202 results on '"Mancuso, Mariateresa"'
Search Results
2. Microsecond Pulsed Electric Fields: An Effective Way to Selectively Target and Radiosensitize Medulloblastoma Cancer Stem Cells
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Tanori, Mirella, Casciati, Arianna, Zambotti, Alessandro, Pinto, Rosanna, Gianlorenzi, Isabella, Pannicelli, Alessandro, Giardullo, Paola, Benassi, Barbara, Marino, Carmela, Mancuso, Mariateresa, and Merla, Caterina
- Published
- 2021
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3. Exposure of the SH-SY5Y Human Neuroblastoma Cells to 50-Hz Magnetic Field: Comparison Between Two-Dimensional (2D) and Three-Dimensional (3D) In Vitro Cultures
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Consales, Claudia, Butera, Alessio, Merla, Caterina, Pasquali, Emanuela, Lopresto, Vanni, Pinto, Rosanna, Pierdomenico, Maria, Mancuso, Mariateresa, Marino, Carmela, and Benassi, Barbara
- Published
- 2021
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4. On the effects of 30.5 GHz sinusoidal wave exposure on glioblastoma organoids.
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Rampazzo, Elena, Persano, Luca, Karim, Nissar, Hodgking, George, Pinto, Rosanna, Casciati, Arianna, Tanori, Mirella, Zambotti, Alessandro, Bresolin, Silvia, Cani, Alice, Pannicelli, Alessandro, Davies, Ilan W., Hancock, Cristopher, Palego, Cristiano, Viola, Giampietro, Mancuso, Mariateresa, and Merla, Caterina
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GLIOBLASTOMA multiforme ,BRAIN tumors ,MILLIMETER waves ,ORGANOIDS ,ROOT-mean-squares ,MEDICAL dosimetry - Abstract
Introduction: Glioblastoma (grade IV) is the most aggressive primary brain tumor in adults, representing one of the biggest therapeutic challenges due to its highly aggressive nature. In this study, we investigated the impact of millimeter waves on tridimensional glioblastoma organoids derived directly from patient tumors. Our goal was to explore novel therapeutic possibilities in the fight against this challenging disease. Methods: The exposure setup was meticulously developed in-house, and we employed a comprehensive dosimetry approach, combining numerical and experimental methods. Biological endpoints included a global transcriptional profiling analysis to highlight possible deregulated pathways, analysis of cell morphological changes, and cell phenotypic characterization which are all important players in the control of glioblastoma progression. Results and discussion: Our results revealed a significant effect of continuous millimeter waves at 30.5 GHz on cell proliferation and apoptosis, although without affecting the differentiation status of glioblastoma cells composing the organoids. Excitingly, when applying a power level of 0.1 W (Root Mean Square), we discovered a remarkable (statistically significant) therapeutic effect when combined with the chemotherapeutic agent Temozolomide, leading to increased glioblastoma cell death. These findings present a promising interventional window for treating glioblastoma cells, harnessing the potential therapeutic benefits of 30.5 GHz CW exposure. Temperature increase during treatments was carefully monitored and simulated with a good agreement, demonstrating a negligible involvement of the temperature elevation for the observed effects. By exploring this innovative approach, we pave the way for improved future treatments of glioblastoma that has remained exceptionally challenging until now. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Role of Apolipoprotein E in the Hippocampus and Its Impact following Ionizing Radiation Exposure.
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Casciati, Arianna, Pasquali, Emanuela, De Stefano, Ilaria, Braga-Tanaka, Ignacia, Tanaka, Satoshi, Mancuso, Mariateresa, Antonelli, Francesca, and Pazzaglia, Simonetta
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DEVELOPMENTAL neurobiology ,APOLIPOPROTEIN E ,IONIZING radiation ,CELL receptors ,RADIATION exposure ,PERIPHERAL nervous system ,NEURAL stem cells - Abstract
Apolipoprotein E (ApoE) is a lipid carrier in both the peripheral and the central nervous systems (CNSs). Lipid-loaded ApoE lipoprotein particles bind to several cell surface receptors to support membrane homeostasis and brain injury repair. In the brain, ApoE is produced predominantly by astrocytes, but it is also abundantly expressed in most neurons of the CNS. In this study, we addressed the role of ApoE in the hippocampus in mice, focusing on its role in response to radiation injury. To this aim, 8-week-old, wild-type, and ApoE-deficient (ApoE
−/− ) female mice were acutely whole-body irradiated with 3 Gy of X-rays (0.89 Gy/min), then sacrificed 150 days post-irradiation. In addition, age-matching ApoE−/− females were chronically whole-body irradiated (20 mGy/d, cumulative dose of 3 Gy) for 150 days at the low dose-rate facility at the Institute of Environmental Sciences (IES), Rokkasho, Japan. To seek for ApoE-dependent modification during lineage progression from neural stem cells to neurons, we have evaluated the cellular composition of the dentate gyrus in unexposed and irradiated mice using stage-specific markers of adult neurogenesis. Our findings indicate that ApoE genetic inactivation markedly perturbs adult hippocampal neurogenesis in unexposed and irradiated mice. The effect of ApoE inactivation on the expression of a panel of miRNAs with an established role in hippocampal neurogenesis, as well as its transcriptional consequences in their target genes regulating neurogenic program, have also been analyzed. Our data show that the absence of ApoE−/− also influences synaptic functionality and integration by interfering with the regulation of mir-34a, mir-29b, and mir-128b, leading to the downregulation of synaptic markers PSD95 and synaptophysin mRNA. Finally, compared to acute irradiation, chronic exposure of ApoE null mice yields fewer consequences except for the increased microglia-mediated neuroinflammation. Exploring the function of ApoE in the hippocampus could have implications for developing therapeutic approaches to alleviate radiation-induced brain injury. [ABSTRACT FROM AUTHOR]- Published
- 2024
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6. Involvement of Mitochondria in the Selective Response to Microsecond Pulsed Electric Fields on Healthy and Cancer Stem Cells in the Brain.
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Casciati, Arianna, Taddei, Anna Rita, Rampazzo, Elena, Persano, Luca, Viola, Giampietro, Cani, Alice, Bresolin, Silvia, Cesi, Vincenzo, Antonelli, Francesca, Mancuso, Mariateresa, Merla, Caterina, and Tanori, Mirella
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CANCER stem cells ,NEURAL stem cells ,ELECTRIC fields ,MITOCHONDRIA ,CELL membranes ,CELL physiology ,MICROSCOPY - Abstract
In the last few years, pulsed electric fields have emerged as promising clinical tools for tumor treatments. This study highlights the distinct impact of a specific pulsed electric field protocol, PEF-5 (0.3 MV/m, 40 μs, 5 pulses), on astrocytes (NHA) and medulloblastoma (D283) and glioblastoma (U87 NS) cancer stem-like cells (CSCs). We pursued this goal by performing ultrastructural analyses corroborated by molecular/omics approaches to understand the vulnerability or resistance mechanisms triggered by PEF-5 exposure in the different cell types. Electron microscopic analyses showed that, independently of exposed cells, the main targets of PEF-5 were the cell membrane and the cytoskeleton, causing membrane filopodium-like protrusion disappearance on the cell surface, here observed for the first time, accompanied by rapid cell swelling. PEF-5 induced different modifications in cell mitochondria. A complete mitochondrial dysfunction was demonstrated in D283, while a mild or negligible perturbation was observed in mitochondria of U87 NS cells and NHAs, respectively, not sufficient to impair their cell functions. Altogether, these results suggest the possibility of using PEF-based technology as a novel strategy to target selectively mitochondria of brain CSCs, preserving healthy cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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7. Innovative Multilayer Electrospun Patches for the Slow Release of Natural Oily Extracts as Dressings to Boost Wound Healing.
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Fiaschini, Noemi, Carnevali, Fiorella, Van der Esch, Stephen Andrew, Vitali, Roberta, Mancuso, Mariateresa, Sulli, Maria, Diretto, Gianfranco, Negroni, Anna, and Rinaldi, Antonio
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WOUND healing ,HEALING ,NEEM oil ,HYPERICUM perforatum ,TREATMENT effectiveness ,CONTACT angle - Abstract
Electrospinning is an advanced manufacturing strategy used to create innovative medical devices from continuous nanoscale fibers that is endowed with tunable biological, chemical, and physical properties. Innovative medical patches manufactured entirely by electrospinning are discussed in this paper, using a specific plant-derived formulation "1 Primary Wound Dressing©" (1-PWD) as an active pharmaceutical ingredient (API). 1-PWD is composed of neem oil (Azadirachta indica A. Juss.) and the oily extracts of Hypericum perforatum (L.) flowers, according to the formulation patented by the ENEA of proven therapeutic efficacy as wound dressings. The goal of this work is to encapsulate this API and demonstrate that its slow release from an engineered electrospun patch can increase the therapeutic efficacy for wound healing. The prototyped patch is a three-layer core–shell membrane, with a core made of fibers from a 1-PWD-PEO blend, enveloped within two external layers made of medical-grade polycaprolactone (PCL), ensuring mechanical strength and integrity during manipulation. The system was characterized via electron microscopy (SEM) and chemical and contact angle tests. The encapsulation, release, and efficacy of the API were confirmed by FTIR and LC-HRMS and were validated via in vitro toxicology and scratch assays. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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8. The Genetic Control of Chemically and Radiation-Induced Skin Tumorigenesis: A Study with Carcinogenesis-Susceptible and Carcinogenesis-Resistant Mice
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Pazzaglia, Simonetta, Mancuso, Mariateresa, Rebessi, Simonetta, Di Majo, Vincenzo, Tanori, Mirella, Biozzi, Guido, Covelli, Vincenzo, and Saran, Anna
- Published
- 2002
9. Nanodiamond Effects on Cancer Cell Radiosensitivity: The Interplay between Their Chemical/Physical Characteristics and the Irradiation Energy.
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Varzi, Veronica, Fratini, Emiliano, Falconieri, Mauro, Giovannini, Daniela, Cemmi, Alessia, Scifo, Jessica, Di Sarcina, Ilaria, Aprà, Pietro, Sturari, Sofia, Mino, Lorenzo, Tomagra, Giulia, Infusino, Erminia, Landoni, Valeria, Marino, Carmela, Mancuso, Mariateresa, Picollo, Federico, and Pazzaglia, Simonetta
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RADIATION tolerance ,CANCER cells ,CHEMICAL stability ,CELL survival ,NANODIAMONDS ,DNA damage - Abstract
Nanoparticles are being increasingly studied to enhance radiation effects. Among them, nanodiamonds (NDs) are taken into great consideration due to their low toxicity, inertness, chemical stability, and the possibility of surface functionalization. The objective of this study is to explore the influence of the chemical/physical properties of NDs on cellular radiosensitivity to combined treatments with radiation beams of different energies. DAOY, a human radioresistant medulloblastoma cell line was treated with NDs—differing for surface modifications [hydrogenated (H-NDs) and oxidized (OX-NDs)], size, and concentration—and analysed for (i) ND internalization and intracellular localization, (ii) clonogenic survival after combined treatment with different radiation beam energies and (iii) DNA damage and apoptosis, to explore the nature of ND–radiation biological interactions. Results show that chemical/physical characteristics of NDs are crucial in determining cell toxicity, with hydrogenated NDs (H-NDs) decreasing either cellular viability when administered alone, or cell survival when combined with radiation, depending on ND size and concentration, while OX-NDs do not. Also, irradiation at high energy (γ-rays at 1.25 MeV), in combination with H-NDs, is more efficient in eliciting radiosensitisation when compared to irradiation at lower energy (X-rays at 250 kVp). Finally, the molecular mechanisms of ND radiosensitisation was addressed, demonstrating that cell killing is mediated by the induction of Caspase-3-dependent apoptosis that is independent to DNA damage. Identifying the optimal combination of ND characteristics and radiation energy has the potential to offer a promising therapeutic strategy for tackling radioresistant cancers using H-NDs in conjunction with high-energy radiation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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10. A biodistribution study of two differently shaped plant virus nanoparticles reveals new peculiar traits
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Lico, Chiara, Giardullo, Paola, Mancuso, Mariateresa, Benvenuto, Eugenio, Santi, Luca, and Baschieri, Selene
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- 2016
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11. Nonlinear Radiation-Induced Cataract Using the Radiosensitive Ptch1 +/- Mouse Model
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De Stefano, Ilaria, Giardullo, Paola, Tanno, Barbara, Leonardi, Simona, Pasquali, Emanuela, Babini, Gabriele, Saran, Anna, and Mancuso, Mariateresa
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- 2016
12. A combined ANXA2-NDRG1-STAT1 gene signature predicts response to chemoradiotherapy in cervical cancer
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Buttarelli, Marianna, Babini, Gabriele, Raspaglio, Giuseppina, Filippetti, Flavia, Battaglia, Alessandra, Ciucci, Alessandra, Ferrandina, Gabriella, Petrillo, Marco, Marino, Carmela, Mancuso, Mariateresa, Saran, Anna, Villani, Maria Elena, Desiderio, Angiola, D’Ambrosio, Chiara, Scaloni, Andrea, Scambia, Giovanni, and Gallo, Daniela
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- 2019
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13. Design and Implementation of an Accessible 3D Bioprinter: Benchmarking the Performance of a Home-Made Bioprinter against a Professional Bioprinter.
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D'Atanasio, Paolo, Fiaschini, Noemi, Rinaldi, Antonio, Zambotti, Alessandro, Cantini, Lorenzo, Mancuso, Mariateresa, and Antonelli, Francesca
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BIOPRINTING ,3-D printers ,CELL growth ,CELL survival ,PROFESSIONAL employees ,CELL culture - Abstract
The tremendous application potential of 3D bioprinting in the biomedical field is witnessed by the ever-increasing interest in this technology over the past few years. In particular, the possibility of obtaining 3D cellular models that mimic tissues with precision and reproducibility represents a definitive advance for in vitro studies dealing with the biological mechanisms of cell growth, death and proliferation and is at the basis of the responses of healthy and pathological tissues to drugs and therapies. However, the impact of 3D bioprinting on research is limited by the high costs of professional 3D bioprinters, which represent an obstacle to the widespread access and usability of this technology. In this work, we present a 3D bioprinter that was developed in-house by modifying a low-cost commercial 3D printer by replacing the default extruder used to print plastic filaments with a custom-made syringe extruder that is suitable for printing bioinks. The modifications made to the 3D printer include adjusting the size of the extruder to accommodate a 1 mL syringe and reducing the extruder's size above the printer. To validate the performance of the home-made bioprinter, some main printing characteristics, the cell vitality and the possibility of bioprinting CAD-designed constructs were benchmarked against a renowned professional 3D bioprinter by RegenHu. According to our findings, our in-house 3D bioprinter was mostly successful in printing a complex glioblastoma tumor model with good performances, and it managed to maintain a cell viability that was comparable to that achieved by a professional bioprinter. This suggests that an accessible open-source 3D bioprinter could be a viable option for research and development (R&D) laboratories interested in pre-commercial 3D bioprinting advancements. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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14. Late Effects of Chronic Low Dose Rate Total Body Irradiation on the Heart Proteome of ApoE −/− Mice Resemble Premature Cardiac Ageing.
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Azimzadeh, Omid, Merl-Pham, Juliane, Subramanian, Vikram, Oleksenko, Kateryna, Krumm, Franziska, Mancuso, Mariateresa, Pasquali, Emanuela, Tanaka III, Ignacia B., Tanaka, Satoshi, Atkinson, Michael J., Tapio, Soile, and Moertl, Simone
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CARDIOVASCULAR diseases risk factors ,TRANSFORMING growth factors-beta ,ENERGY metabolism ,HEART ,ANIMAL experimentation ,IMMUNOHISTOCHEMISTRY ,RADIATION ,RISK assessment ,DOSE-response relationship (Radiation) ,PROTEOMICS ,OXIDATIVE stress ,IMMUNOBLOTTING ,CELLULAR signal transduction ,RADIATION doses ,APOLIPOPROTEINS ,AGING ,RESEARCH funding ,MASS spectrometry ,GENE expression profiling ,RADIATION injuries ,MICE ,PHYSIOLOGICAL effects of radiation ,DISEASE risk factors - Abstract
Simple Summary: Epidemiological evidence supports an increased risk of cardiovascular diseases (CVD) at doses and dose rates much lower than previously believed. However, the molecular mechanism involved in cardiac damage after chronic irradiation has not been fully elucidated. Here, we studied the proteome of mice hearts chronically irradiated with a very low dose (1 mGy/day) or with a low dose (20 mGy/day) for 300 days. Changes in the proteome were further validated by immunoblotting, enzyme activity assays, immunohistochemistry, and targeted transcriptomics. The data presented here demonstrate that chronic low-dose total body irradiation induces biological changes in mouse cardiac tissue that resemble the effects of premature cardiac ageing. A comprehensive understanding of the molecular mechanisms of CVD following chronic low dose irradiation will enable the identification of target molecules or pathways which may be used in bioassays for measuring endpoints relevant to radiation risk assessment. Recent epidemiologic studies support an association between chronic low-dose radiation exposure and the development of cardiovascular disease (CVD). The molecular mechanisms underlying the adverse effect of chronic low dose exposure are not fully understood. To address this issue, we have investigated changes in the heart proteome of ApoE deficient (ApoE
−/− ) C57Bl/6 female mice chronically irradiated for 300 days at a very low dose rate (1 mGy/day) or at a low dose rate (20 mGy/day), resulting in cumulative whole-body doses of 0.3 Gy or 6.0 Gy, respectively. The heart proteomes were compared to those of age-matched sham-irradiated ApoE−/− mice using label-free quantitative proteomics. Radiation-induced proteome changes were further validated using immunoblotting, enzyme activity assays, immunohistochemistry or targeted transcriptomics. The analyses showed persistent alterations in the cardiac proteome at both dose rates; however, the effect was more pronounced following higher dose rates. The altered proteins were involved in cardiac energy metabolism, ECM remodelling, oxidative stress, and ageing signalling pathways. The changes in PPARα, SIRT, AMPK, and mTOR signalling pathways were found at both dose rates and in a dose-dependent manner, whereas more changes in glycolysis and ECM remodelling were detected at the lower dose rate. These data provide strong evidence for the possible risk of cardiac injury following chronic low dose irradiation and show that several affected pathways following chronic irradiation overlap with those of ageing-associated heart pathology. [ABSTRACT FROM AUTHOR]- Published
- 2023
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15. The Patched 1 Tumor-Suppressor Gene Protects the Mouse Lens from Spontaneous and Radiation-Induced Cataract
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De Stefano, Ilaria, Tanno, Barbara, Giardullo, Paola, Leonardi, Simona, Pasquali, Emanuela, Antonelli, Francesca, Tanori, Mirella, Casciati, Arianna, Pazzaglia, Simonetta, Saran, Anna, and Mancuso, Mariateresa
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- 2015
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16. Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma.
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Marchetti, Luca, Novelli, Flavia, Tanno, Barbara, Leonardi, Simona, Hizam, Veronica Mohamed, Arcangeli, Caterina, Santi, Luca, Baschieri, Selene, Lico, Chiara, and Mancuso, Mariateresa
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TUMOR growth ,MEDULLOBLASTOMA ,PRECANCEROUS conditions ,LABORATORY mice ,NANOMEDICINE ,ANIMAL disease models ,PLANT viruses ,DOXORUBICIN - Abstract
Sonic hedgehog medulloblastoma (SHH-MB) accounts for 25–30% of all MBs, and conventional therapy results in severe long-term side effects. New targeted therapeutic approaches are urgently needed, drawing also on the fields of nanoparticles (NPs). Among these, plant viruses are very promising, and we previously demonstrated that tomato bushy stunt virus (TBSV), functionalized on the surface with CooP peptide, specifically targets MB cells. Here, we tested the hypothesis that TBSV-CooP can specifically deliver a conventional chemotherapeutic drug (i.e., doxorubicin, DOX) to MB in vivo. To this aim, a preclinical study was designed to verify, by histological and molecular methods, if multiple doses of DOX-TBSV-CooP were able to inhibit tumor progression of MB pre-neoplastic lesions, and if a single dose was able to modulate pro-apoptotic/anti-proliferative molecular signaling in full-blown MBs. Our results demonstrate that when DOX is encapsulated in TBSV-CooP, its effects on cell proliferation and cell death are similar to those obtained with a five-fold higher dose of non-encapsulated DOX, both in early and late MB stages. In conclusion, these results confirm that CooP-functionalized TBSV NPs are efficient carriers for the targeted delivery of therapeutics to brain tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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17. Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease.
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Vitali, Roberta, Palone, Francesca, De Stefano, Ilaria, Fiorente, Chiara, Novelli, Flavia, Pasquali, Emanuela, Fratini, Emiliano, Tanori, Mirella, Leonardi, Simona, Tanno, Barbara, Colantoni, Eleonora, Soldi, Sara, Galletti, Serena, Grimaldi, Maria, Morganti, Alessio Giuseppe, Fuccio, Lorenzo, Pazzaglia, Simonetta, Pioli, Claudio, Mancuso, Mariateresa, and Vesci, Loredana
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RADIATION injuries ,LABORATORY mice ,ANIMAL disease models ,BIOMARKERS ,ANIMAL models in research ,IRRADIATION ,DOSE-response relationship (Radiation) ,ENDOMETRIOSIS - Abstract
Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures. Using the selected protocol (10 Gy/day × 4 days), we assessed PRD through tissue (number and length of colon crypts) and molecular (expression of genes involved in oxidative stress, cell damage, inflammation, and stem cell markers) analyses at short (3 h or 3 days after X-ray) and long (38 days after X-rays) post-irradiation times. The results show that a primary damage response in term of apoptosis, inflammation, and surrogate markers of oxidative stress was found, thus determining a consequent impairment of cell crypts differentiation and proliferation as well as a local inflammation and a bacterial translocation to mesenteric lymph nodes after several weeks post-irradiation. Changes were also found in microbiota composition, particularly in the relative abundance of dominant phyla, related families, and in alpha diversity indices, as an indication of dysbiotic conditions induced by irradiation. Fecal markers of intestinal inflammation, measured during the experimental timeline, identified lactoferrin, along with elastase, as useful non-invasive tools to monitor disease progression. Thus, our preclinical model may be useful to develop new therapeutic strategies for PRD treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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18. In Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model.
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Giovannini, Daniela, De Angelis, Cinzia, Astorino, Maria Denise, Fratini, Emiliano, Cisbani, Evaristo, Bazzano, Giulia, Ampollini, Alessandro, Piccinini, Massimo, Nichelatti, Enrico, Trinca, Emiliano, Nenzi, Paolo, Mancuso, Mariateresa, Picardi, Luigi, Marino, Carmela, Ronsivalle, Concetta, and Pazzaglia, Simonetta
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PROTON beams ,LABORATORY mice ,MEDULLOBLASTOMA ,ANIMAL disease models ,LINEAR accelerators ,PROTON therapy - Abstract
Protons are now increasingly used to treat pediatric medulloblastoma (MB) patients. We designed and characterized a setup to deliver proton beams for in vivo radiobiology experiments at a TOP-IMPLART facility, a prototype of a proton-therapy linear accelerator developed at the ENEA Frascati Research Center, with the goal of assessing the feasibility of TOP-IMPLART for small animal proton therapy research. Mice bearing Sonic-Hedgehog (Shh)-dependent MB in the flank were irradiated with protons to test whether irradiation could be restricted to a specific depth in the tumor tissue and to compare apoptosis induced by the same dose of protons or photons. In addition, the brains of neonatal mice at postnatal day 5 (P5), representing a very small target, were irradiated with 6 Gy of protons with two different collimated Spread-Out Bragg Peaks (SOBPs). Apoptosis was visualized by immunohistochemistry for the apoptotic marker caspase-3-activated, and quantified by Western blot. Our findings proved that protons could be delivered to the upper part while sparing the deepest part of MB. In addition, a comparison of the effectiveness of protons and photons revealed a very similar increase in the expression of cleaved caspase-3. Finally, by using a very small target, the brain of P5-neonatal mice, we demonstrated that the proton irradiation field reached the desired depth in brain tissue. Using the TOP-IMPLART accelerator we established setup and procedures for proton irradiation, suitable for translational preclinical studies. This is the first example of in vivo experiments performed with a "full-linac" proton-therapy accelerator. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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19. Targeting of Tomato Bushy Stunt Virus with a Genetically Fused C-End Rule Peptide.
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Marchetti, Luca, Simon-Gracia, Lorena, Lico, Chiara, Mancuso, Mariateresa, Baschieri, Selene, Santi, Luca, and Teesalu, Tambet
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PEPTIDES ,NANOMEDICINE ,PEPTIDE receptors ,TOMATOES ,CONFOCAL microscopy ,FLOW cytometry - Abstract
Homing peptides are widely used to improve the delivery of drugs, imaging agents, and nanoparticles (NPs) to their target sites. Plant virus-based particles represent an emerging class of structurally diverse nanocarriers that are biocompatible, biodegradable, safe, and cost-effective. Similar to synthetic NPs, these particles can be loaded with imaging agents and/or drugs and functionalized with affinity ligands for targeted delivery. Here we report the development of a peptide-guided Tomato Bushy Stunt Virus (TBSV)-based nanocarrier platform for affinity targeting with the C-terminal C-end rule (CendR) peptide, RPARPAR (RPAR). Flow cytometry and confocal microscopy demonstrated that the TBSV-RPAR NPs bind specifically to and internalize in cells positive for the peptide receptor neuropilin-1 (NRP-1). TBSV-RPAR particles loaded with a widely used anticancer anthracycline, doxorubicin, showed selective cytotoxicity on NRP-1-expressing cells. Following systemic administration in mice, RPAR functionalization conferred TBSV particles the ability to accumulate in the lung tissue. Collectively, these studies show the feasibility of the CendR-targeted TBSV platform for the precision delivery of payloads. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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20. Oncogenic Radiation Abscopal Effects In Vivo: Interrogating Mouse Skin
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Mancuso, Mariateresa, Leonardi, Simona, Giardullo, Paola, Pasquali, Emanuela, Tanori, Mirella, De Stefano, Ilaria, Casciati, Arianna, Naus, Christian C., Pazzaglia, Simonetta, and Saran, Anna
- Published
- 2013
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21. Dose and Spatial Effects in Long-Distance Radiation Signaling In Vivo: Implications for Abscopal Tumorigenesis
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Mancuso, Mariateresa, Giardullo, Paola, Leonardi, Simona, Pasquali, Emanuela, Casciati, Arianna, De Stefano, Ilaria, Tanori, Mirella, Pazzaglia, Simonetta, and Saran, Anna
- Published
- 2013
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22. Safety in Rats of a Novel Nasal Spray Formulation for the Prevention of Airborne Viral Infections.
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Tanori, Mirella, Pitaro, Michele, Fratini, Emiliano, Colantoni, Eleonora, Amoresano, Angela, Celentano, Simona, Chiaramonte, Barbara, and Mancuso, Mariateresa
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AIRBORNE infection ,VIRUS diseases ,INTRANASAL medication ,NASAL mucosa ,VIRAL transmission ,RATS ,SALINE solutions - Abstract
Hexedra+
® is a nasal spray containing hydroxypropyl methylcellulose, beta-cyclodextrin, and usnic acid. It has been developed with the aim of reducing the risk of transmission of airborne viral infections, with particular reference to influenza and COVID-19. As part of the preclinical development of the product, we carried out a study on thirty male Wistar rats divided into three study groups and treated with Hexedra+, an alternative formulation containing a double concentration of usnic acid (0.015% instead of 0.0075%) or saline solution. Products were administered at the dose of 30 μL into each nostril, three times a day for seven consecutive days by means of a micropipette. By the end of the treatment period, no significant changes were observed in body weight. Histological examination of nasal mucosa and soft organs did not show any significant difference in the three study groups. Serum transaminase level remained in the normal limit in all the animals treated. The serum level of usnic acid was measured in order to assess the absorption of the molecule through the nasal mucosa. By the end of the study period, the usnic acid serum level was negligible in all the animals treated. In conclusion, the safety profile of Hexedra+ appears favorable in the animal model studied. [ABSTRACT FROM AUTHOR]- Published
- 2023
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23. Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways.
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Cuciniello, Rossana, Di Meo, Francesco, Sulli, Maria, Demurtas, Olivia Costantina, Tanori, Mirella, Mancuso, Mariateresa, Villano, Clizia, Aversano, Riccardo, Carputo, Domenico, Baldi, Alfonso, Diretto, Gianfranco, Filosa, Stefania, and Crispi, Stefania
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GRAPE seed extract ,GENE expression ,ANTINEOPLASTIC agents ,OLIGOMERIC proanthocyanidins ,BIOMOLECULES ,VITIS vinifera ,GRAPES - Abstract
Grapevine (Vitis vinifera L.) seeds are rich in polyphenols including proanthocyanidins, molecules with a variety of biological effects including anticancer action. We have previously reported that the grape seed semi-polar extract of Aglianico cultivar (AGS) was able to induce apoptosis and decrease cancer properties in different mesothelioma cell lines. Concomitantly, this extract resulted in enriched oligomeric proanthocyanidins which might be involved in determining the anticancer activity. Through transcriptomic and metabolomic analyses, we investigated in detail the anticancer pathway induced by AGS. Transcriptomics analysis and functional annotation allowed the identification of the relevant causative genes involved in the apoptotic induction following AGS treatment. Subsequent biological validation strengthened the hypothesis that MDM2 could be the molecular target of AGS and that it could act in both a p53-dependent and independent manner. Finally, AGS significantly inhibited tumor progression in a xenograft mouse model of mesothelioma, confirming also in vivo that MDM2 could act as molecular player responsible for the AGS antitumor effect. Our findings indicated that AGS, exerting a pro-apoptotic effect by hindering MDM2 pathway, could represent a novel source of anticancer molecules. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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24. Characterization Of Blood–Brain Barrier Crossing And Tumor Homing Peptides By Molecular Dynamics Simulations
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Arcangeli, Caterina, Lico, Chiara, Baschieri, Selene, and Mancuso, Mariateresa
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conformational flexibility ,essential dynamics ,Time Factors ,Protein Conformation ,brain ,Hydrogen Bonding ,free energy landscapes ,Molecular Dynamics Simulation ,theranostic platform ,Drug Delivery Systems ,Blood-Brain Barrier ,peptides ,Solvents ,Animals ,Humans ,Nanoparticles ,Thermodynamics ,Amino Acid Sequence ,Oligopeptides ,Original Research - Abstract
Introduction The new frontier of tumor diagnosis and treatment relies on the development of delivery strategies capable of allowing the specific targeting of the diagnostic agents/chemotherapeutics, avoiding side effects. In the case of brain tumors, achieving this goal is made more difficult by the presence of the blood–brain barrier (BBB). Peptides have been revealed as excellent candidates for both BBB crossing and specific cancer homing. Nanoparticles (NPs), functionalized with BBB crossing and tumor homing (TH) peptides, are emerging as smart theranostic systems. However, there is still poor knowledge concerning the molecular structure and dynamical properties of these peptides, essential requirements for a suitable functionalization of the delivery systems themselves. Methods In this work, by means of molecular dynamics (MD) simulations, we have extensively characterized the structural and dynamical behavior of several peptides, known to be endowed of BBB crossing and TH properties. Results The simulations point out that, on the basis of their conformational dynamics, the peptides can be classified in two main groups: 1) peptides assuming a specific structural conformation, a feature that could be important for interacting with the molecular target but that may limit their use as functionalizing molecules and 2) highly flexible peptides whose interaction with the target may be independent of a particular structural conformation and that may represent good candidates for the functionalization of theranostic NP-based platforms. Discussion Such findings may be useful for the de novo designing of NP-based delivery systems., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/wp8npbWb754
- Published
- 2019
25. Oncogenic Bystander Radiation Effects in Patched Heterozygous Mouse Cerebellum
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Mancuso, Mariateresa, Pasquali, Emanuela, Leonardi, Simona, Tanori, Mirella, Rebessi, Simonetta, Di Majo, Vincenzo, Pazzaglia, Simonetta, Toni, Maria Pia, Pimpinella, Maria, Covelli, Vincenzo, and Saran, Anna
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- 2008
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26. Liver Steatosis and Steatohepatitis Alter Bile Acid Receptors in Brain and Induce Neuroinflammation: A Contribution of Circulating Bile Acids and Blood-Brain Barrier.
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Fiaschini, Noemi, Mancuso, Mariateresa, Tanori, Mirella, Colantoni, Eleonora, Vitali, Roberta, Diretto, Gianfranco, Lorenzo Rebenaque, Laura, Stronati, Laura, and Negroni, Anna
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OCCLUDINS , *FARNESOID X receptor , *BILE acids , *G protein coupled receptors , *BLOOD-brain barrier , *NON-alcoholic fatty liver disease , *FATTY liver , *NEUROINFLAMMATION - Abstract
A tight relationship between gut-liver diseases and brain functions has recently emerged. Bile acid (BA) receptors, bacterial-derived molecules and the blood-brain barrier (BBB) play key roles in this association. This study was aimed to evaluate how non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) impact the BA receptors Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5) expression in the brain and to correlate these effects with circulating BAs composition, BBB integrity and neuroinflammation. A mouse model of NAFLD was set up by a high-fat and sugar diet, and NASH was induced with the supplementation of dextran-sulfate-sodium (DSS) in drinking water. FXR, TGR5 and ionized calcium-binding adaptor molecule 1 (Iba-1) expression in the brain was detected by immunohistochemistry, while Zonula occludens (ZO)-1, Occludin and Plasmalemmal Vesicle Associated Protein-1 (PV-1) were analyzed by immunofluorescence. Biochemical analyses investigated serum BA composition, lipopolysaccharide-binding protein (LBP) and S100β protein (S100β) levels. Results showed a down-regulation of FXR in NASH and an up-regulation of TGR5 and Iba-1 in the cortex and hippocampus in both treated groups as compared to the control group. The BA composition was altered in the serum of both treated groups, and LBP and S100β were significantly augmented in NASH. ZO-1 and Occludin were attenuated in the brain capillary endothelial cells of both treated groups versus the control group. We demonstrated that NAFLD and NASH provoke different grades of brain dysfunction, which are characterized by the altered expression of BA receptors, FXR and TGR5, and activation of microglia. These effects are somewhat promoted by a modification of circulating BAs composition and by an increase in LBP that concur to damage BBB, thus favoring neuroinflammation. [ABSTRACT FROM AUTHOR]
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- 2022
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27. Gut–Brain Axis: Insights from Hippocampal Neurogenesis and Brain Tumor Development in a Mouse Model of Experimental Colitis Induced by Dextran Sodium Sulfate.
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Vitali, Roberta, Prioreschi, Clara, Lorenzo Rebenaque, Laura, Colantoni, Eleonora, Giovannini, Daniela, Frusciante, Sarah, Diretto, Gianfranco, Marco-Jiménez, Francisco, Mancuso, Mariateresa, Casciati, Arianna, and Pazzaglia, Simonetta
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DEVELOPMENTAL neurobiology ,BRAIN tumors ,SODIUM sulfate ,NEURAL development ,DEXTRAN sulfate ,COLITIS ,DEXTRAN ,IDIOPATHIC diseases - Abstract
Chronic inflammatory bowel disorders (IBD) are idiopathic diseases associated with altered intestinal permeability, which in turn causes an exaggerated immune response to enteric antigens in a genetically susceptible host. A rise in psych cognitive disorders, such as anxiety and depression, has been observed in IBD patients. We here report investigations on a model of chemically induced experimental colitis by oral administration of sodium dextran sulfate (DSS) in C57BL/6 mice. We investigate, in vivo, the crosstalk between the intestine and the brain, evaluating the consequences of intestinal inflammation on neuroinflammation and hippocampal adult neurogenesis. By using different DSS administration strategies, we are able to induce acute or chronic colitis, simulating clinical characteristics observed in IBD patients. Body weight loss, colon shortening, alterations of the intestinal mucosa and fecal metabolic changes in amino acids-, lipid- and thiamine-related pathways are observed in colitis. The activation of inflammatory processes in the colon is confirmed by macrophage infiltration and increased expression of the proinflammatory cytokine and oxidative stress marker (Il-6 and iNOS). Interestingly, in the hippocampus of acutely DSS-treated mice, we report the upregulation of inflammatory-related genes (Il-6, Il-1β, S-100, Tgf-β and Smad-3), together with microgliosis. Chronic DSS treatment also resulted in neuroinflammation in the hippocampus, indicated by astrocyte activation. Evaluation of stage-specific neurogenesis markers reveals deficits in the dentate gyrus after acute and chronic DSS treatments, indicative of defective adult hippocampal neurogenesis. Finally, based on a possible causal relationship between gut-related inflammation and brain cancer, we investigate the impact of DSS-induced colitis on oncogenesis, using the Ptch1
+/− /C57BL/6 mice, a well-established medulloblastoma (MB) mouse model, finding no differences in MB development between untreated and DSS-treated mice. In conclusion, in our experimental model, the intestinal inflammation associated with acute and chronic colitis markedly influences brain homeostasis, impairing hippocampal neurogenesis but not MB oncogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2022
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28. Colonic inflammation accelerates the progression of liver disease: A protective role of dipotassium glycyrrhizate.
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Fiaschini, Noemi, Negroni, Anna, Palone, Francesca, Vitali, Roberta, Colantoni, Eleonora, Laudadio, Ilaria, Mancuso, Mariateresa, Cucchiara, Salvatore, and Stronati, Laura
- Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) and its more severe and progressive form, non-alcoholic steatohepatitis (NASH) is increasing worldwide. Gut inflammation seems to concur to the pathogenesis of NASH. No drugs are currently approved for NASH treatment. To investigate if inflamed gut directly contributes to the progression of NASH through gut epithelial and vascular barrier impairment and to evaluate the efficacy of dipotassium glycyrrhizate (DPG) to improve the liver disease. A NASH model was set up by feeding mice, for 8 and 13 weeks, with high fat diet with high fructose and glucose (HFD-FG) supplemented periodically with dextran sulfate sodium (DSS) in drinking water. A group was also treated with DPG by gavage. Histological, immunohistochemical and molecular analysis were performed. DSS-induced colitis increased steatosis, inflammatory (IL-6, TNFα, NLRP3, MCP-1) as well as fibrotic (TGF-β, α-SMA) mediator expression in HFD-FG mice. Beneficial effect of DPG was associated with restoration of intestinal epithelial and vascular barriers, evaluated respectively by ZO-1 and PV-1 expression, that are known to limit bacterial translocation. Colonic inflammation strongly contributes to the progression of NASH, likely by favouring bacterial translocation. DPG treatment could represent a novel strategy to reduce liver injury. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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29. MiRNA-Mediated Fibrosis in the Out-of-Target Heart following Partial-Body Irradiation.
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Tanno, Barbara, Novelli, Flavia, Leonardi, Simona, Merla, Caterina, Babini, Gabriele, Giardullo, Paola, Kadhim, Munira, Traynor, Damien, Medipally, Dinesh K. R., Meade, Aidan D., Lyng, Fiona M., Tapio, Soile, Marchetti, Luca, Saran, Anna, Pazzaglia, Simonetta, and Mancuso, Mariateresa
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X-rays ,COLLAGEN ,SKELETAL muscle ,CELL culture ,ANIMAL experimentation ,MICRORNA ,FIBROSIS ,RADIATION injuries ,HEART diseases - Abstract
Simple Summary: Radiation exposure has been linked to non-cancer effects such as heart disease. This study aimed to investigate radiation-induced heart disease in mice where the radiation exposure was either administered to the whole body or only to the bottom third of the body (partial body). Radiation damage was found in the hearts of mice following both whole-body and partial-body exposure. MiRNAs released from directly irradiated skeletal muscle cells in vitro were shown to result in damaging effects in unirradiated ventricular cardiac cells. This study suggests that a partial-body exposure to radiation should be thought of as a systemic effect rather than only an effect on the exposed tissue. Recent reports have shown a link between radiation exposure and non-cancer diseases such as radiation-induced heart disease (RIHD). Radiation exposures are often inhomogeneous, and out-of-target effects have been studied in terms of cancer risk, but very few studies have been carried out for non-cancer diseases. Here, the role of miRNAs in the pathogenesis of RIHD was investigated. C57Bl/6J female mice were whole- (WBI) or partial-body-irradiated (PBI) with 2 Gy of X-rays or sham-irradiated (SI). In PBI exposure, the lower third of the mouse body was irradiated, while the upper two-thirds were shielded. From all groups, hearts were collected 15 days or 6 months post-irradiation. The MiRNome analysis at 15 days post-irradiation showed that miRNAs, belonging to the myomiR family, were highly differentially expressed in WBI and PBI mouse hearts compared with SI hearts. Raman spectral data collected 15 days and 6 months post-irradiation showed biochemical differences among SI, WBI and PBI mouse hearts. Fibrosis in WBI and PBI mouse hearts, indicated by the increased deposition of collagen and the overexpression of genes involved in myofibroblast activation, was found 6 months post-irradiation. Using an in vitro co-culture system, involving directly irradiated skeletal muscle and unirradiated ventricular cardiac human cells, we propose the role of miR-1/133a as mediators of the abscopal response, suggesting that miRNA-based strategies could be relevant for limiting tissue-dependent reactions in non-directly irradiated tissues. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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30. Immature cancer cell discrimination using combined high frequency Electromagnetic Fields and dielectrophoresis forces
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Dalmay, Claire, Manczak, Rémi, Saada, Sofiane, Provent, Thomas, Bessette, Barbara, Lalloué, Fabrice, Casciati, Arianna, Tanori, Mirella, Merla, Caterina, Mancuso, Mariateresa, Porcù, Elena, Rampazzo, Elena, Persano, Luca, Viola, Giampetro, Baristiran Kaynak, Canan, Kaynak, Mehmet, Palego, Cristiano, Pothier, Arnaud, RF-ELITE : RF-Electronique Imprimée pour les Télécommunications et l'Energie (XLIM-RFEI), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Contrôle de l’Activation Cellulaire, Progression Tumorale et Résistance thérapeutique (CAPTuR), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Agenzia Nazionale per le nuove Tecnologie, l’energia e lo sviluppo economico sostenibile (ENEA), Universita degli Studi di Padova, Innovations for High Performance Microelectronics (IHP), and Bangor University
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[SPI.ELEC]Engineering Sciences [physics]/Electromagnetism ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2020
31. Loss of tyrosinase activity confers increased skin tumor susceptibility in mice
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Saran, Anna, Spinola, Monica, Pazzaglia, Simonetta, Peissel, Bernard, Tiveron, Cecilia, Tatangelo, Laura, Mancuso, Mariateresa, Covelli, Vincenzo, Giovannelli, Lisa, Pitozzi, Vanessa, Pignatiello, Carmen, Milani, Silvano, Dolara, Piero, and Dragani, Tommaso A
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- 2004
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32. High incidence of medulloblastoma following X-ray-irradiation of newborn Ptc1 heterozygous mice
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Pazzaglia, Simonetta, Mancuso, Mariateresa, Atkinson, Michael J, Tanori, Mirella, Rebessi, Simonetta, Majo, Vincenzo Di, Covelli, Vincenzo, Hahn, Heidi, and Saran, Anna
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- 2002
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33. Effects of Ultra-Short Pulsed Electric Field Exposure on Glioblastoma Cells.
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Casciati, Arianna, Tanori, Mirella, Gianlorenzi, Isabella, Rampazzo, Elena, Persano, Luca, Viola, Giampietro, Cani, Alice, Bresolin, Silvia, Marino, Carmela, Mancuso, Mariateresa, and Merla, Caterina
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ELECTRIC fields ,CANCER stem cells ,GLIOBLASTOMA multiforme ,BRAIN cancer ,CANCER patients - Abstract
Glioblastoma multiforme (GBM) is the most common brain cancer in adults. GBM starts from a small fraction of poorly differentiated and aggressive cancer stem cells (CSCs) responsible for aberrant proliferation and invasion. Due to extreme tumor heterogeneity, actual therapies provide poor positive outcomes, and cancers usually recur. Therefore, alternative approaches, possibly targeting CSCs, are necessary against GBM. Among emerging therapies, high intensity ultra-short pulsed electric fields (PEFs) are considered extremely promising and our previous results demonstrated the ability of a specific electric pulse protocol to selectively affect medulloblastoma CSCs preserving normal cells. Here, we tested the same exposure protocol to investigate the response of U87 GBM cells and U87-derived neurospheres. By analyzing different in vitro biological endpoints and taking advantage of transcriptomic and bioinformatics analyses, we found that, independent of CSC content, PEF exposure affected cell proliferation and differentially regulated hypoxia, inflammation and P53/cell cycle checkpoints. PEF exposure also significantly reduced the ability to form new neurospheres and inhibited the invasion potential. Importantly, exclusively in U87 neurospheres, PEF exposure changed the expression of stem-ness/differentiation genes. Our results confirm this physical stimulus as a promising treatment to destabilize GBM, opening up the possibility of developing effective PEF-mediated therapies. [ABSTRACT FROM AUTHOR]
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- 2022
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34. Introduction to the Special LDLensRad Focus Issue.
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Ainsbury, Elizabeth A., Dalke, Claudia, Mancuso, Mariateresa, Kadhim, Munira, Quinlan, Roy A., Azizova, Tamara, Dauer, Lawrence T., Dynlacht, Joseph R., Tanner, Rick, and Hamada, Nobuyuki
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LABORATORY animals ,RADIATION doses ,CATARACT - Abstract
Recent epidemiological and experimental animal data, as well as reanalyses of data previously accumulated, indicate that the lens of the eye is more radiosensitive than was previously thought. This has resulted in a reduction of the occupational lens dose limit within the European Union countries, Japan and elsewhere. This Commentary introduces the work done by the LDLensRad Consortium contained within this Focus Issue, towards advancement of understanding of the mechanisms of low dose radiation cataract. [ABSTRACT FROM AUTHOR]
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- 2022
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35. Protective role of 17β-estradiol on medulloblastoma development in Patched1 heterozygous mice
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Mancuso, Mariateresa, Leonardi, Simona, Ceccarelli, Manuela, Pasquali, Emanuela, Stefano, Ilaria De, Prisco, Maria Grazia, Rebessi, Simonetta, Tanori, Mirella, Scambia, Giovanni, Majo, Vincenzo Di, Pazzaglia, Simonetta, Saran, Anna, and Gallo, Daniela
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- 2010
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36. Activity of tyrosine kinase inhibitor Dasatinib in neuroblastoma cells in vitro and in orthotopic mouse model
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Vitali, Roberta, Mancini, Camillo, Cesi, Vincenzo, Tanno, Barbara, Piscitelli, Marta, Mancuso, Mariateresa, Sesti, Fabiola, Pasquali, Emanuela, Calabretta, Bruno, Dominici, Carlo, and Raschellà, Giuseppe
- Published
- 2009
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37. Re: Modulation of basal and squamous cell carcinoma by endogenous estrogen in mouse models of skin cancer
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Mancuso, Mariateresa, Gallo, Daniela, and Saran, Anna
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- 2009
38. PARP-1 cooperates with Ptc1 to suppress medulloblastoma and basal cell carcinoma
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Tanori, Mirella, Mancuso, Mariateresa, Pasquali, Emanuela, Leonardi, Simona, Rebessi, Simonetta, Di Majo, Vincenzo, Guilly, Marie-Noëlle, Giangaspero, Felice, Covelli, Vincenzo, Pazzaglia, Simonetta, and Saran, Anna
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- 2008
39. Gut-brain axis: does intestinal inflammation affect hippocampal neurogenesis and medulloblastoma development?
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Casciati, Arianna, Mancuso, Mariateresa, Vitali, Roberta, and Pazzaglia, Simonetta
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- 2023
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40. Permittivity measurements of brain cancer cell solutions: towards the electric characterisation of single cancer stem cells
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Gamal, Wesam, Tanori, Mirella, Casciati, Arianna, Mancuso, Mariateresa, Persano, Luca, Viola, Giampetro, Saada, Sofiane, Bessette, Barbara, Lalloué, Fabrice, Pothier, Arnaud, Palego, Cristiano, Merla, Caterina, RF-ELITE : RF-Electronique Imprimée pour les Télécommunications et l'Energie (XLIM-RFEI), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Agenzia Nazionale per le nuove Tecnologie, l’energia e lo sviluppo economico sostenibile (ENEA), Universita degli Studi di Padova, Contrôle de l’Activation Cellulaire, Progression Tumorale et Résistance thérapeutique (CAPTuR), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), and Bangor University
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[SPI]Engineering Sciences [physics] ,[SPI.ELEC]Engineering Sciences [physics]/Electromagnetism ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2018
41. Developmental and oncogenic effects of Insulin-like Growth Factor-I in Ptc1+/- mouse cerebellum
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Di Majo Vincenzo, Leonardi Simona, Pasquali Emanuela, Mancuso Mariateresa, Santone Melissa, Tanori Mirella, Rebessi Simonetta, Saran Anna, and Pazzaglia Simonetta
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Medulloblastoma is amongst the most common malignant brain tumors in childhood, arising from neoplastic transformation of granule neuron precursors (GNPs) of the cerebellum via deregulation of pathways involved in cerebellar development. Deregulation of the Sonic hedgehog/Patched1 (Shh/Ptc1) signaling pathway predisposes humans and mice to medulloblastoma. In the brain, insulin-like growth factor (IGF-I) plays a critical role during development as a neurotrophic and neuroprotective factor, and in tumorigenesis, as IGF-I receptor is often activated in medulloblastomas. Results To investigate the mechanisms of genetic interactions between Shh and IGF signaling in the cerebellum, we crossed nestin/IGF-I transgenic (IGF-I Tg) mice, in which transgene expression occurs in neuron precursors, with Ptc1+/- knockout mice, a model of medulloblastoma in which cancer develops in a multistage process. The IGF-I transgene produced a marked brain overgrowth, and significantly accelerated tumor development, increasing the frequency of pre-neoplastic lesions as well as full medulloblastomas in Ptc1+/-/IGF-I Tg mice. Mechanistically, tumor promotion by IGF-I mainly affected preneoplastic stages through de novo formation of lesions, while not influencing progression rate to full tumors. We also identified a marked increase in survival and proliferation, and a strong suppression of differentiation in neural precursors. Conclusions As a whole, our findings indicate that IGF-I overexpression in neural precursors leads to brain overgrowth and fosters external granular layer (EGL) proliferative lesions through a mechanism favoring proliferation over terminal differentiation, acting as a landscape for tumor growth. Understanding the molecular events responsible for cerebellum development and their alterations in tumorigenesis is critical for the identification of potential therapeutic targets.
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- 2010
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42. Low Dose of Dipotassium Glycyrrhizate Counteracts Atherosclerosis Progression in Apoe–/– Female Mice.
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Palone, Francesca, Pasquali, Emanuela, Giardullo, Paola, Stronati, Laura, Vitali, Roberta, and Mancuso, Mariateresa
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MICE ,ATHEROSCLEROTIC plaque ,ATHEROSCLEROSIS ,LICORICE (Plant) - Abstract
Low Dose of Dipotassium Glycyrrhizate Counteracts Atherosclerosis Progression in Apoe-/- Female Mice Serum cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) concentrations were also evaluated at the same time points by Mouse Cholesterol ELISA Kit (MyBioSource and EMELCA Bioscience, Breda, The Netherlands) and by HDK and LDL/VLDL Quantitation Kit (Sigma-Aldrich), respectively. Our results showed that the cortisol level is not modulated by DPG treatment (serum cortisol: matched controls [CN]: 12.37 ng/mL ± 1.86; DPG 12.70 ng/mL ± 0.59, I p i = 0.25; Fig. Effect of DPG on serum cortisol and cholesterol levels in female ApoE-/- mice and age-matched controls (CN) 14 weeks after treatment. [Extracted from the article]
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- 2019
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43. PPARα Is Necessary for Radiation-Induced Activation of Noncanonical TGFβ Signaling in the Heart.
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Subramanian, Vikram, Borchard, Sabine, Azimzadeh, Omid, Sievert, Wolfgang, Merl-Pham, Juliane, Mancuso, Mariateresa, Pasquali, Emanuela, Multhoff, Gabriele, Popper, Bastian, Zischka, Hans, Atkinson, Michael J., and Tapio, Soile
- Published
- 2018
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44. Nonlinear Radiation-Induced Cataract Using the Radiosensitive Ptch1+/- Mouse Model.
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De Stefano, Ilaria, Giardullo, Paola, Tanno, Barbara, Leonardi, Simona, Pasquali, Emanuela, Babini, Gabriele, Saran, Anna, and Mancuso, Mariateresa
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RADIATION-induced abnormalities ,CATARACT ,OPACITY (Optics) ,ANIMAL models in research ,X-rays ,DISEASE susceptibility - Abstract
While most of the evidence for radiation-induced late health effects relates to cancer, there has been increasing interest recently in the development of non-cancer diseases, including lens opacity, observed in populations exposed to low-dose radiation. In a recent study, we reported that mice heterozygous for the Patched1 ( Ptch1) gene represented a novel and powerful animal model for this disorder, and a useful tool for investigating the mechanisms of radiogenic cataract development. Given the ongoing and considerable uncertainty in allowable lens dose levels and the existence of a threshold for the development of cataracts, we tested the effects of a decreasing range of radiation doses (2 Gy, 1 Gy and 0.5 Gy X rays) by irradiating groups of Ptch1
+/- mice at 2 days of age. Our findings showed that at this dose range, acute exposure of this highly susceptible mouse model did not induce macroscopically detectable cataracts, and only the 2 Gy irradiated mice showed microscopic alterations of the lens. Molecular analyses performed to evaluate the induction of epithelial-mesenchymal transition (EMT) and subsequent fibrotic alterations in mouse lens cells also indicated the existence of a dose threshold for such effects in the mouse model used. The mechanisms of cataractogenesis remain unclear, and further experimental studies are essential to elucidate those mechanisms specific for cataract initiation and development after irradiation, as well as the underlying genetic factors controlling cataract susceptibility. [ABSTRACT FROM AUTHOR]- Published
- 2016
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45. Gender Effect in Experimental Models of Human Medulloblastoma: Does the Estrogen Receptor β Signaling Play a Role?
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Ciucci, Alessandra, Meco, Daniela, De Stefano, Ilaria, Travaglia, Daniele, Zannoni, Gian Franco, Scambia, Giovanni, Riccardi, Riccardo, Saran, Anna, Mancuso, Mariateresa, and Gallo, Daniela
- Subjects
MEDULLOBLASTOMA ,SEX factors in disease ,ESTROGEN receptors ,CELLULAR signal transduction ,SEX ratio ,CANCER cell proliferation - Abstract
Background: The male-to-female sex ratio for medulloblastoma (MB) is approximately 1.5∶1, female gender being also a favorable prognostic factor. This study aimed at evaluating the impact of gender on MB tumorigenesis. Methods: In vitro activity of 17β-estradiol (E
2 ), DPN [2,3-bis(4-hydroxyphenyl)-propionitrile, a selective estrogen receptor β (ERβ)-agonist], PPT [4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, a selective ERα-agonist] or DHT (5 alpha-dihydrotestosterone) was evaluated in three human MB cell lines. D283 Med cells were transplanted into athymic mice. Results: A significant expression of ERβ, with little or no ERα, and low AR (androgen receptor) was found in MB cell lines. The compounds tested did not affect cell proliferation. In vivo, we observed a significantly lower growth of D283 Med in nude female mice compared to males. At microscopic examination, tumors from females showed a shift towards differentiation, as evaluated by lower nestin, and higher NSE (neuron-specific enolase) and GFAP (glial fibrillary acidic protein) expression compared to males. Tumors from females also showed lower Ki67 and p53 expression. The wild-type ERβ protein (ERβ1) was lost in male tumors, while it was a permanent feature in females, and a strong negative correlation was found between Ki67 and ERβ1 expression. Conversely, tumor levels of ERβ2 and ERβ5 did not significantly differ between genders. Increased levels of cyclin-dependent kinase inhibitor p21 were observed in females, suggesting that estrogen may decrease tumor growth through blocking cell cycle progression. An inhibition of the insulin-like growth factor I (IGF-I) signaling was also evident in females. Conclusion: We provides mechanistic evidence supporting the idea that ERβ1 signaling may have pro-differentiation and tumor suppressive function in medulloblastomas. [ABSTRACT FROM AUTHOR]- Published
- 2014
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46. Biodistribution and acute toxicity of a nanofluid containing manganese iron oxide nanoparticles produced by a mechanochemical process.
- Author
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Bellusci, Mariangela, La Barbera, Aurelio, Padella, Franco, Mancuso, Mariateresa, Pasquo, Alessandra, Grollino, Maria Giuseppa, Leter, Giorgio, Nardi, Elisa, Cremisini, Carlo, Giardullo, Paola, and Pacchierotti, Francesca
- Published
- 2014
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47. Abscopal effect of radiation therapy: Interplay between radiation dose and p53 status.
- Author
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Strigari, Lidia, Mancuso, Mariateresa, Ubertini, Valentina, Soriani, Antonella, Giardullo, Paola, Benassi, Marcello, D'Alessio, Daniela, Leonardi, Simona, Soddu, Silvia, and Bossi, Gianluca
- Subjects
- *
RADIOTHERAPY , *CANCER cells , *TUMORS , *COLON cancer , *P53 antioncogene - Abstract
Purpose: This study investigates whether the abscopal effect induced by radiation-therapy (RT) is able to sterilize non-irradiated tumour cells through bystander signals. Material and methods: Wild-type (wt)-p53 or p53-null HCT116 human colon cancer cells were xenografted into both flanks of athymic female nude mice. When tumours reached a volume of 0.2 cm3, irradiation was performed, under strict dose monitoring, with a dedicated mobile accelerator designed for intra-Operative-RT (IORT). A dose of 10 or 20 Gy (IR groups), delivered by a 10 MeV electron beam, was delivered to a tumour established in one side flank, leaving the other non-irradiated (NIR groups). A subset of mice were sacrificed early on to carry out short-term molecular analyses. Results: All directly-irradiated tumours, showed a dose-dependent delayed and reduced regrowth, independent of the p53 status. Importantly, a significant effect on tumour-growth inhibition was also demonstrated in NIR wt-p53 tumours in the 20 Gy-irradiation group, with a moderate effect also evident after 10 Gy-irradiation. In contrast, no significant difference was observed in the NIR p53-null tumours, independent of the dose delivered. Molecular analyses indicate that p53-dependent signals might be responsible for the abscopal effect in our model system, via a pro-apoptotic pathway. Conclusions: We suggest that the interplay between delivered dose and p53 status might help to sterilize out-of-field tumour cells. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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48. Developmental and Oncogenic Radiation Effects on Neural Stem Cells and Their Differentiating Progeny in Mouse Cerebellum.
- Author
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Tanori, Mirella, Pasquali, Emanuela, Leonardi, Simona, Casciati, Arianna, Giardullo, Paola, Stefano, Ilaria, Mancuso, Mariateresa, Saran, Anna, and Pazzaglia, Simonetta
- Subjects
NEURAL stem cells ,DNA damage ,CELL differentiation ,LABORATORY mice ,GENETIC toxicology ,MEDULLOBLASTOMA ,CEREBELLUM ,CANCER - Abstract
A bstract Neural stem cells are highly susceptible to radiogenic DNA damage, however, little is known about their mechanisms of DNA damage response (DDR) and the long-term consequences of genotoxic exposure. Patched1 heterozygous mice ( Ptc1
+/− ) provide a powerful model of medulloblastoma (MB), a frequent pediatric tumor of the cerebellum. Irradiation of newborn Ptc1+/− mice dramatically increases the frequency and shortens the latency of MB. In this model, we investigated the mechanisms through which multipotent neural progenitors (NSCs) and fate-restricted progenitor cells (PCs) of the cerebellum respond to DNA damage induced by radiation, and the long-term developmental and oncogenic consequences. These responses were assessed in mice exposed to low (0.25 Gy) or high (3 Gy) radiation doses at embryonic day 13.5 (E13.5), when NSCs giving rise to the cerebellum are specified but the external granule layer (EGL) has not yet formed, or at E16.5, during the expansion of granule PCs to form the EGL. We found crucial differences in DDR and apoptosis between NSCs and fate-restricted PCs, including lack of p21 expression in NSCs. NSCs also appear to be resistant to oncogenesis from low-dose radiation exposure but more vulnerable at higher doses. In addition, the pathway to DNA repair and the pattern of oncogenic alterations were strongly dependent on age at exposure, highlighting a differentiation-stage specificity of DNA repair pathways in NSCs and PCs. These findings shed light on the mechanisms used by NSCs and PCs to maintain genome integrity during neurogenesis and may have important implications for radiation risk assessment and for development of targeted therapies against brain tumors. S tem C ells 2013;31:2506-2516 [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
49. Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum.
- Author
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Pazzaglia, Simonetta, Tanno, Barbara, De Stefano, Ilaria, Giardullo, Paola, Leonardi, Simona, Merla, Caterina, Babini, Gabriele, Tuncay Cagatay, Seda, Mayah, Ammar, Kadhim, Munira, Lyng, Fiona M., von Toerne, Christine, Khan, Zohaib N., Subedi, Prabal, Tapio, Soile, Saran, Anna, and Mancuso, Mariateresa
- Subjects
MICRORNA ,EXOSOMES ,IONIZING radiation ,CEREBELLUM ,PROTEOMICS ,CELL communication - Abstract
Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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- View/download PDF
50. The estrogen receptor beta agonist diarylpropionitrile (DPN) inhibits medulloblastoma development via anti-proliferative and pro-apototic pathways
- Author
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Mancuso, Mariateresa, Leonardi, Simona, Giardullo, Paola, Pasquali, Emanuela, Borra, Fabiana, Stefano, Ilaria De, Prisco, Maria Grazia, Tanori, Mirella, Scambia, Giovanni, Majo, Vincenzo Di, Pazzaglia, Simonetta, Saran, Anna, and Gallo, Daniela
- Subjects
- *
MEDULLOBLASTOMA , *SEX factors in disease , *ESTROGEN receptors , *LABORATORY mice , *CARCINOGENESIS , *PRECANCEROUS conditions , *ADRENERGIC beta agonists , *OVARIECTOMY , *THERAPEUTICS - Abstract
Abstract: Gender-related differences in medulloblastoma (MB) development have been reported with a higher incidence in males (slightly above 60%) than in females, female gender being also a significantly favorable prognostic factor in MB. The present study focused on the evaluation of the mechanisms by which estrogens protect against MB formation. To this end, we used a well characterized mouse model of MB – the Patched1 heterozygous mice. Ovariectomized mice were treated with 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), a highly potent ERβ agonist, or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT), a highly potent ERα agonist. Our results show that the ERβ selective agonist DPN significantly inhibits development of MB preneoplastic lesions when compared with untreated ovariectomized mice, restoring the final incidence to that observed in the intact controls, and that these effects were achieved via activation of anti-proliferative and pro-apototic pathways. On the other hand, the ERα selective agonist PPT did not influence MB tumorigenesis relative to untreated ovariectomized mice. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF
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