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Background:Periostin is a secreted adhesion protein, normally expressed in mesenchime-derived cells. Aberrant expression of the periostin gene in epithelial tumours seems to play a role in angiogenesis and metastases.Aims:To investigate periostin expression in a consecutive series of breast carcinomas and correlate it with established biological and prognostic factors.Methods:A consecutive series of 206 breast carcinomas was investigated by immunohistochemistry with a specific antiperiostin antibody. Immunohistochemical expression of oestrogen and progesterone receptors, Ki-67 (MIB-1), HER-2/neu, VEGF-A, VEGFR-1 and VEGFR-2 was analysed. Periostin expression was also investigated in MCF-7 and MDA-468 cell lines by immunohistochemistry, western blot and quantitative RT-PCR. Localisation of periostin was investigated in MCF-7 cells by the green fluorescent protein (GFP) approach.Results:Periostin was highly expressed in carcinoma cells, but not in normal breast tissues. The pattern of expression was mainly cytoplasmic. However, in 12% of cases a nuclear reactivity was observed. Nuclear periostin significantly correlated with tumour size, and with expression of oestrogen receptor, progesterone receptor, VEGF-A, VEGFR-1 and VEGFR-2. A nuclear localisation of periostin was also observed in MCF-7 and MDA-468 cell lines. In MCF-7 cells the nuclear localisation of periostin was also shown by transfection of a vector expressing a GFP-periostin chimeric protein.Conclusions:Results indicate that the aberrant gene expression of periostin in breast cancer cells is associated with an abnormal nuclear localisation of the protein. The nuclear localisation of periostin in breast cancer may induce significant biological effects.

Introduction/BackgroundPatients (pts) with ovarian cancer experiencing a platinum-sensitive (PS) recurrence are generally re-exposed to platinum agents (PCT). The addition of bevacizumab (BEV) or PARP inhibitors (PARPi) as concomitant and/or maintenance therapy has shown to improve progression free survival (PFS). In the absence of direct comparisons coming from randomized trials (RCTs), we have performed a network meta-analysis to evaluate differences in terms of efficacy between BEV and PARPi in pts with PS recurrent ovarian cancer (rOC), according to BRCA status.MethodologyWe searched PubMed, Embase and Medline for RCTs involving pts with PS rOC treated with BEV (n=3, 1563 pts) or PARPi (n=5, 1839 pts). Only trials with PFS as primary endpoint were included. Analyses have been done pooling pts who had received PARPi in three groups, according to the available data on BRCA genes status: all comers (AC), BRCA mutated pts (BRCAm) and BRCA wild-type pts (BRCAwt). A frequentist approach has been used with R statistical software. To rank the effect size of treatments, surface under the cumulative ranking value (SUCRA) has been applied.ResultsIn AC pts, PARPi improved PFS compared to BEV (hazard ratio [HR]=0.70, 95% CI 0.54–0.91). In BRCAm pts the gain in PFS for PARPi was even higher compared to BEV (HR=0.46, 95% CI 0.36–0.59). In BRCAwt pts the benefit of PARPi over BEV was not statistically significant (HR=0.87, 95% CI 0.63–1.20) but PARPi had the highest likelihood of being ranked as the best treatment in terms of efficacy according to SUCRA (90% and 60%, respectively for PARPi and BEV).ConclusionAccording to indirect comparisons, PARPi performed the best for the treatment of PS rOC, especially in BRCAm pts who had not previously received PARPi. BEV could be still an option in BRCAwt pts.DisclosureFabio Puglisi: Roche, AstraZeneca (honoraria and research founding). No conflict of interest is to be declared for the remaining authors. The authors receive no financial support for this study.

Purpose To evaluate the in vivo effect of adding gefitinib to preoperative chemotherapy on the EGFR-dependent p42/44 MAPK in operable breast cancer (BC) patients. Secondary aims: to evaluate EGFR, (p)-EGFR, Ki67, apoptotic index (TUNEL test) and VEGFR2 expression from baseline to surgery, percentage of pathologic complete response (pCR), and toxicity. Patients and Methods 90 patients with stage II-IIIA BC have been randomized to receive epirubicin 90 mg/sqm and paclitaxel 175 mg/sqm on day 1 plus: gefitinib 250 mg daily from day 5 to 16 (Arm A, intermittent), gefitinib 250 mg daily from day 1 to 21 (Arm B, continuous), or placebo (Arm C). Treatment plan: 4 courses every 3 weeks, followed by surgery. Results After preoperative therapy, 86/90 patients underwent surgery; 46 patients (51%) received breast conservative surgery. A pCR was observed in 4 patients. No significant differences in the expression of p42/44 MAPK, EGFR, (p)-EGFR, VEGFR2, proliferation index and apoptosis were observed comparing the combined Arms A + B vs C, and comparing Arm A vs B. Hematologic toxicities were not significantly different comparing Arms A + B vs Arm C, and comparing Arm A vs B. Significantly higher skin and mucosal toxicities were observed when comparing the two gefitinib Arms (A + B) vs Arm C (32% vs 9.6%, P  = 0.018; 57% vs 29%, P  = 0.009 respectively), while no significant differences were observed comparing Arm A vs B. Conclusion Adding gefitinib to chemotherapy did not result in different effects on the EGFR-dependent pathway, proliferation, apoptosis and VEGFR2 expression as compared to placebo, while enhancing skin and mucosal toxicity. The two schedules of gefitinib (intermittent vs continuous) did not result in different biologic effects.

Objective: The aim of this study is to determine the safety and the efficacy of amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study. Methods: Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–amifampridine–placebo sequence or amifampridine–placebo–amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Quantitative Myasthenia Gravis score and Myasthenia Gravis–specific Activities of Daily Living Profile score. The secondary outcome measures comprised changes from baseline of Myasthenia Gravis Composite score, Myasthenia Gravis Quality of Life scale—15 questions, Fatigue Severity Scale, and Carlo Besta Neurological Institute–Myasthenia Gravis scale. Statistical analyses were assessed using a switchback model for three-period, two-treatment crossover design. Results: A total of 10 patients were screened, enrolled, and treated. Transient paresthesias (60%) were the only amifampridine phosphate–related adverse events reported. Four patients were randomized to receive placebo–amifampridine–placebo sequence and three patients to receive amifampridine–placebo–amifampridine sequence. The co-primary objectives were statistically met (Quantitative Myasthenia Gravis score: p = 0.0003 and Myasthenia Gravis–specific Activities of Daily Living Profile score: p = 0.0006), as well as all the secondary endpoints (Myasthenia Gravis Composite score: p < 0.0001, Myasthenia Gravis Quality of Life scale—15 questions: p = 0.0025, Fatigue Severity Scale: p = 0.0061, and Carlo Besta Neurological Institute–Myasthenia Gravis scale: p = 0.0014). Conclusion: Despite the low number of patients, MuSK-001 study provided evidence that amifampridine phosphate, in the range of 30–60 mg daily dose, was safe and effective in treating muscle-specific kinase myasthenia gravis, suggesting the need for a large multi-center trial to confirm these results.

Début 1990, le Bénin adoptait une constitution démocratique. Le pays ratifia de nombreuses conventions internationales, garantissant le respect des principes des droits de l’Homme. Une série d’évaluations et de réformes des services publics furent planifiées, visant à garantir la « bonne gouvernance » et la mise en place d’un État de droit. La justice y occupait une place centrale. Parmi les premiers textes à être adoptés, figurait le Code des personnes et de la famille de 2004, qui abrogea le « droit coutumier », jugé discriminatoire à l’égard des femmes. Cet article reviendra tout d’abord sur le contexte et les enjeux de l’adoption de ce Code, largement inspiré du droit français. En se basant sur le cas précis des conflits d’héritage et du parcours de ceux qui saisissent la justice, il analysera ensuite les effets de ce nouveau dispositif sur les dynamiques familiales à Cotonou. À partir d’une enquête ethnographique, cette contribution montre comment le droit et les procédures judiciaires sont mobilisés par certains héritiers pour reconfigurer les rapports de genre et de générations, mais aussi et surtout pour renégocier la clé de répartition des biens en famille.

Début 1990, le Bénin adoptait une constitution démocratique. Le pays ratifia de nombreuses conventions internationales, garantissant le respect des principes des droits de l'Homme. Une série d'évaluations et de réformes des services publics furent planifiées, visant à garantir la « bonne gouvernance » et la mise en place d'un État de droit. La justice y occupait une place centrale. Parmi les premiers textes à être adoptés, figurait le Code des personnes et de la famille de 2004, qui abrogea le « droit coutumier », jugé discriminatoire à l'égard des femmes. Cet article reviendra tout d'abord sur le contexte et les enjeux de l'adoption de ce Code, largement inspiré du droit français. En se basant sur le cas précis des conflits d'héritage et du parcours de ceux qui saisissent la justice, il analysera ensuite les effets de ce nouveau dispositif sur les dynamiques familiales à Cotonou. À partir d'une enquête ethnographique, cette contribution montre comment le droit et les procédures judiciaires sont mobilisés par certains héritiers pour reconfigurer les rapports de genre et de générations, mais aussi et surtout pour renégocier la clé de répartition des biens en famille. At the beginning of 1990, the Republic of Benin adopted a democratic constitution. The country ratified a series of international agreements, including the International Covenant on Civil and Political Rights and the International Covenant on Economic, Social and Cultural Rights (1990). In line with the idea of guaranteeing \"good governance\" and rule of law, assessments were conducted and public service reforms were implemented, including within the ministry of justice. As a part of these reforms, the 2004 Code on Persons and Family—which was meant to promote women's rights and unify the previously dual legal system—was one of the first texts to be adopted. With inheritance disputes as an entry point, this paper looks at the itineraries of those who decided to take legal actions and analyzes the effects of the Code on family dynamics in Cotonou. It shows how those on the lower rungs of family hierarchies use the law and legal proceedings in order to renegotiate how properties are shared, and to redefine gender and generational relationships.

Début 1990, le Bénin adoptait une constitution démocratique. Le pays ratifia de nombreuses conventions internationales, garantissant le respect des principes des droits de l'Homme. Une série d'évaluations et de réformes des services publics furent planifiées, visant à garantir la « bonne gouvernance » et la mise en place d'un État de droit. La justice y occupait une place centrale. Parmi les premiers textes à être adoptés, figurait le Code des personnes et de la famille de 2004, qui abrogea le « droit coutumier », jugé discriminatoire à l'égard des femmes. Cet article reviendra tout d'abord sur le contexte et les enjeux de l'adoption de ce Code, largement inspiré du droit français. En se basant sur le cas précis des conflits d'héritage et du parcours de ceux qui saisissent la justice, il analysera ensuite les effets de ce nouveau dispositif sur les dynamiques familiales à Cotonou. À partir d'une enquête ethnographique, cette contribution montre comment le droit et les procédures judiciaires sont mobilisés par certains héritiers pour reconfigurer les rapports de genre et de générations, mais aussi et surtout pour renégocier la clé de répartition des biens en famille.

En 2004, le Bénin adopte un Code des personnes et de la famille, destiné à mettre fin au dualisme juridique en droit privé et à l’application du droit « traditionnel », jugé discriminatoire. Avec pour élément phare la notion d’égalité, le nouveau Code est souvent décrit comme le « Code des femmes » par les citoyens ordinaires et par les professionnels du droit de Cotonou. D’où vient cette réputation ? En détaillant le contexte de son adoption ainsi que la manière dont le nouveau texte a été présenté aux citoyenꞏeꞏs, cet article permettra tout d’abord de mieux comprendre la manière dont il est perçu. Avec les litiges de succession comme étude de cas, il s’intéressera à celles et ceux qui l’utilisent, à l’usage qu’ils en font et aux conséquences sur les rapports de genre, les relations familiales et l’accès aux biens communs à Cotonou.

En 2004, le Bénin adopte un Code des personnes et de la famille, destiné à mettre fin au dualisme juridique en droit privé et à l’application du droit « traditionnel », jugé discriminatoire. Avec pour élément phare la notion d’égalité, le nouveau Code est souvent décrit comme le « Code des femmes » par les citoyens ordinaires et par les professionnels du droit de Cotonou. D’où vient cette réputation ? En détaillant le contexte de son adoption ainsi que la manière dont le nouveau texte a été présenté aux citoyen·ne·s, cet article permettra tout d’abord de mieux comprendre la manière dont il est perçu. Avec les litiges de succession comme étude de cas, il s’intéressera à celles et ceux qui l’utilisent, à l’usage qu’ils en font et aux conséquences sur les rapports de genre, les relations familiales et l’accès aux biens communs à Cotonou. In 2004, Benin adopted a Code of Persons and the Family, designed to put an end to the legal dualism in private law and the application of “traditional\" law, which was considered discriminatory. Focusing on the notion of equality, the new Code is often described as the “Women’s Code” by ordinary citizens and legal practitioners in Cotonou. How did this name come about? By detailing the context in which it was adopted and the way in which the new text was introduced to citizens, this article will first provide a better understanding of the way in which it is perceived. Using succession disputes as a case study, it focuses on those who use it, how they use it and the consequences on gender relations, family relations and access to commons in Cotonou.