Metastasis Suppressors and the Tumor Microenvironment

The most dangerous attribute of cancer cells is their ability to metastasize. Throughout the process of metastasis, tumor cells interact with other tumor cells, host cells and extracellular molecules. This brief review explores how a new class of molecules – metastasis suppressors – regulate tumor cell–microenvironmental interactions. Data are presented which demonstrate that metastasis suppressors act at multiple steps of the metastatic cascade. A brief discussion for how metastasis suppressor regulation of cellular interactions might be exploited is presented

Arquivos do Instituto Biológico

usada popularmente por suas propriedades antiparasitárias. Avaliou-se com este estudo a eficácia in vitro de extratos hidroetanólicos de C. ambrosioides sobre a postura e a eclodibilidade larval de Rhipicephalus (Boophilus) microplus (Canestrini, 1888) (Acari: Ixodidae), usando o teste de imersão de fêmeas ingurgitadas adultas. Os tratamentos foram constituídos por extratos feitos com 5%, 10% e 25% de C. ambrosioides (massa/volume), água destilada e veículo (constituído de propilenoglicol a 5%, etanol a 25% e água destilada). Dez teleóginas foram distribuídas de forma homogênea para cada grupo e imersas por 5 minutos em cada um dos extratos testados. Os extratos feitos com 5%, 10% e 25% de C. ambrosioides apresentaram eficácias médias de 13,27%, 22,56% e 31,87%, respectivamente. Estes resultados indicam que, nas concentrações usadas, os extratos de C. ambrosioides não apresentam potencial para o controle das cepas pesquisadas de R. (B.) microplus

Rocaglamide breaks TRAIL resistance in HTLV-1-associated adult T-cell leukemia/lymphoma by translational suppression of c-FLIP expression

The human T-cell leukemia virus type-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATL) is incurable by currently known therapies. ATL samples and cell lines derived from ATL patients show restricted sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and CD95 ligand (CD95L). We have recently shown that HTLV-1-infected cells express elevated levels of cellular caspase-8 FLICE-inhibitory protein (c-FLIP) conferring resistance to receptor-mediated apoptosis. This finding underscores the demand to develop new strategies for treatment of ATL. In this study, we show that the naturally occurring herbal compound Rocaglamide (Roc) sensitizes CD95L- and TRAIL-induced apoptosis in HTLV-1-infected cells by downregulation of c-FLIP expression. Investigation of the molecular mechanism of Roc-mediated downregulation of c-FLIP revealed that it inhibits phosphorylation of the translation initiation factor 4E (eIF4E), a key factor that controls the rate-limiting step of translation, through inhibition of the MEK–ERK–MNK1 signaling pathway. This event prevents de novo synthesis of short-lived proteins such as c-FLIP in HTLV-1-infected cells. Our data suggest that Roc may serve as an adjuvant for TRAIL-based anticancer therapy