FLAVIO TOKESHI
Projetos de Pesquisa
Unidades Organizacionais
SCCIRGR-62, Hospital Universitário
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- Activation of the Adipose Tissue NLRP3 Inflammasome Pathway in Cancer Cachexia(2021) JESUS, Joyce de Cassia Rosa de; MURARI, Ariene Soares de Pinho; RADLOFF, Katrin; MORAES, Ruan Carlos Macedo de; FIGUEREDO, Raquel Galvao; PESSOA, Ana Flavia Marcal; ROSA-NETO, Jose Cesar; MATOS-NETO, Emidio Marques; ALCANTARA, Paulo S. M.; TOKESHI, Flavio; MAXIMIANO, Linda Ferreira; BIN, Fang Chia; FORMIGA, Fernanda Bellotti; OTOCH, Jose P.; SEELAENDER, MariliaBackground Cachexia is a paraneoplastic syndrome that accompanies and compromises cancer treatment, especially in advanced stages, affecting the metabolism and function of several organs. The adipose tissue is the first to respond to the presence of the tumor, contributing to the secretion of factors which drive the systemic inflammation, a hallmark of the syndrome. While inflammation is a defensive innate response, the control mechanisms have been reported to be disrupted in cachexia. On the other hand, little is known about the role of NLRP3 inflammasome in this scenario, a multiprotein complex involved in caspase-1 activation and the processing of the cytokines IL-1 beta and IL-18. Aim based on the evidence from our previous study with a rodent model of cachexia, we examined the activation of the NLRP3 inflammasome pathway in two adipose tissue depots obtained from patients with colorectal cancer and compared with that another inflammatory pathway, NF-kappa B. Results For CC we found opposite modulation in ScAT and PtAT for the gene expression of TLR4, Caspase-1 (cachectic group) and for NF-kappa B p50, NF-kappa B p65, IL-1 beta. CD36, expression was decreased in both depots while that of NLRP3 and IL-18 was higher in both tissues, as compared with controls and weight stable patients (WSC). Caspase-1 basal protein levels in the ScAT culture supernatant were higher in WSC and (weight stable patients) CC, when compared to controls. Basal ScAT explant culture medium IL-1 beta and IL-18 protein content in ScAT supernatant was decreased in the WSC and CC as compared to CTL explants. Conclusions The results demonstrate heterogeneous responses in the activation of genes of the NLRP3 inflammasome pathway in the adipose tissue of patients with cancer cachexia, rendering this pathway a potential target for therapy aiming at decreasing chronic inflammation in cancer.
- Myokines in treatment-na & iuml;ve patients with cancer-associated cachexia(2021) CASTRO, Gabriela S. de; CORREIA-LIMA, Joanna; SIMOES, Estefania; ORSSO, Camila E.; XIAO, Jingjie; GAMA, Leonardo R.; GOMES, Silvio P.; GONCALVES, Daniela Caetano; COSTA, Raquel G. F.; RADLOFF, Katrin; LENZ, Ulrike; TARANKO, Anna E.; BIN, Fang Chia; FORMIGA, Fernanda B.; GODOY, Louisie G. L. de; SOUZA, Rafael P. de; NUCCI, Luis H. A.; FEITOZA, Mario; CASTRO, Claudio C. de; TOKESHI, Flavio; ALCANTARA, Paulo S. M.; OTOCH, Jose P.; RAMOS, Alexandre F.; LAVIANO, Alessandro; COLETTI, Dario; MAZURAK, Vera C.; PRADO, Carla M.; SEELAENDER, MariliaCancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-na & iuml;ve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways. (c) 2020 The Author(s).