 3 and 6 µmol/L in comparison to the control, but there was no difference in relation to the effect of TrSOD. Ab-TrSOD, when compared to TrSOD, promoted a decrease in the formation of ROS of 19% and 14% at the concentrations of 1 and 6 µmol/L, respectively, indicating that this recombinant form was more effective in reducing oxidative stress compared to SOD without the cell-penetrating peptide (CPP). Together, these results indicate that the fusion of SOD with these CPP increased the antioxidant capacity of fibroblasts, identified by the reduction in the generation of ROS. In addition, such molecules, in the concentrations initially used, were not toxic to the cells, opening perspectives for the development of products for antioxidant protection of the skin that may have therapeutic and cosmetic application.
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Antioxidantes , Transativadores , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Transativadores/metabolismo , Escherichia coli/metabolismo , Superóxido Dismutase/metabolismo , Estresse Oxidativo , Peptídeos/farmacologia , Peptídeos/metabolismoRESUMO
Aim: To synthesize HER2 aptamer-conjugated iron oxide nanoparticles with a coating of poly(2-(dimethylamino) ethyl methacrylate)-poly(2-methacryloyloxyethylphosphorylcholine) block copolymer (IONPPPs). Methods: Characterization covered molecular structure, chemical composition, thermal stability, magnetic characteristics, aptamer interaction, crystalline nature and microscopic features. Subsequent investigations focused on IONPPPs for in vitro cancer cell identification. Results: Results demonstrated high biocompatibility of the diblock copolymer with no significant toxicity up to 150 µg/ml. The facile coating process yielded the IONPP complex, featuring a 13.27 nm metal core and a 3.10 nm polymer coating. Functionalized with a HER2-targeting DNA aptamer, IONPPP enhanced recognition in HER2-amplified SKBR3 cells via magnetization separation. Conclusion: These findings underscore IONPPP's potential in cancer research and clinical applications, showcasing diagnostic efficacy and HER2 protein targeting in a proof-of-concept approach.
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Neoplasias da Mama , Nanopartículas , Nylons , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Polímeros/química , Metacrilatos/química , Nanopartículas Magnéticas de Óxido de Ferro , Nanopartículas/químicaRESUMO
Composites of magnetite nanoparticles encapsulated with polymers attract interest for many applications, especially as theragnostic agents for magnetic hyperthermia, drug delivery, and magnetic resonance imaging. In this work, magnetite nanoparticles were synthesized by coprecipitation and encapsulated with different polymers (Eudragit S100, Pluronic F68, Maltodextrin, and surfactants) by nano spray drying technique, which can produce powders of nanoparticles from solutions or suspensions. Transmission and scanning electron microscopy images showed that the bare magnetite nanoparticles have 10.5 nm, and after encapsulation, the particles have approximately 1 µm, with size and shape depending on the material's composition. The values of magnetic saturation by SQUID magnetometry and mass residues by thermogravimetric analysis were used to characterize the magnetic content in the materials, related to their magnetite/polymer ratios. Zero-field-cooling and field-cooling (ZFC/FC) measurements showed how blocking temperatures of the powders of the composites are lower than that of bare magnetite, possibly due to lower magnetic coupling, being an interesting system to study magnetic interactions of nanoparticles. Furthermore, studies of cytotoxic effect, hydrodynamic size, and heating capacity for hyperthermia (according to the application of an alternate magnetic field) show that these composites could be applied as a theragnostic material for a non-invasive administration such as nasal.
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The growing area of tissue engineering has the potential to alleviate the shortage of tissues and organs for transplantation, and electrospun biomaterial scaffolds are extremely promising devices for translating engineered tissues into a clinical setting. However, to be utilized in this capacity, these medical devices need to be sterile. Traditional methods of sterilization are not always suitable for biomaterials, especially as many commonly used biomedical polymers are sensitive to chemical-, thermal- or radiation-induced damage. Therefore, the objective of this study was to evaluate the suitability of ozone gas for sterilizing electrospun scaffolds of polycaprolactone (PCL), a polymer widely utilized in tissue engineering and regenerative medicine applications, by evaluating if scaffolds composed of either nanofibres or microfibres were differently affected by the sterilization method. The sterility, morphology, mechanical properties, physicochemical properties, and response of cells to nanofibrous and microfibrous PCL scaffolds were assessed after ozone gas sterilization. The sterilization process successfully sterilized the scaffolds and preserved most of their initial attributes, except for mechanical properties. However, although the scaffolds became weaker after sterilization, they were still robust enough to use as tissue engineering scaffolds and this treatment increased the proliferation of L929 fibroblasts while maintaining cell viability, suggesting that ozone gas treatment may be a suitable technique for the sterilization of polymer scaffolds which are significantly damaged by other methods.
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Eletricidade , Ozônio/química , Poliésteres/química , Poliésteres/farmacologia , Alicerces Teciduais/química , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Teste de Materiais , Camundongos , Peso Molecular , Nanofibras/química , Propriedades de Superfície , Temperatura , Engenharia TecidualRESUMO
In a joint project of IPT (Instituto de Pesquisas Tecnológicas do Estado de São Paulo) and Vallée S.A., the growth of BHK-21 cells, used for the production of a vaccine against foot-and-mouth disease, was studied. The present work aimed the evaluation of the influence of and dissolved oxygen concentration on this growth. Assays were performed in a 2 L stirred bioreactor, with a BHK-21 cell line supplied by Vallée S.A. The culture medium contained glucose, several amino acids, vitamins and bovine serum. Seven experiments were performed, in which pH varied between 6.8 and 7.4, and the dissolved oxygen concentration between 2 and 60(per cent) of air saturation. The definition of optimal values was based on analysis of cell productivity and amounts of cells produced at the point at which the cultures attained maximal cell concentration. Optimal values for these paramenters were observed at pH 7.2 and 10 per cente dissolved oxygen concentration.