41 results on '"Morandi, L."'
Search Results
2. Sequential analyses of bovid tooth enamel and dentine collagen (δ18O, δ13C, δ15N): new insights into animal husbandry between the Late Neolithic and the Early Bronze Age at Tana del Barletta (Ligurian Prealps)
- Author
-
Morandi, L. F., Frémondeau, D., Müldner, G., and Maggi, R.
- Published
- 2021
- Full Text
- View/download PDF
3. The relict landslide in bimsoils in downtown Genova, Italy: a new modeling approach
- Author
-
Napoli, M L, primary, Barbero, M, additional, Minuto, D, additional, Morandi, L, additional, and Ullah, H, additional
- Published
- 2023
- Full Text
- View/download PDF
4. Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: comment
- Author
-
Bandera, A., Nobili, A., Tettamanti, M., Harari, S., Bosari, S., Mannucci, P. M., Scudeller, L., Fusetti, G., Rusconi, L., Dell'Orto, S., Prati, D., Valenti, L., Giovannelli, S., Manunta, M., Lamorte, G., Ferrari, F., Gori, A., Muscatello, A., Mangioni, D., Alagna, L., Bozzi, G., Lombardi, A., Ungaro, R., Ancona, G., Zuglian, G., Bolis, M., Iannotti, N., Ludovisi, S., Comelli, A., Renisi, G., Biscarini, S., Castelli, V., Palomba, E., Fava, M., Fortina, V., Peri, C. A., Saltini, P., Viero, G., Itri, T., Ferroni, V., Pastore, V., Massafra, R., Liparoti, A., Muheberimana, T., Giommi, A., Bianco, R., De Azevedo, R. M., Chitani, G. E., Peyvandi, F., Gualtierotti, R., Ferrari, B., Rossio, R., Boasi, N., Pagliaro, E., Massimo, C., De Caro, M., Montano, N., Vigone, B., Bellocchi, C., Carandina, A., Fiorelli, E., Melli, V., Tobaldini, E., Blasi, F., Aliberti, S., Spotti, M., Terranova, L., Misuraca, S., D'Adda, A., Della Fiore, S., Di Pasquale, M., Contarini, M. M. M., Ori, M., Morlacchi, L., Rossetti, V., Gramegna, A., Pappalettera, M., Cavallini, M., Buscemi, A., Vicenzi, M., Rota, I., Costantino, G., Solbiati, M., Furlan, L., Mancarella, M., Colombo, G., Fanin, A., Passarella, M., Monzani, V., Canetta, C., Rovellini, A., Barbetta, L., Billi, F., Folli, C., Accordino, S., Maira, D., C. M., Hu, Motta, I., Scaramellini, N., Fracanzani, A. L., Lombardi, R., Cespiati, A., Cesari, M., Lucchi, T., Proietti, M., Calcaterra, L., Mandelli, C., Coppola, C., Cerizza, A., Pesenti, A. M., Grasselli, G., Galazzi, A., Monti, I., Galbussera, A. A., Crisafulli, E., Girelli, D., Maroccia, A., Gabbiani, D., Busti, F., Vianello, A., Biondan, M., Sartori, F., Faverio, P., Pesci, A., Zucchetti, S., Bonfanti, P., Rossi, M., Beretta, I., Spolti, A., Elia, D., Cassandro, R., Caminati, A., Cipollone, F., Guagnano, M. T., D'Ardes, D., Rossi, I., Vezzani, F., Spanevello, A., Cherubino, F., Visca, D., Contoli, M., Papi, A., Morandi, L., Battistini, N., Moreo, G. L., Iannuzzi, P., Fumagalli, D., Leone, S., Bandera, A, Nobili, A, Tettamanti, M, Harari, S, Bosari, S, Mannucci, P, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferrari, F, Gori, A, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Peyvandi, F, Gualtierotti, R, Ferrari, B, Rossio, R, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Della Fiore, S, Di Pasquale, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalli, D, and Leone, S
- Subjects
Adult ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Critical Care ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Ce - Letter to the Editor ,MEDLINE ,Cohort Studies ,Hospital ,Internal Medicine ,Medicine ,Humans ,Hospital Mortality ,Intensive care medicine ,Aged ,Aged, 80 and over ,business.industry ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,Respiration, Artificial ,Hospitals ,Hospitalization ,Survival Rate ,Italy ,Emergency Medicine ,business ,Human - Abstract
During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO
- Published
- 2022
5. Correction to: Sequential analyses of bovid tooth enamel and dentine collagen (δ18O, δ13C, δ15N): new insights into animal husbandry between the Late Neolithic and the Early Bronze Age at Tana del Barletta (Ligurian Prealps)
- Author
-
Morandi, L. F., Frémondeau, D., Müldner, G., and Maggi, R.
- Published
- 2022
- Full Text
- View/download PDF
6. 'Seeing Shit': Assessing the Visibility of Dung Tempering in Ancient Pottery Using an Experimental Approach.
- Author
-
Amicone, S., Morandi, L. F., and Gur-Arieh, S.
- Subjects
MANURES ,TEMPERING ,POTTERY ,ANIMAL droppings ,FUNGAL spores - Abstract
Widespread ethnographic evidence exists for the addition of animal dung to clay during the process of ceramic production. However, conclusive evidence of dung tempering in archaeological ceramics is relatively rare. The aim of this study is to ascertain whether, and under which conditions, dung tempering of pottery is identifiable. To answer these questions, we assessed whether a combination of micro-particle analysis in loose sediment and thin-section petrography can reveal the addition of dung to the clay paste by focusing on faecal spherulites, ash pseudomorphs, phytoliths and coprophilous fungal spores. We analysed several series of experimentally produced ceramic briquettes tempered with different types of dung and dung ash, which were fired at a range of increasing temperatures. Our study shows that the identification of dung tempering represents a challenge, and it depends on a number of different factors, among others the original presence of dung markers in the dung used, the manufacturing process, the firing temperatures and the firing atmosphere. Overall, through a multidisciplinary approach, our work clarifies a variety of issues connected to the identification of dung in ancient pottery, highlighting the role of faecal spherulites as the most promising proxy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
7. Sequential analyses of bovid tooth enamel and dentine collagen (δ18O, δ13C, δ15N): new insights into animal husbandry between the Late Neolithic and the Early Bronze Age at Tana del Barletta (Ligurian Prealps)
- Author
-
Morandi, L. F., Frémondeau, D., Müldner, G., and Maggi, R.
- Abstract
Tana del Barletta is an upland cave used from the Late Neolithic to the Middle Bronze Age, located in the vicinity of the coast in Liguria (NW Italy). The excavation revealed the presence of a faunal assemblage dominated by caprine and cattle remains. In order to gain new data on late prehistoric farming strategies (e.g. seasonal mobility, coastal grazing, animal diet), intra-tooth series of stable oxygen and carbon isotopes have been obtained from cattle and sheep/goat tooth enamel, along with intra-tooth series of nitrogen and carbon isotopes from cattle dentine collagen. Due to the prevalence of maxillary teeth, a modern calf has also been analysed to assess intra-individual isotopic differences between the maxillary and mandibular dentition. Modern data on oxygen isotope values of meteoric water from different altitudes around the area of the site were used as a reference for interpretation. The results indicate that the water ingested by the herd was mostly characterised by particularly low δ18O values, highlighting the importance of the uplands for the late prehistoric farmers of the region. However, the input of water sourced from lower elevations, especially during the winter months, cannot be dismissed. In addition, the nitrogen isotopic composition of cattle collagen rules out the ingestion of salt-tolerant vegetation or seaweed, suggesting that grazing did not occur directly on the coastal plain. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
8. Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines
- Author
-
Carla Rohrer Bley, Caterina Tonon, Nina Simona Tresch, Katarzyna J. Nytko, Daniel Fuchs, Luca Morandi, University of Zurich, Nytko, Katarzyna J, Tresch N.S., Fuchs D., Morandi L., Tonon C., Rohrer Bley C., and Nytko K.J.
- Subjects
10253 Department of Small Animals ,Veterinary medicine ,3400 General Veterinary ,Cell Line ,Dogs ,In vivo ,SF600-1100 ,O-6-methylguanine-DNA methyltransferase (MGMT) ,Temozolomide ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Dog Diseases ,11434 Center for Clinical Studies ,brain tumour ,chemoradiation ,Clonogenic assay ,DNA Modification Methylases ,neoplasms ,630 Agriculture ,General Veterinary ,Brain Neoplasms ,Chemistry ,Tumor Suppressor Proteins ,in vitro ,Original Articles ,Glioma ,Methylation ,digestive system diseases ,Dacarbazine ,O‐6‐methylguanine‐DNA methyltransferase (MGMT) ,DNA Repair Enzymes ,Cell culture ,Canine Glioma ,dog ,DNA methylation ,Cancer research ,570 Life sciences ,biology ,Original Article ,medicine.drug - Abstract
Background Similar to human glioblastoma patients, glial tumours in dogs have high treatment resistance and a guarded prognosis. In human medicine, the addition of temozolomide to radiotherapy leads to a favourable outcome in vivo as well as a higher antiproliferative effect on tumour cells in vitro. Objectives The aim of the study was to determine the radio‐ and temozolomide‐sensitivity of three canine glial tumour cell lines and to investigate a potential additive cytotoxic effect in combined treatment. Additionally, we wanted to detect the level of MGMT promoter methylation in these cell lines and to investigate a potential association between MGMT promoter methylation and treatment resistance. Methods Cells were treated with various concentrations of temozolomide and/or irradiated with 4 and 8 Gy. Radiosensitization by temozolomide was evaluated using proliferation assay and clonogenic assay, and MGMT DNA methylation was investigated using bisulfite next‐generation sequencing. Results In all tested canine cell lines, clonogenicity was inhibited significantly in combined treatment compared to radiation alone. All canine glial cell lines tested in this study were found to have high methylation levels of MGMT promoter. Conclusions Hence, an additive effect of combined treatment in MGMT negative canine glial tumour cell lines in vitro was detected. This motivates to further investigate the association between treatment resistance and MGMT, such as MGMT promoter methylation status., Temozolomide pre‐treatment enhanced the cytotoxic effect or irradiation in canine glioma cell lines. Clonogenic cell survival assay was used as a readout.
- Published
- 2021
9. Shared epigenetic alterations between oral cancer and periodontitis: A preliminary study
- Author
-
Andrea Gabusi, Davide B. Gissi, Sara Grillini, Martina Stefanini, Achille Tarsitano, Claudio Marchetti, Maria Pia Foschini, Lucio Montebugnoli, Luca Morandi, Gabusi A., Gissi D.B., Grillini S., Stefanini M., Tarsitano A., Marchetti C., Foschini M.P., Montebugnoli L., and Morandi L.
- Subjects
oral squamous cell carcinoma ,Otorhinolaryngology ,DNA methylation analysi ,periodontal disease ,13 gene panel ,General Dentistry - Abstract
Introduction: We recently developed a non-invasive sampling procedure for oral squamous cell carcinoma (OSCC) detection based on DNA methylation analysis of a panel of 13 genes. Oral cancer, as well as acute and chronic inflammatory diseases, may influence the methylation level of several genes in the oral cavity. In the present study, we evaluated the presence of periodontal disease (PD) and the methylation status using our 13-gene panel. Methods: Oral brushing specimens were collected from three different patient groups: 23 gingival OSCC patients, 15 patients affected by PD, and 15 healthy volunteers lacking evidence of PD. DNA methylation analysis was performed and each sample was determined to be positive or negative based on a predefined cut-off value. Results: Positive results were found for 23/23 OSCC patients, 3/15 PD patients, and 0/15 samples from healthy volunteers. The GP1BB and MIR193 genes in the PD group exhibited mean methylation levels similar to OSCC patients. ZAP70 showed different methylation levels among three groups. Conclusion: Preliminary data identified shared epigenetic alterations between PD and OSCC patients in two inflammatory genes (GP1BB and MIR193). This study may help to identify potential links between the two diseases and serve as a starting point for the future research focused on pathogenesis.
- Published
- 2022
10. DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome
- Author
-
Francesco Ravaioli, Michele Zampieri, Luca Morandi, Chiara Pirazzini, Camilla Pellegrini, Sara De Fanti, Noémie Gensous, Gian Luca Pirazzoli, Luisa Sambati, Alessandro Ghezzo, Fabio Ciccarone, Anna Reale, Daniela Monti, Stefano Salvioli, Paola Caiafa, Miriam Capri, Alexander Bürkle, Maria Moreno-Villanueva, Paolo Garagnani, Claudio Franceschi, Maria Giulia Bacalini, Ravaioli F., Zampieri M., Morandi L., Pirazzini C., Pellegrini C., De Fanti S., Gensous N., Pirazzoli G.L., Sambati L., Ghezzo A., Ciccarone F., Reale A., Monti D., Salvioli S., Caiafa P., Capri M., Burkle A., Moreno-Villanueva M., Garagnani P., Franceschi C., and Bacalini M.G.
- Subjects
ribosomal genes ,Down syndrome, ribosomal genes, rDNA, aging, DNA methylation ,DNA methylation ,ddc:570 ,Down syndrome ,aging ,Genetics ,Molecular Medicine ,rDNA ,Settore BIO/10 ,Genetics (clinical) - Abstract
Control of ribosome biogenesis is a critical aspect of the regulation of cell metabolism. As ribosomal genes (rDNA) are organized in repeated clusters on chromosomes 13, 14, 15, 21, and 22, trisomy of chromosome 21 confers an excess of rDNA copies to persons with Down syndrome (DS). Previous studies showed an alteration of ribosome biogenesis in children with DS, but the epigenetic regulation of rDNA genes has not been investigated in adults with DS so far. In this study, we used a targeted deep-sequencing approach to measure DNA methylation (DNAm) of rDNA units in whole blood from 69 adults with DS and 95 euploid controls. We further evaluated the expression of the precursor of ribosomal RNAs (RNA45S) in peripheral blood mononuclear cells (PBMCs) from the same subjects. We found that the rDNA promoter tends to be hypermethylated in DS concerning the control group. The analysis of epihaplotypes (the combination of methylated and unmethylated CpG sites along the same DNA molecule) showed a significantly lower intra-individual diversity in the DS group, which at the same time was characterized by a higher interindividual variability. Finally, we showed that RNA45S expression is lower in adults with DS. Collectively, our results suggest a rearrangement of the epigenetic profile of rDNA in DS, possibly to compensate for the extranumerary rDNA copies. Future studies should assess whether the regulation of ribosome biogenesis can contribute to the pathogenesis of DS and explain the clinical heterogeneity characteristic of the syndrome.
- Published
- 2022
11. Endometrioid Cancer Associated With Endometriosis: From the Seed and Soil Theory to Clinical Practice
- Author
-
Alberto Farolfi, Amelia Altavilla, Luca Morandi, Laura Capelli, Elisa Chiadini, Giovanna Prisinzano, Giorgia Gurioli, Marianna Molari, Daniele Calistri, Maria Pia Foschini, Ugo De Giorgi, Farolfi A., Altavilla A., Morandi L., Capelli L., Chiadini E., Prisinzano G., Gurioli G., Molari M., Calistri D., Foschini M.P., and De Giorgi U.
- Subjects
Cancer Research ,Oncology ,endometriosi ,endometrioid adenocarcinoma of the endometrium ,mismatch repair (MMR) deficiency ,tumor dissemination ,uterine carcinoma - Abstract
Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. It is still debated whether endometriosis is a disease that can predispose to the pathogenesis of endometrial cancer outside the uterus. Deficiencies in mismatch repair (MMR) genes are a known risk factor for developing endometrioid cancer. Starting from two cases of patients with abnormal MMR endometrioid carcinoma of the uterus and synchronous endometrioid carcinoma in non-ovarian and ovarian endometriosis, we performed a somatic mutation profile and phylogenetic analysis of the lesions in order to identify if they were metastasis or primary de novo tumors. In the first case, we identified de novo activating mutations in PIK3CA and KRAS in endometrioid cancer lesions but not in endometriosis. Although the acquisition of a de novo mutation in ESR1 and a decrease in mutant allele fraction (MAF) from the endometrial tumor to the localizations in the endometriosis lesions, the clonal relationship was confirmed by the limited number of heteroplasmic mutations in D-loop mitochondrial DNA region. In the other case, the clonal behavior was demonstrated by the overlap of MAF at each site. Our data support the hypothesis of a retrograde dissemination of tumor cells, moving from the primary carcinoma in the endometrium to ectopic sites of endometriosis where localizations of tumor arise.
- Published
- 2022
12. A 13-Gene DNA Methylation Analysis Using Oral Brushing Specimens as an Indicator of Oral Cancer Risk: A Descriptive Case Report
- Author
-
Roberto Rossi, Davide B. Gissi, Andrea Gabusi, Viscardo Paolo Fabbri, Tiziana Balbi, Achille Tarsitano, Luca Morandi, Rossi R., Gissi D.B., Gabusi A., Fabbri V.P., Balbi T., Tarsitano A., and Morandi L.
- Subjects
Brushing ,stomatognathic diseases ,DNA methylation ,Oral squamous cell carcinoma ,Clinical Biochemistry ,Oral leukoplakia ,Prognosis ,Diagnosi - Abstract
Analysis of genetic or epigenetic markers from saliva or brushing specimens has been proposed as a diagnostic aid to identify patients at risk of developing oral cancer. However, no reliable non-invasive molecular method for this purpose is commercially available. In the present report, we describe the potential application of a procedure based on a 13-gene DNA methylation analysis using oral brushing samples from a patient affected by oral leukoplakia who developed two metachronous oral carcinomas during the follow-up period. A positive or a negative score was calculated for each brushing sample based on a predefined cut-off value. In this patient, a positive score was detected in the oral leukoplakia diagnosed more than 2 years before the development of oral squamous cell carcinoma and subsequently in clinically healthy mucosa 8 months before the appearance of a secondary tumor. This suggests a potential role of our procedure as an indicator of oral cancer risk.
- Published
- 2022
13. DNA Methylation of steroidogenic enzymes in benign adrenocortical tumors: New insights in aldosterone-producing Adenomas
- Author
-
Guido Di Dalmazi, Valentina Vicennati, Uberto Pagotto, Francesca Ambrosi, Beatrice Rubin, Valeria Maffeis, Francesco Fallo, Sofia Asioli, Luca Morandi, Donatella Santini, Catia Pilon, Ambrogio Fassina, Antonio De Leo, Di Dalmazi G., Morandi L., Rubin B., Pilon C., Asioli S., Vicennati V., De Leo A., Ambrosi F., Santini D., Pagotto U., Maffeis V., Fassina A., and Fallo F.
- Subjects
Male ,0301 basic medicine ,steroidogenesis ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biochemistry ,law.invention ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,law ,Gonadal Steroid Hormones ,Aldosterone ,Polymerase chain reaction ,Adrenal cortex ,Chemistry ,APCC ,Methylation ,Middle Aged ,Enzymes ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,CYP17A1 ,030220 oncology & carcinogenesis ,Adrenocortical Adenoma ,DNA methylation ,Female ,Metabolic Networks and Pathways ,Adult ,Cortisol secretion ,medicine.medical_specialty ,Biology ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,Steroidogenic enzymes ,Internal medicine ,medicine ,Humans ,Aged ,Biochemistry (medical) ,DNA Methylation ,APA ,Adrenal Cortex Neoplasms ,CYP11B2 ,CYP11B1 ,Cross-Sectional Studies ,030104 developmental biology ,HSD3B1 ,HSD3B2 ,Cancer research ,Steroidogenesis ,methylation - Abstract
Context DNA methylation has been identified among putative regulatory mechanisms for CYP11B2 expression in primary aldosteronism. Objective The objective of this work is to investigate DNA methylation and expression of genes encoding steroidogenic enzymes in benign adrenocortical tumors. Design and Setting This cross-sectional study took place at university hospitals. Patients We collected fresh-frozen tissues from patients with benign adrenocortical adenomas (n = 48) (nonfunctioning n = 9, autonomous cortisol secretion n = 9, Cushing syndrome n = 17, aldosterone-producing [APA] n = 13) and adrenal cortex adjacent to APA (n = 12). We collected formalin-fixed, paraffin-embedded (FFPE) specimens of paired APA and concurrent aldosterone-producing cell clusters (APCCs) (n = 6). Intervention DNA methylation levels were evaluated by quantitative bisulfite next-generation sequencing in fresh-frozen tissues (CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD3B1, HSD3B2, NR5A1, STAR, and TSPO) and FFPE APA/APCC paired samples (CYP11B2). CYP11B1, CYP11B2, CYP17, CYP21, and STAR gene expressions were examined by quantitative real-time polymerase chain reaction. Main Outcome Measure The main outcome measure was DNA methylation. Results CYP11B2 methylation levels were significantly lower in APA than in other adrenal tissues (P < .001). Methylation levels of the remaining genes were comparable among groups. Overall, CYP11B2 expression and DNA methylation were negatively correlated (ρ = –0.379; P = .003). In FFPE-paired APA/APCC samples, CYP11B2 methylation level was significantly lower in APA than in concurrent APCCs (P = .028). Conclusions DNA methylation plays a regulatory role for CYP11B2 expression and may contribute to aldosterone hypersecretion in APA. Lower CYP11B2 methylation levels in APA than in APCCs may suggest an APCC-to-APA switch via progressive CYP11B2 demethylation. Conversely, DNA methylation seems not to be relevant in regulating the expression of genes encoding steroidogenic enzymes other than CYP11B2.
- Published
- 2021
14. Holocene Evolution of Minor Mountain Lacustrine Basins in the Northern Apennines, Italy: The Lake Moo Case Study
- Author
-
Stefano Segadelli, Kei Ogata, Marco Cocuccioni, Stefano Gambini, Luca Martelli, Lionello F. Morandi, Gabriele Oppo, Segadelli, S., Ogata, K., Cocuccioni, M., Gambini, S., Martelli, L., Morandi, L. F., and Oppo, G.
- Subjects
historical archive ,geological event ,topographic lineament ,General Earth and Planetary Sciences ,Northern Apennines ,historical archives ,geological events ,high-resolution mapping ,Northern Apennine - Abstract
Sedimentary systems developed in small (
- Published
- 2022
15. Role of PLCγ1 in the modulation of cell migration and cell invasion in glioblastoma
- Author
-
Lucio Cocco, Luca Morandi, Giulia Ramazzotti, Anna Maria Billi, Maria Vittoria Marvi, Lucia Manzoli, Sofia Asioli, Veronica Papa, Diego Mazzatenta, Stefano Ratti, Matilde Y. Follo, Sara Mongiorgi, James A. McCubrey, Matteo Zoli, Pann-Ghill Suh, Marvi M.V., Mongiorgi S., Ramazzotti G., Follo M.Y., Billi A.M., Zoli M., Mazzatenta D., Morandi L., Asioli S., Papa V., McCubrey J.A., Suh P.-G., Manzoli L., Cocco L., and Ratti S.
- Subjects
Cancer Research ,Overexpression ,PLCγ1 ,Cell ,Brain tumor ,Motility ,Biology ,Invasion ,Cell Movement ,Cell Line, Tumor ,Gene expression ,Genetics ,medicine ,Animals ,Humans ,Gene silencing ,Neoplasm Invasiveness ,Molecular Biology ,Migration ,Cell Proliferation ,Silencing ,Brain Neoplasms ,Biomarker ,Glioblastoma ,Cell migration ,Cell cycle ,medicine.disease ,Rats ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Cell culture ,Cancer research ,Molecular Medicine ,Signal Transduction - Abstract
Phosphoinositide-specific phospholipases C (PLCs) are a class of enzymes involved in several cell activities, such as cell cycle regulation, proliferation, differentiation and cytoskeletal dynamics. Among these enzymes, PLCγ1 is one of the most expressed PLCs in the brain, contributing to a complex network in the developing nervous system. Several studies have shown that PLCγ1 signaling imbalance is linked to several brain disorders, including glioblastoma, the most aggressive brain tumor in adults. Indeed, it has been demonstrated a link between PLCγ1 inhibition and the arrest of glioma cell motility of fetal rat brain aggregates and the impairment of cell invasion abilities following its down-regulation. This study aims to determine the pathological influence of PLCγ1 in glioblastoma, through a translational study which combines in silico data, data from glioblastoma patients' samples and data on engineered cell lines. We found out that PLCγ1 gene expression correlates with the pathological grade of gliomas, and it is higher in fifty patients' glioblastoma tissue samples compared to twenty healthy controls. Moreover, it was demonstrated that PLCγ1 silencing in U87-MG leads to a reduction in cell migration and invasion abilities. The opposite trend was observed following PLCγ1 overexpression, suggesting an interesting possible involvement of PLCγ1 in gliomas' aggressiveness.
- Published
- 2022
16. Two more families supporting the existence of monogenic spinocerebellar ataxia 48.
- Author
-
Palombo F, Vaisfeld A, Tropeano VC, Ormanbekova D, Bacchi I, Fiorini C, Peruzzi A, Morandi L, Liguori R, Carelli V, and Rizzo G
- Subjects
- Humans, Male, Female, Middle Aged, TATA-Box Binding Protein genetics, Adult, Alleles, Mutation genetics, Spinocerebellar Ataxias genetics, Pedigree, Ubiquitin-Protein Ligases genetics
- Abstract
The reduced penetrance of TBP intermediate alleles and the recently proposed possible digenic TBP/STUB1 inheritance raised questions on the possible mechanism involved opening a debate on the existence of SCA48 as a monogenic disorder. We here report clinical and genetic results of two apparently unrelated patients carrying the same STUB1 variant(c.244G > T;p.Asp82Tyr) with normal TBP alleles and a clinical picture fully resembling SCA48, including cerebellar ataxia, dysarthria and mild cognitive impairment. This report provides supportive evidence that this specific ataxia can also occur as a monogenic disease, considering classical TBP allelic ranges., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
17. Direct healthcare costs of oral cancer: A retrospective study from a tertiary care center.
- Author
-
Gissi DB, Suàrez-Fernandez C, Rossi R, Vitali F, Marzi Manfroni A, Gabusi A, Morandi L, Balbi T, Montebugnoli L, Foschini MP, and Tarsitano A
- Subjects
- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Italy, Adult, Aged, 80 and over, Neoplasm Staging, Carcinoma, Squamous Cell economics, Carcinoma, Squamous Cell surgery, Carcinoma, Squamous Cell therapy, Mouth Neoplasms economics, Mouth Neoplasms surgery, Tertiary Care Centers economics, Health Care Costs
- Abstract
The aim of this study was to retrospectively evaluate the direct costs of OSCC treatment and postsurgical surveillance in a tertiary hospital in northeast Italy. Sixty-three consecutive patients surgically treated for primitive OSCC at S. Orsola Hospital in Bologna (Italy) between January 2018 and January 2020 were analyzed. Billing records of the Emilia Romagna healthcare system and institutional costs were used to derive specific costs for the following clinical categories: operating theatre costs, intensive and ordinary hospitalization, radiotherapy, chemotherapy, postsurgical complications, visits, and examinations during the follow-up period. The study population comprised 17 OSCC patients classified at stage I, 14 at stage II, eight at stage III, and 24 at stage IV. The estimated mean total direct cost for OSCC treatment and postsurgical surveillance was €26 338.48 per patient (stage I: €10 733, stage II: €19 642.9, stage III: €30 361.4, stage IV: €39 957.2). An advanced diagnosis (stages III and IV), complex surgical procedure, and loco-regional recurrences resulted in variables that were significantly associated with a higher cost of OSCC treatment and postsurgical surveillance. Redirection of funds used for OSCC treatment to screening measures may be an effective strategy to improve overall health outcomes and optimize national health resources., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
18. Thirteen-gene DNA methylation analysis of oral brushing samples: A potential surveillance tool for periodic monitoring of treated patients with oral cancer.
- Author
-
Gissi DB, Rossi R, Lenzi J, Tarsitano A, Gabusi A, Balbi T, Montebugnoli L, Marchetti C, Foschini MP, and Morandi L
- Subjects
- Humans, DNA Methylation, Case-Control Studies, Neoplasm Recurrence, Local genetics, Recurrence, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell surgery, Mouth Neoplasms genetics, Mouth Neoplasms surgery
- Abstract
Background: We evaluated the prognostic role of 13-gene DNA methylation analysis by oral brushing repeatedly performed during the follow-up of patients surgically treated for oral cancer., Methods: This is a nested case-control study including 61 patients for a total of 64 outcomes (2/61 patients experienced multiple relapses). Samples were collected at baseline (4-10 months after OSCC resection) and repeatedly every 4-10 months until relapse or death. DNA methylation scores were classified as persistently positive, persistently negative, or mixed., Results: Twenty cases who had persistently positive scores and 30 cases with mixed scores had, respectively, an almost 42-fold (p < 0.001) and 32-fold (p = 0.006) higher likelihood of relapse, compared to 14 patients with persistently negative scores. The last score before reoccurrence was positive in 18/19 secondary events., Conclusions: The 13-gene DNA methylation analysis may be considered for the surveillance of patients treated for oral carcinoma., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
19. Genomic Profiling of Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System Suggests Novel Potential Therapeutic Targets.
- Author
-
Agostinelli C, Morandi L, Righi S, Cirillo L, Iommi M, Tonon C, Mazzatenta D, Zoli M, Rossi M, Bagnato G, Broccoli A, Lodi R, Zinzani PL, Sabattini E, Giannini C, and Asioli S
- Subjects
- Humans, In Situ Hybridization, Fluorescence, Phosphatidylinositol 3-Kinases genetics, Central Nervous System metabolism, Central Nervous System pathology, Prognosis, Genomics, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 metabolism, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Primary diffuse large B-cell lymphoma of the primary central nervous system (CNS-DLBCL) is an aggressive disease, with dismal prognosis despite the use of high-dose methotrexate-based polychemotherapy. Our study aimed to expand the biologic profiles of CNS-DLBCL and to correlate them with clinical/imaging findings to gain diagnostic insight and possibly identify new therapeutic targets. We selected 61 CNS-DLBCL whose formalin-fixed paraffin-embedded samples were available at first diagnosis. These were investigated by immunohistochemistry, cMYC rearrangements were explored by fluorescence in situ hybridization, and CNS-DLBCL mutated genes were evaluated by next-generation sequencing. CD10, BCL6, and IRF4 were observed in 16%, 83.6%, and 93% of cases, respectively. As typical of CNS lymphoma, 10 (16.4%) of 61 cases were classified as germinal center (GCB) type and 51 (83.6%) of 61 as non-germinal center (non-GCB) type according to the Hans algorithm. Double-expression status for BCL2 and cMYC was detected in 36 (59%) of 61 cases whereas 25 (41%) of 61 were non-DE. Rearrangement of the cMYC gene was detected in 2 cases, associated with BCL6 translocation only in 1 case MYD88, PIM1, CD79B, and TP53 were mutated in 54.5%, 53.5%, 30.2%, and 18.4% cases, respectively. Novel mutations not previously reported in CNS-DLBCL were found: AIP in 23.1%, PI3KCA in 15%, NOTCH1 in 11.4%, GNAS in 8.1%, CASP8 in 7.9%, EGFR in 6.4%, PTEN in 5.1, and KRAS in 2.6% of cases. Survival was significantly longer for patients with mutated MYD88 (8.7 months vs 1.7 months; log-rank test = 5.43; P = .020) and for patients with mutated CD79B (10.8 months vs 2.5 months; log-rank test = 4.64; P = .031). MYD88 and CD79B predicted a longer survival in patients affected by CNS-DLBCL. Notably, we identified novel mutations that enrich the mutational landscape of CNS-DLBCL, suggest a role of PTEN-PI3K-AKT and receptor tyrosine kinase-RAS-mitogen-activated protein kinase signaling in a subset of CNS-DLBCL, and provide new potential therapeutic targets., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
20. SARS-CoV-2 infection as a model to study the effect of cinnamaldehyde as adjuvant therapy for viral pneumonia.
- Author
-
Vezzani B, Perrone M, Carinci M, Palumbo L, Tombolato A, Tombolato D, Daminato C, Gentili V, Rizzo R, Campo G, Morandi L, Papi A, Spadaro S, Casolari P, Contoli M, Pinton P, and Giorgi C
- Abstract
Background: The recent pandemic outbursts, due to SARS-CoV-2, have highlighted once more the central role of the inflammatory process in the propagation of viral infection. The main consequence of COVID-19 is the induction of a diffuse pro-inflammatory state, also defined as a cytokine storm, which affects different organs, but mostly the lungs. We aimed to prove the efficacy of cinnamaldehyde, the active compound of cinnamon, as an anti-inflammatory compound, able to reduce SARS-CoV-2 induced cytokine storm., Results: We enrolled 53 COVID-19 patients hospitalized for respiratory failure. The cohort was composed by 39 males and 13 females, aged 65.0 ± 9.8 years. We reported that COVID-19 patients have significantly higher IL-1β and IL-6 plasma levels compared to non-COVID-19 pneumonia patients. In addition, human mononuclear cells (PBMCs) isolated from SARS-CoV-2 infected patients are significantly more prone to release pro-inflammatory cytokines upon stimuli. We demonstrated, using in vitro cell models, that macrophages are responsible for mediating the pro-inflammatory cytokine storm while lung cells support SARS-CoV-2 replication upon viral infection. In this context, cinnamaldehyde administration significantly reduces SARS-CoV-2-related inflammation by inhibiting NLRP3 mediated IL-1β release in both PBMCs and THP-1 macrophages, as well as viral replication in CaLu-3 epithelial cells. Lastly, aerosol-administered cinnamaldehyde was able to significantly reduce IL-1β release in an in vivo lung-inflammatory model., Conclusion: The obtained results suggest the possible use of cinnamaldehyde as a co-adjuvant preventive treatment for COVID-19 disease together with vaccination, but also as a promising dietary supplement to reduce, more broadly, viral induced inflammation., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
21. Quadrato Motor Training (QMT) is associated with DNA methylation changes at DNA repeats: A pilot study.
- Author
-
Marson F, Zampieri M, Verdone L, Bacalini MG, Ravaioli F, Morandi L, Chiarella SG, Vetriani V, Venditti S, Caserta M, Raffone A, Dotan Ben-Soussan T, and Reale A
- Subjects
- Humans, Female, Pilot Projects, Epigenesis, Genetic, DNA, Ribosomal, DNA Methylation, Movement
- Abstract
The control of non-coding repeated DNA by DNA methylation plays an important role in genomic stability, contributing to health and healthy aging. Mind-body practices can elicit psychophysical wellbeing via epigenetic mechanisms, including DNA methylation. However, in this context the effects of movement meditations have rarely been examined. Consequently, the current study investigates the effects of a specifically structured movement meditation, called the Quadrato Motor Training (QMT) on psychophysical wellbeing and on the methylation level of repeated sequences. An 8-week daily QMT program was administered to healthy women aged 40-60 years and compared with a passive control group matched for gender and age. Psychological well-being was assessed within both groups by using self-reporting scales, including the Meaning in Life Questionnaire [MLQ] and Psychological Wellbeing Scale [PWB]). DNA methylation profiles of repeated sequences (ribosomal DNA, LINE-1 and Alu) were determined in saliva samples by deep-sequencing. In contrast to controls, the QMT group exhibited increased Search for Meaning, decreased Presence of Meaning and increased Positive Relations, suggesting that QMT may lessen the automatic patterns of thinking. In the QMT group, we also found site-specific significant methylation variations in ribosomal DNA and LINE-1 repeats, consistent with increased genome stability. Finally, the correlations found between changes in methylation and psychometric indices (MLQ and PWB) suggest that the observed epigenetic and psychological changes are interrelated. Collectively, the current results indicate that QMT may improve psychophysical health trajectories by influencing the DNA methylation of specific repetitive sequences., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Marson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
- Full Text
- View/download PDF
22. Natural Killer Cells in SARS-CoV-2-Vaccinated Subjects with Increased Effector Cytotoxic CD56 dim Cells and Memory-Like CD57 + NKG2C + CD56 dim Cells.
- Author
-
Gentili V, Bortolotti D, Morandi L, Rizzo S, Schiuma G, Beltrami S, Casciano F, Papi A, Contoli M, Zauli G, and Rizzo R
- Subjects
- Humans, SARS-CoV-2, COVID-19 Vaccines, Killer Cells, Natural, COVID-19 prevention & control, Antineoplastic Agents
- Abstract
Background: The infection and negative effects of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus) virus are mitigated by vaccines. It is unknown whether vaccination has worked by eliciting robust protective innate immune responses with high affinity., Methods: Twenty healthy volunteers received three doses of Comirnaty (Pfizer Australia Pty Ltd.) and were evaluated 9 months after the second vaccination and 1 month after the booster dose. The exclusion criteria were the presence of adverse effects following the vaccination, a history of smoking, and heterologous immunization. The inclusion criteria were the absence of prior Coronavirus Disease (COVID)-19 history, the absence of adverse effects, and the absence of comorbidities. Specific phenotype and levels of CD107a and granzyme production by blood NK (natural killer) cells were analyzed after exposure to SARS-CoV-2 spike antigen (Wuhan, Alpha B.1.1.7, Delta B.1.617.2, and Omicron B1.1.529 variants), and related with anti-SARS-CoV-2 antibody production., Results: The booster dose caused early NK CD56dim subset activation and memory-like phenotype., Conclusions: We report the relevance of the innate immune response, especially NK cells, to SARS-CoV-2 vaccines to guarantee efficient protection against the infection following a booster dose., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)
- Published
- 2023
- Full Text
- View/download PDF
23. Management of malignant pleural effusion in Italian clinical practice: a nationwide survey.
- Author
-
Mei F, Tamburrini M, Gonnelli F, Morandi L, Bonifazi M, Sediari M, Berardino ADM, Barisione E, Failla G, Zuccatosta L, Papi A, Gasparini S, and Marchetti G
- Subjects
- Humans, Talc, Pleura, Italy, Pleural Effusion, Malignant therapy, Pleural Diseases
- Abstract
Background: Pleural disease (PD), particularly malignant pleural effusion (MPE), is a common cause of hospital admission and its prevalence is rising worldwide. Recent advances in diagnostic and therapeutic options, such as Indwelling Pleural Catheters (IPCs), have simplified PD treatment, allowing an effective outpatients management. Therefore, dedicated pleural services can improve PD care, guaranteeing specialized management and optimizing time and cost. We aimed to provide an overview on MPE management in Italy, mainly focused on distribution and characteristics of pleural services and IPCs use., Methods: A nationwide survey, endorsed by the Italian Thoracic Society, was distributed by email to members of selected subgroups in 2021., Results: Ninety (23%) members replied, most of whom being pulmonologists (91%). MPE resulted the most common cause of pleural effusion and was managed with heterogenous approaches, including talc pleurodesis via slurry (43%), talc poudrage (31%), repeated thoracentesis (22%) and IPCs insertion (2%). The setting of IPC insertion was inpatient care in 48% of cases, with a predominance of draining frequency every other day. IPC management mainly relied on caregivers (42%). The presence of a pleural service was reported by 37% of respondents., Conclusions: The present study provides an extensive overview of MPE management in Italy, showing a highly heterogeneous approach, a scarce prevalence of out-patient pleural services, and a still limited adoption of IPCs, mainly due to lack of dedicated community care systems. This survey emphasizes the need of promoting a higher spreading of pleural services and an innovative healthcare delivery with more favourable cost-benefit ratio., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
24. Triple combination of lomustine, temozolomide and irradiation reduces canine glioma cell survival in vitro.
- Author
-
Fuchs D, Rohrer Bley C, Morandi L, Tonon C, Weyland MS, and Nytko KJ
- Subjects
- Animals, Dogs, Temozolomide pharmacology, Temozolomide therapeutic use, Lomustine therapeutic use, Lomustine pharmacology, Dacarbazine pharmacology, Dacarbazine therapeutic use, Cell Survival, Glioma veterinary, Glioma drug therapy, Dog Diseases drug therapy
- Abstract
Background: Combined chemoradiation offers a promising therapeutic strategy for dogs with glioma. The alkylating agents temozolomide (TMZ) and lomustine (CCNU) penetrate the blood-brain barrier, and doses for dogs are established. Whether such combinations are clinically advantageous remains to be explored together with tumour-specific markers., Objective: To investigate if triple combination of lomustine, temozolomide and irradiation reduces canine glioma cell survival in vitro., Methods: We evaluated the sensitising effect of CCNU alone and in combination with TMZ-irradiation in canine glioma J3T-BG cells and long-term drug-exposed subclones by using clonogenic survival and proliferation assays. Bisulphite-SEQ and Western Blot were used to investigate molecular alterations., Results: TMZ (200 μM) or CCNU alone (5 μM) reduced the irradiated survival fraction (4 Gy) from 60% to 38% (p = 0.0074) and 26% (p = 0.0002), respectively. The double-drug combination reduced the irradiated survival fraction (4 Gy) more potently to 12% (p < 0.0001). After long-term drug exposure, both subclones show higher IC
50 values against CCNU and TMZ. For CCNU-resistant cells, both, single-drug CCNU (p = 0.0006) and TMZ (p = 0.0326) treatment combined with irradiation (4 Gy) remained effective. The double-drug-irradiation combination reduced the cell survival by 86% (p < 0.0001), compared to 92% in the parental (nonresistant) cell line. For TMZ-resistant cells, only the double-drug combination with irradiation (4 Gy) reduced the cell survival by 88% (p = 0.0057) while single-drug treatment lost efficacy. Chemoresistant cell lines demonstrated higher P-gp expression while MGMT-methylation profile analysis showed a general high methylation level in the parental and long-term treated cell lines., Conclusions: Our findings indicate that combining CCNU with TMZ-irradiation significantly reduces canine glioma cell survival. Such a combination could overcome current challenges of therapeutic resistance to improve overall patient survival., (© 2023 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)- Published
- 2023
- Full Text
- View/download PDF
25. Shared epigenetic alterations between oral cancer and periodontitis: A preliminary study.
- Author
-
Gabusi A, Gissi DB, Grillini S, Stefanini M, Tarsitano A, Marchetti C, Foschini MP, Montebugnoli L, and Morandi L
- Subjects
- Humans, DNA Methylation, Squamous Cell Carcinoma of Head and Neck genetics, Epigenesis, Genetic, Mouth Neoplasms pathology, Carcinoma, Squamous Cell pathology, Periodontitis genetics, Head and Neck Neoplasms genetics
- Abstract
Introduction: We recently developed a non-invasive sampling procedure for oral squamous cell carcinoma (OSCC) detection based on DNA methylation analysis of a panel of 13 genes. Oral cancer, as well as acute and chronic inflammatory diseases, may influence the methylation level of several genes in the oral cavity. In the present study, we evaluated the presence of periodontal disease (PD) and the methylation status using our 13-gene panel., Methods: Oral brushing specimens were collected from three different patient groups: 23 gingival OSCC patients, 15 patients affected by PD, and 15 healthy volunteers lacking evidence of PD. DNA methylation analysis was performed and each sample was determined to be positive or negative based on a predefined cut-off value., Results: Positive results were found for 23/23 OSCC patients, 3/15 PD patients, and 0/15 samples from healthy volunteers. The GP1BB and MIR193 genes in the PD group exhibited mean methylation levels similar to OSCC patients. ZAP70 showed different methylation levels among three groups., Conclusion: Preliminary data identified shared epigenetic alterations between PD and OSCC patients in two inflammatory genes (GP1BB and MIR193). This study may help to identify potential links between the two diseases and serve as a starting point for the future research focused on pathogenesis., (© 2022 The Authors. Oral Diseases published by Wiley Periodicals LLC.)
- Published
- 2023
- Full Text
- View/download PDF
26. Phospholipases in Gliomas: Current Knowledge and Future Perspectives from Bench to Bedside.
- Author
-
Marvi MV, Neri I, Evangelisti C, Ramazzotti G, Asioli S, Zoli M, Mazzatenta D, Neri N, Morandi L, Tonon C, Lodi R, Franceschi E, McCubrey JA, Suh PG, Manzoli L, and Ratti S
- Subjects
- Humans, Phospholipases metabolism, Brain metabolism, Phospholipids, Brain Neoplasms therapy, Glioma therapy
- Abstract
Phospholipases are essential intermediaries that work as hydrolyzing enzymes of phospholipids (PLs), which represent the most abundant species contributing to the biological membranes of nervous cells of the healthy human brain. They generate different lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid, representing key elements of intra- and inter-cellular signaling and being involved in the regulation of several cellular mechanisms that can promote tumor progression and aggressiveness. In this review, it is summarized the current knowledge about the role of phospholipases in brain tumor progression, focusing on low- and high-grade gliomas, representing promising prognostic or therapeutic targets in cancer therapies due to their influential roles in cell proliferation, migration, growth, and survival. A deeper understanding of the phospholipases-related signaling pathways could be necessary to pave the way for new targeted therapeutic strategies.
- Published
- 2023
- Full Text
- View/download PDF
27. Epigenomic and somatic mutations of pituitary tumors with clinical and pathological correlations in 111 patients.
- Author
-
Guaraldi F, Morandi L, Zoli M, Mazzatenta D, Righi A, Evangelisti S, Ambrosi F, Tonon C, Giannini C, Lloyd RV, and Asioli S
- Subjects
- Male, Humans, Epigenomics, Transcription Factors genetics, Mutation genetics, Cell Cycle Proteins genetics, Molecular Chaperones genetics, Pituitary Neoplasms genetics, Pituitary Neoplasms pathology, RNA, Long Noncoding, Adenoma genetics, Adenoma pathology, Neuroendocrine Tumors pathology, MicroRNAs genetics
- Abstract
Objective: To profile clinically non-aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation/differentiation, microRNAs (miRNA)/long noncoding RNA (LncRNA)-post-transcriptional regulators and therapy targets., Design: Retrospective observational study., Patients and Measurements: A total of 64 non-aggressive and 41 aggressive PAs/PitNETs and 6 pituitary carcinomas treated by endoscopic surgery with ≥1-year follow-up were included. Somatic mutations of 17 genes and DNA methylation of 22 genes were assessed. Ten normal pituitaries were used as control., Results: We found at least one mutation in 17 tumours, including 6/64 non-aggressive, 10/41 aggressive PAs/PitNETs, and 1/6 pituitary carcinoma. AIP (N = 6) was the most frequently mutated gene, followed by NOTCH (4), and TP53 (3). Hypermethylation of PARP15, LINC00599, ZAP70 was more common in aggressive than non-aggressive PAs/PITNETs (p < .05). Lower levels of methylation of AIP, GNAS and PDCD1 were detected in aggressive PAs/PITNETs than non-aggressive ones (p < .05). For X-linked genes, males presented higher level of methylation of FLNA, UXT and MAGE family (MAGEA11, MAGEA1, MAGEC2) genes in aggressive vs. non-aggressive PAs/PITNETs (p < .05). In pituitary carcinomas, methylation of autosomal genes PARP15, LINC00599, MIR193 and ZAP70 was higher than in PAs/PITNETs, while X-linked genes methylation level was lower., Conclusions: Somatic mutations and methylation levels of genes involved in cell proliferation/differentiation, miRNA/LncRNA-post-transcriptional regulators and targets of antineoplastic therapies are different in non-aggressive and in aggressive PAs/PitNETs. Methylation profile also varies according to gender. Combined genetic-epigenetic analysis, in association with clinico-radiological-pathological data, may be of help in predicting PA/PitNET behaviour., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
28. The Additional Value of Lower Respiratory Tract Sampling in the Diagnosis of COVID-19: A Real-Life Observational Study.
- Author
-
Morandi L, Torsani F, Forini G, Tamburrini M, Carnevale A, Pecorelli A, Giganti M, Piattella M, Guzzinati I, Papi A, and Contoli M
- Abstract
Background: Since December 2019, SARS-CoV-2 has been causing cases of severe pneumonia in China and has spread all over the world, putting great pressure on health systems. Nasopharyngeal swab (NPS) sensitivity is suboptimal. When the SARS-CoV-2 infection is suspected despite negative NPSs, other tests may help to rule out the infection. Objectives: To evaluate the yield of the lower respiratory tract (LRT) isolation of SARS-CoV-2. To evaluate the correlations between SARS-CoV-2 detection and clinical symptoms, and laboratory values and RSNA CT review scores in suspect patients after two negative NPSs. To assess the safety of bronchoscopy in this scenario. Method: A retrospective analysis of data from LRT sampling (blind nasotracheal aspiration or bronchial washing) for suspected COVID-19 after two negative NPS. Chest CT scans were reviewed by two radiologists using the RSNA imaging classification. Results: SARS-CoV-2 was detected in 14/99 patients (14.1%). A correlation was found between SARS-CoV2 detection on the LRT and the presence of a cough as well as with typical CT features. Typical CT resulted in 57.1% sensitivity, 80.8% accuracy and 92.3% NPV. Neither severe complications nor infections in the personnel were reported. Conclusions: In suspect cases after two negative swabs, CT scan revision can help to rule out COVID-19. In selected cases, with consistent CT features above all, LRT sampling can be of help in confirming COVID-19., Competing Interests: Dr Morandi, L. reports personal fees from Boehringer Ingelheim and Chiesi Farmaceutici outside the submitted work. Dr Contoli reports grants, personal fees and nonfinancial support from Chiesi; personal fees and nonfinancial support from AstraZeneca; personal fees and nonfinancial support from Boehringer Ingelheim; personal fees and nonfinancial support from Alk-Abello; grants, personal fees and nonfinancial support from GlaxoSmithKline; personal fees and nonfinancial support from Novartis; personal fees and nonfinancial support from Zambon; and grants from the University of Ferrara, Italy, outside the submitted work. Dr Papi, A. reports grants, personal fees, nonfinancial support from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici TEVA and Sanofi/Regeneron; personal fees, nonfinancial support from Mundipharma, Zambon and Novartis; grants, personal fees and nonfinancial support from Menarini; personal fees from Roche; grants from Fondazione Maugeri; grants from Fondazione Chiesi; and personal fees from Edmondpharma, outside the submitted work. Drs Torsani, F., Forini, G., Padovani, M., Carnevale, A., Pecorelli, A., Piattella, M. and Guzzinati, I. report no conflict of interest for the present work.
- Published
- 2022
- Full Text
- View/download PDF
29. In Vivo Parieto-Occipital White Matter Metabolism Is Correlated with Visuospatial Deficits in Adult DM1 Patients.
- Author
-
Evangelisti S, Gramegna LL, De Pasqua S, Rochat MJ, Morandi L, Mitolo M, Bianchini C, Vornetti G, Testa C, Avoni P, Liguori R, Lodi R, and Tonon C
- Abstract
Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by a (CTG) expansion in the DM protein kinase (DMPK) gene, representing the most common adult muscular dystrophy, characterized by a multisystem involvement with predominantly skeletal muscle and brain affection. Neuroimaging studies showed widespread white matter changes and brain atrophy in DM1, but only a few studies investigated the role of white matter metabolism in the pathophysiology of central nervous system impairment. We aim to reveal the relationship between the metabolic profile of parieto-occipital white matter (POWM) as evaluated with proton MR spectroscopy technique, with the visuoperceptual and visuoconstructional dysfunctions in DM1 patients. MR spectroscopy (3 Tesla) and neuropsychological evaluations were performed in 34 DM1 patients (19 F, age: 46.4 ± 12.1 years, disease duration: 18.7 ± 11.6 years). The content of neuro-axonal marker N-acetyl-aspartate, both relative to Creatine (NAA/Cr) and to myo-Inositol (NAA/mI) resulted significantly lower in DM1 patients compared to HC (p-values < 0.0001). NAA/Cr and NAA/mI correlated with the copy of the Rey-Osterrieth complex figure (r = 0.366, p = 0.033; r = 0.401, p = 0.019, respectively) and with Street’s completion tests scores (r = 0.409, p = 0.016; r = 0.341, p = 0.048 respectively). The proportion of white matter hyperintensities within the MR spectroscopy voxel did not correlate with the metabolite content. In this study, POWM metabolic alterations in DM1 patients were not associated with the white matter morphological changes and correlated with specific neuropsychological deficits.
- Published
- 2022
- Full Text
- View/download PDF
30. Humoral and adaptive immune responses to the SARS-CoV-2 vaccine.
- Author
-
Rizzo R, Bortolotti D, Morandi L, Rizzo S, Schiuma G, Beltrami S, Papi A, and Contoli M
- Subjects
- Antibodies, Neutralizing, Antibodies, Viral, COVID-19 Vaccines, Humans, Immunity, Humoral, SARS-CoV-2, Vaccination, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention & control, Viral Vaccines
- Abstract
Vaccines against SARS-CoV-2 ameliorate infection and adverse outcomes from SARS-CoV-2. Elicitation of high affinity and durable protective antibody responses is a hallmark of a successful humoral immune response to vaccination. To assess the relevance of serum levels of SARS-CoV-2 specific antibodies and to further characterize the immune response to SARS-CoV-2 vaccines, we report i) the levels of spike-binding and neutralizing antibodies to SARS-COV-2 in the sera of 30 healthy volunteers at nine months after the second vaccination dose of mRNA vaccine and one month after the booster dose; ii) the levels of IFN-γ production by blood T cells exposed to SARS-CoV-2 spike antigen (Wuhan, Alpha B.1.1.7, Delta B.1.617.2, and Omicron B1.1.529 variants); and iii) the specific phenotype of T cells related with exposure to SARS-CoV-2 spike antigen. We observed that the booster dose induced increased humoral and adaptive immune responses and led to early activation of the memory CD8+ T subset., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
31. Case Report: Optic Atrophy and Nephropathy With m.13513G>A/MT-ND5 mtDNA Pathogenic Variant.
- Author
-
Barone V, La Morgia C, Caporali L, Fiorini C, Carbonelli M, Gramegna LL, Bartiromo F, Tonon C, Morandi L, Liguori R, Petrini A, Brugnano R, Del Sordo R, Covarelli C, Morroni M, Lodi R, and Carelli V
- Abstract
Isolated complex I deficiency represents the most common mitochondrial respiratory chain defect involved in mitochondrial disorders. Among these, the mitochondrial DNA (mtDNA) m.13513G>A pathogenic variant in the NADH dehydrogenase 5 subunit gene (MT-ND5) has been associated with heterogenous manifestations, including phenotypic overlaps of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes, Leigh syndrome, and Leber's hereditary optic neuropathy (LHON). Interestingly, this specific mutation has been recently described in patients with adult-onset nephropathy. We, here, report the unique combination of LHON, nephropathy, sensorineural deafness, and subcortical and cerebellar atrophy in association with the m.13513G>A variant., Competing Interests: VC acts as a consultant on boards for GenSight Biologics, Chiesi Farmaceutici, Stealth Biotherapeutics, and Pretzel Therapeutics and is PI in sponsored clinical trials by Santhera Pharmaceuticals, GenSight Biologics, Stealth Biotherapeutics. CL: consultancies for Chiesi Farmaceutici, Regulatory Pharma Net, and Thenewway srl; speaker honoraria from Santhera Pharmaceuticals, Chiesi Farmaceutici, Regulatory Pharma Net, Thenewway srl, First Class srl, and Biologix; PI/SI for clinical trials sponsored GenSight Biologics and Santhera Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barone, La Morgia, Caporali, Fiorini, Carbonelli, Gramegna, Bartiromo, Tonon, Morandi, Liguori, Petrini, Brugnano, Del Sordo, Covarelli, Morroni, Lodi and Carelli.)
- Published
- 2022
- Full Text
- View/download PDF
32. Neuroplasticity Mechanisms in Frontal Brain Gliomas: A Preliminary Study.
- Author
-
Mitolo M, Zoli M, Testa C, Morandi L, Rochat MJ, Zaccagna F, Martinoni M, Santoro F, Asioli S, Badaloni F, Conti A, Sturiale C, Lodi R, Mazzatenta D, and Tonon C
- Abstract
Background: Pathological brain processes may induce adaptive cortical reorganization, however, the mechanisms underlying neuroplasticity that occurs in the presence of lesions in eloquent areas are not fully explained. The aim of this study was to evaluate functional compensatory cortical activations in patients with frontal brain gliomas during a phonemic fluency task and to explore correlations with cognitive performance, white matter tracts microstructural alterations, and tumor histopathological and molecular characterization., Methods: Fifteen patients with frontal glioma were preoperatively investigated with an MRI study on a 3T scanner and a subgroup underwent an extensive neuropsychological assessment. The hemispheric laterality index (LI) was calculated through phonemic fluency task functional MRI (fMRI) activations in the frontal, parietal, and temporal lobe parcellations. Diffusion-weighted images were acquired for all patients and for a group of 24 matched healthy volunteers. Arcuate Fasciculus (AF) and Frontal Aslant Tract (FAT) tractography was performed using constrained spherical deconvolution diffusivity modeling and probabilistic fiber tracking. All patients were operated on with a resective aim and underwent adjuvant therapies, depending on the final diagnosis., Results: All patients during the phonemic fluency task fMRI showed left hemispheric dominance in temporal and parietal regions. Regarding frontal regions (i.e., frontal operculum) we found right hemispheric dominance that increases when considering only those patients with tumors located on the left side. These latter activations positively correlate with verbal and visuo-spatial short-term memory, and executive functions. No correlations were found between the left frontal operculum and cognitive performance. Furthermore, patients with IDH-1 mutation and without TERT mutation, showed higher rightward frontal operculum fMRI activations and better cognitive performance in tests measuring general cognitive abilities, semantic fluency, verbal short-term memory, and executive functions. As for white matter tracts, we found left and right AF and FAT microstructural alterations in patients with, respectively, left-sided and right-side glioma compared to controls., Conclusions: Compensatory cortical activation of the corresponding region in the non-dominant hemisphere and its association with better cognitive performance and more favorable histopathological and molecular tumor characteristics shed light on the neuroplasticity mechanisms that occur in the presence of a tumor, helping to predict the rate of post-operative deficit, with the final goal of improving patients'quality of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mitolo, Zoli, Testa, Morandi, Rochat, Zaccagna, Martinoni, Santoro, Asioli, Badaloni, Conti, Sturiale, Lodi, Mazzatenta and Tonon.)
- Published
- 2022
- Full Text
- View/download PDF
33. DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome.
- Author
-
Ravaioli F, Zampieri M, Morandi L, Pirazzini C, Pellegrini C, De Fanti S, Gensous N, Pirazzoli GL, Sambati L, Ghezzo A, Ciccarone F, Reale A, Monti D, Salvioli S, Caiafa P, Capri M, Bürkle A, Moreno-Villanueva M, Garagnani P, Franceschi C, and Bacalini MG
- Abstract
Control of ribosome biogenesis is a critical aspect of the regulation of cell metabolism. As ribosomal genes (rDNA) are organized in repeated clusters on chromosomes 13, 14, 15, 21, and 22, trisomy of chromosome 21 confers an excess of rDNA copies to persons with Down syndrome (DS). Previous studies showed an alteration of ribosome biogenesis in children with DS, but the epigenetic regulation of rDNA genes has not been investigated in adults with DS so far. In this study, we used a targeted deep-sequencing approach to measure DNA methylation (DNAm) of rDNA units in whole blood from 69 adults with DS and 95 euploid controls. We further evaluated the expression of the precursor of ribosomal RNAs (RNA45S) in peripheral blood mononuclear cells (PBMCs) from the same subjects. We found that the rDNA promoter tends to be hypermethylated in DS concerning the control group. The analysis of epihaplotypes (the combination of methylated and unmethylated CpG sites along the same DNA molecule) showed a significantly lower intra-individual diversity in the DS group, which at the same time was characterized by a higher interindividual variability. Finally, we showed that RNA45S expression is lower in adults with DS. Collectively, our results suggest a rearrangement of the epigenetic profile of rDNA in DS, possibly to compensate for the extranumerary rDNA copies. Future studies should assess whether the regulation of ribosome biogenesis can contribute to the pathogenesis of DS and explain the clinical heterogeneity characteristic of the syndrome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AT declared a shared affiliation with the authors MZ, AR, and PC to the handling editor at the time of review., (Copyright © 2022 Ravaioli, Zampieri, Morandi, Pirazzini, Pellegrini, De Fanti, Gensous, Pirazzoli, Sambati, Ghezzo, Ciccarone, Reale, Monti, Salvioli, Caiafa, Capri, Bürkle, Moreno-Villanueva, Garagnani, Franceschi and Bacalini.)
- Published
- 2022
- Full Text
- View/download PDF
34. Impact of phospholipase C β1 in glioblastoma: a study on the main mechanisms of tumor aggressiveness.
- Author
-
Ratti S, Marvi MV, Mongiorgi S, Obeng EO, Rusciano I, Ramazzotti G, Morandi L, Asioli S, Zoli M, Mazzatenta D, Suh PG, Manzoli L, and Cocco L
- Subjects
- Cell Proliferation genetics, Humans, Phospholipase C beta genetics, Phospholipase C beta metabolism, Brain Neoplasms genetics, Brain Neoplasms pathology, Glioblastoma pathology, Glioma pathology
- Abstract
Glioblastoma represents the most lethal brain tumor in adults. Several studies have shown the key role of phospholipase C β1 (PLCβ1) in the regulation of many mechanisms within the central nervous system suggesting PLCβ1 as a novel signature gene in the molecular classification of high-grade gliomas. This study aims to determine the pathological impact of PLCβ1 in glioblastoma, confirming that PLCβ1 gene expression correlates with glioma's grade, and it is lower in 50 glioblastoma samples compared to 20 healthy individuals. PLCβ1 silencing in cell lines and primary astrocytes, leads to increased cell migration and invasion, with the increment of mesenchymal transcription factors and markers, as Slug and N-Cadherin and metalloproteinases. Cell proliferation, through increased Ki-67 expression, and the main survival pathways, as β-catenin, ERK1/2 and Stat3 pathways, are also affected by PLCβ1 silencing. These data suggest a potential role of PLCβ1 in maintaining a normal or less aggressive glioma phenotype., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
35. Endometrioid Cancer Associated With Endometriosis: From the Seed and Soil Theory to Clinical Practice.
- Author
-
Farolfi A, Altavilla A, Morandi L, Capelli L, Chiadini E, Prisinzano G, Gurioli G, Molari M, Calistri D, Foschini MP, and De Giorgi U
- Abstract
Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. It is still debated whether endometriosis is a disease that can predispose to the pathogenesis of endometrial cancer outside the uterus. Deficiencies in mismatch repair (MMR) genes are a known risk factor for developing endometrioid cancer. Starting from two cases of patients with abnormal MMR endometrioid carcinoma of the uterus and synchronous endometrioid carcinoma in non-ovarian and ovarian endometriosis, we performed a somatic mutation profile and phylogenetic analysis of the lesions in order to identify if they were metastasis or primary de novo tumors. In the first case, we identified de novo activating mutations in PIK3CA and KRAS in endometrioid cancer lesions but not in endometriosis. Although the acquisition of a de novo mutation in ESR1 and a decrease in mutant allele fraction (MAF) from the endometrial tumor to the localizations in the endometriosis lesions, the clonal relationship was confirmed by the limited number of heteroplasmic mutations in D-loop mitochondrial DNA region. In the other case, the clonal behavior was demonstrated by the overlap of MAF at each site. Our data support the hypothesis of a retrograde dissemination of tumor cells, moving from the primary carcinoma in the endometrium to ectopic sites of endometriosis where localizations of tumor arise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Farolfi, Altavilla, Morandi, Capelli, Chiadini, Prisinzano, Gurioli, Molari, Calistri, Foschini and De Giorgi.)
- Published
- 2022
- Full Text
- View/download PDF
36. Molecular Fingerprint of BMD Patients Lacking a Portion in the Rod Domain of Dystrophin.
- Author
-
Capitanio D, Moriggi M, Barbacini P, Torretta E, Moroni I, Blasevich F, Morandi L, Mora M, and Gelfi C
- Subjects
- Exons genetics, Humans, Muscles metabolism, Phenotype, Tandem Mass Spectrometry, Dystrophin genetics, Dystrophin metabolism, Muscular Dystrophy, Duchenne genetics
- Abstract
BMD is characterized by a marked heterogeneity of gene mutations resulting in many abnormal dystrophin proteins with different expression and residual functions. The smaller dystrophin molecules lacking a portion around exon 48 of the rod domain, named the D8 region, are related to milder phenotypes. The study aimed to determine which proteins might contribute to preserving muscle function in these patients. Patients were subdivided, based on the absence or presence of deletions in the D8 region, into two groups, BMD1 and BMD2. Muscle extracts were analyzed by 2-D DIGE, label-free LC-ESI-MS/MS, and Ingenuity pathway analysis (IPA). Increased levels of proteins typical of fast fibers and of proteins involved in the sarcomere reorganization characterize BMD2. IPA of proteomics datasets indicated in BMD2 prevalence of glycolysis and gluconeogenesis and a correct flux through the TCA cycle enabling them to maintain both metabolism and epithelial adherens junction. A 2-D DIGE analysis revealed an increase of acetylated proteoforms of moonlighting proteins aldolase, enolase, and glyceraldehyde-3-phosphate dehydrogenase that can target the nucleus promoting stem cell recruitment and muscle regeneration. In BMD2, immunoblotting indicated higher levels of myogenin and lower levels of PAX7 and SIRT1/2 associated with a set of proteins identified by proteomics as involved in muscle homeostasis maintenance.
- Published
- 2022
- Full Text
- View/download PDF
37. A 13-Gene DNA Methylation Analysis Using Oral Brushing Specimens as an Indicator of Oral Cancer Risk: A Descriptive Case Report.
- Author
-
Rossi R, Gissi DB, Gabusi A, Fabbri VP, Balbi T, Tarsitano A, and Morandi L
- Abstract
Analysis of genetic or epigenetic markers from saliva or brushing specimens has been proposed as a diagnostic aid to identify patients at risk of developing oral cancer. However, no reliable non-invasive molecular method for this purpose is commercially available. In the present report, we describe the potential application of a procedure based on a 13-gene DNA methylation analysis using oral brushing samples from a patient affected by oral leukoplakia who developed two metachronous oral carcinomas during the follow-up period. A positive or a negative score was calculated for each brushing sample based on a predefined cut-off value. In this patient, a positive score was detected in the oral leukoplakia diagnosed more than 2 years before the development of oral squamous cell carcinoma and subsequently in clinically healthy mucosa 8 months before the appearance of a secondary tumor. This suggests a potential role of our procedure as an indicator of oral cancer risk.
- Published
- 2022
- Full Text
- View/download PDF
38. Role of PLCγ1 in the modulation of cell migration and cell invasion in glioblastoma.
- Author
-
Marvi MV, Mongiorgi S, Ramazzotti G, Follo MY, Billi AM, Zoli M, Mazzatenta D, Morandi L, Asioli S, Papa V, McCubrey JA, Suh PG, Manzoli L, Cocco L, and Ratti S
- Subjects
- Animals, Cell Line, Tumor, Cell Movement, Cell Proliferation, Gene Expression Regulation, Neoplastic, Humans, Neoplasm Invasiveness genetics, Rats, Signal Transduction, Brain Neoplasms metabolism, Glioblastoma pathology
- Abstract
Phosphoinositide-specific phospholipases C (PLCs) are a class of enzymes involved in several cell activities, such as cell cycle regulation, proliferation, differentiation and cytoskeletal dynamics. Among these enzymes, PLCγ1 is one of the most expressed PLCs in the brain, contributing to a complex network in the developing nervous system. Several studies have shown that PLCγ1 signaling imbalance is linked to several brain disorders, including glioblastoma, the most aggressive brain tumor in adults. Indeed, it has been demonstrated a link between PLCγ1 inhibition and the arrest of glioma cell motility of fetal rat brain aggregates and the impairment of cell invasion abilities following its down-regulation. This study aims to determine the pathological influence of PLCγ1 in glioblastoma, through a translational study which combines in silico data, data from glioblastoma patients' samples and data on engineered cell lines. We found out that PLCγ1 gene expression correlates with the pathological grade of gliomas, and it is higher in fifty patients' glioblastoma tissue samples compared to twenty healthy controls. Moreover, it was demonstrated that PLCγ1 silencing in U87-MG leads to a reduction in cell migration and invasion abilities. The opposite trend was observed following PLCγ1 overexpression, suggesting an interesting possible involvement of PLCγ1 in gliomas' aggressiveness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
39. Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines.
- Author
-
Tresch NS, Fuchs D, Morandi L, Tonon C, Rohrer Bley C, and Nytko KJ
- Subjects
- Animals, Cell Line, DNA Modification Methylases genetics, DNA Modification Methylases metabolism, DNA Repair Enzymes genetics, DNA Repair Enzymes metabolism, Dacarbazine pharmacology, Dogs, Humans, Temozolomide pharmacology, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Brain Neoplasms drug therapy, Brain Neoplasms radiotherapy, Brain Neoplasms veterinary, Dog Diseases drug therapy, Dog Diseases radiotherapy, Glioma drug therapy, Glioma radiotherapy, Glioma veterinary
- Abstract
Background: Similar to human glioblastoma patients, glial tumours in dogs have high treatment resistance and a guarded prognosis. In human medicine, the addition of temozolomide to radiotherapy leads to a favourable outcome in vivo as well as a higher antiproliferative effect on tumour cells in vitro., Objectives: The aim of the study was to determine the radio- and temozolomide-sensitivity of three canine glial tumour cell lines and to investigate a potential additive cytotoxic effect in combined treatment. Additionally, we wanted to detect the level of MGMT promoter methylation in these cell lines and to investigate a potential association between MGMT promoter methylation and treatment resistance., Methods: Cells were treated with various concentrations of temozolomide and/or irradiated with 4 and 8 Gy. Radiosensitization by temozolomide was evaluated using proliferation assay and clonogenic assay, and MGMT DNA methylation was investigated using bisulfite next-generation sequencing., Results: In all tested canine cell lines, clonogenicity was inhibited significantly in combined treatment compared to radiation alone. All canine glial cell lines tested in this study were found to have high methylation levels of MGMT promoter., Conclusions: Hence, an additive effect of combined treatment in MGMT negative canine glial tumour cell lines in vitro was detected. This motivates to further investigate the association between treatment resistance and MGMT, such as MGMT promoter methylation status., (© 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
40. Validation of oral brushing as a non-invasive technique for the identification of feline oral squamous cell carcinoma by DNA methylation and TP53 mutation analysis.
- Author
-
Renzi A, Morandi L, Bellei E, Marconato L, Rigillo A, Aralla M, Lenzi J, Bettini G, Tinto D, and Sabattini S
- Subjects
- Animals, Cats, Mutation, Prospective Studies, Reproducibility of Results, Cat Diseases diagnosis, Cat Diseases genetics, DNA Methylation, Mouth Neoplasms diagnosis, Mouth Neoplasms genetics, Mouth Neoplasms veterinary, Squamous Cell Carcinoma of Head and Neck diagnosis, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck veterinary, Tumor Suppressor Protein p53 genetics
- Abstract
Feline oral squamous cell carcinoma (FOSCC) is a frequent and progressively invasive tumour. Early lesions are difficult to recognize based on the sole clinical examination and may be misinterpreted as non-neoplastic. Mutations of TP53 and epigenetic alterations of specific genes are present in FOSCC and may be early detected. Aim of this prospective study was to investigate the DNA methylation pattern of a 17-gene panel and TP53 mutational status of FOSCC cytological samples obtained by oral brushing. Results were compared with a control group, in order to validate this non-invasive procedure for the screening of FOSCC. In FOSCC, the same analyses were carried out on the corresponding histological sample, if available. Thirty-five FOSCC and 60 controls were included. Mutations of TP53 were detected in 17 FOSCC brushings (48%) and in none of the controls (P < .001). Six genes (ZAP70, FLI1, MiR124-1, KIF1A, MAGEC2 and MiR363) were differentially methylated in FOSCC and were included in a methylation score. An algorithm based on TP53 mutational status and methylation score allowed to differentiate FOSCC from controls with a 69% sensitivity and a 97% specificity (accuracy, 86%). In 19 FOSCC histological samples, TP53 mutational status was fully concordant with brushings and a positive methylation score was observed in all cases. These results are promising for the identification of FOSCC by oral brushing, although some factors may limit the accuracy of this technique and further studies are required to assess its reproducibility in clinical practice., (© 2021 John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
41. Intron 4-5 hTERT DNA Hypermethylation in Merkel Cell Carcinoma: Frequency, Association with Other Clinico-pathological Features and Prognostic Relevance.
- Author
-
Ricci C, Morandi L, Ambrosi F, Righi A, Gibertoni D, Maletta F, Agostinelli C, Corradini AG, Uccella S, Asioli S, Sessa F, La Rosa S, Papotti MG, and Asioli S
- Subjects
- Aged, Aged, 80 and over, Carcinoma, Merkel Cell mortality, Carcinoma, Merkel Cell pathology, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Prognosis, Skin Neoplasms mortality, Skin Neoplasms pathology, Carcinoma, Merkel Cell genetics, DNA Methylation genetics, Skin Neoplasms genetics, Telomerase genetics
- Abstract
Merkel cell carcinoma (MCC) is an aggressive skin tumor with neuroendocrine differentiation, mainly affecting elderly population or immunocompromised individuals. As methylation of the human telomerase reverse transcriptase (mhTERT) has been shown to be a prognostic factor in different tumors, we investigated its role in MCC, in particular in intron 4-5 where rs10069690 has been mapped and recognized as a cancer susceptibility locus. DNA methylation analysis of hTERT gene was assessed retrospectively in a cohort of 69 MCC patients from the University of Bologna, University of Turin and University of Insubria. Overall mortality was evaluated with Kaplan-Meier curves and multivariable Royston-Parmar models. High levels of mhTERT (mhTERT
high ) (HR = 2.500, p = 0.015) and p63 (HR = 2.659, p = 0.016) were the only two clinico-pathological features significantly associated with a higher overall mortality at the multivariate analysis. We did not find different levels of mhTERT between MCPyV (+) and (-) cases (21 vs 14, p = 0.554); furthermore, mhTERThigh was strongly associated with older age (80.5 vs 72 years, p = 0.026), no angioinvasion (40.7% vs 71.0%, p = 0.015), lower Ki67 (50 vs 70%, p = 0.005), and PD-L1 expressions in both tumor (0 vs 3%, p = 0.021) and immune cells (0 vs 10%, p = 0.002). mhTERT is a frequently involved epigenetic mechanism and a relevant prognostic factor in MCC. In addition, it belongs to the shared oncogenic pathways of MCC (MCPyV and UV-radiations) and it could be crucial, together with other epigenetic and genetic mechanisms as gene amplification, in determining the final levels of hTERT mRNA and telomerase activity in these patients., (© 2021. The Author(s).)- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.