Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism

Resilient SMES, Institutions and Justice. Evidence in Italy

AbstractThe recent financial crisis (2008) seriously affected the credibility of European and Italian institutions. It was also characterized by a general pessimism and low expectations of economic operators, especially firms. In literature, relationships between the quality of institutions and economic activities have been widely investigated. They show how the judicial system, the regulatory authorities and governance are important aspects for the quality of institutions.The main conclusion of existing literature, or the necessity of a reform of judicial system, is the basis of this work. Thus, here there is an attempt to investigate the performances of the judicial system, considering the low and poor level of its effects on firms' performances. In particular, in this work, there is a simple empirical analysis (data paucity is the big limit) in order to investigate the consequences of an efficient, long-time justice on resilient firms' confidence and perspective. Those resilient firms, able to overcome the financial crisis, show their ability in surviving, even if justice doesn't help them

Domini collettivi tra sud, centro e nord : Prospettive e nostalgie

El presente estudio se ocupa de la propiedad colectiva en Italia desde su nacimiento histórico, pero sobre todo en su estado presente en las diversas regiones del país. Se analiza la situación en el norte alpino; en la región central montañosa de los Apeninos y especialmente al interior del Estado Pontificio y se la compara con la región meridional donde la presencia en forma de universitas civium tiene un alcance territorial mucho menor. El trabajo recupera la evolución al interior de esas tres grandes regiones geográficas, donde la propiedad colectiva ha tenido una rica variedad de formas organizacionales en los distintos estados previos a la unificación. Sigue con la evolución durante la Italia unificada, desde la ley 1766 del 16 de junio de 1927 que declaró la indisponibilidad de las tierras a la ley 168 del 20 de noviembre de 2017 que ha dado la personalidad jurídica a los entes gestores de la propiedad colectiva de derecho privado y una autonomía estatutaria que les autoriza a crear sus propias normas. El trabajo finaliza presentando algunos desafíos actuales de gestión.The present study deals with collective property in Italy since its historical birth, but especially in its present state in the various regions of the country. The situation in the alpine north is analyzed; in the mountainous central region of the Apennines and especially in the interior of the Papal State and is compared with the southern region where the presence in the form of universitas civium has a much smaller territorial scope. The work recovers the evolution within these three great geographical regions, where collective property has had a rich variety of organizational forms in the different states prior to unification. It continues with the evolution during the unified Italy, from the law 1766 of June 16, 1927 that declared the unavailability of the lands to the law 168 of November 20, 2017 that has given the juridical personality to the entities managing the collective property of private law and a statutory autonomy that authorizes them to create their own rules. The work ends by presenting some current management challenges.Universidad Nacional de La Plata (UNLP) - Facultad de Ciencias Jurídicas y Sociale

Credibilidad y testimonio cristiano

El acto de fe cristiana afecta a la totalidad de la persona que se ve interpelada y afectada en su esfera cognoscitiva, afectiva y voluntaria, al verse puesta en relación con un testimonio absolutamente fiable y atendible, que es el fundamento de la certeza del creer. En el presente escrito, el autor recorre sintéticamente tres momentos: la hermenéutica del testimonio; la lógica del testimonio y, finalmente, la ontología del testimonio. El análisis de la credibilidad y su relación con el testimonio se realiza prevalentemente, aunque no exclusivamente, desde un horizonte eclesiológico

Domini collettivi tra sud, centro e nord : Prospettive e nostalgie

El presente estudio se ocupa de la propiedad colectiva en Italia desde su nacimiento histórico, pero sobre todo en su estado presente en las diversas regiones del país. Se analiza la situación en el norte alpino; en la región central montañosa de los Apeninos y especialmente al interior del Estado Pontificio y se la compara con la región meridional donde la presencia en forma de universitas civium tiene un alcance territorial mucho menor. El trabajo recupera la evolución al interior de esas tres grandes regiones geográficas, donde la propiedad colectiva ha tenido una rica variedad de formas organizacionales en los distintos estados previos a la unificación. Sigue con la evolución durante la Italia unificada, desde la ley 1766 del 16 de junio de 1927 que declaró la indisponibilidad de las tierras a la ley 168 del 20 de noviembre de 2017 que ha dado la personalidad jurídica a los entes gestores de la propiedad colectiva de derecho privado y una autonomía estatutaria que les autoriza a crear sus propias normas. El trabajo finaliza presentando algunos desafíos actuales de gestión.The present study deals with collective property in Italy since its historical birth, but especially in its present state in the various regions of the country. The situation in the alpine north is analyzed; in the mountainous central region of the Apennines and especially in the interior of the Papal State and is compared with the southern region where the presence in the form of universitas civium has a much smaller territorial scope. The work recovers the evolution within these three great geographical regions, where collective property has had a rich variety of organizational forms in the different states prior to unification. It continues with the evolution during the unified Italy, from the law 1766 of June 16, 1927 that declared the unavailability of the lands to the law 168 of November 20, 2017 that has given the juridical personality to the entities managing the collective property of private law and a statutory autonomy that authorizes them to create their own rules. The work ends by presenting some current management challenges.Universidad Nacional de La Plata (UNLP) - Facultad de Ciencias Jurídicas y Sociale

Domini collettivi tra sud, centro e nord : Prospettive e nostalgie

El presente estudio se ocupa de la propiedad colectiva en Italia desde su nacimiento histórico, pero sobre todo en su estado presente en las diversas regiones del país. Se analiza la situación en el norte alpino; en la región central montañosa de los Apeninos y especialmente al interior del Estado Pontificio y se la compara con la región meridional donde la presencia en forma de universitas civium tiene un alcance territorial mucho menor. El trabajo recupera la evolución al interior de esas tres grandes regiones geográficas, donde la propiedad colectiva ha tenido una rica variedad de formas organizacionales en los distintos estados previos a la unificación. Sigue con la evolución durante la Italia unificada, desde la ley 1766 del 16 de junio de 1927 que declaró la indisponibilidad de las tierras a la ley 168 del 20 de noviembre de 2017 que ha dado la personalidad jurídica a los entes gestores de la propiedad colectiva de derecho privado y una autonomía estatutaria que les autoriza a crear sus propias normas. El trabajo finaliza presentando algunos desafíos actuales de gestión.The present study deals with collective property in Italy since its historical birth, but especially in its present state in the various regions of the country. The situation in the alpine north is analyzed; in the mountainous central region of the Apennines and especially in the interior of the Papal State and is compared with the southern region where the presence in the form of universitas civium has a much smaller territorial scope. The work recovers the evolution within these three great geographical regions, where collective property has had a rich variety of organizational forms in the different states prior to unification. It continues with the evolution during the unified Italy, from the law 1766 of June 16, 1927 that declared the unavailability of the lands to the law 168 of November 20, 2017 that has given the juridical personality to the entities managing the collective property of private law and a statutory autonomy that authorizes them to create their own rules. The work ends by presenting some current management challenges.Universidad Nacional de La Plata (UNLP) - Facultad de Ciencias Jurídicas y Sociale

<em>CYP2D6 </em>genotype and adjuvant tamoxifen:meta-analysis of heterogeneous study populations

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1), CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.</p

Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer

Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R2: 53%, P&lt;10?77). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P&lt;0.001). DM-Tam was influenced by body mass index (P&lt;0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43–0.91; P=0.013). Low (&lt;14?nM) compared with high (&gt;35?nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04–4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS

Système de parentèle et transmission intergénérationnelle des compétences dans les petites entreprises du Sud de l’Italie

L’Italie a toujours été caractérisée par une présence considérable de petites et moyennes entreprises à gestion familiale. Selon les estimations du Family Firm Institut, notre pays enregistre une présence d’entreprises à gestion familiale d’environ 83 %. L’histoire récente de l’industrie italienne démontre que la famille y détient encore un rôle déterminant. Le présent travail aura pour but d’analyser les déterminants du succès des entreprises familiales en considérant certains aspects socio-démographiques. Plus particulièrement, nous essaierons de vérifier si et dans quelle mesure les changements générationnels et les relations parentales à l’intérieur de l’entreprise peuvent devenir des facteurs de croissance ou limiter son évolution. Nous tenterons d’analyser l’impact de la nouvelle catégorie de dirigeants à l’intérieur d’une entreprise familiale, pour savoir s’il peut être considéré comme le résultat d’un processus de stabilité et de continuité, dans un pays comme l’Italie qui oscille encore entre valeurs du passé et nouvelles cultures d’entreprise.Italy was always characterized by a considerable presence of small and medium-sized enterprises with family management. According to estimates’ of Family Firm Institute, our country records a presence of enterprises to family management from approximately 83%. The recent history of Italian industry shows that the family still holds a determining role there. The purpose of this work will be to analyze the determinants of the success of the family companies by considering certain socio-demographic aspects. More particularly, we will try to check if and up to what point the generational changes and the parental relations inside the company can become growth promoters or limit its evolution. We will try to analyze the impact of the new category of leaders inside a family company, to know if it can be regarded as the result of a process of stability and continuity, in a country as Italy which still oscillates between values of last and new cultures entrepreneurial

Pharmacogenetic testing affects choice of therapy among women considering tamoxifen treatment

Abstract Background Pharmacogenetic testing holds major promise in allowing physicians to tailor therapy to patients based on genotype. However, there is little data on the impact of pharmacogenetic test results on patient and clinician choice of therapy. CYP2D6 testing among tamoxifen users offers a potential test case of the use of pharmacogenetic testing in the clinic. We evaluated the effect of CYP2D6 testing in clinical practice to determine whether genotype results affected choice of hormone therapy in a prospective cohort study. Methods Women planning to take or currently taking tamoxifen were considered eligible. Participants were enrolled in an informational session that reviewed the results of studies of CYP2D6 genotype on breast cancer recurrence. CYP2D6 genotyping was offered to participants using the AmpliChip CYP450 Test. Women were classified as either poor, intermediate, extensive or ultra-rapid metabolizers. Results were provided to clinicians without specific treatment recommendations. Follow-up was performed with a structured phone interview 3 to 6 months after testing to evaluate changes in medication. Results A total of 245 women were tested and 235 completed the follow-up survey. Six of 13 (46%) women classified as poor metabolizers reported changing treatment compared with 11 of 218 (5%) classified as intermediate, extensive or ultra-rapid metabolizers (P &lt; 0.001). There was no difference in treatment choices between women classified as intermediate and extensive metabolizers. In multi-variate models that adjusted for age, race/ethnicity, educational status, method of referral into the study, prior knowledge of CYP2D6 testing, the patients' CYP2D6 genotype was the only significant factor that predicted a change in therapy (odds ratio 22.8; 95% confidence interval 5.2 to 98.8). Genetic testing did not affect use of co-medications that interact with CYP2D6. Conclusions CYP2D6 genotype testing led to changes in therapy among poor metabolizers, even in the absence of definitive data that an alternative medicine improved outcomes. Pharmacogenetic testing can affect choice of therapy, even in the absence of definitive data on clinical impact