Os efeitos da equiparação da união estável ao casamento para fins sucessórios: uma análise crítica dos efeitos dos Recursos Extraordinários 878.694 e 646.721

O presente trabalho tem o objetivo de analisar as principais consequências e efeitos do julgamento dos Recursos Extraordinários 878.694 e 646.721 pelo Supremo Tribunal Federal, que reconheceu a inconstitucionalidade do artigo 1.790 do Código Civil e equiparou as uniões estáveis homoafetivas às formadas por casais héteros. Este trabalho pretende, de início, analisar, através de pesquisa bibliográfica, a trajetória do conceito de família ao longo do tempo no ordenamento jurídico brasileiro, até a chegada ao entendimento atual, momento em que a Constituição Federal de 1988 passou a abranger outras modalidades além da formada pelo casamento. Em seguida, através de uma análise dos votos dos ministros, buscará expor os argumentos os quais levaram ao novo entendimento firmado pela Suprema Corte, que passou a aplicar o artigo 1.829 do CC/2002 aos companheiros. Por fim, buscará verificar os principais questionamentos doutrinários e lacunas deixadas após o reconhecimento da inconstitucionalidade do referido artigo, e suas implicações na prática jurídica brasileira, no âmbito do direito sucessório

MHV-68 producing mIFN␣1 is severely attenuated in vivo and effectively protects mice against challenge with wt MHV-68

Corrigendum Corrigendum to "MHV-68 producing mIFN␣1 is severely attenuated in vivo and effectively protects mice against challenge with wt MHV-68" [Vaccine 29 (2011) In this study, we focused on the effects of interferon-␣ (IFN-␣) on both the lytic and latent phase of MHV-68 infection, as exerted by the constitutive release of IFN-␣1 by a clone of MHV-68 genetically modified to produce this cytokine (MHV-68mIFN␣1). Although the MHV-68mIFN␣1 recombinant virus exhibited in vitro replication features indistinguishable from those of the wild type MHV-68, its pathological properties were severely attenuated in vivo in immunocompetent mice and not in mice rendered genetically unresponsive to type I IFN, suggesting that a stronger immune response was primed in the presence of the cytokine. Notably, MHV-68mIFN␣1 attenuation did not result in a reduced level of longterm spleen latency establishment. These results prompted us to evaluate the efficacy of MHV-68mIFN␣1 in a prophylactic vaccination regimen aimed at inhibiting the symptoms of acute virus infection and the establishment of long-term latency after MHV-68 challenge. Our results show that mice vaccinated with MHV-68mIFN␣1, administered as a live-attenuated or partially inactivated (by Psoralen and UV treatment) vaccine, were protected against the challenge with wt MHV-68 from all phases of infection. The ability of MHV-68mIFN␣1 to produce IFN-␣ at the site of the infection, thus efficiently stimulating the immune system in case of virus reactivation from latency, makes this recombinant virus a safer live-attenuated vaccine as compared to the previously reported latency-deficient clones

Interferon-α-Conditioned Human Monocytes Combine a Th1-Orienting Attitude with the Induction of Autologous Th17 Responses: Role of IL-23 and IL-12

IFN-α exerts multiple effects leading to immune protection against pathogens and cancer as well to autoimmune reactions by acting on monocytes and dendritic cells. We analyzed the versatility of human monocytes conditioned by IFN-α towards dendritic cell differentiation (IFN-DC) in shaping the autologous T-helper response. Priming of naïve CD4 T cells with autologous IFN-DC in the presence of either SEA or anti-CD3, resulted, in addition to a prominent expansion of CXCR3+ IFN-γ-producing CD4 Th1 cells, in the emergence of two distinct subsets of IL-17-producing CD4 T cells: i) a predominant Th17 population selectively producing IL-17 and expressing CCR6; ii) a minor Th1/Th17 population, producing both IL-17 and IFN-γ. After phagocytosis of apoptotic cells, IFN-DC induced Th17 cell expansion and IL-17 release. Notably, the use of neutralizing antibodies revealed that IL-23 was an essential cytokine in mediating Th17 cell development by IFN-DC. The demonstration of the IFN-DC-induced expansion of both Th1 and Th17 cell populations reveals the intrinsic plasticity of these DC in orienting the immune response and provides a mechanistic link between IFN-α and the onset of autoimmune phenomena, which have been correlated with both IL-17 production and exposure to IFN-α

Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in breast cancer.</p> <p>Methods</p> <p>The expression levels of TLR3, TLR4 and TLR9 were analyzed on tumors from 74 patients with breast cancer. The analysis was performed by immunohistochemistry.</p> <p>Results</p> <p>Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4 and TLR9. Tumors showed high expression of TLRs expression levels by cancer cells, especially TLR4 and 9. Nevertheless, a significant percentage of tumors also showed TLR4 expression by mononuclear inflammatory cells (21.6%) and TLR9 expression by fibroblast-like cells (57.5%). Tumors with high TLR3 expression by tumor cell or with high TLR4 expression by mononuclear inflammatory cells were significantly associated with higher probability of metastasis. However, tumours with high TLR9 expression by fibroblast-like cells were associated with low probability of metastasis.</p> <p>Conclusions</p> <p>The expression levels of TLR3, TLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness in breast cancer. TLRs may represent therapeutic targets in breast cancer.</p

Biotherapy of Cancer: Break the Barriers to Foster Translation oF knowledge

Biotherapy of cancer holds great promise for its potential to lead to the identification of novel, selective, and effective treatments against cancer. However, the clinical development of biopharmaceuticals and biotherapy products is hampered by several and diverse barriers. Herein, we will address some of the critical issues identified both at the national and European level as the major obstacles for the translation of knowledge into clinical applications in the field of biotherapy and immunotherapy of cancer. We will also illustrate specific initiatives undertaken both in Europe and in Italy in order to support the translational and clinical research and that are expected to have a favorable impact on the process of clinical development of novel and more effective therapeutic interventions against cancer. The contents of this article are directly referred to the event “International Clinical Trials’ Day on Biotherapy of Cancer” organized in the context of the OECI Genoa 2008, with the sponsorship of Alliance Against Cancer (ACC) and the Istituto Superiore di Sanità (ISS, the Italian National Institute of Health), and under the auspices of the European Clinical Research Infrastructures Network (ECRIN). This event sees the active participation of representatives of the ISS and of the Italian Network for Tumor Biotherapy, both involved in a project recently funded by ACC and aimed at the promotion of clinical research in the field of cancer biotherapy and immunotherapy, through the creation of a national network of clinical cancer research centers and GMP facilities dedicated to the production of biological drugs and advanced medicinal products. </jats:p

IFN-α enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing, and processing

Abstract Cross-presentation allows antigen-presenting cells to present exogenous antigens to CD8+ T cells, playing an essential role in controlling infections and tumor development. IFN-α induces the rapid differentiation of human mono-cytes into dendritic cells, known as IFN-DCs, highly efficient in mediating cross-presentation, as well as the cross-priming of CD8+ T cells. Here, we have investigated the mechanisms underlying the cross-presentation ability of IFN-DCs by studying the intracellular sorting of soluble ovalbumin and nonstructural-3 protein of hepatitis C virus. Our results demonstrate that, independently from the route and mechanism of antigen entry, IFN-DCs are extraordinarily competent in preserving internalized proteins from early degradation and in routing antigens toward the MHC class-I processing pathway, allowing long-lasting, cross-priming capacity. In IFN-DCs, both early and recycling endosomes function as key compartments for the storage of both antigens and MHC-class I molecules and for proteasome- and transporter-associated with Ag processing–dependent auxiliary cross-presentation pathways. Because IFN-DCs closely resemble human DCs naturally occurring in vivo in response to infections and other danger signals, these findings may have important implications for the design of vaccination strategies in neoplastic or chronic infectious diseases