RESUMO
HER2-positive breast cancer, accounting for 15 % of the total breast cancer patient population, carries in itself a bad prognosis, which has now become much better after the advent of anti-HER2 drugs. HER2-targeted therapy has significantly improved disease free- and overall survival in HER2-positive breast cancer, and has rendered better disease control both in the early and advanced disease setting. Trastuzumab treatment duration is often prolonged and poses significant time and resource challenges both on the treatment institutions and on the patient. The recent development of a subcutaneous formulation has meant a significant advance in this respect. We review the drug development of the compound and the current evidence on its use.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Descoberta de Drogas , Feminino , Humanos , Injeções Subcutâneas , Receptor ErbB-2/metabolismo , TrastuzumabRESUMO
The aim of this study was to determine the apoptotic pathways and mechanisms involved in electronegative LDL [LDL(-)]-induced apoptosis in RAW 264.7 macrophages and the role of Nrf2 in this process. Incubation of RAW 264.7 macrophages with LDL(-) for 24 h resulted in dose-dependent cell death. Activated caspases were shown to be involved in the apoptosis induced by LDL(-); incubation with the broad caspase inhibitor z-VAD prevented apoptosis in LDL(-)-treated cells. CD95 (Fas), CD95 ligand (FasL), CD36 and the tumor necrosis factor (TNF) ligand Tnfsf10 were overexpressed in LDL(-)-treated cells. However, Bax, Bcl-2 and Mcl-1 protein levels remained unchanged after LDL(-) treatment. LDL(-) promoted hyperpolarization of the mitochondrial membrane, elevated reactive oxygen species (ROS) production and translocation of Nrf2 to the nucleus, a process absent in cells treated with native LDL. Elicited peritoneal macrophages from Nrf2-deficient mice exhibited an elevated apoptotic response after challenge with LDL(-), together with an increase in the production of ROS in the absence of alterations in CD36 expression. These results provide evidence that CD36 expression induced by LDL(-) is Nrf2-dependent. Also, it was demonstrated that Nrf2 acts as a compensatory mechanism of LDL(-)-induced apoptosis in macrophages.
Assuntos
Apoptose , Lipoproteínas LDL/metabolismo , Macrófagos Peritoneais/patologia , Fator 2 Relacionado a NF-E2/fisiologia , Animais , Biomarcadores/metabolismo , Western Blotting , Antígenos CD36/genética , Antígenos CD36/metabolismo , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , Feminino , Imunofluorescência , Perfilação da Expressão Gênica , Humanos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Ethanolic extracts from 15 plant species, representing eight different families, used in traditional medicine in Ecuador were evaluated for antiinflammatory and antioxidant activities. Conyza floribunda, Eupatorium articulatum, Bonafousia longituba, Bonafousia sananho, Tagetes pusilla and Piper lenticellosum extracts showed a significant antiinflammatory activity in vivo in the carrageenan-induced paw oedema model in mice. The extracts were also tested in vitro for their ability to inhibit lipid peroxidation and to scavenge superoxide and hydroxyl radicals. E. articulatum extract possesses both activities. Baccharis trinervis, E. articulatum and Phytolacca rivinoides extracts were active as antioxidants.