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.
- G(D3) ganglioside-enriched extracellular vesicles stimulate melanocyte migration(2019) OTAKE, Andreia Hanada; SAITO, Renata de Freitas; DUARTE, Ana Paula Marques; RAMOS, Alexandre Ferreira; CHAMMAS, RogerMelanomas often accumulate gangliosides, sialic acid-containing glycosphingolipids found in the outer leaflet of plasma membranes, as disialoganglioside G(D3) and its derivatives. Here, we have transfected the G(D3) synthase gene (ST8Sia I) in a normal melanocyte cell line in order to evaluate changes in the biological behavior of non-transformed cells. G(D3) -synthase expressing cells converted G(M3) into G(D3) and accumulated both G(D3) and its acetylated form, 9-O-acetyl-G(D3). Melanocytes were rendered more migratory on laminin-1 surfaces. Cell migration studies using the different transfectants, either treated or not with the glucosylceramide synthase inhibitor D-1-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-l-propanol (PPPP), allowed us to show that while G(M3) is a negative regulator of melanocyte migration, G(D3) increases it. We showed that gangliosides were shed to the matrix by migrating cells and that GD3 synthase transfected cells shed extracellular vesicles (EVs) enriched in G(D3). EVs enriched in G(D3) stimulated cell migration of G(D3) negative cells, as observed in time lapse microscopy studies. Otherwise, EVs shed by G(M3) (+ve)G(D3)(-ve) cells impaired migration and diminished cell velocity in cells overexpressing G(D3). The balance of antimigratory G(M3) and promigratory G(D3) gangliosides in melanocytes could be altered not only by the overexpression of enzymes such as ST8Sia I, but also by the horizontal transfer of ganglioside enriched extracellular vesicles. This study highlights that extracellular vesicles transfer biological information also through their membrane components, which include a variety of glycosphingolipids remodeled in disease states such as cancer.