CARACTERIZAÇÃO DE RESÍDUOS DA FUNDIÇÃO DE FERRO E AVALIAÇÃO DE POSSÍVEIS APLICAÇÕES NA CONSTRUÇÃO CIVIL

A geração e a disposição de resíduos oriundos da fundição de metaisdespertam a necessidade de alternativas que promovam seu melhorreaproveitamento em processos produtivos. Assim, este estudo realizoua caracterização química, mineralógica e granulométrica de resíduosde fundição de ferro cinzento e nodular e avaliou sua aplicabilidade naconstrução civil. A areia verde, escória e material particulado apresentaramem sua composição química a presença majoritária de dióxido de silício(SiO2), além de óxido de alumínio (Al2O3), óxido de potássio (K2O) e óxidode ferro (Fe2O3). A análise mineralógica revelou a presença de quartzo emtodos os resíduos e de hematita, na escória. Os três resíduos apresentaramgranulometrias compreendidas entre 0,002 e 0,6 mm. Identificou-se que osresíduos possuem potencialidade de uso na produção de cimento, argamassase materiais cerâmicos, como substituintes parciais dos agregados miúdos doconcreto e como material da camada de sub-base de pavimentos.The generation and disposal of foundry waste result in the need for alternatives or solutions that promote a better waste reuse in the production processes. Having this in mind, this study carried out the chemical, mineralogical and granulometric characterization of gray and nodular iron foundry wastes and evaluated their applicability in civil construction. The green sand, slag and particulate material presented, in their chemical composition, the major presence of SiO2, followed by Al2O3, K2O and Fe2O3. The mineralogical analysis revealed the presence of quartz in all residues and hematite in the slag.These three residues had particle sizes ranging from 0.002 to 0.6 mm. It was identified that the residues have great potentiality of use in the production of cement, concrete as material of the sub-base layer of pavements

MCT4 blockade increases the efficacy of immune checkpoint blockade

Background & Aims Intratumoral lactate accumulation and acidosis impair T-cell function and antitumor immunity. Interestingly, expression of the lactate transporter monocarboxylate transporter (MCT) 4, but not MCT1, turned out to be prognostic for the survival of patients with rectal cancer, indicating that single MCT4 blockade might be a promising strategy to overcome glycolysis-related therapy resistance. Methods To determine whether blockade of MCT4 alone is sufficient to improve the efficacy of immune checkpoint blockade (ICB) therapy, we examined the effects of the selective MCT1 inhibitor AZD3965 and a novel MCT4 inhibitor in a colorectal carcinoma (CRC) tumor spheroid model co-cultured with blood leukocytes in vitro and the MC38 murine CRC model in vivo in combination with an antibody against programmed cell death ligand-1(PD-L1). Results Inhibition of MCT4 was sufficient to reduce lactate efflux in three-dimensional (3D) CRC spheroids but not in two-dimensional cell-cultures. Co-administration of the MCT4 inhibitor and ICB augmented immune cell infiltration, T-cell function and decreased CRC spheroid viability in a 3D co-culture model of human CRC spheroids with blood leukocytes. Accordingly, combination of MCT4 and ICB increased intratumoral pH, improved leukocyte infiltration and T-cell activation, delayed tumor growth, and prolonged survival in vivo. MCT1 inhibition exerted no further beneficial impact. Conclusions These findings demonstrate that single MCT4 inhibition represents a novel therapeutic approach to reverse lactic-acid driven immunosuppression and might be suitable to improve ICB efficacy

MCT4 blockade increases the efficacy of immune checkpoint blockade

Background & Aims Intratumoral lactate accumulation and acidosis impair T-cell function and antitumor immunity. Interestingly, expression of the lactate transporter monocarboxylate transporter (MCT) 4, but not MCT1, turned out to be prognostic for the survival of patients with rectal cancer, indicating that single MCT4 blockade might be a promising strategy to overcome glycolysis-related therapy resistance.Methods To determine whether blockade of MCT4 alone is sufficient to improve the efficacy of immune checkpoint blockade (ICB) therapy, we examined the effects of the selective MCT1 inhibitor AZD3965 and a novel MCT4 inhibitor in a colorectal carcinoma (CRC) tumor spheroid model co-cultured with blood leukocytes in vitro and the MC38 murine CRC model in vivo in combination with an antibody against programmed cell death ligand-1(PD-L1).Results Inhibition of MCT4 was sufficient to reduce lactate efflux in three-dimensional (3D) CRC spheroids but not in two-dimensional cell-cultures. Co-administration of the MCT4 inhibitor and ICB augmented immune cell infiltration, T-cell function and decreased CRC spheroid viability in a 3D co-culture model of human CRC spheroids with blood leukocytes. Accordingly, combination of MCT4 and ICB increased intratumoral pH, improved leukocyte infiltration and T-cell activation, delayed tumor growth, and prolonged survival in vivo. MCT1 inhibition exerted no further beneficial impact.Conclusions These findings demonstrate that single MCT4 inhibition represents a novel therapeutic approach to reverse lactic-acid driven immunosuppression and might be suitable to improve ICB efficacy