218 pubblicazioni classificate nel seguente modo:

Cisplatin as a Xenobiotic Agent: Molecular Mechanisms of Actions and Clinical Applications in Oncology
JOURNAL OF XENOBIOTICS
Autore/i: Cecati, M; Pozzi, V; Pompei, V; Schiavoni, V; Fumarola, S; Romagnoli, A; Tossetta, G; Montana, A; Polizzi, A; Sartini, D; Campagna, R
Classificazione: 1 Contributo su Rivista
Abstract: Cisplatin, a platinum-based compound, is a cornerstone of modern chemotherapy and remains widely used against a variety of solid tumors, including testicular, ovarian, lung, bladder, and head and neck cancers. Its anticancer activity is primarily attributed to the formation of DNA crosslinks, which obstruct replication and repair, ultimately leading to apoptosis. However, the clinical value of cisplatin is constrained by two major challenges: its toxic profile and the development of resistance. Cisplatin toxicity arises from its interaction not only with tumor DNA but also with proteins and nucleic acids in healthy tissues, resulting in a range of adverse effects, including, but not limited to, nephrotoxicity, ototoxicity, neurotoxicity, and gastrointestinal injury. In pediatric patients, permanent hearing loss represents a particularly debilitating complication. On the other hand, tumor cells can evade cisplatin cytotoxicity through diverse mechanisms, including reduced intracellular drug accumulation, enhanced DNA repair, detoxification by thiol-containing molecules, and alterations in apoptotic signaling. These resistance pathways severely compromise treatment outcomes and often necessitate alternative or combination strategies. This review examines the chemical structure of cisplatin, the molecular mechanisms of cisplatin cytotoxicity and cisplatin-induced resistance, as well as the main applications in cancer management and the complications associated with its clinical use.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/352075

Radioresistance of head and neck squamous cell carcinoma: exploring the contribution of nicotinamide N-methyltransferase enzyme
63° Congresso della Società Italiana di Biochimica e Biologia Molecolare (SIB), Palermo, 10-12 Settembre, 2025
Autore/i: Pompei, V; Petrone, V; Chirico, R; Skvortsova, Ii; Matteucci, C; Emanuelli, M; Sartini, D
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/347553

Urinary Cell-Free DNA as a potential diagnostic biomarker for bladder cancer in older adults
63° Congresso della Società Italiana di Biochimica e Biologia Molecolare (SIB), Palermo, 10-12 Settembre, 2025
Autore/i: Pozzi, V; Campagna, R; Sartini, D; Cormio, A; Milanese, G; Galosi, Ab; Emanuelli, M; Cecati, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/347552

Catechol-o-methyltransferase, a promising diagnostic marker for non-invasive detection of human urothelial carcinoma
63° Congresso della Società Italiana di Biochimica e Biologia Molecolare (SIB), Palermo, 10-12 Settembre, 2025
Autore/i: Cecati, M; Campagna, R; Sartini, D; Cormio, A; Milanese, G; Galosi, Ab; Emanuelli, M; Pozzi, V
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/347554

Enhancing cisplatin efficacy in triple-negative breast cancer through pon2 silencing: insights from FTIRM analysis
Congresso di Chimica Bioinorganica della Società Chimica Italiana (SCI), Caserta, 30 Giugno – 2 Luglio 2025
Autore/i: Giorgini, E; Santoni, C; Notarstefano, V; Campagna, R; Pozzi, V; Sartini, D; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/347595

Antiretroviral treatment modulates HERV-K and oncogenic genes to restore radiosensitivity in head and neck squamous cell carcinoma
53° Congresso Nazionale della Società Italiana di Microbiologia (SIM), Catania 19-22 Settembre 2025
Autore/i: Petrone, V; Fanelli, M; Pompei, V; Giudice, M; Cipriani, C; Grelli, S; Minutolo, A; Sinibaldi-Vallebona, P; Balestrieri, E; Sartini, D; Skvortsova, Ii; Matteucci, C; Chirico, R
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/348779

Paraoxonase-2 in osteosarcoma: potential for the development of a targeted anticancer therapy
GiovenTUM 2025: il futuro della biochimica si incontra a Firenze. Firenze, 9 Giugno 2025.
Autore/i: Campagna, R; Pompei, V; Gerini, E; Pozzi, V; Salvolini, E; Sartini, D; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/345402

Treatment of osteosarcoma and Merkel cell carcinoma cell lines with inhibitors of nicotinamide N-methyltransferase: potential for the development of targeted therapeutic strategy
Atti del 5th Workshop of the SIB group “Tumor Biochemistry”, Torino, June 9-10th, 2025
Autore/i: Pompei, V; Serritelli, En; Gerini, E; Campagna, R; Pozzi, V; Van Haren, Mj; Martin, Ni; Emanuelli, M; Sartini, D
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/345513

Catechol-O-methyltransferase, a potential biomarker for non-invasive diagnosis of human urothelial carcinoma
BIOCHIMICA CLINICA
Autore/i: Cecati, M; Campagna, R; Sartini, D; Cormio, A; Milanese, G; Galosi, Ab; Emanuelli, M; Pozzi, V
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/349702

Nicotinamide N-methyltransferase as a determinant for resistance to radiotherapy in head and neck cancer
BIOCHIMICA CLINICA
Autore/i: Pompei, V; Petrone, V; Chirico, R; Van Haren, Mj; Martin, Ni; Skvortsova, I; Matteucci, C; Emanuelli, M; Sartini, Davide
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/349703

Deepening Cisplatin sensitivity on Oral Squamous cell Carcinoma cell lines after PON2 knockdown: A FTIRM investigation
SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
Autore/i: Belloni, A; Campagna, R; Notarstefano, V; Pozzi, V; Orilisi, G; Pompei, V; Togni, L; Mascitti, M; Sartini, D; Giorgini, E; Santarelli, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Cisplatin is a platinum-based chemotherapy drug with antimicrobial and antitumoral activity, largely used for a long time in the treatment of several cancers, including the Oral Squamous Cell Carcinoma (OSCC), which is one of the most frequent neoplasms of the oral cavity. Due to its aggressiveness and metastatic invasion, OSCC is characterized by poor outcome, often related also to chemoresistance mechanisms. The intracellular enzyme paraoxonase-2 (PON2) normally acts defending cells from the damages induced by Reactive Oxygen Species. Hence, in cancer cells, this enzyme can shield the potential of cisplatin, triggering a resistance mechanism. Based on this evidence, PON2 knockdown seems to be a valuable way to enhance the effects of chemotherapy, escaping this resistance. In this study, HOC621 and HSC-3 OSCC cell lines submitted to PON2 silencing were analyzed by Fourier Transform Infrared Microspectroscopy to evaluate the time-dependent changes occurring in these cells after cisplatin treatment. Spectral data were statistically analyzed by multivariate and univariate analyses and compared with MTT results. Positive feedback on cisplatin efficacy was found in both cell lines submitted to PON2 knockdown, even if with a different response. In particular, a less growth was found in PON2 silenced HOC 621 cells, respect to HSC-3 ones. Moreover, specific spectral markers (A1172/ATOT, A1053/ATOT, A967/A1080, and A992/ATOT band area ratios) were identified and statistically analyzed (p < 0.05): cellular alterations mainly in nucleic acids and carbohydrates were found in both cell lines, although more evident in HOC 621 ones, which therefore appeared to be more affected by chemotherapy treatment
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/339652

Small Molecule Inhibitors of Nicotinamide N-Methyltransferase Enzyme for the Treatment of Osteosarcoma and Merkel Cell Carcinoma: Potential for the Development of a Targeted Therapeutic Strategy
BIOMOLECULES
Autore/i: Pompei, V; Cecati, M; Serritelli, En; Gerini, E; Campagna, R; Pozzi, V; Van Haren, Mj; Martin, Ni; Emanuelli, M; Sartini, D
Classificazione: 1 Contributo su Rivista
Abstract: Nicotinamide N-methyltransferase (NNMT) enzyme catalyzes the N-methylation of nicotinamide and its overexpression has been reported in many neoplasms, favoring traits featuring an aggressive tumor cell phenotype. Our recent data demonstrated that NNMT upregulation in osteosarcoma (OS) and Merkel cell carcinoma (MCC) led to a significant increase in cell proliferation and migration ability, together with a reduction in sensitivity to chemotherapeutic treatment. Based on these findings, we investigated the impact of small molecule NNMT inhibitors 5-amino-1-methyl quinolinium (5-AMQ), 6-methoxynicotinamide (6MeONa) and Eli Lilly’s pyrimidine 5-carboxamide (EL-1) on U-2 OS and Saos-2 OS cell lines and MCC13 and MCC26 MCC cell lines. Following incubation of the cells with these compounds, cell viability, reactive oxygen species (ROS) production and apoptosis induction were evaluated. Cells were then subjected to combined treatment with inhibitors and cisplatin (CDDP), and viability and ROS levels were further analyzed. Our results clearly illustrate that cells treated with NNMT inhibitors underwent significant reductions in viability, increased ROS production and activation of apoptotic pathways. Given the association of NNMT with cancer aggressiveness, inhibiting its catalytic activity might present a novel strategy for counteracting cancer growth and chemoresistance, providing the rationale for an effective anti-cancer therapy based on the use of specific NNMT inhibitors.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/349701

Curcumin and its Analogues in Oral Squamous Cell Carcinoma: State-of-the-art and Therapeutic Potential
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
Autore/i: Schiavoni, V; Emanuelli, M; Sartini, D; Salvolini, E; Pozzi, V; Campagna, R
Classificazione: 1 Contributo su Rivista
Abstract: Oral Squamous Cell Carcinoma (OSCC) is the most common cancer arising from squamous epithelium in the oral cavity and is characterized by high aggressiveness and metastatic potential, which together with a late diagnosis results in a 5-year survival rate of only 50% of patients. The therapeutic options for OSCC management are limited and largely influenced by the cancer stage. While radical surgery can be curative in early stage of disease, most cases require adjuvant therapies, including chemotherapy and radiotherapy which, however, often achieve poor curative rates and are associated with important negative effects. Therefore, there is an urgent need to discover new alternative treatment strategies to improve patients’ outcomes. Several medicinal herbs are being studied for their preventive or therapeutic effect in several diseases, including cancer. In particular, the Indian spice curcumin, largely used in oriental countries, has been studied as a chemopreventive or adjuvant agent for different malignancies. Indeed, curcumin is characterized by important biological properties, including antioxidant, anti-inflammatory, and anticancer effects, which could also be exploited in OSCC. However, due to its limited bioavailability and poor aqueous solubility, this review is focused on studies designing new synthetic analogues and developing novel types of curcumin delivery systems to improve its pharmacokinetic and biological properties. Thus, this review analyses the potential therapeutic role of curcumin in OSCC by providing an overview of current in vitro and in vivo studies demonstrating the beneficial effects of curcumin and its analogues in OSCC.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/330965

NNMT expression in preeclampsia: Analyses on placental tissues and cell lines
PLACENTA
Autore/i: Tossetta, G; Campagna, R; Fantone, S; Di Simone, N; Pompei, V; Giannubilo, Sr; Ciavattini, A; Sartini, D; Emanuelli, M; Marzioni, D
Classificazione: 1 Contributo su Rivista
Abstract: Objective: Preeclampsia (PE) is a multisystem disorder characterized by new onset hypertension and proteinuria during pregnancy. Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyzes the N-methylation of nicotinamide (NAM) to form 1-methylnicotinamide (MNA) and S-adenosyl-L-homocysteine (SAH). The aim of this study was to investigate NNMT expression in normal and PE placentas, and evaluate whether hypoxia, oxidative stress and inflammation could modulate NNMT expression. Materials and methods: Immunohistochemistry and Western blot were performed on first trimester, normal term and PE placentas. NNMT expression was also evaluated in HTR-8/SVneo and BeWo cell lines under hypoxic, oxidative stress (by H2O2) and inflammatory (by TNF-α) conditions. Results: NNMT was expressed in cytotrophoblast and syncytiotrophoblast of first, third and PE placentas. Endothelial vessels were positive for NNMT expression in first and third trimester but mainly negative in PE placentas. NNMT expression did not change from first to third trimester but significantly decreased in PE placentas compared to control placentas. NNMT was expressed in the cytoplasm of both HTR-8/SVneo and BeWo cell lines, and its expression was not altered by syncytialization. Hypoxia decreased NNMT expression in BeWo but not HTR-8/SVneo cells while oxidative stress did not alter NNMT expression in both cell lines. TNF-α treatment significantly decreased NNMT expression in both cell lines. Conclusions: Low NNMT expression found in PE placentas may represent a response to the hypoxia and inflammation featuring this disorder. Therefore, the enzyme could contribute to the normal human placental development, by defending trophoblast cells form PE-induced damages.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/348093

Role of paraoxonase-2 enzyme in human osteosarcoma: contribution to cell proliferation, migration and chemosensitivity
4th Workshop of the SIB group “Tumor Biochemistry” ““Biochemical Dynamics in Tumor Microenvironment: new insights and implications”, Catania, September 16-17th, 2024
Autore/i: Pompei, V; Gerini, E; Salvolini, E; Rubini, C; Goteri, G; Emanuelli, M; Sartini, D.
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/336063

Inhibitors of nicotinamide N-methyltransferase as tools for cancer treatment: effect on cell proliferation, apoptosis, oxidative stress and chemosensitivity.
Inhibitors of nicotinamide N-methyltransferase as tools for cancer treatment: effect on cell proliferation, apoptosis, oxidative stress and chemosensitivity.
Autore/i: Serritelli, En; Pompei, V; Van Haren, Mj; Martin, Ni; Sartini, D; Emanuelli, M.
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/336062

Involvement of nicotinamide N-methyltransferase enzyme in radioresistance of head and neck squamous cell carcinoma cell
BIOCHIMICA CLINICA
Autore/i: Sartini, D; Pompei, V; Petrone, V; Serritelli, En; Chirico, R; Minutolo, A; Balestrieri, E; Skvortsova, I; Matteucci, C; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/336912

Paraoxonase-2 shRNA-mediated gene silencing suppresses proliferation and migration, while promotes chemosensitivity in clear cell renal cell carcinoma cell lines
JOURNAL OF CELLULAR BIOCHEMISTRY
Autore/i: Schiavoni, Valentina; Emanuelli, Monica; Campagna, Roberto; Cecati, Monia; Sartini, Davide; Milanese, Giulio; Galosi, Andrea Benedetto; Pozzi, Valentina; Salvolini, Eleonora
Classificazione: 1 Contributo su Rivista
Abstract: Clear cell renal cell carcinoma (ccRCC) represents the most common subtype of renal tumor. Despite recent advances in identifying novel target molecules, the prognosis of patients with ccRCC continues to be poor, mainly due to the lack of sensitivity to chemo- and radiotherapy and because of one-third of renal cell carcinoma patients displays metastatic disease at diagnosis. Thus, identifying new molecules for early detection and for developing effective targeted therapies is mandatory. In this work, we focused on paraoxonase-2 (PON2), an intracellular membrane-bound enzyme ubiquitously expressed in human tissues, whose upregulation has been reported in a variety of malignancies, thus suggesting its possible role in cancer cell survival and proliferation. To investigate PON2 involvement in tumor cell metabolism, human ccRCC cell lines were transfected with plasmid vectors coding short harpin RNAs targeting PON2 transcript and the impact of PON2 silencing on cell viability, migration, and response to chemotherapeutic treatment was then explored. Our results showed that PON2 downregulation was able to trigger a decrease in proliferation and migration of ccRCC cells, as well as an enhancement of cell sensitivity to chemotherapy. Thus, taken together, data reported in this study suggest that the enzyme may represent an interesting therapeutic target for ccRCC.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/329592

Contribution of the Paraoxonase-2 Enzyme to Cancer Cell Metabolism and Phenotypes
BIOMOLECULES
Autore/i: Campagna, R; Serritelli, En; Salvolini, E; Schiavoni, V; Cecati, M; Sartini, D; Pozzi, V; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Paraoxonase-2 (PON2) is a ubiquitously expressed intracellular protein that is localized in the perinuclear region, the endoplasmic reticulum (ER), and mitochondria, and is also associated with the plasma membrane. PON2 functions as an antioxidant enzyme by reducing the levels of reactive oxygen species (ROS) in the mitochondria and ER through different mechanisms, thus having an anti-apoptotic effect and preventing the formation of atherosclerotic lesions. While the antiatherogenic role played by this enzyme has been extensively explored within endothelial cells in association with vascular disorders, in the last decade, great efforts have been made to clarify its potential involvement in both blood and solid tumors, where PON2 was reported to be overexpressed. This review aims to deeply and carefully examine the contribution of this enzyme to different aspects of tumor cells by promoting the initiation, progression, and spread of neoplasms.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/327434

Knockdown of nicotinamide N-methyltransferase suppresses proliferation, migration and chemoresistance of Merkel cell carcinoma cells in vitro
HUMAN CELL
Autore/i: Pozzi, V; Molinelli, E; Campagna, R; Serritelli, En; Cecati, M; De Simoni, E; Sartini, D; Goteri, G; Martin, Ni; van Haren, Mj; Salvolini, E; Simonetti, O; Offidani, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Merkel cell carcinoma (MCC) is an aggressive skin cancer, with a propensity for early metastasis. Therefore, early diagnosis and the identification of novel targets become fundamental. The enzyme nicotinamide N-methyltransferase (NNMT) catalyzes the reaction of N-methylation of nicotinamide and other analogous compounds. Although NNMT overexpression was reported in many malignancies, the significance of its dysregulation in cancer cell phenotype was partly clarified. Several works demonstrated that NNMT promotes cancer cell proliferation, migration, and chemoresistance. In this study, we investigated the possible involvement of this enzyme in MCC. Preliminary immunohistochemical analyses were performed to evaluate NNMT expression in MCC tissue specimens. To explore the enzyme function in tumor cell metabolism, MCC cell lines have been transfected with plasmids encoding for short hairpin RNAs (shRNAs) targeting NNMT mRNA. Preliminary immunohistochemical analyses showed elevated NNMT expression in MCC tissue specimens. The effect of enzyme downregulation on cell proliferation, migration, and chemosensitivity was then evaluated through MTT, trypan blue, and wound healing assays. Data obtained clearly demonstrated that NNMT knockdown is associated with a decrease of cell proliferation, viability, and migration, as well as with enhanced sensitivity to treatment with chemotherapeutic drugs. Taken together, these results suggest that NNMT could represent an interesting MCC biomarker and a promising target for targeted anti-cancer therapy.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/327436

Involvement of paraoxonase-2 enzyme in human osteosarcoma cell proliferation, migration and chemosensitivity
FEBS OPENBIO
Autore/i: Gerini, E; Pompei, V; Salvolini, E; Rubini, C; Goteri, G; Emanuelli, M; Sartini, D.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/332613

FTIRM analyses as a tool to explore cisplatin sensitivity of oral squamous cell carcinoma cell lines after PON2 knockdown
FEBS OPENBIO
Autore/i: Campagna, R; Belloni, A; Notarstefano, V; Pozzi, V; Orilisi, G; Togni, L; Mascitti, M; Sartini, D; Giorgini, E; Santarelli, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/332612

Targeting nicotinamide N-methyltransferase decreased aggressiveness of osteosarcoma cells
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Autore/i: Serritelli, En; Sartini, D; Campagna, R; Pozzi, V; Martin, Ni; van Haren, Mj; Salvolini, E; Cecati, M; Rubini, C; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Background: Osteosarcoma (OS) is a primary bone malignancy that mostly affects young people, characterized by high metastatic potential, and a marked chemoresistance that is responsible for disease relapse in most patients. Therefore, it is necessary to identify novel molecules to setup targeted strategies to improve the clinical outcome. The enzyme nicotinamide Nmethyltransferase (NNMT) catalyses the N-methylation of nicotinamide and other analogs, playing a crucial role in the biotransformation of drugs and xenobiotics. NNMT overexpression was reported in a wide variety of cancers, and several studies demonstrated that is able to promote cell proliferation, migration and resistance to chemotherapy. The aim of this study was to explore the potential involvement of NNMT in OS. Methods: Immunohistochemical analyses have been performed to evaluate NNMT expression in selected OS and healthy bone tissue samples. Subsequently, OS cell lines have been transfected with vectors targeting NNMT mRNA (shRNAs) and the impact of this downregulation on migration, cell proliferation, and response to chemotherapeutic treatment was also analysed by wound healing, MTT, SRB and Trypan blue assays, respectively. Results: Results showed that OS samples display a significantly higher NNMT expression compared with healthy tissue. Preliminary results suggest that NNMT silencing in OS cell lines is associated to a decrease of cell proliferation and migration, as well as to enhanced sensitivity to chemotherapy. Data obtained showed that NNMT may represent an interesting marker for OS detection and a promising target for effective anti-cancer therapy.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/327435

Exploring the role of paraoxonase-2 in human clear cell renal cell carcinoma: in vitro effect of shRNA-mediated gene silencing on cell proliferation and chemosensitivity
62° Congresso della Società Italiana di Biochimica e Biologia Molecolare (SIB), Firenze, 7-9 Settembre, 2023
Autore/i: Campagna, R; Schiavoni, V; Pozzi, V; Sartini, D; Milanese, G; Galosi, Ab; Emanuelli, M; Salvolini, E
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/324074

Involvment of the enzyme nicotinamide N-methyltransferase in proliferation, invasive capacity and chemosensitivity of human osteosarcoma.
34a Riunione Nazionale “A. Castellani” dei Dottorandi di Ricerca in Discipline Biochimiche, 5-9 Giugno 2023, Brallo di Pregola (PV).
Autore/i: Serritelli, En; Pozzi, V; Campagna, R; Sartini, D; Salvolini, E; Rubini, C; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/318951

Enhanced expression of nicotinamide N-methyltransferase in human osteosarcoma: potential role in tumor growth and chemoresistance
62° Congresso della Società Italiana di Biochimica e Biologia Molecolare (SIB), Firenze, 7-9 Settembre, 2023.
Autore/i: Serritelli, En; Pozzi, V; Campagna, R; Sartini, D; Salvolini, E; Rubini, C; Goteri, G; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/324073

Nicotinamide N-methyltransferase: a key enzyme of pyridine metabolism and a target for human osteosarcoma treatment
“Deciphering and Reshaping Nucleic Acids” 1st Workshop of the SIB group “Nucleic Acids”, October 5th and 6th, 2023, Aula Circolare, University of Calabria, Rende (CS).
Autore/i: Campagna, R; Serritelli, E. N.; Pozzi, V; Sartini, D; Salvolini, E; Rubini, C; Goteri, G; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/324072

Nicotinamide N-methyltransferase, a promising marker for human Merkel cell carcinoma
Understanding cancer metabolism: exploring tumor heterogeneity to advance cancer therapy. 3rd BDT Workshop, Sezione Biochimica dei Tumori, Società Italina di Biochimica e Biologia Molecolare (SIB), Catanzaro, 29-30 Giugno, 2023.
Autore/i: Pozzi, V; Molinelli, E; Campagna, R; Serritelli, En; Cecati, M; Sartini, D; Goteri, G; Salvolini, E; Simonetti, O; Offidani, A; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/318212

Enzymes Dysregulation in Cancer: From Diagnosis to Therapeutical Approaches
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Autore/i: Pozzi, V; Campagna, R; Sartini, D; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/324071

Paraoxonase-2 expression in oral squamous cell carcinoma
HUMAN CELL
Autore/i: Campagna, R; Pozzi, V; Salvucci, A; Togni, L; Mascitti, M; Sartini, D; Salvolini, E; Santarelli, A; Lo Muzio, L; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/313648

Immunohistochemical expression of nicotinamide N-methyltransferase in lymph node metastases from cutaneous malignant melanoma
HUMAN CELL
Autore/i: Sartini, Davide; Molinelli, Elisa; Pozzi, Valentina; Campagna, Roberto; Salvolini, Eleonora; Rubini, Corrado; Goteri, Gaia; Simonetti, Oriana; Campanati, Anna; Offidani, Annamaria; Emanuelli, Monica
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/306463

The Effect and the Potential Use of Magnetic–Dam Barrier in Guided Bone Regeneration: A Laboratory Study
APPLIED SCIENCES
Autore/i: Memè, L; Bambini, F; Gallusi, G; Sartini, D; Pozzi, V; Emanuelli, M; Strappa, Em; Mummolo, S
Classificazione: 1 Contributo su Rivista
Abstract: Guided bone regeneration (GBR) has been shown to be an optimal technique to accelerate the bone regeneration process thanks to the action of membrane barriers that promote tissue healing through the process of osteogenesis, inducing the repopulation with osteoprogenitor cells that prevent the invasion of non-osteogenic tissue. However, current membranes, such as expanded polytetrafluoroethylene or rubber dam, have some disadvantages that could potentially reduce the effectiveness of GBR. Recently, some scaffolds with magnetic properties have been tested to promote rapid osteogenesis. The aim of this laboratory study was to evaluate the intensity of the magnetic field generated by a custom-made rubber dam magnetised with neodymium-iron-boron (Nd2F14B) (three layers of latex filled with Nd2F14B powder on the inner surface) and to understand the effects of such a membrane on cell viability. A magnetic field of 750 G, 400 G, and 900 G was generated on the surface and on the long and wide sides of 3 and 2 cm in contact with the rubber dam. At a distance of 1 mm from the magnetic dam, a magnetic field of 300 G, 150 G, and 400 G was measured on the surface and on the long and wide sides of the rubber dam, respectively. After 72 h, the MG-63 osteoblast-like line showed a slight decrease in cell proliferation (85 ± 10) compared with the unmodified dam (95 ± 6) and the cell control population. According to our findings, this magnetic cofferdam is able to generate a static magnetic field and significantly affect cell proliferation in contrast to other nonabsorbable membranes. Further laboratory studies and subsequent clinical trials are needed to evaluate the significant improvements that can be achieved by using this type of magnetic rubber dam in GBR.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/313649

Role Played by Paraoxonase-2 Enzyme in Cell Viability, Proliferation and Sensitivity to Chemotherapy of Oral Squamous Cell Carcinoma Cell Lines
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Autore/i: Campagna, R; Belloni, A; Pozzi, V; Salvucci, A; Notarstefano, V; Togni, L; Mascitti, M; Sartini, D; Giorgini, E; Salvolini, E; Santarelli, A; Lo Muzio, L; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Oral squamous cell carcinoma represents the most aggressive and frequent form of head and neck cancer. Due to drug resistance, the 5-year survival rate of patients with advanced disease is less than 50%. In order to identify molecular targets for effective oral cancer treatment, we focused on paraoxonase-2 enzyme. Indeed, based on data previously obtained from preliminary immunohistochemistry and Western blot analyses performed on tissue specimens, the enzyme was found to be upregulated in tumor compared with normal oral mucosa. Therefore, paraoxonase-2 gene silencing was achieved in HSC-3 and HOC621 oral cancer cell lines, and the effect on cell proliferation, viability, apoptosis induction and sensitivity to cisplatin and 5-fluorouracil treatment was evaluated. Fourier Transform InfraRed Microspectroscopy analyzed alterations of cellular macromolecules upon treatment. Enzyme level and cell proliferation were also determined in cisplatin-resistant clones obtained from HOC621 cell line, as well as in parental cells. Reported data showed that paraoxonase-2 knockdown led to a reduction of cell proliferation and viability, as well as to an enhancement of sensitivity to cisplatin, together with the activation of apoptosis pathway. Spectroscopical data demonstrated that, under treatment with cisplatin, oxidative damage exerted on lipids and proteins was markedly more evident in cells down-regulating paraoxonase-2 compared to controls. Interestingly, enzyme expression, as well as cell proliferation were significantly higher in cisplatin-resistant compared with control HOC621 cells. Taken together these results seem to candidate the enzyme as a promising target for molecular treatment of this neoplasm.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/310087

Paraoxonase-2 is upregulated in triple negative breast cancer and contributes to tumor progression and chemoresistance
HUMAN CELL
Autore/i: Campagna, R; Pozzi, V; Giorgini, S; Morichetti, D; Goteri, G; Sartini, D; Serritelli, En; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Triple negative breast cancer (TNBC) displays a high aggressive behavior, tendency to relapse and early metastasize, leading to poor prognosis. The lack of estrogen receptors, and human epidermal growth factor receptor 2, prevents the use of endocrine or molecular targeted therapy, being therapeutical options for TNBC managements mostly limited to surgery, radiotherapy and mainly chemotherapy. While an important number of TNBCs initially responds to chemotherapy, they are prone to develop chemoresistance over the time. Thus, there is an urgent need to identify novel molecular targets to improve the outcome of chemotherapy in TNBC. In this work we focused on the enzyme paraoxonase-2 (PON2) which has been reported to be overexpressed in several tumors contributing to cancer aggressiveness and chemoresistance. Through a case– control study, we analyzed PON2 immunohistochemical expression in breast cancer molecular subtypes Luminal A, Luminal B, Luminal B HER2+, HER2 + and TNBC. Subsequently, we evaluated the in vitro effect of PON2 downregulation on cell proliferation and response to chemotherapeutics. Our results showed that the PON2 expression levels were significantly upregulated in the infiltrating tumors related to the subtypes Luminal A, HER2+ and TNBC compared to the healthy tissue. Furthermore, PON2 downregulation led to a decrease in cell proliferation of breast cancer cells, and significantly enhanced the cytotoxicity of chemotherapeutics on the TNBC cells. Although further analyses are necessary to deeply understand the mechanisms by which the enzyme could participate to breast cancer tumorigenesis, our results seem to demonstrate that PON2 could represent a promising molecular target for TNBC treatment.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/313647

Recent Advances in the Management of Clear Cell Renal Cell Carcinoma: Novel Biomarkers and Targeted Therapies
CANCERS
Autore/i: Schiavoni, V; Campagna, R; Pozzi, V; Cecati, M; Milanese, G; Sartini, D; Salvolini, E; Galosi, Ab; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Renal cell carcinoma (RCC) belongs to a heterogenous cancer group arising from renal tubular epithelial cells. Among RCC subtypes, clear cell renal cell carcinoma (ccRCC) is the most common variant, characterized by high aggressiveness, invasiveness and metastatic potential, features that lead to poor prognosis and high mortality rate. In addition, diagnosis of kidney cancer is incidental in the majority of cases, and this results in a late diagnosis, when the stage of the disease is advanced and the tumor has already metastasized. Furthermore, ccRCC treatment is complicated by its strong resistance to chemo- and radiotherapy. Therefore, there is active ongoing research focused on identifying novel biomarkers which could be useful for assessing a better prognosis, as well as new molecules which could be used for targeted therapy. In this light, several novel targeted therapies have been shown to be effective in prolonging the overall survival of ccRCC patients. Thus, the aim of this review is to analyze the actual state-of-the-art on ccRCC diagnosis, prognosis and therapeutic options, while also reporting the recent advances in novel biomarker discoveries, which could be exploited for a better prognosis or for targeted therapy.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/318211

Nicotinamide N-methyltransferase, a promising marker for human osteosarcoma
BIOCHIMICA CLINICA
Autore/i: Pozzi, V; Serritelli, En; Campagna, R; Sartini, D; Salvolini, E; Rubini, C; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/307321

FTIRM: an analytical approach to test the effectiveness of cisplatin treatment on PON2 silenced otscc cells
XLVIII Congresso Nazionale di Chimica Inorganica, Pisa, 6-9 Settembre 2022
Autore/i: Belloni, A; Notarstefano, V; Campagna, R; Pozzi, V; Sartini, D; Giorgini, E; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/307241

Paraoxonase-2 (PON2) is upregulated in triple negative breast cancer and contributes to the tumor progression and chemoresistance
Congresso della Sezione Tosco-Umbro-Marchigiana (TUM) sella Società Italiana di Biochimica e Biologia Molecolare (SIB), 1 Dicembre 2022, Perugia
Autore/i: Campagna, R; Giorgini, S; Morichetti, D; Sartini, D; Pozzi, V; Goteri, G; Emanuelli, M.
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/310089

Paraoxonase-2: a novel molecular target to enhance chemosensitivity in melanoma and triple negative breast cancer cells
2nd DiSVA-MaSBiC Annual Symposium, 13-14 Ottobre2022, Ancona
Autore/i: Campagna, R; Bacchetti, T; Salvolini, E; Pozzi, V; Serritelli, E; Giorgini, S; Molinelli, E; Simonetti, O; Sartini, D; Campanati, A; Ferretti, G; Goteri, G; Offidani, A; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/307322

Role of nicotinamide N-methyltransferase in human osteosarcoma: in vitro effect of shRNA-mediated gene silencing on tumorigenicity
Congresso della Sezione Tosco-Umbro-Marchigiana (TUM) sella Società Italiana di Biochimica e Biologia Molecolare (SIB), 1 Dicembre 2022, Perugia
Autore/i: Serritelli, En; Pozzi, V; Campagna, R; Sartini, D; Salvolini, E; Rubini, C; Emanuelli, M.
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/310088

Role of paraoxonase-2 in triple-negative breast cancer: effect of shRNA-mediated gene silencing on cell proliferation and chemosensitivity
16° Congresso Nazionale della Federazione Italiana Scienze della Vita (FISV), Reggia di Portici (Napoli), 14-16 Settembre 2022
Autore/i: Campagna, R; Giorgini, S; Morichetti, D; Sartini, D; Pozzi, V; Goteri, G; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/307224

Effects of Fermented Wheat Germ Extract on Oral Cancer Cells: An In Vitro Study
NUTRITION AND CANCER
Autore/i: Zhurakivska, K; Risteli, M; Salo, T; Sartini, D; Salvucci, A; Troiano, G; Lo Muzio, L; Emanuelli, M.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/292072

Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms
BIOMOLECULES
Autore/i: Pozzi, V; Campagna, R; Sartini, D; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Gastrointestinal (GI) neoplasms include esophageal, gastric, colorectal, hepatic, and pancreatic cancers. They are characterized by asymptomatic behavior, being responsible for diagnostic delay. Substantial refractoriness to chemo- and radiotherapy, exhibited by late-stage tumors, contribute to determine poor patient outcome. Therefore, it is of outmost importance to identify new molecular targets for the development of effective therapeutic strategies. In this study, we focused on the enzyme nicotinamide N-methyltransferase (NNMT), which catalyzes the N-methylation reaction of nicotinamide and whose overexpression has been reported in numerous neoplasms, including GI cancers. The aim of this review was to report data illustrating NNMT involvement in these tumors, highlighting its contribution to tumor cell phenotype. Cited works clearly demonstrate the interesting potential use of enzyme level determination for both diagnostic and prognostic purposes. NNMT was also found to positively affect cell viability, proliferation, migration, and invasiveness, contributing to sustain in vitro and in vivo tumor growth and metastatic spread. Moreover, enzyme upregulation featuring tumor cells was significantly associated with enhancement of resistance to treatment with chemotherapeutic drugs. Taken together, these results strongly suggest the possibility to target NNMT for setup of molecular-based strategies to effectively treat GI cancers.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/307221

C. spinosa L. subsp. rupestris Phytochemical Profile and Effect on Oxidative Stress in Normal and Cancer Cells
MOLECULES
Autore/i: Bacchetti, T; Campagna, R; Sartini, D; Cecati, M; Morresi, C; Bellachioma, L; Martinelli, E; Rocchetti, G; Lucini, L; Ferretti, G; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Spices, widely used to improve the sensory characteristics of food, contain several bioactive compounds as well, including polyphenols, carotenoids, and glucosynolates. Acting through multiple pathways, these bioactive molecules affect a wide variety of cellular processes involved in molecular mechanisms important in the onset and progress of human diseases. Capparis spinosa L. is an aromatic plant characteristic of the Mediterranean diet. Previous studies have reported that different parts (aerial parts, roots, and seeds) of C. spinosa exert various pharmacological activities. Flower buds of C. spinosa contain several bioactive compounds, including polyphenols and glucosinolates. Two different subspecies of C. spinosa L., namely, C. spinosa L. subsp. spinosa, and C. spinosa L. subsp. rupestris, have been reported. Few studies have been carried out in C. spinosa L. subsp. rupestris. The aim of our study was to investigate the phytochemical profile of floral buds of the less investigated species C. spinosa subsp. rupestris. Moreover, we investigated the effect of the extract from buds of C. spinosa subsp. rupestris (CSE) on cell proliferation, intracellular ROS levels, and expression of the antioxidant and anti-apoptotic enzyme paraoxonase-2 (PON2) in normal and cancer cells. T24 cells and Caco-2 cells were selected as models of advanced-stage human bladder cancer and human colorectal adenocarcinoma, respectively. The immortalized human urothelial cell line (UROtsa) and human dermal fibroblast (HuDe) were chosen as normal cell models. Through an untargeted metabolomic approach based on ultra-high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS), our results demonstrate that C. spinosa subsp. rupestris flower buds contain polyphenols and glucosinolates able to exert a higher cytotoxic effect and higher intracellular reactive oxygen species (ROS) production in cancer cells compared to normal cells. Moreover, upregulation of the expression of the enzyme PON2 was observed in cancer cells. In conclusion, our data demonstrate that normal and cancer cells are differentially sensitive to CSE, which has different effects on PON2 gene expression as well. The overexpression of PON2 in T24 cells treated with CSE could represent a mechanism by which tumor cells protect themselves from the apoptotic process induced by glucosinolates and polyphenols.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/307222

Epithelial Biological Response to Machined Titanium vs. PVD Zirconium-Coated Titanium: An In Vitro Study
MATERIALS
Autore/i: Meme', Lucia; Sartini, Davide; Pozzi, Valentina; Emanuelli, Monica; Strappa, Enrico M; Bittarello, Paolo; Bambini, Fabrizio; Gallusi, Gianni
Classificazione: 1 Contributo su Rivista
Abstract: The aim of this study was to compare the epithelial biological response to machined titanium Ti-6Al-4V grade 5 and titanium Ti-6Al-4V grade 5 coated with zirconia (ZrN) by physical vapor deposition (PVD). Human keratinocytes were cultured in six-well plates. Machined titanium TiAl4V4 grade 5 (T1) and ZrN-coated titanium TiAl4V4 grade 5 (T2) discs were placed in two different wells. The remaining two wells served as control (C). Scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) were performed to compare the T1 and T2 surfaces. Subsequent analyses were performed to explore the effect of T1 and T2 contact with human keratinocyte HUKE cell lines. Cell viability was evaluated using a trypan blue exclusion test and MTT assay. Cell lysates from C, T1, and T2 were Western blotted to evaluate E-cadherin and Integrin-alpha 6 beta 4 expression. SEM revealed that T2 was smoother and more homogeneous than T1. EDS showed homogeneous and uniform distribution of ZrN coating on T2. Cell viability analyses did not show significant differences between T1 and T2. Furthermore, E-cadherin and Integrin-alpha 6 beta 4 expressions of the epithelial cells cultured in T1 and T2 were similar. Therefore, titanium Ti-6Al-4V grade 5 surfaces coated with ZrN by PVD seem to be similar substrates to the uncoated surfaces for keratinocyte adhesion and proliferation.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/308643

The Double-Edged Sword of Oxidative Stress in Skin Damage and Melanoma: From Physiopathology to Therapeutical Approaches
ANTIOXIDANTS
Autore/i: Emanuelli, M; Sartini, D; Molinelli, E; Campagna, R; Pozzi, V; Salvolini, E; Simonetti, O; Campanati, A; Offidani, A
Classificazione: 1 Contributo su Rivista
Abstract: The skin is constantly exposed to exogenous and endogenous sources of reactive oxygen species (ROS). An adequate balance between ROS levels and antioxidant defenses is necessary for the optimal cell and tissue functions, especially for the skin, since it must face additional ROS sources that do not affect other tissues, including UV radiation. Melanocytes are more exposed to oxidative stress than other cells, also due to the melanin production process, which itself contributes to generating ROS. There is an increasing amount of evidence that oxidative stress may play a role in many skin diseases, including melanoma, being the primary cause or being a cofactor that aggravates the primary condition. Indeed, oxidative stress is emerging as another major force involved in all the phases of melanoma development, not only in the arising of the malignancy but also in the progression toward the metastatic phenotype. Furthermore, oxidative stress seems to play a role also in chemoresistance and thus has become a target for therapy. In this review, we discuss the existing knowledge on oxidative stress in the skin, examining sources and defenses, giving particular consideration to melanocytes. Therefore, we focus on the significance of oxidative stress in melanoma, thus analyzing the possibility to exploit the induction of oxidative stress as a therapeutic strategy to improve the effectiveness of therapeutic management of melanoma.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/298762

PON2 silencing to evaluate the effectiveness of Cisplatin treatment in OSCC cells by FTIRM analyses
Merck Young Symposium 2021, Rimini (IT), 22-24 November, 2021.
Autore/i: Belloni, A; Notarstefano, A; Salvucci, A; Campagna, R; Spinelli, G; Sartini, D; Giorgini, E; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/301279

Immunohistochemical analysis of paraoxonase-2 in actinic keratosis and squamous cell carcinoma
61° Congresso Nazionale della Società Italiana di Biochimica e Biologia Molecolare (SIB), Virtual Edition, 23-24 Settembre 2021
Autore/i: Campagna, R; Sartini, D; Lucarini, G; Salvolini, E; Molinelli, E; Brisigotti, V; Campanati, A; Bacchetti, T; Ferretti, G; Offidani, A; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/291905

Beyond Nicotinamide Metabolism: Potential Role of Nicotinamide N‐Methyltransferase as a Biomarker in Skin Cancers
CANCERS
Autore/i: Campagna, R; Pozzi, V; Sartini, D; Salvolini, E; Brisigotti, V; Molinelli, E; Campanati, A; Offidani, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: kin cancers (SC) collectively represent the most common type of malignancy in white populations. SC includes two main forms: malignant melanoma and non-melanoma skin cancer (NMSC). NMSC includes different subtypes, namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma (MCC), and keratoacanthoma (KA), together with the two pre-neoplastic conditions Bowen disease (BD) and actinic keratosis (AK). Both malignant melanoma and NMSC are showing an increasing incidence rate worldwide, thus representing an important challenge for health care systems, also because, with some exceptions, SC are generally characterized by an aggressive behavior and are often diagnosed late. Thus, identifying new biomarkers suitable for diagnosis, as well as for prognosis and targeted therapy is mandatory. Nicotinamide N-methyltransferase (NNMT) is an enzyme that is emerging as a crucial player in the progression of several malignancies, while its substrate, nicotinamide, is known to exert chemopreventive effects. Since there is increasing evidence regarding the involvement of this enzyme in the malignant behavior of SC, the current review aims to summarize the state of the art as concerns NNMT role in SC and to support future studies focused on exploring the diagnostic and prognostic potential of NNMT in skin malignancies and its suitability for targeted therapy.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/295329

Saliva proteomics as fluid signature of inflammatory and immune mediated skin diseases
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Autore/i: Campanati, A; Martina, E; Diotallevi, F; Radi, G; Marani, A; Sartini, D; Emanuelli, M; Kontochristopoulos, G; Rigopoulos, D; Gregoriou, S; Offidani, A
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/291522

Esterase-Sensitive Prodrugs of a Potent Bisubstrate Inhibitor of Nicotinamide N-Methyltransferase (NNMT) Display Cellular Activity
BIOMOLECULES
Autore/i: Van Haren, Mj; Gao, Y; Buijs, N; Campagna, R; Sartini, D; Emanuelli, M; Mateuszuk, L; Kij, A; Chlopicki, S; Escudé Martinez de Castilla, P; Schiffelers, R; Martin, Ni
Classificazione: 1 Contributo su Rivista
Abstract: A recently discovered bisubstrate inhibitor of Nicotinamide N-methyltransferase (NNMT) was found to be highly potent in biochemical assays with a single digit nanomolar IC50 value but lacking in cellular activity. We, here, report a prodrug strategy designed to translate the observed potent biochemical inhibitory activity of this inhibitor into strong cellular activity. This prodrug strategy relies on the temporary protection of the amine and carboxylic acid moieties of the highly polar amino acid side chain present in the bisubstrate inhibitor. The modification of the carboxylic acid into a range of esters in the absence or presence of a trimethyl-lock (TML) amine protecting group yielded a range of candidate prodrugs. Based on the stability in an aqueous buffer, and the confirmed esterase-dependent conversion to the parent compound, the isopropyl ester was selected as the preferred acid prodrug. The isopropyl ester and isopropyl ester-TML prodrugs exhibit improved cell permeability, which also translates to significantly enhanced cellular activity as established using assays designed to measure the enzymatic activity of NNMT in live cells.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/292073

Differential immunohistochemical expression of paraoxonase-2 in actinic keratosis and squamous cell carcinoma
HUMAN CELL
Autore/i: Sartini, D; Campagna, R; Lucarini, G; Pompei, V; Salvolini, E; Mattioli-Belmonte, M; Molinelli, E; Brisigotti, V; Campanati, A; Bacchetti, T; Ferretti, G; Offidani, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/291523

Treatment‐related dysgeusia in oral and oropharyngeal cancer: A comprehensive review
NUTRIENTS
Autore/i: Togni, L.; Mascitti, M.; Vignigni, A.; Alia, S.; Sartini, D.; Barlattani, A.; Emanuelli, M.; Santarelli, A.
Classificazione: 1 Contributo su Rivista
Abstract: Oral cancer is the most common tumor of the head and neck region. Its management is based on surgical and systemic therapies. Taste disorders represent the most common side effect of these treatments; indeed, dysgeusia is noted by 70% of oral cancer patients. Despite survival remaining the primary endpoint of cancer patients, taste impairments can cause psychological distress. This comprehensive review describes the last decade’s knowledge from the literature regarding taste alterations in patients with oral and oropharyngeal squamous cell carcinoma. A total of 26 articles in English, including prospective, cross‐sectional, and case–control studies, and clinical trials were evaluated. Literature analysis shows that anti‐cancer treatments can destroy taste cells, decrease and alter their receptors, and interrupt nerve transmission. Furthermore, the tumour itself can destroy the oral mucosal lining, which encloses the taste buds. Dysgeusia typically occurs in 3– 4 weeks of treatments, and usually taste sensation is recovered within 3–12 months. However, some patients exhibit incomplete or no recovery, even several years later. Thus, dysgeusia can become a chronic issue and negatively influence patients’ quality of life, worsening their dysphagia and their nutritional status. Physicians should be focused on preventing oncological treatment‐related symptoms, offering the most suitable personalized support during therapy.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/293485

Expression of Paraoxonase-2 in Different Stages of Cutaneous T Cell Lymphoma: Is It a Potential Biomarker for Aggressiveness?
BLOOD
Autore/i: Morsia, E; Rupoli, S; Molinelli, E; Sartini, D; Offidani, A; Emanuelli, M; Salvolini, E; Olivieri, A; Goteri, G
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/295149

Nicotinamide N-methyltransferase gene silencing enhances chemosensitivity of melanoma cell lines
PIGMENT CELL & MELANOMA RESEARCH
Autore/i: Campagna, R; Salvolini, E; Pompei, V; Pozzi, V; Salvucci, A; Molinelli, E; Brisigotti, V; Sartini, D; Campanati, A; Offidani, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Melanoma accounts for less than 5% of all cutaneous neoplasms but is responsible for the greater part of skin cancer-related deaths. Therefore, the identification of molecules that could serve as the therapeutic target is urgent. This study focused on the enzyme nicotinamide N-methyltransferase (NNMT). The effect of NNMT knockdown on cell proliferation and migration of A375 melanoma cells was evaluated by MTT and wound healing assays, respectively. Viability of A375 cells downregulating NNMT was also explored under treatment with dacarbazine, a chemotherapeutic drug approved for advanced melanoma treatment. The impact of enzyme knockdown on cell proliferation and chemosensitivity was also investigated in WM-115 melanoma cells. Results obtained demonstrated that NNMT silencing led to a significant reduction of cell proliferation and migration of A375 cells. Moreover, enzyme downregulation was associated with an increase of melanoma cells sensitivity to treatment with dacarbazine. Analogous effects induced by enzyme knockdown on cell proliferation and chemosensitivity were also found in the WM-115 cell line. Our data seem to demonstrate that NNMT could represent a promising molecular target for the effective treatment of this form of skin cancer.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/290822

Macrocyclic peptides as allosteric inhibitors of nicotinamide N-methyltransferase (NNMT)
RSC CHEMICAL BIOLOGY
Autore/i: Van Haren, Mj; Zhang, Y; Thijssen, V; Buijs, N; Gao, Y; Mateuszuk, L; Fedak, Fa; Kij, A; Campagna, R; Sartini, D; Emanuelli, M; Chlopicki, S; Jongkees, Sak; Martin, Ni
Classificazione: 1 Contributo su Rivista
Abstract: Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide to form 1-methylnicotinamide (MNA) using S-adenosyl-l-methionine (SAM) as the methyl donor. The complexity of the role of NNMT in healthy and disease states is slowly being elucidated and provides an indication that NNMT may be an interesting therapeutic target for a variety of diseases including cancer, diabetes, and obesity. Most inhibitors of NNMT described to date are structurally related to one or both of its substrates. In the search for structurally diverse NNMT inhibitors, an mRNA display screening technique was used to identify macrocyclic peptides which bind to NNMT. Several of the cyclic peptides identified in this manner show potent inhibition of NNMT with IC50 values as low as 229 nM. The peptides were also found to downregulate MNA production in cellular assays. Interestingly, substrate competition experiments reveal that these cyclic peptide inhibitors are noncompetitive with either SAM or NA indicating they may be the first allosteric inhibitors reported for NNMT.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/291903

Nicotinamide N-Methyltransferase in Head and Neck Tumors: A Comprehensive Review
BIOMOLECULES
Autore/i: Togni, L; Mascitti, M; Sartini, D; Campagna, R; Pozzi, V; Salvolini, E; Offidani, A; Santarelli, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: The head and neck tumors (HNT) are a heterogeneous group of diseases ranging from benign to malignant lesions, with distinctive molecular and clinical behaviors. Several studies have highlighted the presence of an altered metabolic phenotype in HNT, such as the upregulation of nicotinamide N-methyltransferase (NNMT). However, its biological effects have not been completely disclosed and the role of NNMT in cancer cell metabolism remains unclear. Therefore, this comprehensive review aims to evaluate the available literature regarding the biological, diagnostic, and prognostic role of NNMT in HNT. NNMT was shown to be significantly overexpressed in all of the evaluated HNT types. Moreover, its upregulation has been correlated with cancer cell migration and adverse clinical outcomes, such as high-pathological stage, lymph node metastasis, and locoregional recurrences. However, in oral squamous cell carcinoma (OSCC) these associations are still debated, and several studies have failed to demonstrate the prognostic significance of NNMT. The shRNA-mediated gene silencing efficiently suppressed the NNMT gene expression and exhibited a clear inhibitory effect on cell proliferation, promoting the expression of apoptosis-related proteins and modulating the cell cycle. NNMT could represent a new molecular biomarker and a new target of molecular-based therapy, although further studies on larger patient cohorts are needed to explore its biological role in HNT.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/295330

The Utility of Nicotinamide N-Methyltransferase as a Potential Biomarker to Predict the Oncological Outcomes for Urological Cancers: An Update
BIOMOLECULES
Autore/i: Campagna, R; Pozzi, V; Spinelli, G; Sartini, D; Milanese, G; Galosi, Ab; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation reaction of nicoti-namide, using S-adenosyl-L-methionine as the methyl donor. Enzyme overexpression has been described in many non-neoplastic diseases, as well as in a wide range of solid malignancies. This review aims to report and discuss evidence available in scientific literature, dealing with NNMT expression and the potential involvement in main urologic neoplasms, namely, renal, bladder and prostate cancers. Data illustrated in the cited studies clearly demonstrated NNMT upregulation (pathological vs. normal tissue) in association with these aforementioned tumors. In addition to this, enzyme levels were also found to correlate with key prognostic parameters and patient survival. Interestingly, NNMT overexpression also emerged in peripheral body fluids, such as blood and urine, thus leading to the candidate enzyme having promising biomarkers for the early and non-invasive detection of these cancers. Examined results undoubtedly showed NNMT as having the capacity to promote cell proliferation, migration and invasiveness, as well as its potential participation in fundamental events highlighting cancer progression, metastasis and resistance to chemo-and radiotherapy. In the light of this evidence, it is reasonable to attribute to NNMT a promising role as a potential biomarker for the diagnosis and prognosis of urologic neoplasms, as well as a molecular target for effective anti-cancer treatment. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/291902

Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics
JOURNAL OF MEDICINAL CHEMISTRY
Autore/i: Gao, Y; van Haren, Mj; Buijs, N; Innocenti, P; Zhang, Y; Sartini, D; Campagna, R; Emanuelli, M; Parsons, Rb; Jespers, W; Gutiérrez-de-Terán, H; van Westen, Gjp; Martin, Ni
Classificazione: 1 Contributo su Rivista
Abstract: Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-L-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/291901

Nicotinamide N-methyltransferase in endothelium protects against oxidant stress-induced endothelial injury
BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH
Autore/i: Campagna, R; Mateuszuk, Ł; Wojnar-Lason, K; Kaczara, P; Tworzydło, A; Kij, A; Bujok, R; Mlynarski, J; Wang, Y; Sartini, D; Emanuelli, M; Chlopicki, S
Classificazione: 1 Contributo su Rivista
Abstract: Nicotinamide N-methyltransferase (NNMT, EC 2.1.1.1.) plays an important role in the growth of many different tumours and is also involved in various non-neoplastic disorders. However, the presence and role of NNMT in the endothelium has yet to be specifically explored. Here, we characterized the functional activity of NNMT in the endothelium and tested whether NNMT regulates endothelial cell viability. NNMT in endothelial cells (HAEC, HMEC-1 and EA.hy926) was inhibited using two approaches: pharmacological inhibition of the enzyme by NNMT inhibitors (5-amino-1-methylquinoline – 5MQ and 6-methoxynicotinamide – JBSF-88) or by shRNAmediated silencing. Functional inhibition of NNMT was confirmed by LC/MS/MS-based analysis of impaired MNA production. The effects of NNMT inhibition on cellular viability were analyzed in both the absence and presence of menadione. Our results revealed that all studied endothelial lines express relatively high levels of functionally active NNMT compared with cancer cells (MDA-MB-231). Although the aldehyde oxidase 1 enzyme was also expressed in the endothelium, the further metabolites of N1-methylnicotinamide (N1-methyl-2-pyridone-5-carboxamide and N1-methyl-4-pyridone-3-carboxamide) generated by this enzyme were not detected, suggesting that endothelial NNMT-derived MNA was not subsequently metabolized in the endothelium by aldehyde oxidase 1. Menadione induced a concentration-dependent decrease in endothelial viability as evidenced by a decrease in cell number that was associated with the upregulation of NNMT and SIRT1 expression in the nucleus in viable cells. The suppression of the NNMT activity either by NNMT inhibitors or shRNA-based silencing significantly decreased the endothelial cell viability in response to menadione. Furthermore, NNMT inhibition resulted in nuclear SIRT1 expression downregulation and upregulation of the phosphorylated form of SIRT1 on Ser47. In conclusion, our results suggest that the endothelial nuclear NNMT/SIRT1 pathway exerts a cytoprotective role that safeguards endothelial cell viability under oxidant stress insult.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/290823

Paraoxonase-2: A potential biomarker for skin cancer aggressiveness
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Autore/i: Bacchetti, T; Salvolini, E; Pompei, V; Campagna, R; Molinelli, E; Brisigotti, V; Togni, L; Lucarini, G; Sartini, D; Campanati, A; Mattioli-Belmonte, M; Rubini, C; Ferretti, G; Offidani, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Background: Cutaneous neoplasms include melanoma and non-melanoma skin cancers (NMSCs). Among NMSCs, basal cell carcinoma (BCC) represents the most common lesion. On the contrary, although accounting for less than 5% of all skin cancers, melanoma is responsible for most of cutaneous malignancy-related deaths. Paraoxonase-2 (PON2) is an intracellular enzyme exerting a protective role against production of reactive oxygen species within mitochondrial respiratory chain. Recently, a growing attention has been focused on exploring the role of PON2 in cancer. The aim of this study was to investigate the diagnostic and prognostic role of PON2 in skin neoplasms. Materials and methods: 36 cases of BCC, distinguished between nodular and infiltrative lesions, as well as 29 melanoma samples were analysed by immunohistochemistry to evaluate PON2 protein expression. Subsequent statistical analyses were carried out to explore the existence of correlations between intratumour enzyme levels and clinicopathological features. Results: Results obtained showed PON2 overexpression in BCCs compared with controls. In particular, distinguishing between less and more aggressive tumour forms, we found no significant differences in enzyme levels between nodular BCCs and controls. Conversely, PON2 expression was significantly higher in infiltrative BCCs compared with controls. Moreover, the enzyme was strongly upregulated in melanoma samples with respect to controls. Interestingly, PON2 levels were positively correlated with Breslow thickness, Clark level, regression, mitoses, lymph node metastases, primary tumour (pT) parameter and pathological stage. Conclusions: Reported findings seem to suggest that PON2 expression levels could be positively related with tumour aggressiveness of both BCC and melanoma.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/285972

Effects of fermented wheat germ extract on the oral squamous cell carcinoma. An in vitro study
VIII International Symposium Advances in oral Cancer – Online, 24-25 Settembre 2020
Autore/i: Zhurakivska, K; Troiano, G; Risteli, M; Salo, T; Sartini, D; Salvucci, A; Lo Muzio, L; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/284957

Differential expression of nicotinamide N-methyltransferase in primary and recurrent ameloblastomas and odontogenic keratocysts
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Autore/i: Mascitti, M; Sartini, D; Togni, L; Pozzi, V; Rubini, C; Santarelli, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: Background: Odontogenic tumours are a group of rare heterogeneous diseases that range from hamartomatous tissue proliferations to benign and malignant neoplasms. Recurrences can occur after 10 years, so long-term clinical and radiological follow-up is required. The study of the molecular mechanisms involved in the development of these lesions is necessary to identify new prognostic markers. In this study, we evaluate the possible role of nicotinamide N-methyltransferase (NNMT) in ameloblastomas (AM) and odontogenic keratocysts (OKC). Materials and methods: A total of 105 surgical specimens of primary and recurrent lesions were obtained from 55 patients (25 AM, 30 OKC). In particular, 50 AMs (25 primary, 25 recurrences) and 55 OKCs (30 primary, 25 recurrences) were retrieved. We carried out immunohistochemical analyses to evaluate the cytoplasmic expression of NNMT, measuring the percentage of positive cells and the value of NNMT expression intensity. Results: NNMT expression was significantly higher in recurrent than primary AMs (P =.0430). This result was confirmed by staining intensity, showing more cases with moderate/intense staining in recurrent AMs (P =.0470). NNMT expression was significantly lower in recurrent than primary OKC (P =.0014). Staining intensity showed more cases with moderate/intense staining in primary OKCs (P =.0276). Conclusions: This report is the first to evaluate NNMT expression in odontogenic lesions and to demonstrate a differential expression in recurrent AMs and OKCs, suggesting that there is potential for use of NNMT as prognostic marker. © 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/278206

Differential expression of nicotinamide n-methyltransferase in cutaneous keratoacanthoma and squamous cell carcinoma: an immunohistochemical study
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Autore/i: Sartini, D; Pompei, V; Lucarini, G; Rubini, C; Molinelli, E; Brisigotti, V; Salvolini, E; Campanati, A; Offidani, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/272909

Cancer stem cell enrichment is associated with enhancement of nicotinamide N-methyltransferase expression
IUBMB LIFE
Autore/i: Pozzi, V; Salvolini, E; Lucarini, G; Salvucci, A; Campagna, R; Rubini, C; Sartini, D; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Abstract: The cancer stem cell theory states that a subset of tumor cells, termed cancer stem cells (CSCs), has the ability to self-renew and differentiate within the tumors. According to this theory, CSCs would be mainly responsible for tumor initiation, progression, resistance to therapy, recurrence, and metastasis. In this study, a culture system was setup to enrich CSCs from bladder cancer (T24), lung cancer (A549), colorectal cancer (CaCo-2), and osteosarcoma (MG63) cell lines, through sphere formation. Magnetic-activated cell sorting was also used to further increase CSC enrichment. Subsequently, molecular characterization of CSC-enriched cell populations and parental cells was carried out, by exploring the expression levels of stem markers and the enzyme nicotinamide N-methyltransferase (NNMT). Results obtained showed a significant upregulation of stem cell markers in CSC-enriched populations, obtained upon sphere formation, compared with parental counterparts. Moreover, NNMT expression levels were markedly increased in samples enriched with CSCs with respect to control cells. Considering the fundamental role played by CSCs in carcinogenesis, reported data strengthen the hypothesis that sustains a pivotal role of NNMT in cancer growth and metastasis. In addition, these findings could represent an important achievement for the development of new and effective anticancer therapies, based on CSC-associated targets.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/278211

Bladder Cancer Chemosensitivity is Affected by Paraoxonase-2 Expression
ANTIOXIDANTS
Autore/i: Fumarola, S; Cecati, M; Sartini, D; Ferretti, G; Milanese, G; Galosi, Ab; Pozzi, V; Campagna, R; Morresi, C; Emanuelli, M; Bacchetti, T.
Classificazione: 1 Contributo su Rivista
Abstract: The goal of the current study was to identify potential roles of paraoxonase-2 in bladder carcinogenesis. T24 bladder cancer cells were transfected with plasmids inducing paraoxonase-2 silencing or overexpression. Upon the selection of clones stably down-or upregulating paraoxonase-2, cell proliferation, migration, and the production of reactive oxygen species were evaluated, before and after treatment with cisplatin and gemcitabine, used alone or in combination. The activity levels of both caspase-3 and caspase-8 were also analyzed. shRNA-mediated gene silencing and the overexpression of paraoxonase-2 revealed that the enzyme was able to promote both the proliferation and migration of T24 cells. Moreover, the knockdown of paraoxonase-2 was significantly associated with a reduced cell viability of T24 cells treated with chemotherapeutic drugs and led to both an increase of reactive oxygen species production and caspase-3 and caspase-8 activation. Conversely, under treatment with anti-neoplastic compounds, a higher proliferative capacity was found in T24 cells overexpressing paraoxonase-2 compared with controls. In addition, upon enzyme upregulation, both the production of reactive oxygen species and activation of caspase-3 and caspase-8 were reduced. Although further analyses will be required to fully understand the involvement of paraoxonase-2 in bladder tumorigenesis and in mechanisms leading to the development of chemoresistance, the data reported in this study seem to demonstrate that the enzyme could exert a great impact on tumor progression and susceptibility to chemotherapy, thus suggesting paraoxonase-2 as a novel and interesting molecular target for effective bladder cancer treatment.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/278198

Paraoxonase-2 Silencing Enhances Sensitivity of A375 Melanoma Cells to Treatment with Cisplatin
ANTIOXIDANTS
Autore/i: Campagna, R; Bacchetti, T; Salvolini, E; Pozzi, V; Molinelli, E; Brisigotti, V; Sartini, D; Campanati, A; Ferretti, G; Offidani, A; Emanuelli, M.
Classificazione: 1 Contributo su Rivista
Abstract: Melanoma represents the most aggressive skin cancer, being responsible for the majority of deaths related with these neoplasms. Despite chemotherapy represents a frontline approach for management of the advanced stages of the disease, it displayed poor response rates and short-term efficacy due to melanoma cell resistance. Therefore, the discovery of molecules that can be used for effective targeted therapy of melanoma is crucial. In this study, we evaluated the impact of paraoxonase-2 (PON2) silencing on proliferation, viability, and resistance to treatment of the A375 melanoma cell line with chemotherapeutic drugs dacarbazine (DTIC) and cisplatin (CDDP). Due to the enzymes ability to counteract oxidative stress, we also evaluated the effect of enzyme knockdown on reactive oxygen species (ROS) production in cells treated with CDDP. The data reported clearly demonstrated that PON2 knockdown led to a significant reduction of cell proliferation and viability, as well as to an enhancement of A375 sensitivity to CDDP treatment. Moreover, enzyme downregulation was associated with an increase of ROS production in CDDP-treated cells. Although further analyses will be necessary to understand how PON2 could influence melanoma cell metabolism and phenotype, our results seem to suggest that the enzyme may serve as an interesting molecular target for effective melanoma treatment.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/285973

Immunohistochemical expression of nicotinamide N-methyltransferase in cutaneous basal and squamous cell carcinomas
60° Congresso Nazionale della Società Italiana di Biochimica e Biologia Molecolare (SIB), Lecce, 18-20 Settembre 2019
Autore/i: Pompei, V; Salvolini, E; Rubini, C; Lucarini, G; Molinelli, E; Brisigotti, V; Sartini, D; Campanati, A; Offidani, A; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/270404

Nicotinamide N-methyltransferase inhibition in endothelial cell lines: effect on the cellular phenotype, cell viability and bioenergetic balance
60° Congresso Nazionale della Società Italiana di Biochimica e Biologia Molecolare (SIB), Lecce, 18-20 Settembre 2019
Autore/i: Campagna, R; Mateuszuk, L; Kus, K; Sartini, D; Fumarola, S; Chlopicki, S; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/270403

New markers for odontogenic lesions: role of the Nicotinamide N-methyltransferase
FRONTIERS IN PHYSIOLOGY
Autore/i: Luconi, E; Mascitti, M; Giannatempo, G; Lo Muzio, L; Sartini, D; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/272912

Expression of nicotinamide N-methyltransferase in non-melanoma skin cancers
FEBS OPENBIO
Autore/i: Pompei, V; Sartini, D; Brisigotti, V; Rubini, C; Offidani, A; Emanuelli, M; Salvolini, E
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/268871

Role of paraoxonase-2 in bladder cancer: effect of shRNA-mediated gene silencing on cell proliferation and tumourigenicity
FEBS OPENBIO
Autore/i: Fumarola, S; Cecati, M; Morresi, C; Sartini, D; Ferretti, G; Bacchetti, T; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/268870

Nicotinamide N-methyltransferase in nonmelanoma skin cancers
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Autore/i: Pompei, V; Salvolini, E; Rubini, C; Lucarini, G; Molinelli, E; Brisigotti, V; Pozzi, V; Sartini, D; Campanati, A; Offidani, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/270386

Nitric oxide synthase and VEGF expression in full-term placentas of obese women
HISTOCHEMISTRY AND CELL BIOLOGY
Autore/i: Salvolini, E; Vignini, A; Sabbatinelli, J; Lucarini, G; Pompei, V; Sartini, D; Cester, Am; Ciavattini, A; Mazzanti, L; Emanuelli, Monica
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/270384

Analysis of nicotinamide N-methyltransferase in oral malignant melanoma and potential prognostic significance
MELANOMA RESEARCH
Autore/i: Mascitti, M; Santarelli, A; Sartini, D; Rubini, C; Colella, G; Salvolini, E; Ganzetti, G; Offidani, A; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/263183

Effect of High Glucose-Induced Oxidative Stress on Paraoxonase 2 Expression and Activity in Caco-2 Cells
CELLS
Autore/i: Morresi, C; Cianfruglia, L; Sartini, D; Cecati, M; Fumarola, S; Emanuelli, M; Armeni, T; Ferretti, G; Bacchetti, T
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/272911

Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT) with Enhanced Activity
JOURNAL OF MEDICINAL CHEMISTRY
Autore/i: Gao, Y; van Haren, Mj; Moret, Ee; Rood, Jjm; Sartini, D; Salvucci, Alessia; Emanuelli, M; Craveur, P; Babault, N; Jin, J; Martin, Ni
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/268868

Overexpression of nicotinamide N-methyltransferase in HSC-2 OSCC cell line: effect on apoptosis and cell proliferation
CLINICAL ORAL INVESTIGATIONS
Autore/i: Seta, R; Mascitti, M; Campagna, R; Sartini, D; Fumarola, S; Santarelli, A; Giuliani, M; Cecati, M; Muzio, Ll; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/259054

Nicotinamide N-methyltransferase inhibition in endothelium: effect on the cellular phenotype, viability and bio-energetics
44th FEBS Congress, Krakow, 6-11 Luglio 2019
Autore/i: Campagna, R; Mateuszuk, L; Kus, K; Sartini, D; Fumarola, S; Emanuelli, M; Chlopicki, S
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/268869

Expression of nicotinamide N-methyltransferase in oral malignant melanoma
Atti del 15° Congresso Nazionale della Federazione Italiana Scienze della Vita (FISV), Roma, 18-21 Settembre 2018
Autore/i: Mascitti, M; Santarelli, A; Rubini, C; Salvolini, E; Pompei, Veronica; Sartini, D; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/259339

Glycoxidative Stress and Paraoxonase-2 in Intestinal Cells: Effect of Apple Polyphenols - 3rd European Summer School on Nutrigenomics
LIFESTYLE GENOMICS
Autore/i: Bacchetti, Tiziana; Morresi, Camilla; Sartini, Davide; Fumarola, Stefania; Emanuelli, Monica; Ferretti, Gianna
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/260472

NNMT: potential involvement in oral malignant melanoma
MINERVA STOMATOLOGICA
Autore/i: Togni, Lucrezia; Sartini, D; Troiano, G; Lo Muzio, L; Procaccini, M; Emanuelli, M; Santarelli, A
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/259267

Nicotinamide N-methyltransferase: potential involvement in cutaneous malignant melanoma
MELANOMA RESEARCH
Autore/i: Ganzetti, G; Sartini, D; Campanati, A; Rubini, C; Molinelli, E; Brisigotti, V; Cecati, M; Pozzi, V; Campagna, R; Offidani, A; Emanuelli, M.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/255050

The kinetic analysis of the N-methylation of 4-phenylpyridine by nicotinamide N-methyltransferase: Evidence for a novel mechanism of substrate inhibition
THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Autore/i: van Haren, Mj; Thomas, Mg; Sartini, D; Barlow, Dj; Ramsden, Db; Emanuelli, M; Klamt, F; Martin, Ni; Parsons, Rb
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/259048

Expression of extracellular matrix and adhesion proteins in pelvic organ prolapse
CELLULAR AND MOLECULAR BIOLOGY
Autore/i: Cecati, Monia; Corradetti, Alessandra; Sartini, Davide; Pozzi, Valentina; Giannubilo, Stefano R; Saccucci, Franca; Ciavattini, Andrea; Emanuelli, Monica
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/258552

Clinical performance and utility of a NNMT-based urine test for bladder cancer
THE INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS
Autore/i: Pozzi, Valentina; DI RUSCIO, Giulia; Sartini, Davide; Campagna, Roberto; Seta, Riccardo; Fulvi, Paola; Vici, A; Milanese, G; Brandoni, G; Galosi, Andrea Benedetto; Montironi, Rodolfo; Cecati, Monia; Emanuelli, Monica
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251978

Survivin-Based Treatment Strategies for Squamous Cell Carcinoma
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Autore/i: Santarelli, A; Mascitti, M; Lo Russo, L; Sartini, D; Troiano, G; Emanuelli, M; Lo Muzio, L
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/259050

Involvement of transforming growth factor beta 1 in the transcriptional regulation of nicotinamide N-methyltransferase in clear cell renal cell carcinoma
CELLULAR AND MOLECULAR BIOLOGY
Autore/i: Campagna, R; Cecati, M; Pozzi, V; Fumarola, S; Pompei, V; Milanese, G; Galosi, Ab; Sartini, D; Emanuelli, M
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/259055

Role of paraoxonase-2 in chemoresistance in T24 human bladder cancer cells
Atti del 15° Congresso Nazionale della Federazione Italiana Scienze della Vita (FISV), Roma, 18-21 Settembre 2018
Autore/i: Bacchetti, T; Morresi, C; Cecati, M; Fumarola, S; Sartini, D; Ferretti, G; Emanuelli, M
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/259340

Effect of nicotinamide N-methyltransferase gene silencing on endothelial bioenergetics.
17th Symposium on Purine and Pyrimidine Metabolism in Man, Gdansk, Poland, 20-24 September 2017
Autore/i: Campagna, R; Mateuszuk, L; Kaczara, P; Sartini, D; Emanuelli, M; Chlopicki, S
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/301252

Nicotinamide N-methyltransferase: a new potential biomarker for cutaneous malignant melanoma
Atti del 59° Congresso Nazionale della Società Italiana di Biochimica e Biologia Molecolare (SIB), Caserta, 20-22 Settembre 2017
Autore/i: Ganzetti, G; Sartini, D; Campanati, A; Molinelli, E; Brisigotti, V; Cecati, M; Pozzi, V; Campagna, R; Fumarola, S; Rubini, C; Offidani, A; Emanuelli, M.
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251981

Diagnostic and prognostic role of nicotinamide N-methyltransferase in cutaneous malignant melanoma
BIOCHIMICA CLINICA
Autore/i: Ganzetti, G; Sartini, D; Campanati, A; Rubini, C; Molinelli, Elisa; Brisigotti, Valerio; Fumarola, Stefania; Cecati, M; Pozzi, V; Campagna, Roberto; Offidani, A; Emanuelli, M.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251984

Nicotinamide N-methyltransferase gene silencing in endothelial cell lines: molecular and phenotypic characterization
Atti del 25th Krakow Conference on Endothelium, 20th-21st October 2017, Krakow
Autore/i: Campagna, R; Mateuszuk, L; Kaczara, P; Sartini, D; Cecati, M; Fumarola, S; Emanuelli, M; Chlopicki, STEFAN KAROL
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251985

Identification of paraoxonase-2 as potential biomarker for bladder cancer
ANTICANCER RESEARCH
Autore/i: Marsili, Chiara; Ferretti, Gianna; Sartini, Davide; Milanese, Giulio; Galosi, Andrea Benedetto; Emanuelli, Monica; Bacchetti, Tiziana
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/246590

Use of supercharged cover screw as static magnetic field generator for bone healing, 2nd part: in vivo enhancement of bone regeneration in rabbits
JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS
Autore/i: Bambini, F; Santarelli, A; Putignano, A; Procaccini, M; Orsini, G; Di Iorio, D; Memè, L; Sartini, D; Emanuelli, M; Lo Muzio, L.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251976

The TDH-GCN5L1-Fbxo15-KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells
NATURE CELL BIOLOGY
Autore/i: Donato, V; Bonora, M; Simoneschi, D; Sartini, Davide; Kudo, Y; Saraf, A; Florens, L; Washburn, Mp; Stadtfeld, M; Pinton, P; Pagano, M.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251128

Glycoxidative Stress and Paraoxonase-2 in Intestinal Cells: Effect of Apple Polyphenols
Atti del 59° Congresso Nazionale della Società Italiana di Biochimica e Biologia Molecolare (SIB), Caserta, 20-22 Settembre 2017
Autore/i: Bacchetti, T; Morresi, Camilla; Turco, I; Ferretti, G; Sartini, D; Fumarola, S; Emanuelli, M.
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251983

Exploring the role of paraoxonase-2 in bladder cancer: analyses performed on tissue samples, urines and cell cultures
ONCOTARGET
Autore/i: Bacchetti, Tiziana; Sartini, Davide; Pozzi, Valentina; Cacciamani, Tiziana; Ferretti, Gianna; Emanuelli, Monica
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/246589

Molecular analysis of endometrial inflammation in preterm birth
CELLULAR AND MOLECULAR BIOLOGY
Autore/i: Cecati, Monia; Sartini, Davide; Campagna, Roberto; Biagini, Alessandra; Ciavattini, Andrea; Emanuelli, Monica; Giannubilo, Stefano Raffaele
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/246588

Use of supercharged cover screw as static magnetic field generator for bone healing, 1st part: in vitro enhancement of osteoblast-like cell differentiation
JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS
Autore/i: Bambini, Fabrizio; Santarelli, Andrea; Putignano, Angelo; Procaccini, Maurizio; Orsini, Giovanna; Meme', Lucia; Sartini, Davide; Emanuelli, Monica; Lo Muzio, L.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/246090