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454 results on '"Pontecorvi P"'

209. Update regarding the role of PD-L1 in oncocytic thyroid lesions on cytological samples

Author

Dell'Aquila, Marco, Tralongo, Pietro, Granitto, Alessia, Martini, Maurizio, Capodimonti, Sara, Curatolo, Mariangela, Fiorentino, Vincenzo, Pontecorvi, Alfredo, Fadda, Guido, Lombardi, Celestino Pio, Raffaelli, Maco, Pantanowitz, Liron, Larocca, Luigi Maria, and Rossi, Esther Diana

Abstract

AimsSeveral papers have shown that programmed death-ligand 1 (PD-L1) expression is a relevant predictive biomarker in anti-PD-L1 cancer immunotherapy. While its role in several human cancers is correlated with poor prognosis and resistance to anticancer therapies, in thyroid cancers the role of PD-L1 remains questionable. Few articles have studied PD-L1 in thyroid fine-needle aspiration cytology (FNAC), demonstrating a possible correlation with papillary thyroid carcinoma. However, its role in oncocytic thyroid lesions remains controversial. We accordingly examine the performance of PD-L1 immunostaining in liquid based cytology (LBC) from oncocytic lesions.MethodsFrom January 2019 to March 2021, 114 thyroid lesions diagnosed by FNAC from lesions with a predominant oncocytic component, were enrolled for evaluation by PD-L1 immunostaining on both LBC and corresponding histology samples.ResultsThe FNAC cohort included 51 benign (B, negative controls), 4 atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS), 57 follicular lesions (follicular neoplasm/suspicious for FN, FN/SFN) and 2 suspicious for malignancy (SFM) cases. Fifty-four cases (11B, 2 AUS/FLUS, 39 FN/SFN and 2 SFM) had histological follow-up including: 1B case resulted as a hyperplastic oxyphilic nodule in Hashimoto thyroiditis (HT), 10B as goitre, 2 AUS/FLUS cases as oncocytic adenomas (OAs); 39 FN/SFN included 27 OAs, 4 FA and 8 oncocytic follicular carcinoma (OFC). The two SFM cases were diagnosed on histopathology as OAs. Increased plasma membrane and cytoplasmic PD-L1 expression were found in 47 cases of the LBC cases (41.2%). Among the histological series, 67.3% of OAs and 75% of OFC had PD-L1 expression, while negative PD-L1 was found in hyperplastic oncocytic cells in HT. A positivity in more than 30% of the neoplastic cells was found in 72.9% of the cases including six OFC.ConclusionsThese data suggest that PD-L1 expression is expressed in oncocytic thyroid lesions. While weak PD-L1 expression failed to discriminate benign from malignant lesions, OFC demonstrated more intense cytoplasmic and membranous expression.

Published
2023
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210. Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer.

Author

Simona Nanni, Aurora Aiello, Agnese Re, Alessandro Guffanti, Valentina Benvenuti, Claudia Colussi, Luis Jaime Castro-Vega, Armando Felsani, Arturo Londono-Vallejo, Maurizio C Capogrossi, Silvia Bacchetti, Carlo Gaetano, Alfredo Pontecorvi, and Antonella Farsetti

Subjects
Medicine, Science
Abstract

In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5' domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa.

Published
2013
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211. Estrogens as Antioxidant Modulators in Human Fertility

Author

A. Mancini, S. Raimondo, M. Persano, C. Di Segni, M. Cammarano, G. Gadotti, A. Silvestrini, A. Pontecorvi, and E. Meucci

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Among treatments proposed for idiopathic male infertility, antiestrogens, like tamoxifen, play a possible role. On the other hand, oxidative stress is a mechanism well recognized for deleterious effects on spermatozoa function. After reviewing the literature on the effects of estrogens in modulation of antioxidant systems, in both sexes, and in different in vivo and in vitro models, we suggest, also on the basis of personal data, that a tamoxifen treatment could be active via an increase in seminal antioxidants.

Published
2013
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219. Evaluation of indices for the measurement of quality in health systems

Author

Clemente Fabrizio, Papi Marco, Pontecorvi Luca, and Menichetti Antonio

Subjects
health services, metrics, statistical quality control, Technology
Abstract

In recent decades different numeric indicators and methods have been used to qualify structured index that express health service components quality performance. The first step of this work is the definition of a model of the system under examination in order to define its measurable constituent entities (dimensions). Among the common measured clinical parameters, a robust metrics, characterizing the constituent entities and the best opportunity tools for the characterization of the results, have been identified. The last step is multi-modal analysis of the results. Using this approach the paper presents an application in the evolution of the cardiological intensive care unit (ICU). Particularly, the attention of this paper is focused on the evolving of the medical team.

Published
2016
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220. Male Fertility and Reduction in Semen Parameters: A Single Tertiary-Care Center Experience

Author

D. Milardi, G. Grande, D. Sacchini, A. L. Astorri, G. Pompa, A. Giampietro, L. De Marinis, A. Pontecorvi, A. G. Spagnolo, and R. Marana

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background. Infertility is both a clinical and a public problem, affecting the life of the couple, the healthcare services, and social environment. Standard semen analysis is the surrogate measure of male fertility in clinical practice. Objective. To provide information about the relationship between semen parameters and spontaneous conception. Methods. We evaluated retrospectively 453 pregnancies that occurred among 2935 infertile couples evaluated at an infertility clinic of a tertiary-care university hospital, between 2004 and 2009. Results. Normal semen analysis was present only in 158 patients; 295 subfertile patients showed alterations in at least one seminal parameter. A reduction in all seminal parameters was observed in 41 patients. Etiological causes of male infertility were identified in 314 patients. Conclusion. Our data highlights the possibility of a spontaneous conception with semen parameters below WHO reference values. Therefore, we support the importance of defining reference values on a population of fertile men. Finally, we analyzed the related ethical issues.

Published
2012
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221. Biochemical Alterations in Semen of Varicocele Patients: A Review of the Literature

Author

Antonio Mancini, Roberto Festa, Sebastiano Raimondo, Andrea Silvestrini, Elena Giacchi, Gian Paolo Littarru, Alfredo Pontecorvi, and Elisabetta Meucci

Subjects
Diseases of the genitourinary system. Urology, RC870-923
Abstract

Oxidative stress is a mechanism underlying different kinds of infertility in human males. However, different results can be observed in relation to the method used for its evaluation. Varicocele patients show a number of biochemical abnormalities, including an altered distribution of coenzyme Q between seminal plasma and sperm cells and also an apparent defect in the utilization of antioxidants. Moreover, an influence of systemic hormones on seminal antioxidant system was observed too. Finally, the effects of surgical treatment on oxidativestress indexes and the possible usefulness of some medical therapies, like coenzyme Q supplementation, are discussed. In conclusion, published data show a role of oxidative stress in varicocele-related male infertility, but at present we do not know the precise molecular mechanisms underlying these phenomena.

Published
2012
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223. MiR-200c sensitizes Olaparib-resistant ovarian cancer cells by targeting Neuropilin 1

Author

Vescarelli, E., Gerini, G., Megiorni, F., Anastasiadou, E., Pontecorvi, P., Solito, L., De Vitis, C., Camero, S., Marchetti, Claudia, Mancini, R., Benedetti Panici, P., Dominici, C., Romano, Federica, Angeloni, A., Marchese, Cinzia, Ceccarelli, Simona, Marchetti C. (ORCID:0000-0001-7098-8956), Romano F., Marchese C., Ceccarelli S., Vescarelli, E., Gerini, G., Megiorni, F., Anastasiadou, E., Pontecorvi, P., Solito, L., De Vitis, C., Camero, S., Marchetti, Claudia, Mancini, R., Benedetti Panici, P., Dominici, C., Romano, Federica, Angeloni, A., Marchese, Cinzia, Ceccarelli, Simona, Marchetti C. (ORCID:0000-0001-7098-8956), Romano F., Marchese C., and Ceccarelli S.

Abstract

Background: Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood. The aim of this study is to identify target genes within the tumor cells that might cause resistance to Olaparib. We focused on Neuropilin 1 (NRP1), a transmembrane receptor expressed in OC and correlated with poor survival, which has been also proposed as a key molecule in OC multidrug resistance. Methods: Using three OC cell lines (UWB, UWB-BRCA and SKOV3) as model systems, we evaluated the biological and molecular effects of Olaparib on OC cell growth, cell cycle, DNA damage and apoptosis/autophagy induction, through MTT and colony forming assays, flow cytometry, immunofluorescence and Western blot analyses. We evaluated NRP1 expression in OC specimens and cell lines by Western blot and qRT-PCR, and used RNA interference to selectively inhibit NRP1. To identify miR-200c as a regulator of NRP1, we used miRNA target prediction algorithms and Pearsons' correlation analysis in biopsies from OC patients. Then, we used a stable transfection approach to overexpress miR-200c in Olaparib-resistant cells. Results: We observed that NRP1 is expressed at high levels in resistant cells (SKOV3) and is upmodulated in partially sensitive cells (UWB-BRCA) upon prolonged Olaparib treatment, leading to poor drug response. Our results show that the selective inhibition of NRP1 is able to overcome Olaparib resistance in SKOV3 cells. Moreover, we demonstrated that miR-200c can target NRP1 in OC cells, causing its downmodulation, and that miR-200c overexpression is a valid approach to restore Olaparib sensitivity in OC resistant cells. Conclusions: These data demonstrate that miR-200c significantly enhanced the anti-cancer efficacy of Olaparib in drug-resistant OC cells

Published
2020

231. Approach to FNA of Thyroid Gland Cysts

Author

Rossi, Esther Diana, Tralongo, Pietro, Fiorentino, Vincenzo, Curatolo, Mariangela, Bruno, Carmine, De Crea, Carmen, Raffaelli, Marco, Pontecorvi, Alfredo, and Larocca, Luigi Maria

Abstract

Fine needle aspiration is a well-known procedure for the diagnosis and management of thyroid lesions, representing the first diagnostic tool for the definition of their nature. In clinical practice, a thyroid nodule can be classified as solid, cystic, and partially cystic based on its internal components. Different thyroid imaging reporting systems and cytologic diagnostic systems have focused their attention on solid nodules, which are more frequently linked with a malignant outcome. In fact, numerous papers demonstrated that nodules with microcalcifications, a taller-than-wide shape, hypoechogeneity, and irregular margins, are more likely to be malignant on histology. Nevertheless, according to the literature, the risk of malignancy in a partially cystic thyroid nodule ranges between 3.3 and 17-5%, including, for instance, the possible diagnosis of a cystic papillary thyroid carcinoma and other malignant entities. Therefore, in the current review article, we are going to discuss the approach to thyroid cystic lesions on fine needle aspiration cytology.

Published
2022
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243. Tu2019 DELTA RADIOMIC FEATURES PREDICT RESECTION MARGIN STATUS AND OVERALL SURVIVAL IN NEOADJUVANT-TREATED PANCREATIC CANCER PATIENTS.

Author

Goodman, Lily C., Bifolco, Alessandro, Wang, Kai, Karalis, John D., Elamir, Ahmed, Wachsmann, Megan B., Capretti, Giovanni, Spaggiari, Paola, Enrico, Sebastian, Balasubramanian, Kishore, Fatimah, Nafeesah, Pontecorvi, Giada, Nebbia, Martina, Polanco, Patricio M., Yopp, Adam, Kaza, Ravi, Pedrosa, Ivan, Zeh, Herbert J., Zerbi, Alessandro, and Wang, Jing

Published
2024
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247. Discovery, preclinical development, and clinical application of pralsetinib in the treatment of thyroid cancer

Author

Locantore, Pietro, Novizio, Roberto, Corsello, Andrea, Paragliola, Rosa Maria, Pontecorvi, Alfredo, and Corsello, Salvatore Maria

Abstract

ABSTRACTIntroductionThe use of targeted drug therapies has substantially increased in the treatment of RET-mutated thyroid and other solid cancers over the last decade. Multi-Kinase Inhibitors (MKI) have been approved by FDA, but limited efficacies and side effects make them uneasy to tolerate. Pralsetinib is an oral highly selective RET inhibitor drug that has been generated and clinically validated to have higher potency and less toxicity.Areas coveredThe present paper offers a brief summary of RET-related thyroid cancer genetics, an overview of the preclinical development of pralsetinib and reviews its clinical validation in the treatment of thyroid cancer.Expert opinionPralsetinib is a new generation oral treatment that has been approved by the FDA for patients with RET-mutated thyroid cancer. Pralsetinib showed a safer toxicity profile compared to previously approved MKI, probably due to lower inhibition of other tyrosine kinases, especially VEGFR. The approval study ARROW trial showed that patients with RET-mutant medullary thyroid cancer had a better overall response rate to pralsetinib compared to standard-of-care treatments. Additional clinical trials or data enrichment of existing databases are desirable in order to verify and further describe the clinical benefit of pralsetinib in such patients to fully understand its pharmacological profile.

Published
2022
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250. A physiological mathematical model of the human thyroid.

Author

Pompa, Marcello, De Gaetano, Andrea, Borri, Alessandro, Farsetti, Antonella, Nanni, Simona, Pontecorvi, Alfredo, and Panunzi, Simona

Subjects
PHYSIOLOGICAL models, ORAL drug administration, THYROID hormone regulation, THYROID gland, MATHEMATICAL models, THYROTROPIN releasing factor, THYROTROPIN receptors, THYROID hormone receptors
Abstract

The thyroid is one of the largest endocrine glands in humans. The thyroid produces two major hormones: thyroxine (T4) and triiodothyronine (T3). The secretion and production of thyroid hormones are controlled via two feedbacks: one positive, where the thyrotropin-releasing hormone (TRH) stimulates the thyroid-stimulating hormone (TSH) that stimulates the production of T3 and T4 hormones; one negative, where high circulating levels of T3 and T4 in turn inhibit the production of both TRH and TSH. T3 and T4 also depend on iodine intake. The present work proposes a comprehensive mathematical model of the thyroid and TSH control system through which both the effect of the hormones and of iodine can be assessed. The proposed model is composed of 22 compartments, which describe the dynamics of iodine, T3, T4, TSH, TRH and Thyroglobulin (Tg) in blood and in the extra-cellular space. The effect of Sodium Iodide Symporter (NIS, a membrane protein mediating iodide transport) and of Thyroperoxidase (TPO, an enzyme involved in the thyroid hormone synthesis) on thyroid metabolism is also described and a gastrointestinal sub-model is incorporated in order to describe the oral administration of iodine, levothyroxine (L-T4) and levothyronine (L-T3). TSH oscillations are described using a series of impulses generated by a biological oscillator. The model has been validated on several independent data sets retrieved from the literature, where euthyroid volunteers underwent different clinical experiments with the oral administration of L-T4 (in 400, 450, 600 μ g dosages) or L-T3 (75 μ g) and with intravenous injections of TRH. • Mathematical description of the HPT axis variable relationships. • Presentation of a new comprehensive mathematical model of the thyroid. • Model performance assessment in reproducing observed data from therapeutic scenarios. • Model sensitivity analysis. [ABSTRACT FROM AUTHOR]

Published
2024
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