Letizia Gnetti
@ao.pr.it
Pathology Unit
University hospital of Parma
RESEARCH INTERESTS
Lung, kidney and gastrointestinal
Scopus Publications
Scopus Publications
Alessandro Leonetti, Veronica Cervati, Roberta Minari, Maura Scarlattei, Michela Verzè, Marianna Peroni, Monica Pluchino, Francesco Bonatti, Fabiana Perrone, Giulia Mazzaschi,et al.
Elsevier BV
Giulia Mazzaschi, Fabiana Perrone, Giuseppe Maglietta, Elda Favari, Michela Verzè, Monica Pluchino, Roberta Minari, Federica Pecci, Letizia Gnetti, Nicoletta Campanini,et al.
Ovid Technologies (Wolters Kluwer Health)
The study investigated the relationship between serum proinflammatory cytokine levels, cholesterol metabolism, and clinical outcome in cancer patients undergoing immune checkpoint inhibitors (ICIs). Peripheral blood was collected before therapy from ICI-treated advanced cancer patients. We retrospectively assessed plasma total cholesterol (TC), ABCA1- and ABCG1-mediated cholesterol efflux (CE), passive diffusion (PD), cholesterol loading capacity (CLC), and serum IL-6, IL-10, and TNF-α. The association between blood cholesterol parameters and inflammatory cytokines and their effect on overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) from ICIs were statistically assessed. Among 70 consecutively enrolled patients (nonsmall cell lung cancer: 94%; renal cell carcinoma: 6%), TC, CLC, and cholesterol PD resulted significantly higher in IL-6low and IL-10low cases (P<0.05), whereas ABCA1-mediated CE was increased in IL-10high patients (P=0.018). Uni- and multivariable analysis revealed meaningfully longer OS and PFS in IL-6low (HR 2.13 and 2.97, respectively) and IL-10low (HR 3.17 and 2.62) groups. At univariate analysis all cholesterol-related indices significantly correlated with OS and PFS, whereas at multivariate only high PD was validated as a protection factor (OS, HR 0.75; PFS, HR 0.84). Finally, uni- and multivariable showed a statistically significant inverse association of CB with ABCG1-CE (OR 0.62), as with IL-6 (OR 0.13) and IL-10 (OR 0.10). In-depth characterization of the interplay between blood cholesterol metabolism and immune-inflammatory cytokines might provide novel insights into the complex relationship among cancer, inflammation, lipids profile, and response to immunotherapy.
Bruno Lorusso, Antonella Nogara, Rodanthi Fioretzaki, Emilia Corradini, Roberta Bove, Giovanni Roti, Andrea Gherli, Anna Montanaro, Gregorio Monica, Filippo Cavazzini,et al.
MDPI AG
Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5–10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4–7 years). The mechanisms underlying this neoplastic disease still remain uncovered. Twenty-seven IH tissue specimens (15 proliferative and 12 involuting) were subjected to hematoxylin and eosin staining and a panel of diagnostic markers by immunohistochemistry. WT1, nestin, CD133, and CD26 were also analyzed. Moreover, CD31pos/CD26pos proliferative hemangioma–derived endothelial cells (Hem-ECs) were freshly isolated, exposed to vildagliptin (a DPP-IV/CD26 inhibitor), and tested for cell survival and proliferation by MTT assay, FACS analysis, and Western blot assay. All IHs displayed positive CD31, GLUT1, WT1, and nestin immunostaining but were negative for D2-40. Increased endothelial cell proliferation in IH samples was documented by ki67 labeling. All endothelia of proliferative IHs were positive for CD26 (100%), while only 10 expressed CD133 (66.6%). Surprisingly, seven involuting IH samples (58.3%) exhibited coexisting proliferative and involuting aspects in the same hemangiomatous lesion. Importantly, proliferative areas were characterized by CD26 immunolabeling, at variance from involuting sites that were always CD26 negative. Finally, in vitro DPP-IV pharmacological inhibition by vildagliptin significantly reduced Hem-ECs proliferation through the modulation of ki67 and induced cell cycle arrest associated with the upregulation of p21 protein expression. Taken together, our findings suggest that CD26 might represent a reliable biomarker to detect proliferative sites and unveil non-regressive IHs after a 12-month life cycle.
Monica Pluchino, Irene Testi, Roberta Minari, Alessandra Dodi, Giulia Airò, Giulia Mazzaschi, Michela Verzè, Alessia Adorni, Letizia Gnetti, Cinzia Azzoni,et al.
Ovid Technologies (Wolters Kluwer Health)
The combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and MEK inhibition in NSCLC are still unknown. Herein, we report a case of a 76-year-old man with a history of smoking who was diagnosed with BRAF V600E-mutant lung adenocarcinoma (PD-L1 > 50%) and subsequently candidate to first-line therapy with pembrolizumab. After 18 months since the start of immunotherapy, computed tomography scan showed disease progression and a second-line therapy with dabrafenib and trametinib was initiated. Seven months later, due to a suspect disease progression, a left supraclavicular lymphadenectomy was performed and next-generation sequencing analysis revealed the appearance of MET exon 14 skipping mutation, while fluorescence in situ hybridization analysis showed MET amplification. The patient is still on BRAF and MEK inhibitor treatment. Our case highlights the relevance of performing tumor tissue rebiopsy at the time of progression during treatment with BRAF/MEK inhibition with the aim of identifying putative mechanisms of resistance.
Claudia Fumarola, Silvia La Monica, Mara Bonelli, Silvia Zoppi, Roberta Alfieri, Maricla Galetti, Letizia Gnetti, Nicoletta Campanini, Giulia Pozzi, Andrea Cavazzoni,et al.
Elsevier BV
Luigi Ventura, Alfonso Fiorelli, Maurizio Rossi, Letizia Gnetti, Giovanni Natale, Yiyang Wang, Paolo Carbognani, Wentao Fang, and David Waller
Elsevier BV
Gianluca Di Rienzo, Alessandro Tafuni, Umberto Maestroni, Livia Ruffini, Enrico Maria Silini, Donatello Gasparro, Francesco Paolo Pilato, and Letizia Gnetti
Siapec Servizi Srl
Summary Background Metastatic prostate adenocarcinoma is a rare event and there are few references to this topic. We report an unusual case of prostate cancer metastasis and review of contemporary literature. Moreover, we discuss the pathogenesis and the clinical aspects of this event. Case presentation A 70-year-old patient was admitted to the hospital for right scrotal pain. The ultrasound examination described an increase in testicular size, suggesting the possibility of orchiepididymitis. Past medical history reported a previous prostate adenocarcinoma. Inflammatory blood tests were normal. Importantly, PSA was 3.3 ng/ml. PET scan positivity in the scrotum raised suspicion of a relapse. Therefore, he underwent right orchiectomy. Conclusion Although metastatic prostate adenocarcinoma is rare, a correct diagnosis is of paramount importance because the therapy changes accordingly. Patients who complain of scrotal pain need to be examined accurately. Although the most common cause behind this symptom is infectious, the patient’s past medical history should be reviewed to exclude previous malignancies.
A. Leonetti, M. Verzè, R. Minari, F. Perrone, L. Gnetti, P. Bordi, M. Pluchino, R. Nizzoli, C. Azzoni, L. Bottarelli,et al.
Springer Science and Business Media LLC
Alessandra Marchese, Rocco Accogli, Annalisa Frizzelli, Alessandro De Simoni, Olha Bondarenko, Roberta Pisi, Gaetano Caramori, Giovanna Pelà, Maria Majori, Letizia Gnetti,et al.
Informa UK Limited
INTRODUCTION
Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic, immune-mediated disease that occurs in patients with asthma and eosinophilia. It is characterized by inflammation of small and medium-caliber blood vessels.
CASE REPORT
In this report we present an unusual clinical case of EGPA with positive anti-neutrophil cytoplasmic antibodies who manifested bilateral pleural effusion. The diagnosis was confirmed through laboratory assessments and bronchial biopsies. The patient was treated with methylprednisolone showing improvement in symptoms.
CONCLUSIONS
our case appears interesting considering the limited evidence of pleural effusion in patients with EGPA documented in the literature.
Francesca Negri, Letizia Gnetti, and Carlo Aschele
Frontiers Media SA
Marco Delsante, Elena Martinelli, Chiara Foroni, Serena Maria Bagnasco, Giovanni Maria Rossi, Silvia Giuliodori, Letizia Gnetti, Ilaria Gandolfni, and Umberto Maggiore
Springer Science and Business Media LLC
Marco Delsante, Elena Martinelli, Chiara Foroni, Serena Maria Bagnasco, Giovanni Maria Rossi, Silvia Giuliodori, Letizia Gnetti, Ilaria Gandolfini, and Umberto Maggiore
Springer Science and Business Media LLC
Fabiana Perrone, Francesco Facchinetti, Benedetta Pellegrino, Roberta Minari, Letizia Gnetti, Cinzia Azzoni, Lorena Bottarelli, Nicoletta Campanini, Juan Francisco Grau-Bejar, Anna Mingozzi,et al.
SAGE Publications
Introduction: Several biomarkers are currently available to address targeted treatments in cancer patients, with lung malignancies representing one of the best examples. Case description: We report the case of a patient affected by advanced non-small cell lung cancer with an uncommon histology and a complex biology. The use of a large next-generation sequencing (NGS) NGS panel allowed us to identify an extremely rare BRAF mutation (V600Q), a MET amplification, a high tumor mutational burden, a germline pathogenetic BRCA1 mutation and a homologous recombination deficiency through RAD51 assay. The treatment decision was driven by the abundance of molecular information. Conclusions: This case highlights that an attentive and critical evaluation of molecular reports is key for the tailoring of treatment algorithms at the patient-level scale.
A. Cavazzoni, G. Digiacomo, F. Volta, R. Alfieri, E. Giovannetti, L. Gnetti, L. Bellini, M. Galetti, C. Fumarola, G. Xu,et al.
Elsevier BV
Francesco Volta, Silvia La Monica, Alessandro Leonetti, Letizia Gnetti, Mara Bonelli, Andrea Cavazzoni, Claudia Fumarola, Maricla Galetti, Kamal Eltayeb, Roberta Minari,et al.
Springer Science and Business Media LLC
Maria Laura Schirripa, , Letizia Gnetti, Edda Emanuela Guareschi, , , and
Negah Scientific Publisher
Tadalafil is an inhibitor of the human enzyme cyclic guanosine monophosphate–specific phosphodiesterase, type 5 (PDE-5). As a mild vasodilator, it is primarily used for the treatment of erectile dysfunction, an increasingly common condition in men. It is also used for treatment of benign prostatic hyperplasia and pulmonary arterial hypertension. Adverse events of this drug are rare. Absolute contraindications include serious cardiac disease. Despite the widespread use of tadalafil, very little is known about its toxicology in forensic pathology and its association with post-mortem redistribution. This study presents a forensic case with possible contribution of tadalafil. The administration of tadalafil might act as a concurrent cause or contributing factor for lethal cardiogenic shock in people with cardiac disease.
Nicola Fusco, Mariia Ivanova, Chiara Frascarelli, Carmen Criscitiello, Bruna Cerbelli, Maria Gemma Pignataro, Angelina Pernazza, Elham Sajjadi, Konstantinos Venetis, Giulia Cursano,et al.
Elsevier BV
Isabelle Opitz, Andrea Bille, Urania Dafni, Kristiaan Nackaerts, Luca Ampollini, Marc de Perrot, Luka Brcic, Ernest Nadal, Konstantinos Syrigos, Steven G. Gray,et al.
Elsevier BV
Luigi Ventura, Letizia Gnetti, Gianluca Milanese, Maurizio Rossi, Ludovica Leo, Sara Cattadori, Mario Silva, Alessandro Leonetti, Roberta Minari, Luca Musini,et al.
Elsevier BV
Melissa Bersanelli, Letizia Gnetti, Francesco Paolo Pilato, Elena Varotti, Federico Quaini, Nicoletta Campanini, Elena Rapacchi, Roberta Camisa, Paolo Carbognani, Enrico Maria Silini,et al.
Open Exploration Publishing
Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC). Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context. Results: High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher for the mTOR pathway proteins. Combined immunophenotypical expression patterns and their correlations with the immune context were uncovered [i.e., mTOR expression in the metastases positively correlated with PD-L1 expression in tumor-infiltrating lymphocytes (TILs), P = 0.019; MET expression was related to PD-1 expression on TILs (P = 0.041, ρ = 0.41) and peritumoral lymphocytes (RILs; P = 0.013, ρ = 0.49)], suggesting the possibility of predicting drug response or resistance to tyrosine kinase, mTOR, or immune checkpoint inhibitors. Conclusions: In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed for their reliable translation into clinical practice. The easy-to-use immunohistochemical method of the present study allowed the identification of different combined expression patterns, providing cues for planning the management of systemic treatment combinations and sequences in an mRCC patient population. The quantitative heterogeneity of the investigated biomarkers suggests that multiple intralesional assays are needed to consider the assessment reliable for clinical considerations.
Francesca Negri, Lorena Bottarelli, Giuseppe Pedrazzi, Michele Maddalo, Ludovica Leo, Gianluca Milanese, Roberto Sala, Michele Lecchini, Nicoletta Campanini, Cecilia Bozzetti,et al.
Frontiers Media SA
IntroductionThe Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab.MethodsImmunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor.ResultsA positive association was found between NICD and Jag1 expression (p &lt; 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823).DiscussionThese results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients.
Jan Hendrik Rüschoff, Martina Haberecker, Zoi Tsourti, Kristiaan Nackaerts, Marc de Perrot, Luka Brcic, Ernest Nadal, Sotirios Tsimpoukis, Steven G. Gray, Luca Ampollini,et al.
Elsevier BV
Jan Hendrik Rüschoff, Martina Haberecker, Zoi Tsourti, Kristiaan Nackaerts, Marc de Perrot, Luka Brcic, Ernest Nadal, Sotirios Tsimpoukis, Steven G. Gray, Luca Ampollini,et al.
Elsevier BV
Giulia Mazzaschi, Fabiana Perrone, Roberta Minari, Michela Verzè, Cinzia Azzoni, Lorena Bottarelli, Monica Pluchino, Maria Pia Armillotta, Annalisa Ubaldi, Annalisa Altimari,et al.
Elsevier BV
Bruno Lorusso, Giuseppe Cerasoli, Angela Falco, Caterina Frati, Gallia Graiani, Denise Madeddu, Antonella Nogara, Emilia Corradini, Giovanni Roti, Elisa Cerretani,et al.
Elsevier BV