Matteo GIULIETTI

Pubblicazioni

Matteo GIULIETTI

 

57 pubblicazioni classificate nel seguente modo:

Nr. doc. Classificazioni
50 1 Contributo su Rivista
2 2 Contributo in Volume
2 4 Contributo in Atti di Convegno (Proceeding)
2 5 Altro
1 8 Tesi di dottorato
Anno
Risorse
2024
Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics? †
CANCERS
Autore/i: Giannella, L.; Piva, F.; Delli Carpini, G.; Di Giuseppe, J.; Grelloni, C.; Giulietti, M.; Sopracordevole, F.; Giorda, G.; Del Fabro, A.; Clemente, N.; Gardella, B.; Bogani, G.; Brasile, O.; Martinello, R.; Caretto, M.; Ghelardi, A.; Albanesi, G.; Stevenazzi, G.; Venturini, P.; Papiccio, M.; Canni, M.; Barbero, M.; Fambrini, M.; Maggi, V.; Uccella, S.; Spinillo, A.; Raspagliesi, F.; Greco, P.; Simoncini, T.; Petraglia, F.; Ciavattini, A.
Classificazione: 1 Contributo su Rivista
Abstract: Background: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. Methods: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). Results: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. Conclusions: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/326331 Collegamento a IRIS

2023
Accurate Analysis of Lipid Building Blocks Using the Tool LipidOne
Lipidomics: Methods and Protocols
Autore/i: Pellegrino, Roberto Maria; Giulietti, Matteo; Alabed, Husam B R; Taddei, Anna Aurora; Buratta, Sandra; Urbanelli, Lorena; Piva, Francesco; Emiliani, Carla
Editore: Springer
Classificazione: 2 Contributo in Volume
Abstract: LC/MS-based analysis techniques combined with specialized lipid platforms allow the qualitative and quantitative determination of thousands of lipid molecules. Each individual molecule can be considered as an assembly of smaller parts, often called building blocks that are the result of a myriad of biochemical synthesis and transformation processes. LipidOne is a new lipidomic tool that automatically highlights all qualitative and quantitative changes in lipid building blocks both among all detected lipid classes and between experimental groups. Thanks to LipidOne, the discovered differences among lipid building blocks can be easily linked to the activity of specific enzymes.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/313708 Collegamento a IRIS

2023
Effects of extremely low-frequency magnetic fields on human MDA-MB-231 breast cancer cells: proteomic characterization
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Autore/i: Lazzarini, Raffaella; Eléxpuru-Zabaleta, Maria; Piva, Francesco; Giulietti, Matteo; Fulgenzi, Gianluca; Tartaglione, Maria Fiorella; Zingaretti, Laura; Tagliabracci, Adriano; Valentino, Matteo; Santarelli, Lory; Bracci, Massimo
Classificazione: 1 Contributo su Rivista
Abstract: : Extremely low-frequency electromagnetic fields (ELF-MF) can modify the cell viability and regulatory processes of some cell types, including breast cancer cells. Breast cancer is a multifactorial disease where a role for ELF-MF cannot be excluded. ELF-MF may influence the biological properties of breast cells through molecular mechanisms and signaling pathways that are still unclear. This study analyzed the changes in the cell viability, cellular morphology, oxidative stress response and alteration of proteomic profile in breast cancer cells (MDA-MB-231) exposed to ELF-MF (50 Hz, 1 mT for 4 h). Non-tumorigenic human breast cells (MCF-10A) were used as control cells. Exposed MDA-MB-231 breast cancer cells increased their viability and live cell number and showed a higher density and length of filopodia compared with the unexposed cells. In addition, ELF-MF induced an increase of the mitochondrial ROS levels and an alteration of mitochondrial morphology. Proteomic data analysis showed that ELF-MF altered the expression of 328 proteins in MDA-MB-231 cells and of 242 proteins in MCF-10A cells. Gene Ontology term enrichment analysis demonstrated that in both cell lines ELF-MF exposure up-regulated the genes enriched in "focal adhesion" and "mitochondrion". The ELF-MF exposure decreased the adhesive properties of MDA-MB-231 cells and increased the migration and invasion cell abilities. At the same time, proteomic analysis, confirmed by Real Time PCR, revealed that transcription factors associated with cellular reprogramming were upregulated in MDA-MB-231 cells and downregulated in MCF-10A cells after ELF-MF exposure. MDA-MB-231 breast cancer cells exposed to 1 mT 50 Hz ELF-MF showed modifications in proteomic profile together with changes in cell viability, cellular morphology, oxidative stress response, adhesion, migration and invasion cell abilities. The main signaling pathways involved were relative to focal adhesion, mitochondrion and cellular reprogramming.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/323173 Collegamento a IRIS

2023
Keratinocytes Exposed to Blue or Red Light: Proteomic Characterization Showed Cytoplasmic Thioredoxin Reductase 1 and Aldo-Keto Reductase Family 1 Member C3 Triggered Expression
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Autore/i: Lazzarini, Raffaella; Tartaglione, Maria Fiorella; Ciarapica, Veronica; Piva, Francesco; Giulietti, Matteo; Fulgenzi, Gianluca; Martelli, Margherita; Ledda, Caterina; Vitale, Ermanno; Malavolta, Marco; Santarelli, Lory; Bracci, Massimo
Classificazione: 1 Contributo su Rivista
Abstract: Several cell-signaling mechanisms are activated by visible light radiation in human keratinocytes, but the key regulatory proteins involved in this specific cellular response have not yet been identified. Human keratinocytes (HaCaT cells) were exposed to blue or red light at low or high irradiance for 3 days in cycles of 12 h of light and 12 h of dark. The cell viability, apoptotic rate and cell cycle progression were analyzed in all experimental conditions. The proteomic profile, oxidative stress and mitochondrial morphology were additionally evaluated in the HaCaT cells following exposure to high-irradiance blue or red light. Low-irradiance blue or red light exposure did not show an alteration in the cell viability, cell death or cell cycle progression. High-irradiance blue or red light reduced the cell viability, induced cell death and cell cycle G2/M arrest, increased the reactive oxygen species (ROS) and altered the mitochondrial density and morphology. The proteomic profile revealed a pivotal role of Cytoplasmic thioredoxin reductase 1 (TXNRD1) and Aldo-keto reductase family 1 member C3 (AKR1C3) in the response of the HaCaT cells to high-irradiance blue or red light exposure. Blue or red light exposure affected the viability of keratinocytes, activating a specific oxidative stress response and inducing mitochondrial dysfunction. Our results can help to address the targets for the therapeutic use of light and to develop adequate preventive strategies for skin damage. This in vitro study supports further in vivo investigations of the biological effects of light on human keratinocytes.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/327397 Collegamento a IRIS

2023
Three-dimensional nuclear architecture distinguishes thyroid cancer histotypes
INTERNATIONAL JOURNAL OF CANCER
Autore/i: Rangel-Pozzo, Aline; Dos Santos, Filipe F; Dettori, Tinuccia; Giulietti, Matteo; Frau, Daniela Virginia; Galante, Pedro A F; Vanni, Roberta; Pathak, Alok; Fischer, Gabor; Gartner, John; Caria, Paola; Mai, Sabine
Classificazione: 1 Contributo su Rivista
Abstract: Molecular markers can serve as diagnostic tools to support pathological analysis in thyroid neoplasms. However, because the same markers can be observed in some benign thyroid lesions, additional approaches are necessary to differentiate thyroid tumor subtypes, prevent overtreatment and tailor specific clinical management. This applies particularly to the recently described variant of thyroid cancer referred to as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This variant has an estimated prevalence of 4.4% to 9.1% of all papillary thyroid carcinomas worldwide. We studied 60 thyroid lesions: 20 classical papillary thyroid carcinoma (CPTC), 20 follicular variant of PTC (FVPTC) and 20 NIFTP. We examined morphological and molecular features to identify parameters that can differentiate NIFTP from the other PTC subtypes. When blindly investigating the nuclear architecture of thyroid neoplasms, we observed that NIFTP has significantly longer telomeres than CPTC and FVPTC. Super-resolved 3D-structured illumination microscopy demonstrated that NIFTP is heterogeneous and that its nuclei contain more densely packed DNA and smaller interchromatin spaces than CPTC and FVPTC, a pattern that resembles normal thyroid tissue. These data are consistent with the observed indolent biological behavior and favorable prognosis associated with NIFTP, which lacks BRAF(V600E) mutations. Of note, next-generation thyroid oncopanel sequencing was unable to distinguish the thyroid cancer histotypes in our study cohort. In summary, our data suggest that 3D nuclear architecture can be a powerful analytical tool to diagnose and guide clinical management of NIFTP.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/323791 Collegamento a IRIS

2023
Copy Number Variations in Pancreatic Cancer: From Biological Significance to Clinical Utility
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Autore/i: Oketch, Daisy J A; Giulietti, Matteo; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, characterized by high tumor heterogeneity and a poor prognosis. Inter- and intra-tumoral heterogeneity in PDAC is a major obstacle to effective PDAC treatment; therefore, it is highly desirable to explore the tumor heterogeneity and underlying mechanisms for the improvement of PDAC prognosis. Gene copy number variations (CNVs) are increasingly recognized as a common and heritable source of inter-individual variation in genomic sequence. In this review, we outline the origin, main characteristics, and pathological aspects of CNVs. We then describe the occurrence of CNVs in PDAC, including those that have been clearly shown to have a pathogenic role, and further highlight some key examples of their involvement in tumor development and progression. The ability to efficiently identify and analyze CNVs in tumor samples is important to support translational research and foster precision oncology, as copy number variants can be utilized to guide clinical decisions. We provide insights into understanding the CNV landscapes and the role of both somatic and germline CNVs in PDAC, which could lead to significant advances in diagnosis, prognosis, and treatment. Although there has been significant progress in this field, understanding the full contribution of CNVs to the genetic basis of PDAC will require further research, with more accurate CNV assays such as single-cell techniques and larger cohorts than have been performed to date.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/327396 Collegamento a IRIS

2022
Effects of the Exposure of Human Non-Tumour Cells to Sera of Pancreatic Cancer Patients
BIOMEDICINES
Autore/i: Sabanovic, Berina; Giulietti, Matteo; Cecati, Monia; Spolverato, Gaya; Benna, Clara; Pucciarelli, Salvatore; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Abstract: Pancreatic ductal adenocarcinoma (PDAC) has high metastatic potential. The "genometastasis" theory proposes that the blood of some cancer patients contains elements able to transform healthy cells by transferring oncogenes. Since findings on genometastasis in PDAC are still scarce, we sought supporting evidence by treating non-tumour HEK293T and hTERT-HPNE human cell lines with sera of PDAC patients. Here, we showed that HEK293T cells have undergone malignant transformation, increased the migration and invasion abilities, and acquired a partial chemoresistance, whereas hTERT-HPNE cells were almost refractory to transformation by patients' sera. Next-generation sequencing showed that transformed HEK293T cells gained and lost several genomic regions, harbouring genes involved in many cancer-associated processes. Our results support the genometastasis theory, but further studies are needed for the identification of the circulating transforming elements. Such elements could also be useful biomarkers in liquid biopsy assays.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/313707 Collegamento a IRIS

2022
Estrogen Related Receptor Alpha (ERRα) a Bridge between Metabolism and Adrenocortical Cancer Progression
CANCERS
Autore/i: Avena, P.; De Luca, A.; Chimento, A.; Nocito, M. C.; Sculco, S.; La Padula, D.; Zavaglia, L.; Giulietti, M.; Hantel, C.; Sirianni, R.; Casaburi, I.; Pezzi, V.
Classificazione: 1 Contributo su Rivista
Abstract: The aim of this study was to investigate the metabolic changes that occur in adrenocortical cancer (ACC) cells in response to the modulation of Estrogen Related Receptor (ERR)α expression and the impact on ACC progression. Proteomics analysis and metabolic profiling highlighted an important role for ERRα in the regulation of ACC metabolism. Stable ERRα overexpression in H295R cells promoted a better mitochondrial fitness and prompted toward a more aggressive phenotype characterized by higher Vimentin expression, enhanced cell migration and spheroids formation. By contrast, a decrease in ERRα protein levels, by molecular (short hairpin RNA) and pharmacological (inverse agonist XCT790) approaches modified the energetic status toward a low energy profile and reduced Vimentin expression and ability to form spheroids. XCT790 produced similar effects on two additional ACC cell lines, SW13 and mitotane-resistant MUC-1 cells. Our findings show that ERRα is able to modulate the metabolic profile of ACC cells, and its inhibition can strongly prevent the growth of mitotane-resistant ACC cells and the progression of ACC cell models to a highly migratory phenotype. Consequently, ERRα can be considered an important target for the design of new therapeutic strategies to fight ACC progression.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/306061 Collegamento a IRIS

2021
Expression and co-expression analyses of TMPRSS2, a key element in COVID-19
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
Autore/i: Piva, F.; Sabanovic, B.; Cecati, M.; Giulietti, M.
Classificazione: 1 Contributo su Rivista
Abstract: The ACE2 receptor is, so far, the best-known host factor for SARS-CoV-2 entry, but another essential element, the TMPRSS2 protease, has recently been identified. Here, we have analysed TMPRSS2 expression data in the lung correlating them with age, sex, diabetes, smoking habits, exposure to pollutant and other stimuli, in order to highlight which factors might alter TMPRSS2 expression, and thus impact the susceptibility to infection and COVID-19 prognosis. Moreover, we reported TMPRSS2 polymorphisms affecting its expression and suggested the ethnic groups more prone to COVID-19. Finally, we also highlighted a gender-specific co-expression between TMPRSS2 and other genes related to SARS-CoV-2 entry, maybe explaining the higher observed susceptibility of infection in men. Our results could be useful in designing potential prevention and treatment strategies regarding the COVID-19.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/286735 Collegamento a IRIS

2021
LipidOne: user-friendly lipidomic data analysis tool for a deeper interpretation in a systems biology scenario
BIOINFORMATICS
Autore/i: Pellegrino, Roberto Maria; Giulietti, Matteo; Alabed, Husam B R; Buratta, Sandra; Urbanelli, Lorena; Piva, Francesco; Emiliani, Carla
Classificazione: 1 Contributo su Rivista
Abstract: LC/MS-based analysis techniques combined with specialized lipid tool allow for the qualitative and quantitative determination of thousands of lipid molecules. Some recent bioinformatics tools have been developed to study changes in the lipid profile in case-control experiments and correlate these changes to different enzyme activity or gene expression. However, the existing tools have the limitation to treat only the assembled lipid molecules. In reality, each individual molecule can be considered as an assembly of smaller parts, often called building blocks. These are the result of a myriad of biochemical synthesis and transformation processes that, from a systems biology perspective, should not be ignored. Here, we present LipidOne, a new lipidomic tool which highlights all qualitative and quantitative changes in lipid building blocks both among all detected lipid classes and among experimental groups. Thanks to LipidOne, even differences in lipid building blocks can now be linked to the activity of specific classes of enzymes, transcripts and genes.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/296825 Collegamento a IRIS

2021
Effects of cxcl12 isoforms in a pancreatic pre-tumour cellular model: Microarray analysis
WORLD JOURNAL OF GASTROENTEROLOGY
Autore/i: Cecati, M.; Giulietti, M.; Righetti, A.; Sabanovic, B.; Piva, F.
Classificazione: 1 Contributo su Rivista
Abstract: BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death among cancers, it is characterized by poor prognosis and strong chemoresistance. In the PDAC microenvironment, stromal cells release different extracellular components, including CXCL12. The CXCL12 is a chemokine promoting the communication between tumour and stromal cells. Six different splicing isoforms of CXCL12 are known (α, β, γ, δ, ϵ, θ) but their role in PDAC has not yet been characterized. AIM To investigate the specific role of α, β, and γ CXCL12 isoforms in PDAC onset. METHODS We used hTERT-HPNE E6/E7/KRasG12D (Human Pancreatic Nestin- Expressing) cell line as a pancreatic pre-tumour model and exposed it to the α, β, and γ CXCL12 isoforms. The altered expression profiles were assessed by microarray analyses and confirmed by Real-Time polymerase chain reaction. The functional enrichment analyses have been performed by Enrichr tool to highlight Gene Ontology enriched terms. In addition, wound healing assays have been carried out to assess the phenotypic changes, in terms of migration ability, induced by the α, β, and γ CXCL12 isoforms. RESULTS Microarray analysis of hTERT-HPNE cells treated with the three different CXCL12 isoforms highlighted that the expression of only a few genes was altered. Moreover, the α and β isoforms showed an alteration in expression of different genes, whereas γ isoform affected the expression of genes also common with α and β isoforms. The β isoform altered the expression of genes mainly involved in cell cycle regulation. In addition, all isoforms affected the expression of genes associated to cell migration, adhesion and cytoskeleton. In vitro cell migration assay confirmed that CXCL12 enhanced the migration ability of hTERT-HPNE cells. Among the CXCL12 splicing isoforms, the γ isoform showed higher induction of migration than α and β isoforms. CONCLUSION Our data suggests an involvement and different roles of CXCL12 isoforms in PDAC onset. However, more investigations are needed to confirm these preliminary observations.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/290958 Collegamento a IRIS

2021
Artificial Neural Networks as a Way to Predict Future Kidney Cancer Incidence in the United States
CLINICAL GENITOURINARY CANCER
Autore/i: Santoni, M.; Piva, F.; Porta, C.; Bracarda, S.; Heng, D. Y.; Matrana, M. R.; Grande, E.; Mollica, V.; Aurilio, G.; Rizzo, M.; Giulietti, M.; Montironi, R.; Massari, F.
Classificazione: 1 Contributo su Rivista
Abstract: Introduction: The incidence of kidney cancer is increasing; it could be counteracted with new ways to predict and detect it. We aimed to implement an artificial neural network in order to predict new cases of renal-cell carcinoma (RCC) in the population using population rate, obesity, smoking incidence, uncontrolled hypertension, and life expectancy data in the United States. Patients and Methods: Statistics were collected on US population numbers, life expectancy, obesity, smoking, and hypertension. We used MATLAB R2018 (MathWorks) software to implement an artificial neural network. Data were repeatedly and randomly divided into training (70%) and validation (30%) subsets. Results: The number of new RCC cases will grow from 44,400 (2020) to 55,400 (2050), an increase of +24.7%. Our data show that preventing hypertension would have the greatest impact on reduction of the incidence, estimated at −775 and −575 cases per year in 2020 and in 2030, respectively. The prevention of obesity and smoking would have a more limited impact, estimated at −64 and −180 cases per year in 2020 and in 2030, respectively, for obesity, and −173 and −21 cases per year in 2020 and in 2030, respectively, for smoking. Conclusions: Our predictions underline the need for accurate studies on RCC-related risk factors to reduce the incidence.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/286733 Collegamento a IRIS

2021
Promising extracellular vesicle-based vaccines against viruses, including SARS-CoV-2
BIOLOGY
Autore/i: Sabanovic, B.; Piva, F.; Cecati, M.; Giulietti, M.
Classificazione: 1 Contributo su Rivista
Abstract: Extracellular vesicles (EVs) are secreted from almost all human cells and mediate intercellular communication by transferring heterogeneous molecules (i.e., DNA, RNAs, proteins, and lipids). In this way, EVs participate in various biological processes, including immune responses. Viruses can hijack EV biogenesis systems for their dissemination, while EVs from infected cells can transfer viral proteins to uninfected cells and to immune cells in order to mask the infection or to trigger a response. Several studies have highlighted the role of native or engineered EVs in the induction of B cell and CD8(+) T cell reactions against viral proteins, strongly suggesting these antigen-presenting EVs as a novel strategy for vaccine design, including the emerging COVID-19. EV-based vaccines overcome some limitations of conventional vaccines and introduce novel unique characteristics useful in vaccine design, including higher bio-safety and efficiency as antigen-presenting systems and as adjuvants. Here, we review the state-of-the-art for antiviral EV-based vaccines, including the ongoing projects of some biotech companies in the development of EV-based vaccines for SARS-CoV-2. Finally, we discuss the limits for further development of this promising class of therapeutic agents.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/290957 Collegamento a IRIS

2021
The Role of Artificial Intelligence in the Diagnosis and Prognosis of Renal Cell Tumors
DIAGNOSTICS
Autore/i: Giulietti, Matteo; Cecati, Monia; Sabanovic, Berina; Andrea, Scirè; Cimadamore, Alessia; Santoni, Matteo; Montironi, Rodolfo; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Abstract: The increasing availability of molecular data provided by next-generation sequencing (NGS) techniques is allowing improvement in the possibilities of diagnosis and prognosis in renal cancer. Reliable and accurate predictors based on selected gene panels are urgently needed for better stratification of renal cell carcinoma (RCC) patients in order to define a personalized treatment plan. Artificial intelligence (AI) algorithms are currently in development for this purpose. Here, we reviewed studies that developed predictors based on AI algorithms for diagnosis and prognosis in renal cancer and we compared them with non-AI-based predictors. Comparing study results, it emerges that the AI prediction performance is good and slightly better than non-AI-based ones. However, there have been only minor improvements in AI predictors in terms of accuracy and the area under the receiver operating curve (AUC) over the last decade and the number of genes used had little influence on these indices. Furthermore, we highlight that different studies having the same goal obtain similar performance despite the fact they use different discriminating genes. This is surprising because genes related to the diagnosis or prognosis are expected to be tumor-specific and independent of selection methods and algorithms. The performance of these predictors will be better with the improvement in the learning methods, as the number of cases increases and by using different types of input data (e.g., non-coding RNAs, proteomic and metabolic). This will allow for more precise identification, classification and staging of cancerous lesions which will be less affected by interpathologist variability.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/290955 Collegamento a IRIS

2020
Role of primary cilium in pancreatic ductal adenocarcinoma (Review)
INTERNATIONAL JOURNAL OF ONCOLOGY
Autore/i: Sabanovic, B.; Giulietti, M.; Piva, F.
Classificazione: 1 Contributo su Rivista
Abstract: The primary cilium is a non-motile cellular structure extending from the apical membrane of epithelial cells that is involved in several processes due to its ability to receive and elaborate different signals. Ciliogenesis and its obliteration are essential for proliferating cells, and several signalling pathways are responsible for their regulation. In fact, the primary cilium is a central hub for numerous signalling pathways implicated in a variety of biological processes, such as the Hedgehog, mammalian target of rapamycin and Wnt pathways. Loss of primary cilia has been recently correlated with different types of tumours, including pancreatic ductal adenocarcinoma (PDAC). K-Ras and HDAC2 were recently identified as possible ciliogenesis regulators in PDAC, likely acting through Aurora A kinase (AURKA) which, in turn, controls inositol polyphosphate-5-phosphatase E. However, the exact molecular mechanisms underlying this regulatory effect remain to be fully elucidated. In the present study, the regulation of the main genes involved in primary cilia assembly/resorption was reconstructed showing the links with the Hedgehog and phosphoinositide 3-kinase/AKT pathways. Finally, by analysing gene expression databases, the regulatory genes that have high probability to be associated with prognosis, histological grade and pathological stage in patients with PDAC have been highlighted. However, further experimental studies are required to reach definitive conclusions on the roles of these genes. Improving our understating of ciliogenesis and its regulators may help develop ciliotherapies using histone deacetylase and AURKA inhibitors, which may induce re-differentiation of tumour cells into normal cells by reducing tumour growth or inducing apoptosis of cancer cells.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/286737 Collegamento a IRIS

2020
Gaining new insights on the Hsp90 regulatory network
BIOINFORMATION
Autore/i: Piva, Francesco; Cecati, Monia; Giulietti, Matteo
Classificazione: 1 Contributo su Rivista
Abstract: The heat shock protein Hsp90 is a molecular chaperon that uses ATP and interacts with various co-chaperone proteins, acting as adapters, in order to carry out the maturation of its target proteins. In physiological conditions, the heat shock proteins (HSPs) favour post-translational modification, protein folding and sub-cellular transport of their "client" proteins. In stress conditions, many misfolded proteins accumulate exposing their hydrophobic residues and these are recognized by HSPs which prevent the aggregation and favour the correct folding. In case this is no longer possible, HSPs mediate elimination of such misfolded proteins, mainly by ubiquitin-proteasome system.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/277183 Collegamento a IRIS

2020
Role of miRNAs in prostate cancer: Do we really know everything?
UROLOGIC ONCOLOGY
Autore/i: Cochetti, G.; Rossi de Vermandois, J. A.; Maula, V.; Giulietti, M.; Cecati, M.; Del Zingaro, M.; Cagnani, R.; Suvieri, C.; Paladini, A.; Mearini, E.
Classificazione: 1 Contributo su Rivista
Abstract: Many different genetic alterations, as well as complex epigenetic interactions, are the basis of the genesis and progression of prostate cancer (CaP). This is the reason why until now the molecular pathways related to development of this cancer were only partly known, and even less those that determine aggressive or indolent tumour behaviour. MicroRNAs (miRNAs) represent a class of about 22 nucleotides long, small non-coding RNAs, which are involved in gene expression regulation at the post-transcriptional level. MiRNAs play a crucial role in regulating several biological functions and preserving homeostasis, as they carry out a wide modulatory activity on various molecular signalling pathways. MiRNA genes are placed in cancer-related genomic regions or in fragile sites, and they have been proven to be involved in the main steps of carcinogenesis as oncogenes or oncosuppressors in many types of cancer, including CaP. We performed a narrative review to describe the relationship between miRNAs and the crucial steps of development and progression of CaP. The aims of this study were to improve the knowledge regarding the mechanisms underlying miRNA expression and their target genes, and to contribute to understanding the relationship between miRNA expression profiles and CaP.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/277029 Collegamento a IRIS

2020
Predicting future cancer burden in the United States by artificial neural networks
FUTURE ONCOLOGY
Autore/i: Piva, Francesco; Tartari, Francesca; Giulietti, Matteo; Aiello, Marco Maria; Cheng, Liang; Lopez-Beltran, Antonio; Mazzucchelli, Roberta; Cimadamore, Alessia; Cerqueti, Roy; Battelli, Nicola; Montironi, Rodolfo; Santoni, Matteo
Classificazione: 1 Contributo su Rivista
Abstract: Aims: To capture the complex relationships between risk factors and cancer incidences in the US and predict future cancer burden. Materials & methods: Two artificial neural network (ANN) algorithms were adopted: a multilayer feed-forward network (MLFFNN) and a nonlinear autoregressive network with eXogenous inputs (NARX). Data on the incidence of the four most common tumors (breast, colorectal, lung and prostate) from 1992 to 2016 (available from National Cancer Institute online datasets) were used for training and validation, and data until 2050 were predicted. Results: The rapid decreasing trend of prostate cancer incidence started in 2010 will continue until 2018-2019; it will then slow down and reach a plateau after 2050, with several differences among ethnicities. The incidence of breast cancer will reach a plateau in 2030, whereas colorectal cancer incidence will reach a minimum value of 35 per 100,000 in 2030. As for lung cancer, the incidence will decrease from 50 per 100,000 (2017) to 31 per 100,000 in 2030 and 26 per 100,000 in 2050. Conclusion: This up-to-date prediction of cancer burden in the US could be a crucial resource for planning and evaluation of cancer-control programs.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/286256 Collegamento a IRIS

2020
Exploring the Spectrum of Kidney Ciliopathies
DIAGNOSTICS
Autore/i: Santoni, Matteo; Piva, Francesco; Cimadamore, Alessia; Giulietti, Matteo; Battelli, Nicola; Montironi, Rodolfo; Cosmai, Laura; Porta, Camillo
Classificazione: 1 Contributo su Rivista
Abstract: Ciliopathies are a group of multi-organ diseases caused by the disruption of the primary cilium. This event leads to a variety of kidney disorders, including nephronophthisis, renal cystic dysplasia, and renal cell carcinoma (RCC). Primary cilium contributes to the regulation of the cell cycle and protein homeostasis, that is, the balance between protein synthesis and degradation by acting on the ubiquitin-proteasome system, autophagy, and mTOR signaling. Many proteins are involved in renal ciliopathies. In particular, fibrocystin (PKHD1) is involved in autosomal recessive polycystic kidney disease (ARPKD), while polycystin-1 (PKD1) and polycystin-2 (PKD2) are implicated in autosomal dominant polycystic kidney disease (ADPKD). Moreover, primary cilia are associated with essential signaling pathways, such as Hedgehog, Wnt, and Platelet-Derived Growth Factor (PDGF). In this review, we focused on the ciliopathies associated with kidney diseases, exploring genes and signaling pathways associated with primary cilium and the potential role of cilia as therapeutic targets in renal disorders.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/286254 Collegamento a IRIS

2020
Sequential or Concomitant Inhibition of Cyclin-Dependent Kinase 4/6 Before mTOR Pathway in Hormone-Positive HER2 Negative Breast Cancer: Biological Insights and Clinical Implications
FRONTIERS IN GENETICS
Autore/i: Occhipinti, G.; Romagnoli, E.; Santoni, M.; Cimadamore, A.; Sorgentoni, G.; Cecati, M.; Giulietti, M.; Battelli, N.; Maccioni, A.; Storti, N.; Cheng, L.; Principato, G.; Montironi, R.; Piva, F.
Classificazione: 1 Contributo su Rivista
Abstract: About 75% of all breast cancers are hormone receptor-positive (HR+). However, the efficacy of endocrine therapy is limited due to the high rate of either pre-existing or acquired resistance. In this work we reconstructed the pathways around estrogen receptor (ER), mTOR, and cyclin D in order to compare the effects of CDK4/6 and PI3K/AKT/mTOR inhibitors. A positive feedback loop links mTOR and ER that support each other. We subsequently considered whether a combined or sequential inhibition of CDK4/6 and PI3K/AKT/mTOR could ensure better results. Studies indicate that inhibition of CDK4/6 activates mTOR as an escape mechanism to ensure cell proliferation. In literature, the little evidence dealing with this topic suggests that pre-treatment with mTOR pathway inhibitors could prevent or delay the onset of CDK4/6 inhibitor resistance. Additional studies are needed in order to find biomarkers that can identify patients who will develop this resistance and in whom the sensitivity to CDK4/6 inhibitors can be restored.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/285502 Collegamento a IRIS

2020
MetaTropismDB: a database of organ-specific metastasis induced by human cancer cell lines in mouse models
DATABASE
Autore/i: Giulietti, M.; Bastianoni, M.; Cecati, M.; Ruzzo, A.; Bracci, M.; Malavolta, M.; Piacenza, F.; Giacconi, R.; Piva, F.
Classificazione: 1 Contributo su Rivista
Abstract: The organotropism is the propensity of metastatic cancer cells to colonize preferably certain distant organs, resulting in a non-random distribution of metastases. In order to shed light on this behaviour, several studies were performed by the injection of human cancer cell lines into immunocompromised mouse models. However, the information about these experiments is spread in the literature. For each xenograft experiment reported in the literature, we annotated both the experimental conditions and outcomes, including details on inoculated human cell lines, mouse models, injection methods, sites of metastasis, organs not colonized, rate of metastasis, latency time, overall survival and the involved genes. We created MetaTropismDB, a freely available database collecting hand-curated data useful to highlight the mechanisms of organ-specific metastasis. Currently, it stores the results of 513 experiments in which injections of 219 human cell lines have been carried out in mouse models. Notably, 296 genes involved in organotropic metastases have been collected. This specialized database allows the researchers to compare the current results about organotropism and plan future experiments in order to identify which tumour molecular signatures establish if and where the metastasis will develop. Database URL:  http://www.introni.it/Metastasis/metastasis.html.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/286734 Collegamento a IRIS

2019
Clinical impact of different exosomes’ protein expression in pancreatic ductal carcinoma patients treated with standard first line palliative chemotherapy
PLOS ONE
Autore/i: Giampieri, R.; Piva, F.; Occhipinti, G.; Bittoni, A.; Righetti, A.; Pagliaretta, S.; Murrone, A.; Bianchi, F.; Amantini, C.; Giulietti, M.; Ricci, G.; Principato, G.; Santoni, G.; Berardi, R.; Cascinu, S.
Classificazione: 1 Contributo su Rivista
Abstract: INTRODUCTION: Pancreatic ductal adenocarcinoma is associated to dismal prognosis despite the use of palliative chemotherapy, partly due to the lack of knowledge of biological processes underlying disease progression. Exosomes have been identified as biomarkers sources in different cancer types. Aim of the study was to analyse the contents of circulating exosomes in patients with pancreatic cancer who received palliative chemotherapy. PATIENTS AND METHODS: Patients were submitted to blood sample collection before chemotherapy (T0) and after 3 months (T3). We quantified by an ELISA-based technique specific proteins of cancer-derived exosomes (CD44,CD44v6,EpCAM,CD9,CD81,Tspan8,Integrin α6,Integrin β4,CD24,CXCR4). We correlated the baseline levels of these factors and changes between T3 and T0 and survival outcomes. Survival analyses were performed by Kaplan-Meier method. Correlation was assessed by log-rank test and level of statistical significance was set at 0.05. Multivariate analysis was performed by logistic regression analysis. RESULTS: Nineteen patients were enrolled. EpCAM T0 levels and increased EpCAM levels from T0 to T3 were those mostly associated with differences in survival. Patients having higher EpCAM had median progression free survival (PFS) of 3.18vs7.31 months (HR:2.82,95%CI:1.03-7.73,p = 0.01). Overall survival (OS) was shorter for patients having higher EpCAM (5.83vs16.45 months,HR:6.16,95%CI:1.93-19.58,p = 0.0001) and also response rates (RR) were worse (20%vs87%,p = 0.015). EpCAM increase during treatment was associated with better median PFS (2.88vs7.31 months,HR:0.24,95%CI:0.04-1.22,p = 0.003). OS was also better (8.75vs11.04 months, HR:0.77,95%CI:0.21-2.73,p = 0.66) and RR were 60%vs20% (p = 0.28). Among clinical factors that might determine changes on PFS and OS, only ECOG PS was associated to significantly worse PFS and OS (p = 0.0137and<0.001 respectively).Multivariate analysis confirmed EpCAM T0 levels and EpCAM T0/T3 changes as independent prognostic factors for PFS. CONCLUSIONS: Pancreatic cancer patients exosomes express EpCAM, whose levels change during treatment. This represents a useful prognostic factor and also suggests that future treatment modalities who target EpCAM should be tested in pancreatic cancer patients selected by exosome EpCAM expression.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/267095 Collegamento a IRIS

2019
CXCL12 and Its Isoforms: Different Roles in Pancreatic Cancer?
JOURNAL OF ONCOLOGY
Autore/i: Righetti, Alessandra; Giulietti, Matteo; Šabanović, Berina; Occhipinti, Giulia; Principato, Giovanni; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Abstract: CXCL12 is a chemokine that acts through CXCR4 and ACKR3 receptors and plays a physiological role in embryogenesis and haematopoiesis. It has an important role also in tumor development, since it is released by stromal cells of tumor microenvironment and alters the behavior of cancer cells. Many studies investigated the roles of CXCL12 in order to understand if it has an anti- or protumor role. In particular, it seems to promote tumor invasion, proliferation, angiogenesis, epithelial to mesenchymal transition (EMT), and metastasis in pancreatic cancer. Nevertheless, some evidence shows opposite functions; therefore research on CXCL12 is still ongoing. These discrepancies could be due to the presence of at least six CXCL12 splicing isoforms, each with different roles. Interestingly, three out of six variants have the highest levels of expression in the pancreas. Here, we report the current knowledge about the functions of this chemokine and then focus on pancreatic cancer. Moreover, we discuss the methods applied in recent studies in order to understand if they took into account the existence of the CXCL12 isoforms.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/268512 Collegamento a IRIS

2019
Different Cardiotoxicity of Palbociclib and Ribociclib in Breast Cancer: Gene Expression and Pharmacological Data Analyses, Biological Basis, and Therapeutic Implications
BIODRUGS
Autore/i: Santoni, M.; Occhipinti, G.; Romagnoli, E.; Miccini, F.; Scoccia, L.; Giulietti, M.; Principato, G.; Saladino, T.; Piva, F.; Battelli, N.
Classificazione: 1 Contributo su Rivista
Abstract: Breast cancer is the most frequent tumor in women. The recent advent of cyclin-dependent kinase (CDK) 4/6 inhibitors palbociclib and ribociclib has represented a major step forward for patients with hormone receptor-positive breast cancer. These two agents have showed similar efficacy in terms of breast cancer outcome but different cardiotoxic effects. In particular, ribociclib, but not palbociclib, has been associated with QT interval prolongation, and the mechanisms underlying this event are still unclear. In order to clarify such difference, we matched the candidate genes associated with QT interval prolongation with genes whose expression is altered following palbociclib or ribociclib treatment. We also investigated whether pharmacokinetic and pharmacodynamic characteristics, such as IC50 (hERG) [concentration of drug producing 50% inhibition (human ether-à-go-go related gene)] and maximum concentration (Cmax), could justify the different effects on QT interval prolongation. Our results show that ribociclib, but not palbociclib, could act by down-regulating the expression of KCNH2 (encoding for potassium channel hERG) and up-regulating SCN5A and SNTA1 (encoding for sodium channels Nav1.5 and syntrophin-α1, respectively), three genes associated with long QT syndrome. Consistent with the cardiotoxicity induced by ribociclib, its IC50 (hERG)/free concentration (Cmax free) ratio is closer to the safety threshold than that of palbociclib. In summary, we hypothesize that the different cardiotoxicity associated with ribociclib and palbociclib could be due to the alteration of potassium and sodium channels induced by ribociclib. A better comprehension of the mechanisms of cardiac channelopathies and drug-induced QT interval prolongation will be fundamental to avoid serious and potentially lethal adverse events and, as a consequence, optimize the management of breast cancer patients.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/277181 Collegamento a IRIS

2018
Emerging biomarkers in bladder cancer identified by network analysis of transcriptomic data
FRONTIERS IN ONCOLOGY
Autore/i: Giulietti, Matteo; Occhipinti, Giulia; Righetti, Alessandra; Bracci, Massimo; Conti, Alessandro; Ruzzo, Annamaria; Cerigioni, Elisabetta; Cacciamani, Tiziana; Principato, Giovanni; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/265218 Collegamento a IRIS

2018
To accelerate the Zika beat: Candidate design for RNA interference-based therapy
VIRUS RESEARCH
Autore/i: Giulietti, M.; Righetti, A.; Cianfruglia, L.; Sabanovic, Berina; Armeni, T.; Principato, G.; Piva, F.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/265220 Collegamento a IRIS

2018
LncRNA co-expression network analysis reveals novel biomarkers for pancreatic cancer
CARCINOGENESIS
Autore/i: Giulietti, Matteo; Righetti, Alessandra; Principato, Giovanni; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/265216 Collegamento a IRIS

2018
Exploring small extracellular vesicles for precision medicine in prostate cancer
FRONTIERS IN ONCOLOGY
Autore/i: Giulietti, Matteo; Santoni, Matteo; Cimadamore, Alessia; Carrozza, Francesco; Piva, Francesco; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Battelli, Nicola; Montironi, Rodolfo
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/265214 Collegamento a IRIS

2018
Risk of fatigue in cancer patients treated with anti programmed cell death-1/anti programmed cell death ligand-1 agents: A systematic review and meta-analysis
IMMUNOTHERAPY
Autore/i: Santoni, Matteo; Conti, Alessandro; Buti, Sebastiano; Bersanelli, Melissa; Foghini, Laura; Piva, Francesco; Giulietti, Matteo; Lusuardi, Lukas; Battelli, Nicola
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/265217 Collegamento a IRIS

2017
The Importance of Saliva for Biomolecule Sampling
Autore/i: Piva, F; Righetti, Alessandra; Giulietti, M; Principato, G
Luogo di pubblicazione: USA
Classificazione: 5 Altro
Abstract: The oral compartment is an interesting source of biomolecules that could support or even replace blood sampling. Although having the evident advantage of minimal invasiveness, saliva employment for biomarker recovery did not gain ground because it was believed that only few blood molecules could be recovered from saliva. Recent evidence shows that, not only most blood molecules can be found in saliva but also that in saliva there are molecules not present in blood. Moreover saliva contains molecules coming from distant sites such as exosomes. Here we discuss recent evidence that makes saliva promising for biomarker sampling.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/257850 Collegamento a IRIS

2017
Identification of candidate miRNA biomarkers for pancreatic ductal adenocarcinoma by weighted gene co-expression network analysis
CELLULAR ONCOLOGY
Autore/i: Giulietti, Matteo; Occhipinti, Giulia; Principato, Giovanni; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Abstract: PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal prognosis which is, among others, due to a lack of suitable biomarkers and therapeutic targets. Previously, basic gene expression analysis methods have been used for their identification, but recently new algorithms have been developed allowing more comprehensive data analyses. Among them, weighted gene co-expression network analysis (WGCNA) has already been applied to several cancer types with promising results. METHODS: We applied WGCNA to miRNA expression data from PDAC patients. Specifically, we processed microarray-based expression data of 2555 miRNAs in serum from 100 PDAC patients and 150 healthy subjects. We identified network modules of co-expressed miRNAs in the healthy subject dataset and verified their preservation in the PDAC dataset. In the non-preserved modules, we selected key miRNAs and carried out functional enrichment analyses of their experimentally known target genes. Finally, we tested their prognostic significance using overall survival analyses. RESULTS: Through WGCNA we identified several miRNAs that discriminate healthy subjects from PDAC patients and that, therefore, may play critical roles in PDAC development. At a functional level, we found that they regulate p53, FoxO and ErbB associated cellular signalling pathways, as well as cell cycle progression and various genes known to be involved in PDAC development. Some miRNAs were also found to serve as novel prognostic biomarkers, whereas others have previously already been proposed as such, thereby validating the WGCNA approach. In addition, we found that these novel data may explain at least some of our previous PDAC gene expression analysis results. CONCLUSIONS: We identified several miRNAs critical for PDAC development using WGCNA. These miRNAs may serve as biomarkers for PDAC diagnosis/prognosis and patient stratification, and as putative novel therapeutic targets.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251598 Collegamento a IRIS

2017
Oligometastases in Genitourinary Tumors: Recent Insights and Future Molecular Diagnostic Approach
EUROPEAN UROLOGY. SUPPLEMENTS
Autore/i: Conti, Alessandro; D'Elia, Carolina; Cheng, Monica; Santoni, Matteo; Piva, Francesco; Brunelli, Matteo; Lopez beltran, Antonio; Giulietti, Matteo; Scarpelli, Marina; Pycha, Armin; Galosi, Andrea Benedetto; Artibani, Walter; Cheng, Liang; Montironi, Rodolfo; Battelli, Nicola; Lusuardi, Lukas
Classificazione: 1 Contributo su Rivista
Abstract: Context: An oligometastatic state is an early event during tumor metastatic spread and is rarely reported in patients with genitourinary tumors. In this condition, the primary tumor has low capacity for distal dissemination because its aggressiveness has not yet reached a maximum. Objective: To review recent findings on the diagnosis and treatment of oligometastatic disease in patients with genitourinary tumors. Evidence acquisition: To identify relevant studies, we reviewed articles in PubMed from January 1966 to September 2017. The search was conducted by combining the words "oligometastasis" or "oligometastatic disease" with "bladder cancer", "genitourinary tumor", "prostate cancer", and "renal cancer". Evidence synthesis: In renal cell carcinoma (RCC), tumors from patients with multiple metastases showed a different gene signature compared to oligometastatic RCC. In addition, an oligometastatic state was an independent prognostic factor for overall survival (OS). Otherwise, the characteristics of oligometastases from bladder cancer remain unclear, as do the clinical and prognostic significance of metastasectomy in this setting. However, patients with oligometastatic prostate cancer have longer recurrence-free survival and OS and seem to benefit from local metastasis-directed therapies. Conclusions: Early detection of oligometastatic disease in patients with genitourinary tumors is fundamental in improving outcomes by identifying patients who would benefit from local approaches with potentially curative rather than palliative intent. Patients with oligometastases in genitourinary tumors show longer survival because of generally lower tumor aggressiveness and potential eligibility for local approaches. Emerging molecular diagnostic techniques will allow early diagnosis of the oligometastatic state and consequently improve patient outcomes.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251597 Collegamento a IRIS

2016
Weighted gene co-expression network analysis reveals key genes involved in pancreatic ductal adenocarcinoma development
CELLULAR ONCOLOGY
Autore/i: Giulietti, Matteo; Occhipinti, Giulia; Principato, Giovanni; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/239184 Collegamento a IRIS

2016
Epithelial to Mesenchymal Transition in Renal Cell Carcinoma: Implications for Cancer Therapy
MOLECULAR DIAGNOSIS & THERAPY
Autore/i: Piva, Francesco; Giulietti, Matteo; Santoni, Matteo; Occhipinti, Giulia; Scarpelli, Marina; Lopez Beltran, Antonio; Cheng, Liang; Principato, Giovanni; Montironi, Rodolfo
Classificazione: 1 Contributo su Rivista
Abstract: Epithelial-to-mesenchymal transition (EMT) is a developmentally vital reversible process by which fully differentiated cells lose their epithelial features and acquire a migratory mesenchymal phenotype. EMT contributes to the metastatic potential of tumors. The expression profile and other biological properties of EMT suggest potential targets for cancer therapy, including in renal-cell carcinoma (RCC). The preclinical and clinical results have substantiated the promises that dysregulated elements leading to EMT can be a potential target in RCC patients. In this study, we illustrated the pathogenic and prognostic role of EMT in RCC. In addition, we reconstructed, by literature analysis, the different pathways implicated in the EMT process, thus supporting the rational for future EMT-directed therapeutic approaches for RCC patients.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/234645 Collegamento a IRIS

2016
The choice of endogenous controls in exosomal microRNA assessments from biofluids
TUMOR BIOLOGY
Autore/i: Occhipinti, Giulia; Giulietti, Matteo; Principato, Giovanni; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/239182 Collegamento a IRIS

2015
Employment of Exosomes for Liquid Biopsies
TRANSLATIONAL BIOMEDICINE
Autore/i: Giulietti, Matteo; Occhipinti, Giulia; Righetti, Alessandra; Armeni, Tatiana; Principato, Giovanni; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/239185 Collegamento a IRIS

2015
A guideline for the annotation of UTR regulatory elements in the UTRsite collection
RNA Bioinformatics
Autore/i: Giulietti, Matteo; Grillo, Giorgio; Liuni, Sabino; Pesole, Graziano
Editore: Springer
Classificazione: 2 Contributo in Volume
Abstract: Gene expression regulatory elements are scattered in gene promoters and pre-mRNAs. In particular, RNA elements lying in untranslated regions (5' and 3'UTRs) are poorly studied because of their peculiar features (i.e., a combination of primary and secondary structure elements) which also pose remarkable computational challenges. Several years ago, we began collecting experimentally characterized UTR regulatory elements, developing the specialized database UTRsite. This paper describes the detailed guidelines to annotate cis-regulatory elements in 5' and 3' UnTranslated Regions (UTRs) by computational analyses, retracing all main steps used by UTRsite curators.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/272496 Collegamento a IRIS

2015
Lgr5 expression, cancer stem cells and pancreatic cancer: Results from biological and computational analyses
FUTURE ONCOLOGY
Autore/i: Andrikou, Kalliopi; Santoni, Matteo; Piva, Francesco; Bittoni, Alessandro; Lanese, Andrea; Pellei, Chiara; Conti, Alessandro; Loretelli, Cristian; Mandolesi, Alessandra; Giulietti, Matteo; Scarpelli, Marina; Principato, Giovanni; Falconi, Massimo; Cascinu, Stefano
Classificazione: 1 Contributo su Rivista
Abstract: AIMS: To determine the relationship between Lgr5 and other stemness markers and pathologic features in pancreatic ductal adenocarcinoma (PDAC) samples. MATERIALS & METHODS: In 69 samples, Lgr5 was analyzed by qRT-PCR together with a panel of 29 genes. Bioinformatic analysis was carried out to identify a possible pathway regulating Lgr5 expression in PDAC. RESULTS: Lgr5 expression was not associated with the expression of tested cancer stem cell markers. Moreover, it was not an independent predictor of survival neither at univariate analysis (p = 0.21) nor at multivariate analysis (p = 0.225). CONCLUSION: Based on the lack of correlation between Lgr5 and tested cancer stem cell markers, Lgr5 does not seem to be a potential stemness marker or prognostic factor in PDAC.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/228967 Collegamento a IRIS

2015
ExportAid: database of RNA elements regulating nuclear RNA export in mammals
BIOINFORMATICS
Autore/i: Giulietti, Matteo; Milantoni, SARA ARMIDA; Armeni, Tatiana; Principato, Giovanni; Piva, Francesco
Classificazione: 1 Contributo su Rivista
Abstract: MOTIVATION: Regulation of nuclear mRNA export or retention is carried out by RNA elements but the mechanism is not yet well understood. To understand the mRNA export process, it is important to collect all the involved RNA elements and their trans-acting factors. RESULTS: By hand-curated literature screening we collected, in ExportAid database, experimentally assessed data about RNA elements regulating nuclear export or retention of endogenous, heterologous or artificial RNAs in mammalian cells. This database could help to understand the RNA export language and to study the possible export efficiency alterations owing to mutations or polymorphisms. Currently, ExportAid stores 235 and 96 RNA elements, respectively, increasing and decreasing export efficiency, and 98 neutral assessed sequences. AVAILABILITY AND IMPLEMENTATION: Freely accessible without registration at http://www.introni.it/ExportAid/ExportAid.html. Database and web interface are implemented in Perl, MySQL, Apache and JavaScript with all major browsers supported.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/206323 Collegamento a IRIS

2015
Computational analysis of the mutations in BAP1, PBRM1 and SETD2 genes reveals the impaired molecular processes in Renal Cell Carcinoma
ONCOTARGET
Autore/i: Piva, Francesco; Giulietti, Matteo; Occhipinti, Giulia; Santoni, Matteo; Massari, Francesco; Sotte, Valeria; Iacovelli, Roberto; Burattini, Luciano; Santini, Daniele; Montironi, Rodolfo; Cascinu, Stefano; Principato, Giovanni
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/228954 Collegamento a IRIS

2015
BAP1, PBRM1 and SETD2 in clear-cell renal cell carcinoma: Molecular diagnostics and possible targets for personalized therapies
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
Autore/i: Piva, Francesco; Santoni, Matteo; Matrana, Marc R.; Satti, Suma; Giulietti, Matteo; Occhipinti, Giulia; Massari, Francesco; Cheng, Liang; Lopez Beltran, Antonio; Scarpelli, Marina; Principato, Giovanni; Cascinu, Stefano; Montironi, Rodolfo
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/228961 Collegamento a IRIS

2014
How much do we know about the coupling of G-proteins to serotonin receptors?
MOLECULAR BRAIN
Autore/i: Giulietti, Matteo; Vivenzio, Viviana; Piva, Francesco; Principato, Giovanni; Bellantuono, Cesario; Nardi, Bernardo
Classificazione: 1 Contributo su Rivista
Abstract: Serotonin receptors are G-protein-coupled receptors (GPCRs) involved in a variety of psychiatric disorders. G-proteins, heterotrimeric complexes that couple to multiple receptors, are activated when their receptor is bound by the appropriate ligand. Activation triggers a cascade of further signalling events that ultimately result in cell function changes. Each of the several known G-protein types can activate multiple pathways. Interestingly, since several G-proteins can couple to the same serotonin receptor type, receptor activation can result in induction of different pathways. To reach a better understanding of the role, interactions and expression of G-proteins a literature search was performed in order to list all the known heterotrimeric combinations and serotonin receptor complexes. Public databases were analysed to collect transcript and protein expression data relating to G-proteins in neural tissues. Only a very small number of heterotrimeric combinations and G-protein-receptor complexes out of the possible thousands suggested by expression data analysis have been examined experimentally. In addition this has mostly been obtained using insect, hamster, rat and, to a lesser extent, human cell lines. Besides highlighting which interactions have not been explored, our findings suggest additional possible interactions that should be examined based on our expression data analysis.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/178702 Collegamento a IRIS

2013
Association of GSK-3β Genetic Variation With GSK-3β Expression, Prefrontal Cortical Thickness, Prefrontal Physiology, and Schizophrenia.
THE AMERICAN JOURNAL OF PSYCHIATRY
Autore/i: Blasi, G; Napolitano, F; Ursini, G; DI GIORGIO, Annabella; Caforio, G; Taurisano, P; Fazio, L; Gelao, B; Attrotto, Mt; Colagiorgio, L; Todarello, G; Piva, Francesco; Papazacharias, A; Masellis, R; Mancini, M; Porcelli, A; Romano, R; Rampino, A; Quarto, T; Giulietti, Matteo; Lipska, Bk; Kleinman, Je; Popolizio, T; Weinberger, Dr; Usiello, A; Bertolino, A.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/109466 Collegamento a IRIS

2013
SpliceAid-F: a database of human splicing factors and their RNA-binding sites
NUCLEIC ACIDS RESEARCH
Autore/i: Giulietti, Matteo; Piva, Francesco; D'Antonio, M; D'Onorio De Meo, P; Paoletti, D; Castrignanò, T; D'Erchia, Am; Picardi, E; Zambelli, F; Principato, Giovanni; Pavesi, G; Pesole, G.
Classificazione: 1 Contributo su Rivista
Abstract: A comprehensive knowledge of all the factors involved in splicing, both proteins and RNAs, and of their interaction network is crucial for reaching a better understanding of this process and its functions. A large part of relevant information is buried in the literature or collected in various different databases. By hand-curated screenings of literature and databases, we retrieved experimentally validated data on 71 human RNA-binding splicing regulatory proteins and organized them into a database called 'SpliceAid-F' (http://www.caspur.it/SpliceAidF/). For each splicing factor (SF), the database reports its functional domains, its protein and chemical interactors and its expression data. Furthermore, we collected experimentally validated RNA-SF interactions, including relevant information on the RNA-binding sites, such as the genes where these sites lie, their genomic coordinates, the splicing effects, the experimental procedures used, as well as the corresponding bibliographic references. We also collected information from experiments showing no RNA-SF binding, at least in the assayed conditions. In total, SpliceAid-F contains 4227 interactions, 2590 RNA-binding sites and 1141 'no-binding' sites, including information on cellular contexts and conditions where binding was tested. The data collected in SpliceAid-F can provide significant information to explain an observed splicing pattern as well as the effect of mutations in functional regulatory elements.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/86564 Collegamento a IRIS

2012
SpliceAid-F: a database of human splicing factors and their RNA binding sites
BITS 2012 - Ninth Annual Meeting of the Bioinformatic Italian Society
Autore/i: Giulietti, Matteo; Piva, Francesco; D’Antonio, M.; D’Onorio De Meo, P.; Castrignanò, T.; Pavesi, G; Pesole, G.
Editore: EMBnet Stichting p/a, CMBI Radboud University, Nijmegen Medical Centre, 6581 GB Nijmegen, The Netherlands
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/86596 Collegamento a IRIS

2012
SpliceAid 2: a database of human splicing factors expression data and RNA target motifs
HUMAN MUTATION
Autore/i: Piva, Francesco; Giulietti, Matteo; Ballone Burini, A.; Principato, Giovanni
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/66341 Collegamento a IRIS

2012
Cross-link immunoprecipitation data to detect polymorphisms lying in splicing regulatory motifs: a method to refine single nucleotide polymorphism selection in association studies
PSYCHIATRIC GENETICS
Autore/i: Piva, Francesco; Giulietti, Matteo; Armeni, Tatiana; Principato, Giovanni
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/74942 Collegamento a IRIS

2012
HTR2A gene polymorphisms and Inward and Outward Personal Meaning Organisations
ACTA NEUROPSYCHIATRICA
Autore/i: Nardi, Bernardo; Piva, Francesco; Turchi, Chiara; Giulietti, Matteo; Castellucci, G.; Arimatea, E.; Rocchetti, D.; Rocchetti, G.; Principato, Giovanni; Tagliabracci, Adriano; Bellantuono, Cesario
Classificazione: 1 Contributo su Rivista
Abstract: Objective: Caregiver behaviours and emotional expressions may induce development of two basic categories of constructing identity and of regulating cognitive and emotional processes: an Inward or an Outward Personal Meaning Organisation (PMO). Inwards read environmental signals through their internal activations. Their emotions are more distinct and reciprocity is more based on physical distance (protection, loneliness). , while Outwards read internal activations through the environment. Their emotions are more blurred and reciprocity is more based on a semantic sight of relations (approval, rules). It has recently been shown that PMO development may also have physiological and genetic bases. In a functional Magnetic Resonance Imaging (fMRI) study Inward and Outward subjects showed different amygdala activation patterns and an association with the SLC6A4 serotonin transporter gene 5-HTTLPR polymorphism. Methods: In this work 149 healthy subjects were examined with respect to Inward and Outward PMOs. We explored the association with 10 serotonin receptor 2A (HTR2A) gene single nucleotide polymorphisms (SNPs) selected by bioinformatics methods. Results: An intronic SNP (rs55948462) was found to be significantly associated with an Inward and an Outward PMOs development. However, after statistical adjustments, these results did not remain significant. Conclusion: We did not find associations between considered SNPs and Inward/Outward PMOs. However the role of HTR2A polymorphisms not considered in this study and that of the other serotonin related genes should be valued. KEYWORDS: personality; serotonin; genetic association studies
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/64461 Collegamento a IRIS

2011
Combined Docking and Molecular Dynamics of agonists and antagonists of 5-HT2c G-coupled Receptor
Autore/i: Massaccesi, L.; Galeazzi, Roberta; Giulietti, M.; Piva, Francesco; Principato, Giovanni
Luogo di pubblicazione: Lecce
Classificazione: 5 Altro
Abstract: XXIV Congresso Nazionale della Società Chimica Italiana Lecce 2011
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/62759 Collegamento a IRIS

2011
Combined docking and molecular dynamics of agonists and antagonists 5-HT2c G-coupled receptor
XXIV Congresso Nazionale della Società Chimica Italiana "Lecce 2011"
Autore/i: Massaccesi, L; Galeazzi, Roberta; Giulietti, M; Piva, Francesco; Principato, Giovanni
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/82828 Collegamento a IRIS

2011
TRAM (Transcriptome Mapper): database-driven creation and analysis of transcriptome maps from multiple sources
BMC GENOMICS
Autore/i: Lenzi, L.; Facchin, F.; Piva, Francesco; Giulietti, Matteo; Pelleri, M. C.; Frabetti, F.; Vitale, L.; Casadei, R.; Canaider, S.; Bortoluzzi, S.; Coppe, A.; Danieli, G. A.; Principato, Giovanni; Ferrari, S.; Strippoli, P.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/66340 Collegamento a IRIS

2011
Bioinformatic analyses to select phenotype affecting polymorphisms in HTR2C gene
HUMAN PSYCHOPHARMACOLOGY
Autore/i: Piva, Francesco; Giulietti, Matteo; Baldelli, L.; Nardi, Bernardo; Bellantuono, Cesario; Armeni, Tatiana; Saccucci, Franca; Principato, Giovanni
Classificazione: 1 Contributo su Rivista
Abstract: Objective Single nucleotide polymorphisms (SNPs) in serotonin related genes influence mental disorders, responses to pharmacological and psychotherapeutic treatments. In planning association studies, researchers that want to investigate new SNPs have to select some among a large number of candidates. Our aim is to guide researchers in the selection of the most likely phenotype affecting polymorphisms. Here, we studied serotonin receptor 2C (HTR2C) SNPs because, till now, only relatively few of about 2000 are investigated. Methods We used the most updated and assessed bioinformatic tools to predict which variations can give rise to biological effects among 2450 HTR2C SNPs. Results We suggest 48 SNPs that are worth considering in future association studies in the field of psychiatry, psychology and pharmacogenomics. Moreover, our analyses point out the biological level probably affected, such as transcription, splicing, miRNA regulation and protein structure, thus allowing to suggest future molecular investigations. Conclusions Although few association studies are available in literature, their results are in agreement with our predictions, showing that our selection methods can help to guide future association studies. Copyright © 2011 John Wiley & Sons, Ltd. key words—computational biology; serotonin; SNP selection; association studies; RNA splicing
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/59187 Collegamento a IRIS

2011
Searching for a relationship between the serotonin receptor 2A gene variations and the development of Inward and Outward Personal Meaning Organizations
PSYCHIATRIC GENETICS
Autore/i: Nardi, Bernardo; Turchi, Chiara; Piva, Francesco; Giulietti, Matteo; Castellucci, G.; Arimatea, E.; Rocchetti, D.; Rocchetti, G.; Principato, Giovanni; Tagliabracci, Adriano; Bellantuono, Cesario
Classificazione: 1 Contributo su Rivista
Abstract: The aim of this study was to explore whether the polymorphisms of the serotonin receptor 2A gene (HTR2A) affect the development of Inward or Outward Personal Meaning Organization (PMO). One hundred and forty-nine healthy unrelated Italians were assessed for PMO using a Post-Rationalist Clinical Interview and two questionnaires: Personal Meaning Questionnaire (Picardi, 2003) and a home-made Mini Questionnaire of Personal Organization. All participants gave their written informed consent to participate. The study was approved by the Ethics Committee of Azienda Universitaria-Ospedaliera Ospedali Riuniti, Ancona.Ten potentially phenotype-affecting single nucleotide polymorphisms at the HTR2A gene were selected by bioinformatics methods. Genomic DNA was extracted from buccal swabs and polymorphisms were genotyped by minisequencing assay.Our findings do not exclude the possibility that the PMOs have a genetic basis and call for further research into the role of genetic factors in their development.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/54338 Collegamento a IRIS

2011
Genetic factors in inward vs outward personality organizations: focus on HTR2A polymorphisms.
QUADERNI ITALIANI DI PSICHIATRIA
Autore/i: Nardi, Bernardo; Piva, Francesco; Turchi, Chiara; Cedraro, M.; Arimatea, E.; Giulietti, Matteo; Principato, Giovanni; Tagliabracci, Adriano; Bellantuono, Cesario
Classificazione: 1 Contributo su Rivista
Abstract: Introduction: reciprocity with primary caregivers drives subjects' adaptive abilities towards the construction of a Personal Meaning Organization (PMO) that is useful with respect to their developmental environment. Those with inward personalities read environmental signals through their internal activations; those with outward personalities read internal activations through the environment. It was recently been shown that PMO development may also have physiological and genetic bases. Because the serotonin receptor 2A gene (HTR2A) is one of the serotoninergic genes associated with personality and behavior, it is expected to exert an influence on PMO development. The aim of this work was to explore possible correlations between HTR2A gene single nucleotide polymorphisms (SNPs) and the inward/outward PMO. Material and methods: we enrolled 149 healthy, unrelated members of our hospital staff (65 males, 84 females; mean ages 42+/- 10.3 and 37.6 +/- 8.7, respectively). Each was classified as having an inward or outward PMO by two trained psychotherapists using a Post-Rationalist Clinical Interview and two self-rating questionnaires for PMO. A mini-sequencing assay was used to assess 20 SNPs at the HTR2A locus in genomic DNA samples from each participant. Results: three intronic HTR2A SNPs (rs2770304, rs55948462, rs61948318) were found to be associated with the development of an inward rather than an outward PMO.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/62555 Collegamento a IRIS

2010
Studio computazionale dei meccanismi di regolazione della trascrizione
Autore/i: Giulietti, Matteo
Editore: Università Politecnica delle Marche
Classificazione: 8 Tesi di dottorato
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/242180 Collegamento a IRIS

2010
An improved in silico selection of phenotype affecting polymorphisms in SLC6A4, HTR1A and HTR2A genes
HUMAN PSYCHOPHARMACOLOGY
Autore/i: Piva, Francesco; Giulietti, M; Nardi, Bernardo; Bellantuono, Cesario; Principato, Giovanni
Classificazione: 1 Contributo su Rivista
Abstract: Objective Among the experimentally assessed DNA variations in serotonin related genes, some influence physiological expression of personality and mental disorders, others alter the responses to pharmacological and/or psychotherapeutic treatments. Because of the huge number of polymorphisms lying in genes and of the great length of time necessary to perform association studies, a selection of the variations being studied is a necessary and crucial step. Methods In this work we used the most updated and assessed bioinformatic tools to predict the phenotype affecting polymorphisms of the human HTR1A, HTR2A and SLC6A4 serotonin related genes. Moreover, we carried out a literature search to collect information about the recent association studies to compare it versus our prediction data. Results Gene polymorphism analysis indicated the variations that are worth considering in the association studies in the field of psychiatry, psychology and pharmacogenomics. The literature revision allowed to show both the few well and the most not enough investigated polymorphisms. Conclusions Our data can be useful to select polymorphisms for new association studies, especially those not yet investigated that can be related to behaviour, mental disorders and individual treatment response. Copyright # 2010 John Wiley & Sons, Ltd. key words—computational biology; serotonin; SNP; association; RNA splicing
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/51928 Collegamento a IRIS

2009
SpliceAid: a database of experimental RNA target motifs bound by splicing proteins in humans
BIOINFORMATICS
Autore/i: Piva, Francesco; Giulietti, M; Nocchi, L; Principato, Giovanni
Classificazione: 1 Contributo su Rivista
Abstract: Summary: The correct post-transcriptional RNA processing is finely regulated by RNA-binding proteins. Unfortunately, there is little experimental information on target RNA sequences of RNA-binding proteins and moreover such experimentally derived target sequences are annotated in a compact form by the score matrices that overestimate the number of possible recognized sequences. We carried out an exhaustive hand curated literature search to create a database, SpliceAid, collecting all the experimentally assessed target RNA sequences that are bound by splicing proteins in humans. We built a web resource, database driven, to easy query SpliceAid and give back the results by an accurate and dynamic graphic representation.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/36966 Collegamento a IRIS




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