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1.
Int J Mol Sci ; 22(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669885

RESUMO

The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Microambiente Tumoral , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Inibidores de Checkpoint Imunológico/farmacologia , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiação
2.
J Hazard Mater ; 192(2): 837-45, 2011 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-21704455

RESUMO

Emerging technologies involving chemical catalytic processes to remove nitrate from water have proven efficient and cost-effective. However, the environmental impact of noble metals and metals at the nanoscale used in these processes has become a topic of serious concern. The aim of this research was to develop a system for evaluating the environmental impact of technologies associated with Pd-based catalytic denitrification. This research performed life cycle assessment (LCA) based on a detailed analysis of the technologies to examine the environmental burden associated with all stages of the removal process. We then applied analytical hierarchy process (AHP) to determine the weights of various burdens. We implemented the proposed system to determine the relative environmental friendliness of 5 processes used for the removal of nitrate. These five methods use Cu-Pd/TNTs, H(2)+Pd-Cu/TiO(2), Pd-Cu/TiO(2), Pd/ZnO, and Pd-Cu/FeO as catalysts for the removal of nitrate. The results indicate that the use of palladium and the consumption of electricity have a major environmental impact; while the use of Pd-Cu/TiO(2) as catalyst was the most environmentally friendly of the five processes evaluated.


Assuntos
Poluentes Ambientais/isolamento & purificação , Nitratos/isolamento & purificação , Paládio/química , Catálise
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