ALEXANDRE FERREIRA RAMOS
Projetos de Pesquisa
Unidades Organizacionais
SIN-86, EACH - Docente
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
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
- New strategies for targeting kinase networks in cancer(2021) YESILKANAL, Ali E.; JOHNSON, Gary L.; RAMOS, Alexandre F.; ROSNER, Marsha RichTargeted strategies against specific driver molecules of cancer have brought about many advances in cancer treatment since the early success of the first small-molecule inhibitor Gleevec. Today, there are a multitude of targeted therapies approved by the Food and Drug Administration for the treatment of cancer. However, the initial efficacy of virtually every targeted treatment is often reversed by tumor resistance to the inhibitor through acquisition of new mutations in the target molecule, or reprogramming of the epigenome, transcriptome, or kinome of the tumor cells. At the core of this clinical problem lies the assumption that targeted treatments will only be efficacious if the inhibitors are used at their maximum tolerated doses. Such aggressive regimens create strong selective pressure on the evolutionary progression of the tumor, resulting in resistant cells. High-dose single agent treatments activate alternative mechanisms that bypass the inhibitor, while high-dose combinatorial treatments suffer from increased toxicity resulting in treatment cessation. Although there is an arsenal of targeted agents being tested clinically and preclinically, identifying the most effective combination treatment plan remains a challenge. In this review, we discuss novel targeted strategies with an emphasis on the recent cross-disciplinary studies demonstrating that it is possible to achieve antitumor efficacy without increasing toxicity by adopting low-dose multitarget approaches to treatment of cancer and metastasis.
- 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).