Ferdinando Auricchio | Università della Campania Luigi Vanvitelli (original) (raw)

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Papers by Ferdinando Auricchio

Oncogene, 2007

In human mammary and prostate cancer cells, steroid hormones or epidermal growth factor (EGF) tri... more In human mammary and prostate cancer cells, steroid hormones or epidermal growth factor (EGF) trigger association of the androgen receptor (AR)-estradiol receptor (ER) (a or b) complex with Src. This interaction activates Src and affects the G1 to S cell cycle progression. In this report, we identify the sequence responsible for the AR/Src interaction and describe a 10 amino-acid peptide that inhibits this interaction. Treatment of the human prostate or mammary cancer cells (LNCaP or MCF-7, respectively) with nanomolar concentrations of this peptide inhibits the androgen-or estradiol-induced association between the AR or the ER and Src the Src/Erk pathway activation, cyclin D1 expression and DNA synthesis, without interfering in the receptor-dependent transcriptional activity. Similarly, the peptide prevents the S phase entry of LNCaP and MCF-7 cells treated with EGF as well as mouse embryo fibroblasts stimulated with androgen or EGF. Interestingly, the peptide does not inhibit the S phase entry and cytoskeletal changes induced by EGF or serum treatment of AR-negative prostate cancer cell lines. The peptide is the first example of a specific inhibitor of steroid receptordependent signal transducing activity. The importance of these results is highlighted by the finding that the peptide strongly inhibits the growth of LNCaP xenografts established in nude mice.

We report herein a stereoselective and straightforward methodology for the synthesis of new andro... more We report herein a stereoselective and straightforward methodology for the synthesis of new androgen receptor ligands with (anti)-agonistic activities. Oxygen-nitrogen replacement in bicalutamide-like structures paves the way to the disclosure of a new class of analogues, including cyclized/nitrogen-substituted derivatives, with promising antiandrogen (or anabolic) activity.

We observed that sex steroid hormones, like growth factors, stimulate the Src/Ras/erk pathway of ... more We observed that sex steroid hormones, like growth factors, stimulate the Src/Ras/erk pathway of cell lines derived from human mammary or prostate cancers. In addition, hormone-dependent pathway activation can be induced in Cos cells, upon transfection of classic steroid receptors. Cross-talks between sex steroid receptors regulate their association with Src and consequent pathway activation. Oestradiol treatment of MCF-7 cells triggers simultaneous association of ER with Src and p85, the regulatory subunit of phosphatidylinositol-3-kinase (PI3-kinase) and activation of Src-and PI3-K-dependent pathways. Activation of the latter pathway triggers cyclin D1 transcription, that is unaffected by Mek-1 activation. This suggests that simultaneous activation of different signalling effectors is required to target different cell cycle components. Thus, a novel reciprocal cross-talk between the two pathways appears to be mediated by the ER. In all tested cells, activation of the signalling pathways has a proliferative role. Transcriptionally inactive ER expressed in NIH 3T3 cells responds to hormone causing Src/Ras/Erk pathway activation and DNA synthesis. This suggests that in these cells genomic activity is required for later events of cell growth.

Molecular biology of the cell, Jan 10, 2015

Steroids and growth factors control neuronal development through their receptors under physiologi... more Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We here report that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes in neuritogenesis stimulated by the non-aromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes in NGF- or androgen-induced neuritogenesis. Additionally, androgen or NGF triggers AR association with TrkA, TrkA interaction with PI3-K δ and downstream activation of PI3-K δ and Rac in PC12 cells. Once associated with AR, filamin A (FlnA) contributes to androgen or NGF neuritogenesis, likely through its interaction with signaling effectors, such as Rac.Our study identifies a previously unrecognized reciprocal cross talk between AR and TrkA, which is controlled by β1 integrin. The contribution of FlnA/AR complex and PI3-K ...

Computer Methods in Applied Mechanics and Engineering, 2015

ABSTRACT We present numerical formulations of Timoshenko beams with only one unknown, the bending... more ABSTRACT We present numerical formulations of Timoshenko beams with only one unknown, the bending displacement, and it is shown that all variables of the beam problem can be expressed in terms of it and its derivatives. We develop strong and weak forms of the problem. The strong form of the problem involves the fourth derivative of the bending displacement, whereas the symmetric weak form involves, somewhat surprisingly, third and second derivatives. Based on these, we develop isogeometric collocation and Galerkin formulations, that are completely locking-free and involve only half the degrees of freedom compared to standard Timoshenko beam formulations. Several numerical tests are presented to demonstrate the performance of the proposed formulations.

International Journal of Fatigue, 2015

ABSTRACT This paper presents a methodology for the numerical fatigue-life assessment of cardiovas... more ABSTRACT This paper presents a methodology for the numerical fatigue-life assessment of cardiovascular balloon-expandable stents. The methodology is based on a global computational approach composed of a mechanical finite element analysis, followed by a fatigue analysis. The method is applied to a classical 316L stainless steel coronary stent design (i.e., the Medinol/Boston Scientific NIR™ stent). Fatigue criteria based on elastic and plastic shakedown concepts for finite and infinite lifetime are used to predict fatigue crack initiation and are calibrated on experimental data related to 316L stainless steel m-size components, manufactured as stents. The results from the fatigue analysis allow to discuss several aspects affecting stent lifetime, such as the applied cyclic loading including systolic–diastolic pressurization and bending. The generality of the proposed methodology encourages further investigations of such an approach for its application to other materials or small-scale components.

International journal for numerical methods in biomedical engineering, 2012

After carotid artery stenting, the plaque remains contained between the stent and the vessel wall... more After carotid artery stenting, the plaque remains contained between the stent and the vessel wall, moving consequently physicians' concerns toward the stent capability of limiting the plaque protrusion, that is, toward vessel scaffolding, to avoid that some debris is dislodged after the procedure. Vessel scaffolding is usually measured as the cell area of the stent in free-expanded configuration, neglecting thus the actual stent configuration within the vascular anatomy. In the present study, we measure the cell area of four different stent designs deployed in a realistic carotid artery model through patient-specific finite element analysis. The results suggest that after deployment, the cell area change along the stent length and the related reduction with respect to the free-expanded configuration are functions of the vessel tapering. Hence, the conclusions withdrawn from the free-expanded configuration appear to be qualitatively acceptable for comparative purposes, but they s...

Journal of steroid biochemistry, 1984

The calf uterus estradiol-17 beta receptor is a phosphoprotein and its hormone binding activity i... more The calf uterus estradiol-17 beta receptor is a phosphoprotein and its hormone binding activity is regulated by two endogenous enzymes both of which have been purified and characterized in detail: a nuclear phosphatase that inactivates the hormone binding sites of the receptor, and a cytosol kinase that activates these sites. Here we report that the kinase is stimulated by Ca2+ and calmodulin. Direct evidence is presented that the receptor is phosphorylated by the kinase and dephosphorylated by the phosphatase.

The Journal of heart valve disease, 2012

Aortic valve-sparing (AVS) procedures have been introduced to treat ascending aorta dilatation an... more Aortic valve-sparing (AVS) procedures have been introduced to treat ascending aorta dilatation and aortic valve insufficiency in the presence of preserved native aortic valve leaflets. Although the surgical technique has been standardized, the choice of best type and size of Dacron graft to be used remains a matter of debate. Herein are presented preliminary results based on a patient-specific finite element model aimed at optimizing the Dacron prosthesis size and shape. Previously, finite element analysis (FEA) has been applied to investigate medical problems and, in particular, to better evaluate the pathophysiology of the aortic root. To date, however, such methodology has not been applied to the patient-specific evaluation of AVS postoperative results. The framework of the FEA study included four steps: (i) the creation of a mathematic model of the patient's aortic root; (ii) the creation of a model for two different Dacron grafts (the standard straight graft and a Valsalva ...

Journal of Steroid Biochemistry, 1986

The calf uterus oestradioLl7fi receptor exists in a hormone binding form, which is phosphorylated... more The calf uterus oestradioLl7fi receptor exists in a hormone binding form, which is phosphorylated on tyrosine, and in a non-hormone binding form, which is dephosphorylated. Two enzymes regulate the number of hormone binding sites of the receptor: a kinase which has been purified from cytosol and a phosphatase purified from nuclei.

Encyclopedia of Computational Mechanics, 2004