RESUMO
Anti-human immunodeficiency virus type-1 (anti-HIV-1) neutralizing monoclonal antibodies are broadening the spectrum of pre- and post-exposure treatment against HIV-1. A better understanding of how these antibodies develop and interact with particular regions of the viral envelope protein is guiding a more rational structure-based immunogen design. The aim of this article is to review the most recent advances in the field, from the development of these particular antibodies during natural HIV-1 infection, to their role preventing infection, boosting endogenous immune responses and clearing both free viral particles and persistently infected cells.
RESUMO
BACKGROUND: Cost-effectiveness analysis of MammaPrint(®) (70-gene signature) in the diagnosis of early breast cancer as a prognosis assay to study the risk of tumor recurrence to administer adjuvant chemotherapy. METHODS: Markov model assuming a cohort of 60-year-old women with breast cancer. Treatment costs and effects were assessed by comparing the 5-year, 10-year and lifetime risk of recurrence using Adjuvant! Online(®) (online algorithm), 70-gene signature or Oncotype DX(®) (21-gene assay). RESULTS: 70-gene signature showed a life expectancy of 23.55 years at lifetime. Life expectancy was lower for 21-gene assay and online algorithm, with associated quality-adjusted life year gains up to 0.23 and 0.75, respectively, with 70-gene signature. At year 5, the mean cost of 21-gene assay, 70-gene signature and online algorithm was 7100, 6380 and 4580, respectively. 70-gene signature was dominant versus 21-gene assay at any time horizon and would be cost-effective from year 7 versus online algorithm (lifetime: 1457 per quality-adjusted life years gained). CONCLUSIONS: 70-gene signature was a dominant strategy over 21-gene assay and was highly cost-effective versus online algorithm.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/economia , Neoplasias da Mama/genética , Perfilação da Expressão Gênica/economia , Testes Genéticos/economia , Custos de Cuidados de Saúde , Programas Nacionais de Saúde/economia , Medicina de Precisão/economia , Algoritmos , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/economia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Custos de Medicamentos , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Cadeias de Markov , Pessoa de Meia-Idade , Modelos Econômicos , Recidiva Local de Neoplasia , Fenótipo , Valor Preditivo dos Testes , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Medição de Risco , Fatores de Risco , Espanha , Fatores de Tempo , Resultado do TratamentoRESUMO
A formalin-fixed paraffin-embedded (FFPE) sample usually yields highly degraded DNA, which limits the use of techniques requiring high-quality DNA, such as Infinium Methylation microarrays. To overcome this restriction, we have applied an FFPE restoration procedure consisting of DNA repair and ligation processes in a set of paired fresh-frozen (FF) and FFPE samples. We validated the FFPE results in comparison with matched FF samples, enabling us to use FFPE samples on the Infinium HumanMethylation450 Methylation array.
Assuntos
Metilação de DNA , Reparo do DNA , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fixadores , Formaldeído , Humanos , Inclusão em ParafinaRESUMO
Bovine viral diarrhea (BVD) infection caused by bovine viral diarrhea virus (BVDV), a Pestivirus of the Flaviviridae family, is an important cause of morbidity, mortality and economical losses in cattle worldwide. E2 protein is the major glycoprotein of BVDV envelope and the main target for neutralising antibodies (NAbs). Different studies on protection against BVDV infection have focused on E2, supporting its putative use in subunit vaccines. A truncated version of type 1a BVDV E2 (tE2) expressed in mammalian cells was used to formulate an experimental oleous monovalent vaccine. Immunogenicity was studied through immunisation of guinea pigs and followed by trials in cattle. Calves of 8-12 months were vaccinated, twice with a 4 week interval, with either a tE2 subunit vaccine (n = 8), a whole virus inactivated vaccine (n = 8) or left untreated as negative control group (n = 8). Four weeks after the last immunisation the animals were experimentally challenged intranasally with a non-cythopathic BVDV strain. Following challenge, BVDV was isolated from all unvaccinated animals, while 6 out of 8 animals vaccinated with tE2 showed complete virological protection indicating that the tE2 vaccine presented a similar performance to a satisfactory whole virus inactivated vaccine.
