Le condotte dei Rossi di Parma : tra conflitti interstatali e «picciole guerre» locali (1447-1482)

Le condotte dei Rossi di Parma al servizio dei duchi di Milano sono considerate come aspetto del patto costituzionale stabilito nel 1447 tra P.M.Rossi e Francesco Sforza, che restò alla base dei rapporti politici tra le due dinastie per 30 anni. Le condotte dei signori parmigiani furono poi influenzate da sviluppi politico-diplomatici e da vicende interne ai Rossi. I documenti rivelano l'abilità di Pier Maria nel mantenere il dialogo con gli Sforza, limitare i conflitti ed evitare le ribellioni dei suoi ambizioni figli, almeno fino al 1482, quando il conflitto scoppiò, come parte della guerra di Ferrara. I rapporti Sforza-Rossi riguardano dunque sia la dimensione semiprivata delle "guerricciole" signorili, sia le relazioni internazionali.This study is focused on the condotte of the Rossi di Parma at the service of the Sforza dukes, as an aspect of the “constitutional” pact established in 1447 between the condottiere Francesco Sforza and Pier Maria Rossi. The pact was the basis for the relationship between the two dinasties for thirty years. The changes in the seigneurial condotte were influenced both by the diplomatic and institutional developments and by the internal issues inside the Rossi family. Documents and sources show the ability of Pier Maria in maintaining the dialogue with the Sforza, as well in settling conflicts and restraining the ambitions of his restless sons, until in 1482 the conflicts bursted out into the Rossi war, collateral to the war of Ferrara. Private war and wider political relationship are both considered and linked

Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers

<p>Abstract</p> <p>Background</p> <p>Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways.</p> <p>Methods</p> <p>We performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts.</p> <p>Results</p> <p>Statistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer.</p> <p>Conclusion</p> <p>A pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers.</p

Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts

Background: A subset of human hepatocellular carcinomas (HCC) exhibit mutations of β-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L-sulfoximine (MSO). Methods: Immunodeficient mice with subcutaneous xenografts of the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with Crisantaspase and/or MSO, and tumour growth was monitored. At the end of treatment, tumour weight and histology were assessed. Serum and tissue amino acids were determined by HPLC. Gene and protein expression were estimated with RT-PCR and western blot and GS activity with a colorimetric method. mTOR activity was evaluated from the phosphorylation of p70S6K1. Results: Crisantaspase and MSO depleted serum glutamine, lowered glutamine in liver and tumour tissue, and inhibited liver GS activity. HepG2 tumour growth was significantly reduced by either Crisantaspase or MSO, and completely suppressed by the combined treatment. The combined treatment was also effective against xenografts of the HC-AFW1 cell line, which is Crisantaspase resistant in vitro. Conclusions: The combination of Crisantaspase and MSO reduces glutamine supply to CTNNB1-mutated HCC xenografts and hinders their growth

No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age

Background : we investigated the association between 9 polymorphisms of genes encoding hemostasis factors and myocardial infarction in a large sample of young patients chosen because they have less coronary atherosclerosis than older patients, and thus their disease is more likely to be related to a genetic predisposition to a prothrombotic state Methods and Results : this nationwide case-control study involved 1210 patients who had survived a first myocardial infarction at an age of 45 years who underwent coronary arteriography in 125 coronary care units and 1210 healthy subjects matched for age, sex, and geographical origin. None of the 9 polymorphisms of genes encoding proteins involved in coagulation (G-455A -fibrinogen: OR, 1.0; CI, 0.8 to 1.2; G1691A factor V: OR, 1.1; CI, 0.6 to 2.1; G20210A factor II: OR, 1.0; CI, 0.5 to 1.9; and G10976A factor VII: OR, 1.0; CI, 0.8 to 1.3), platelet function (C807T glycoprotein Ia: OR, 1.1; CI, 0.9 to 1.3; and C1565T glycoprotein IIIa: OR, 0.9; CI, 0.8 to 1.2), fibrinolysis (G185T factor XIII: OR, 1.2; CI, 0.9 to 1.6; and 4G/5G plasminogen activator inhibitor type 1: OR, 0.9; CI, 0.7 to 1.2), or homocysteine metabolism (C677T methylenetetrahydrofolate reductase: OR, 0.9; CI, 0.8 to 1.1) were associated with an increased or decreased risk of myocardial infarction Conclusions : this study provides no evidence supporting an association between 9 polymorphisms of genes encoding proteins involved in hemostasis and the occurrence of premature myocardial infarction or protection against it

Maletta, Alberico

Biografia del giurista pavese Alberico Maletta, magistrato estense e sforzesco, famoso ambasciatore al servizio degli Sforza