688 results on '"Falvo, E."'
Search Results
2. Alterations of gut microbiota composition in post-finasteride patients: a pilot study
- Author
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Borgo, F., Macandog, A. D., Diviccaro, S., Falvo, E., Giatti, S., Cavaletti, G., and Melcangi, R. C.
- Published
- 2021
- Full Text
- View/download PDF
3. Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rate.
- Author
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Marrocco F, Falvo E, Mosca L, Tisci G, Arcovito A, Reccagni A, Limatola C, Bernardini R, Ceci P, D'Alessandro G, and Colotti G
- Subjects
- Animals, Mice, Survival Rate, Brain, Blood-Brain Barrier, Ferritins, Glioma drug therapy
- Abstract
Gliomas are among the most fatal tumors, and the available therapeutic options are very limited. Additionally, the blood-brain barrier (BBB) prevents most drugs from entering the brain. We designed and produced a ferritin-based stimuli-sensitive nanocarrier with high biocompatibility and water solubility. It can incorporate high amounts of the potent topoisomerase 1 inhibitor Genz-644282. Here, we show that this nanocarrier, named The-0504, can cross the BBB and specifically deliver the payload to gliomas that express high amounts of the ferritin/transferrin receptor TfR1 (CD71). Intranasal or intravenous administration of The-0504 both reduce tumor growth and improve the survival rate of glioma-bearing mice. However, nose-to-brain administration is a simpler and less invasive route that may spare most of the healthy tissues compared to intravenous injections. For this reason, the data reported here could pave the way towards a new, safe, and direct ferritin-based drug delivery method for brain diseases, especially brain tumors., (© 2024. The Author(s).)
- Published
- 2024
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4. Widespread in vivo efficacy of The-0504: A conditionally-activatable nanoferritin for tumor-agnostic targeting of CD71-expressing cancers.
- Author
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Fracasso G, Falvo E, Tisci G, Sala G, Colotti G, Cingarlini S, Tito C, Bibbo S, Frusteri C, Tremante E, Giordani E, Giacomini P, and Ceci P
- Abstract
Background: Cancer is still among the leading causes of death all over the world. Improving chemotherapy and minimizing associated toxicities are major unmet medical needs. Recently, we provided a preliminary preclinical evaluation of a human ferritin (HFt)-based drug carrier (The-0504) that selectively delivers the wide-spectrum topoisomerase I inhibitor Genz-644282 to CD71-expressing tumors. The-0504 has so far been evaluated on four different human tumor xenotransplant models (breast, colorectal, pancreatic and liver cancers)., Methods: Herein, we extend our studies, by: (a) testing DNA damage in vitro, (b) treating eight additional tumor xenograft models in vivo with The-0504; (c) performing pharmacokinetic (PK) studies in rats; and (d) evaluating The-0504 anti-tumor xenotransplant efficacy by optimizing its administration schedule based on PK considerations., Results: Immunofluorescence demonstrated that The-0504 induces foci expressing the DNA double-strand break marker γH2AX. Expression increases up to 4-fold and is more persistent as compared to free Genz-644282. In vivo studies confirmed a remarkable anti-tumor activity of The-0504, resulting in tumor eradication in most murine xenograft models, regardless of embryological origin (e.g. epithelial, mesenchymal or neuroendocrine), and molecular subtypes. PK studies demonstrated a long persistence of The-0504 in rat serum (half-life of about 40 h as compared to 15 h of the free drug), with a 400-fold increase in peak concentrations as compared to the free drug. On this basis, we reduced The-0504 administration frequency from twice to once per week, with no appreciable loss in therapeutic efficacy in mice., Conclusion: The results presented here confirm that The-0504 is highly active against several human tumor xenotransplants, even when administered less frequently than previously reported. The-0504 may be a good candidate for further clinical development in a tumor histotype-agnostic setting., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pierpaolo Ceci and Elisabetta Falvo are inventors on patent application EP3186192B1 held by Thena Biotech that covers fusion proteins based on human ferritins and methods of use thereof. Pierpaolo Ceci is a member (free of charge) of the Scientific Advisory Committee of Thena Biotech. All the authors declare no conflict of interest., (© 2023 The Authors.)
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- 2023
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5. Gut Steroids and Microbiota: Effect of Gonadectomy and Sex
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Diviccaro, S., Fitzgerald, J.A., Cioffi, L., Falvo, E., Crispie, F., Cotter, P.D., O'Mahony, S.M., Giatti, S., Caruso, D., and Melcangi, R.
- Subjects
Ribosomal ,Male ,16S ,gut microbiota ,branched- and short-chain fatty acids ,gastrointestinal tract ,mucosa ,pregnenolone ,sex dimorphism ,sex steroids ,stool ,Animals ,Castration ,Female ,Gas Chromatography-Mass Spectrometry ,Pregnanolone ,Progesterone ,RNA, Ribosomal, 16S ,Rats ,Microbiota ,Pregnenolone ,Settore MED/13 - Endocrinologia ,Settore BIO/10 - Biochimica ,RNA - Abstract
Sex steroids, derived mainly from gonads, can shape microbiota composition; however, the impact of gonadectomy and sex on steroid production in the gut (i.e., gut steroids), and its interaction with microbiota composition, needs to be clarified. In this study, steroid environment and gut steroidogenesis were analysed by liquid chromatography tandem mass spectrometry and expression analyses. Gut microbiota composition as branched- and short-chain fatty acids were determined by 16S rRNA gene sequence analysis and gas chromatography flame ionisation detection, respectively. Here, we first demonstrated that levels of pregnenolone (PREG), progesterone (PROG), and isoallopregnanolone (ISOALLO) were higher in the female rat colon, whereas the level of testosterone (T) was higher in males. Sexual dimorphism on gut steroidogenesis is also reported after gonadectomy. Sex, and more significantly, gonadectomy, affects microbiota composition. We noted that a number of taxa and inferred metabolic pathways were associated with gut steroids, such as positive associations between
- Published
- 2022
6. PHOTOGRAMMETRIC AND FLUORESCENCE SOLUTIONS FOR MONITORING OF HABITAT FORMING ORGANISMS
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Rossi, P., primary, Righi, S., additional, Parente, L., additional, Castagnetti, C., additional, Cattini, S., additional, Di Loro, G., additional, Falvo, E., additional, Grassi, F., additional, Mancini, F., additional, Rovati, L., additional, Simonini, R., additional, and Capra, A., additional
- Published
- 2022
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7. Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles
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Vannucci L, Falvo E, Fornara M, Di Micco P, Benada O, Krizan J, Svoboda J, Hulikova-Capkova K, Morea V, Boffi A, and Ceci P
- Subjects
Medicine (General) ,R5-920 - Abstract
Luca Vannucci1,*, Elisabetta Falvo2,*, Manuela Fornara3, Patrizio Di Micco4, Oldrich Benada1, Jiri Krizan1, Jan Svoboda1, Katarina Hulikova-Capkova1, Veronica Morea3, Alberto Boffi4,5, Pierpaolo Ceci3 1Institute of Microbiology, Academy of Sciences of the Czech Republic, VVI, Prague, Czech Republic; 2Regina Elena Cancer Institute, Pharmacokinetic/Pharmacogenomic Unit, 3National Research Council of Italy, Institute of Molecular Biology and Pathology, 4Department of Biochemical Sciences “A Rossi Fanelli”, University of Rome “Sapienza”, 5Center for Life Nano Science at Sapienza, Italian Institute of Technology, Rome, Italy *These two authors contributed equally to this workBackground: Nanoparticle-based systems are promising for the development of imaging and therapeutic agents. The main advantage of nanoparticles over traditional systems lies in the possibility of loading multiple functionalities onto a single molecule, which are useful for therapeutic and/or diagnostic purposes. These functionalities include targeting moieties which are able to recognize receptors overexpressed by specific cells and tissues. However, targeted delivery of nanoparticles requires an accurate system design. We present here a rationally designed, genetically engineered, and chemically modified protein-based nanoplatform for cell/tissue-specific targeting.Methods: Our nanoparticle constructs were based on the heavy chain of the human protein ferritin (HFt), a highly symmetrical assembly of 24 subunits enclosing a hollow cavity. HFt-based nanoparticles were produced using both genetic engineering and chemical functionalization methods to impart several functionalities, ie, the α-melanocyte-stimulating hormone peptide as a melanoma-targeting moiety, stabilizing and HFt-masking polyethylene glycol molecules, rhodamine fluorophores, and magnetic resonance imaging agents. The constructs produced were extensively characterized by a number of physicochemical techniques, and assayed for selective melanoma-targeting in vitro and in vivo.Results: Our HFt-based nanoparticle constructs functionalized with the α-melanocyte-stimulating hormone peptide moiety and polyethylene glycol molecules were specifically taken up by melanoma cells but not by other cancer cell types in vitro. Moreover, experiments in melanoma-bearing mice indicate that these constructs have an excellent tumor-targeting profile and a long circulation time in vivo.Conclusion: By masking human HFt with polyethylene glycol and targeting it with an α-melanocyte-stimulating hormone peptide, we developed an HFt-based melanoma-targeting nanoplatform for application in melanoma diagnosis and treatment. These results could be of general interest, because the same strategy can be exploited to develop ad hoc nanoplatforms for specific delivery towards any cell/tissue type for which a suitable targeting moiety is available.Keywords: multifunctional nanoparticles, ferritin, nanoplatform, cancer-targeting, melanoma
- Published
- 2012
8. Gut microbiota composition is altered in a preclinical model of type 1 diabetes mellitus: Influence on gut steroids, permeability, and cognitive abilities.
- Author
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Diviccaro S, Falvo E, Piazza R, Cioffi L, Herian M, Brivio P, Calabrese F, Giatti S, Caruso D, and Melcangi RC
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- Rats, Female, Animals, Dysbiosis, Claudin-1, Pregnanolone, Gonadal Steroid Hormones metabolism, Cognition, Permeability, Pregnenolone, Gastrointestinal Microbiome, Diabetes Mellitus, Type 1, Neurosteroids
- Abstract
Sex steroid hormones are not only synthesized from the gonads but also by other tissues, such as the brain (i.e., neurosteroids) and colon (i.e., gut steroids). Gut microbiota can be shaped from sex steroid hormones synthesized from the gonads and locally interacts with gut steroids as in turn modulates neurosteroids. Type 1 diabetes mellitus (T1DM) is characterized by dysbiosis and also by diabetic encephalopathy. However, the interactions of players of gut-brain axis, such as gut steroids, gut permeability markers and microbiota, have been poorly explored in this pathology and, particularly in females. On this basis, we have explored, in streptozotocin (STZ)-induced adult female rats, whether one month of T1DM may alter (I) gut microbiome composition and diversity by 16S next-generation sequencing, (II) gut steroid levels by liquid chromatography-tandem mass spectrometry, (III) gut permeability markers by gene expression analysis, (IV) cognitive behavior by the novel object recognition (NOR) test and whether correlations among these aspects may occur. Results obtained reveal that T1DM alters gut β-, but not α-diversity. The pathology is also associated with a decrease and an increase in colonic pregnenolone and allopregnanolone levels, respectively. Additionally, diabetes alters gut permeability and worsens cognitive behavior. Finally, we reported a significant correlation of pregnenolone with Blautia, claudin-1 and the NOR index and of allopregnanolone with Parasutterella, Gammaproteobacteria and claudin-1. Altogether, these results suggest new putative roles of these two gut steroids related to cognitive deficit and dysbiosis in T1DM female experimental model. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies"., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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9. Diabetic Encephalopathy in a Preclinical Experimental Model of Type 1 Diabetes Mellitus: Observations in Adult Female Rat.
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Falvo E, Giatti S, Diviccaro S, Cioffi L, Herian M, Brivio P, Calabrese F, Caruso D, and Melcangi RC
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- Female, Rats, Male, Animals, Neuroinflammatory Diseases, Maze Learning, Brain metabolism, Hippocampus metabolism, Oxidative Stress, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 metabolism
- Abstract
Patients affected by diabetes mellitus (DM) show diabetic encephalopathy with an increased risk of cognitive deficits, dementia and Alzheimer's disease, but the mechanisms are not fully explored. In the male animal models of DM, the development of cognitive impairment seems to be the result of the concomitance of different processes such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and aberrant synaptogenesis. However, even if diabetic encephalopathy shows some sex-dimorphic features, no observations in female rats have been so far reported on these aspects. Therefore, in an experimental model of type 1 DM (T1DM), we explored the impact of one month of pathology on memory abilities by the novel object recognition test and on neuroinflammation, synaptogenesis and mitochondrial functionality. Moreover, given that steroids are involved in memory and learning, we also analysed their levels and receptors. We reported that memory dysfunction can be associated with different features in the female hippocampus and cerebral cortex. Indeed, in the hippocampus, we observed aberrant synaptogenesis and neuroinflammation but not mitochondrial dysfunction and oxidative stress, possibly due to the results of locally increased levels of progesterone metabolites (i.e., dihydroprogesterone and allopregnanolone). These observations suggest specific brain-area effects of T1DM since different alterations are observed in the cerebral cortex.
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- 2023
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10. Sensing the quantum behaviour of magnetic nanoparticles by electron magnetic resonance
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Fittipaldi, M., Mercatelli, R., Sottini, S., Ceci, P., Falvo, E., and Gatteschi, D.
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Physics::General Physics ,Materials science ,Spin states ,Population ,General Physics and Astronomy ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Quantitative Biology::Cell Behavior ,law.invention ,chemistry.chemical_compound ,law ,Physical and Theoretical Chemistry ,Spin (physics) ,Spectroscopy ,education ,Electron paramagnetic resonance ,education.field_of_study ,Condensed matter physics ,ferritin ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,chemistry ,magnetism ,Excited state ,Magnetic nanoparticles ,EPR ,0210 nano-technology ,Iron oxide nanoparticles - Abstract
We have investigated Magnetic Nanoparticles (MNPs) of spinel type iron oxide (of approximately 8 nm) mineralized in the internal cavity of the bioreactor ferritin nanocage. In particular, we have used Electron Magnetic Resonance, EMR, spectroscopy and taken advantage of the capacity of the protein shells to control the size of the MNPs. EMR measurements in perpendicular and parallel configurations have been recorded at various temperatures. A model based on the giant spin is used to interpret the experimental results. The analysis indicates that the observed quantum behaviour has to be ascribed to the whole MNP and that the thermal population of excited spin states has a strong influence in the EMR behaviour of MNPs.
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- 2016
11. Gene variants associated to malignant thyroid disease in familial adenomatous polyposis: A novel APC germline mutation
- Author
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Martayan, A., Sanchez-Mete, L., Baldelli, R., Falvo, E., Barnabei, A., Conti, L., Giacomini, P., Appetecchia, M., and Stigliano, V.
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- 2010
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12. Physiopathological role of the enzymatic complex 5α-reductase and 3α/β-hydroxysteroid oxidoreductase in the generation of progesterone and testosterone neuroactive metabolites
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Giatti, S., Diviccaro, Silvia, Falvo, E., García-Segura, Luis M., Melcangi, R. C., Ministero dell'Istruzione, dell'Università e della Ricerca, Università degli Studi di Milano, Post-Finasteride Syndrome Foundation, Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (España), Instituto de Salud Carlos III, and European Commission
- Subjects
Translocator protein of 18kd ,Finasteride ,Neuroactive steroids ,Neurodegenerative disorders ,Psychiatric disorders ,Neuroprotection - Abstract
The enzymatic complex 5α-reductase (5α-R) and 3α/3β-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone (PROG) and testosterone (T) into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5α-R and 3α-HSOR and the levels of PROG and T reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. However, in other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5α-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. However, further research is needed to fully understand the consequences of these manipulations, in particular with 5α-R inhibitors. We acknowledge support from MIUR Progetto Eccellenza and Intramural Grant Line-B from Università degli Studi di Milano to SG and Post-Finasteride Foundation to RCM. We also acknowledge support from Agencia Estatal de Investigación, Spain (grant number BFU2017-82754-R), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain and Fondos Feder to LM G-S.
- Published
- 2020
13. Gut Inflammation Induced by Finasteride Withdrawal: Therapeutic Effect of Allopregnanolone in Adult Male Rats.
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Diviccaro S, Giatti S, Cioffi L, Falvo E, Herian M, Caruso D, and Melcangi RC
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- Animals, Rats, Male, Pregnenolone, Receptors, GABA-A, Inflammation drug therapy, Inflammation chemically induced, Finasteride pharmacology, Pregnanolone pharmacology
- Abstract
The treatment with finasteride (i.e., an inhibitor of 5α-reductase) may be associated with different side effects (i.e., depression, anxiety, cognitive impairment and sexual dysfunction) inducing the so-called post finasteride syndrome (PFS). Moreover, previous observations in PFS patients and an experimental model showed alterations in gut microbiota populations, suggesting an inflammatory environment. To confirm this hypothesis, we have explored the effect of chronic treatment with finasteride (i.e., for 20 days) and its withdrawal (i.e., for 1 month) on the levels of steroids, neurotransmitters, pro-inflammatory cytokines and gut permeability markers in the colon of adult male rat. The obtained data demonstrate that the levels of allopregnanolone (ALLO) decreased after finasteride treatment and after its withdrawal. Following the drug suspension, the decrease in ALLO levels correlates with an increase in IL-1β and TNF-α, serotonin and a decrease in dopamine. Importantly, ALLO treatment is able to counteract some of these alterations. The relation between ALLO and GABA-A receptors and/or pregnenolone (ALLO precursor) could be crucial in their mode of action. These observations provide an important background to explore further the protective effect of ALLO in the PFS experimental model and the possibility of its translation into clinical therapy.
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- 2022
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14. Steroidogenic machinery in the adult rat colon
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Diviccaro, S., primary, Giatti, S., additional, Borgo, F., additional, Falvo, E., additional, Caruso, D., additional, Garcia-Segura, L.M., additional, and Melcangi, R.C., additional
- Published
- 2020
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15. Alterations of gut microbiota composition in post-finasteride patients: a pilot study
- Author
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Borgo, F., primary, Macandog, A. D., additional, Diviccaro, S., additional, Falvo, E., additional, Giatti, S., additional, Cavaletti, G., additional, and Melcangi, R. C., additional
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- 2020
- Full Text
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16. Paroxetine effects in adult male rat colon: Focus on gut steroidogenesis and microbiota.
- Author
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Diviccaro S, Giatti S, Cioffi L, Falvo E, Piazza R, Caruso D, and Melcangi RC
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- Animals, Colon, Humans, Male, Rats, Selective Serotonin Reuptake Inhibitors pharmacology, Selective Serotonin Reuptake Inhibitors therapeutic use, Steroids, Microbiota, Paroxetine pharmacology, Paroxetine therapeutic use
- Abstract
Paroxetine, a selective serotonin reuptake inhibitor (SSRI), is prescribed to treat psychiatric disorders, although an off-label SSRI use is also for functional gastrointestinal disorders. The mutual correlation between serotonin and peripheral sex steroids has been reported, however little attention to sex steroids synthesized by gut, has been given so far. Indeed, whether SSRIs, may also influence the gut steroid production, immediately after treatment and/or after suspension, is still unclear. The finding that gut possesses steroidogenic capability is of particular relevance, also for the existence of the gut-microbiota-brain axis, where gut microbiota represents a key orchestrator. On this basis, adult male rats were treated daily for two weeks with paroxetine or vehicle and, 24 h after treatment and at 1 month of withdrawal, steroid environment and gut microbiota were evaluated. Results obtained reveal that paroxetine significantly affects steroid levels, only in the colon but not in plasma. In particular, steroid modifications observed immediately after treatment are not overlap with those detected at withdrawal. Additionally, paroxetine treatment and its withdrawal impact gut microbiota populations differently. Altogether, these results suggest a biphasic effect of the drug treatment in the gut both on steroidogenesis and microbiota., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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17. Sex dimorphism in an animal model of multiple sclerosis: Focus on pregnenolone synthesis
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Giatti, S., primary, Rigolio, R., additional, Diviccaro, S., additional, Falvo, E., additional, Caruso, D., additional, Garcia-Segura, L.M., additional, Cavaletti, G., additional, and Melcangi, R.C., additional
- Published
- 2020
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18. Allopregnanolone: An overview on its synthesis and effects.
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Diviccaro S, Cioffi L, Falvo E, Giatti S, and Melcangi RC
- Subjects
- Progesterone, Neurosteroids, Pregnanolone
- Abstract
Allopregnanolone, a 3α,5α-progesterone metabolite, acts as a potent allosteric modulator of the γ-aminobutyric acid type A receptor. In the present review, the synthesis of this neuroactive steroid occurring in the nervous system is discussed with respect to physiological and pathological conditions. In addition, its physiological and neuroprotective effects are also reported. Interestingly, the levels of this neuroactive steroid, as well as its effects, are sex-dimorphic, suggesting a possible gender medicine based on this neuroactive steroid for neurological disorders. However, allopregnanolone presents low bioavailability and extensive hepatic metabolism, limiting its use as a drug. Therefore, synthetic analogues or a different therapeutic strategy able to increase allopregnanolone levels have been proposed to overcome any pharmacokinetic issues., (© 2021 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)
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- 2022
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19. Image-Based Monitoring of Cracks: Effectiveness Analysis of an Open-Source Machine Learning-Assisted Procedure.
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Parente L, Falvo E, Castagnetti C, Grassi F, Mancini F, Rossi P, and Capra A
- Abstract
The proper inspection of a cracks pattern over time is a critical diagnosis step to provide a thorough knowledge of the health state of a structure. When monitoring cracks propagating on a planar surface, adopting a single-image-based approach is a more convenient (costly and logistically) solution compared to subjective operators-based solutions. Machine learning (ML)- based monitoring solutions offer the advantage of automation in crack detection; however, complex and time-consuming training must be carried out. This study presents a simple and automated ML-based crack monitoring approach implemented in open sources software that only requires a single image for training. The effectiveness of the approach is assessed conducting work in controlled and real case study sites. For both sites, the generated outputs are significant in terms of accuracy (~1 mm), repeatability (sub-mm) and precision (sub-pixel). The presented results highlight that the successful detection of cracks is achievable with only a straightforward ML-based training procedure conducted on only a single image of the multi-temporal sequence. Furthermore, the use of an innovative camera kit allowed exploiting automated acquisition and transmission fundamental for Internet of Things (IoTs) for structural health monitoring and to reduce user-based operations and increase safety.
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- 2022
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20. Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model.
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Conti G, Pitea M, Ossanna R, Opri R, Tisci G, Falvo E, Innamorati G, Ghanem E, Sbarbati A, Ceci P, and Fracasso G
- Abstract
Pancreatic cancer (PC) represents an intriguing topic for researchers. To date, the prognosis of metastasized PC is poor with just 7% of patients exceeding a five-year survival period. Thus, molecular modifications of existing drugs should be developed to change the course of the disease. Our previously generated nanocages of Mitoxantrone (MIT) encapsulated in human H-chain Ferritin (HFt), designated as HFt-MP-PASE-MIT, has shown excellent tumor distribution and extended serum half-life meriting further investigation for PC treatment. Thus, in this study, we used the same nano-formulation to test its cytotoxicity using both in vitro and in vivo assays. Interestingly, both encapsulated and free-MIT drugs demonstrated similar killing capabilities on PaCa44 cell line. Conversely, in vivo assessment in a subcutaneous PaCa44 tumor model of PC demonstrated a remarkable capability for encapsulated MIT to control tumor growth and improve mouse survival with a median survival rate of 65 vs. 33 days for loaded and free-MIT, respectively. Interestingly, throughout the course of mice treatment, MIT encapsulation did not present any adverse side effects as confirmed by histological analysis of various murine tissue organs and body mass weights. Our results are promising and pave the way to effective PC targeted chemotherapy using our HFt nanodelivery platforms.
- Published
- 2021
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21. Effects of paroxetine treatment and its withdrawal on neurosteroidogenesis.
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Giatti S, Diviccaro S, Cioffi L, Falvo E, Caruso D, and Melcangi RC
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- Animals, Hippocampus, Male, Paroxetine adverse effects, Rats, Selective Serotonin Reuptake Inhibitors adverse effects, Neurosteroids, Sexual Dysfunction, Physiological
- Abstract
Selective serotonin reuptake inhibitors (SSRI) show high efficacy in treating depression, however during treatment side effects, like for instance sexual dysfunction, may appear, decreasing compliance. In some cases, this condition will last after drug discontinuation, leading to the so-called post-SSRI sexual dysfunction (PSSD). The etiology of PSSD is still unknown, however a role for neuroactive steroids may be hypothesized. Indeed, these molecules are key physiological regulators of the nervous system, and their alteration has been associated with several neuropathological conditions, including depression. Additionally, neuroactive steroids are also involved in the control of sexual function. Interestingly, sexual dysfunction induced by SSRI treatment has been also observed in animal models. On this basis, we have here evaluated whether a subchronic treatment with paroxetine for two weeks and/or its withdrawal (i.e., a month) may affect the levels of neuroactive steroids in brain areas (i.e., hippocampus, hypothalamus, and cerebral cortex) and/or in plasma and cerebrospinal fluid of male rats. Data obtained indicate that the SSRI treatment alters neuroactive steroid levels and the expression of key enzymes of the steroidogenesis in a brain tissue- and time-dependent manner. Indeed, these observations with the finding that plasma levels of neuroactive steroids are not affected suggest that the effect of paroxetine treatment is directly on neurosteroidogenesis. In particular, a negative impact on the expression of steroidogenic enzymes was observed at the withdrawal. Therefore, it is possible to hypothesize that altered neurosteroidogenesis may also occur in PSSD and consequently it may represent a possible pharmacological target for this disorder., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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22. PO-207 Ferritin-engineered nanoparticles as targeted drug delivery system for cancer treatment
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Damiani, V., primary, Falvo, E., additional, Pitea, M., additional, Fracasso, G., additional, Rossi, C., additional, Sala, G., additional, De Laurenzi, V., additional, and Ceci, P., additional
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- 2018
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23. Three-Dimensional Proteome-Wide Scale Screening for the 5-Alpha Reductase Inhibitor Finasteride: Identification of a Novel Off-Target.
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Giatti S, Di Domizio A, Diviccaro S, Falvo E, Caruso D, Contini A, and Melcangi RC
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- 5-alpha Reductase Inhibitors metabolism, 5-alpha Reductase Inhibitors pharmacology, Animals, Binding Sites, Binding, Competitive, Catecholamines analysis, Catecholamines metabolism, Chromatography, High Pressure Liquid, Databases, Protein, Epinephrine metabolism, Finasteride metabolism, Finasteride pharmacology, Humans, Male, Molecular Docking Simulation, Molecular Dynamics Simulation, Phenylethanolamine N-Methyltransferase chemistry, Protein Binding, Rats, Rats, Sprague-Dawley, Tandem Mass Spectrometry, Thermodynamics, 5-alpha Reductase Inhibitors chemistry, Finasteride chemistry, Phenylethanolamine N-Methyltransferase metabolism
- Abstract
Finasteride, a 5-alpha reductase (5α-R) inhibitor, is a widely used drug for treating androgen-dependent conditions. However, its use is associated with sexual, psychological, and physical complaints, suggesting that other mechanisms, in addition to 5α-R inhibition, may be involved. Here, a multidisciplinary approach has been used to identify potential finasteride off-target proteins. SPILLO-PBSS software suggests an additional inhibitory activity of finasteride on phenylethanolamine N -methyltransferase (PNMT), the limiting enzyme in formation of the stress hormone epinephrine. The interaction of finasteride with PNMT was supported by docking and molecular dynamics analysis and by in vitro assay, confirming the inhibitory nature of the binding. Finally, this inhibition was also confirmed in an in vivo rat model. Literature data indicate that PNMT activity perturbation may be correlated with sexual and psychological side effects. Therefore, results here obtained suggest that the binding of finasteride to PNMT might have a role in producing the side effects exerted by finasteride treatment.
- Published
- 2021
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24. Nanoconstructs for targeting the tumor microenvironment
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Vannucci, L, Rajsiglová, I, Stakeheev, D, Ceci, P, Falvo, E, Babic, M, Kostiv, U, Caja, F, Krizan, J, Vrba, J, Vrba, J. Jr, Vrba, D, Farina, Laura, Lopresto, V, and Ruvio, G.
- Published
- 2016
25. High activity and low toxicity of a novel CD71-targeting nanotherapeutic named The-0504 on preclinical models of several human aggressive tumors.
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Falvo E, Damiani V, Conti G, Boschi F, Messana K, Giacomini P, Milella M, De Laurenzi V, Morea V, Sala G, Fracasso G, and Ceci P
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- Animals, Cell Line, Tumor, Female, Humans, Mice, Mice, Nude, Rats, Antigens, CD metabolism, Biomarkers, Tumor metabolism, Ferritins metabolism, Nanostructures chemistry, Neoplasms genetics, Receptors, Transferrin metabolism
- Abstract
Background: Ferritin receptor (CD71) is an example of a very attractive cancer target, since it is highly expressed in virtually all tumor types, including metastatic loci. However, this target can be considered to be inaccessible to conventional target therapies, due to its presence in many healthy tissues. Here, we describe the preclinical evaluation of a tumor proteases-activatable human ferritin (HFt)-based drug carrier (The-0504) that is able to selectively deliver the wide-spectrum topoisomerase I inhibitor Genz-644282 to CD71-expressing tumors, preventing the limiting toxic effects associated with CD71-targeting therapies., Methods: CD71 expression was evaluated using flow cytometry and immunohistochemistry techniques. The-0504 antiproliferative activity towards several cancer cell lines was assessed in vitro. The-0504 antitumor efficacy and survival benefit were evaluated in different human tumors, which had been grown either as xenografts or patient-derived xenografts in mice. The-0504 toxicology profile was investigated in multiple-cycle repeat-dose study in rodents., Results: In vitro studies indicate that The-0504 is highly specific for CD71 expressing cells, and that there is a relationship between CD71 levels and The-0504 anticancer activity. In vivo treatments with The-0504 showed a remarkable efficacy, eradicating several human tumors of very diverse and aggressive histotypes, such as pancreas, liver and colorectal carcinomas, and triple-negative breast cancer., Conclusions: Durable disease-free survival, persistent antitumor responses after discontinuation of treatment and favorable toxicology profile make The-0504 an ideal candidate for clinical development as a novel, CD71-targeted, low-toxicity alternative to chemotherapy.
- Published
- 2021
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26. Physiopathological Role of Neuroactive Steroids in the Peripheral Nervous System.
- Author
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Falvo E, Diviccaro S, Melcangi RC, and Giatti S
- Subjects
- Animals, Humans, Models, Biological, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, Neurosteroids chemistry, Neurosteroids therapeutic use, Peripheral Nervous System drug effects, Peripheral Nervous System Diseases drug therapy, Peripheral Nervous System Diseases pathology, Peripheral Nervous System Diseases physiopathology, Neurosteroids metabolism, Peripheral Nervous System physiopathology
- Abstract
Peripheral neuropathy (PN) refers to many conditions involving damage to the peripheral nervous system (PNS). Usually, PN causes weakness, numbness and pain and is the result of traumatic injuries, infections, metabolic problems, inherited causes, or exposure to chemicals. Despite the high prevalence of PN, available treatments are still unsatisfactory. Neuroactive steroids (i.e., steroid hormones synthesized by peripheral glands as well as steroids directly synthesized in the nervous system) represent important physiological regulators of PNS functionality. Data obtained so far and here discussed, indeed show that in several experimental models of PN the levels of neuroactive steroids are affected by the pathology and that treatment with these molecules is able to exert protective effects on several PN features, including neuropathic pain. Of note, the observations that neuroactive steroid levels are sexually dimorphic not only in physiological status but also in PN, associated with the finding that PN show sex dimorphic manifestations, may suggest the possibility of a sex specific therapy based on neuroactive steroids.
- Published
- 2020
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27. Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy.
- Author
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Falvo E, Arcovito A, Conti G, Cipolla G, Pitea M, Morea V, Damiani V, Sala G, Fracasso G, and Ceci P
- Abstract
Gastrointestinal tumors, including pancreatic and colorectal cancers, represent one of the greatest public health issues worldwide, leading to a million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different types of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors.
- Published
- 2020
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28. Antibody-drug conjugates: targeting melanoma with cisplatin encapsulated in protein-cage nanoparticles based on human ferritin. Nanoscale
- Author
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Falvo E, Tremante E, Fraioli R, Leonetti C, Zamparelli C, Boffi A, Morea V, Ceci P, and Giacomini P.
- Published
- 2013
29. Physiopathological role of the enzymatic complex 5α-reductase and 3α/β-hydroxysteroid oxidoreductase in the generation of progesterone and testosterone neuroactive metabolites.
- Author
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Giatti S, Diviccaro S, Falvo E, Garcia-Segura LM, and Melcangi RC
- Subjects
- 3-Hydroxysteroid Dehydrogenases genetics, Animals, Brain enzymology, Cholestenone 5 alpha-Reductase genetics, Female, Gene Expression, Humans, Male, Mental Disorders enzymology, Neurodegenerative Diseases enzymology, Neuroprotective Agents, Sex Characteristics, 3-Hydroxysteroid Dehydrogenases physiology, Cholestenone 5 alpha-Reductase physiology, Progesterone metabolism, Testosterone metabolism
- Abstract
The enzymatic complex 5α-reductase (5α-R) and 3α/3β-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone (PROG) and testosterone (T) into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5α-R and 3α-HSOR and the levels of PROG and T reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. However, in other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5α-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. However, further research is needed to fully understand the consequences of these manipulations, in particular with 5α-R inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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30. Reassessment of Protein Stability, DNA Binding, and Protection of Mycobacterium smegmatis Dps
- Author
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Ceci P, Ilari A, Falvo E, Giangiacomo L, and Chiancone E.
- Abstract
The structure and function of Mycobacterium smegmatis Dps (DNA-binding proteins from starved cells) and of the protein studied by Gupta and Chatterji ( Gupta, S., and Chatterji, D. ( 2003) J. Biol. Chem. 278, 5235 - 5241), in which the C terminus that is used for binding DNA contains a histidine tag, have been characterized in parallel. The native dodecamer dissociated reversibly into dimers above pH 7.5 and below pH 6.0, with apparent pK(a) values of similar to 7.65 and 4.75; at pH similar to 4.0, dimers formed monomers. Based on structural analysis, the two dissociation steps have been attributed to breakage of the salt bridges between Glu(157) and Arg(99) located at the 3-fold symmetry axes and to protonation of Asp(66) hydrogen-bonded to Lys(36) across the dimer interface, respectively. The C-terminal tag did not affect subunit dissociation, but altered DNA binding dramatically. At neutral pH, protonation of the histidine tag promoted DNA condensation, whereas in the native C terminus, compensation of negative and positive charges led to DNA binding without condensation. This different mode of interaction with DNA has important functional consequences as indicated by the failure of the native protein to protect DNA from DNase-mediated cleavage and by the efficiency of the tagged protein in doing so as a result of DNA sequestration in the condensates. Chemical protection of DNA from oxidative damage is realized by Dps proteins in a multistep iron oxidation/ uptake/ mineralization process. Dimers have a decreased protection efficiency due to disruption of the dodecamer internal cavity, where iron is deposited and mineralized after oxidation at the ferroxidase center.
- Published
- 2005
31. DNA condensation and self-aggregation of Escherichia coli Dps are coupled phenomena related to the properties of the N-terminus
- Author
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Ceci P, Cellai S, Falvo E, Rivetti C, Rossi GL, and Chiancone E.
- Published
- 2004
32. The Dps protein of Agrobacterium tumefaciens does not bind to DNA but protects it toward oxidative cleavage: x-ray crystal structure, iron binding, and hydroxyl-radical scavenging properties
- Author
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Ceci P., Ilari A, Falvo E., and Chiancone E.
- Abstract
Agrobacterium tumefaciens Dps (DNA-binding proteins from starved cells), encoded by the dps gene located on the circular chromosome of this plant pathogen, was cloned, and its structural and functional properties were determined in vitro. In Escherichia coli Dps, the family prototype, the DNA binding properties are thought to be associated with the presence of the lysine-containing N-terminal tail that extends from the protein surface into the solvent. The x-ray crystal structure of A. tumefaciens Dps shows that the positively charged N-terminal tail, which is 11 amino acids shorter than in the E. coli protein, is blocked onto the protein surface. This feature accounts for the lack of interaction with DNA. The intersubunit ferroxidase center characteristic of Dps proteins is conserved and confers to the A. tumefaciens protein a ferritin-like activity that manifests itself in the capacity to oxidize and incorporate iron in the internal cavity and to release it after reduction. In turn, sequestration of Fe(II) correlates with the capacity of A. tumefaciens Dps to reduce the production of hydroxyl radicals from H2O2 through Fenton chemistry. These data demonstrate conclusively that DNA protection from oxidative damage in vitro does not require formation of a Dps-DNA complex. In vivo, the hydroxyl radical scavenging activity of A. tumefaciens Dps may be envisaged to act in concert with catalase A to counteract the toxic effect of H2O2, the major component of the plant defense system when challenged by the bacterium.
- Published
- 2003
33. Intra- and interparticle magnetism of cobalt-doped iron-oxide nanoparticles encapsulated in a synthetic ferritin cage
- Author
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Skoropata, E., primary, Desautels, R. D., additional, Falvo, E., additional, Ceci, P., additional, Kasyutich, O., additional, Freeland, J. W., additional, and van Lierop, J., additional
- Published
- 2014
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34. Increasing the Magnetic Anisotropy of a Natural System: Co-Doped Magnetite Mineralized in Ferritin Shells.
- Author
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Fantechi E, Innocenti C, Ferretti AM, Falvo E, Ceci P, Pineider F, and Sangregorio C
- Abstract
Iron oxide nanoparticles mineralized within the internal cavity of Ferritin protein cage are extremely appealing for the realization of multifunctional therapeutic and diagnostic agents for cancer treatment by drug delivery, magnetic fluid hyperthermia (MFH) and magnetic resonance imaging. Being the maximum mean size imposed by the internal diameter of the protein shell (ca. 8 nm) too small for the use of these systems in MFH, a valuable strategy for the improvement of the hyperthermic efficiency is increasing the magnetic anisotropy by doping the iron oxide with divalent Co ions. This strategy has been demonstrated to be highly efficient in the case of iron oxide nanoparticles mineralized in Human Ferritin (HFt). However, a deterioration of nanoparticles crystallinity and consequently a reduction of the hyperthermic efficiency were observed with increasing Co-doping. In this contribution, we compare two series of Co-doped iron oxide nanoparticles (Co-doping level up to 15%) mineralized into HFt and into Ferritin from the archaea Pirococcus Furiosus (PfFt), the protein structure of which differs for the nucleation sites, with the aim of increasing the crystalline quality of the inorganic cores for larger Co doping. Highly monodisperse nanoparticles of 6-7 nm were obtained in both series. The structural and magnetic characterization indicate that the PfFt series is less subjected to crystallinity deterioration with increasing Co content with respect to the HFt one. Such difference is reflected in the hyperthermic efficiency, which reaches the maximum value for different intermediate Co-doping (10% and 5% for PfFt and HFt, respectively), and goes to zero for further Co-doping increments.
- Published
- 2019
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35. Cryo-EM structure of the human ferritin-transferrin receptor 1 complex.
- Author
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Montemiglio LC, Testi C, Ceci P, Falvo E, Pitea M, Savino C, Arcovito A, Peruzzi G, Baiocco P, Mancia F, Boffi A, des Georges A, and Vallone B
- Subjects
- Antigens, CD genetics, Antigens, CD metabolism, Apoferritins genetics, Apoferritins metabolism, Arenaviruses, New World genetics, Arenaviruses, New World metabolism, Binding Sites, Cloning, Molecular, Cryoelectron Microscopy, Escherichia coli genetics, Escherichia coli metabolism, Gene Expression, Genetic Vectors chemistry, Genetic Vectors metabolism, HeLa Cells, Hemochromatosis Protein chemistry, Hemochromatosis Protein genetics, Hemochromatosis Protein metabolism, Humans, Plasmodium vivax genetics, Plasmodium vivax metabolism, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Protozoan Proteins genetics, Protozoan Proteins metabolism, Receptors, Transferrin genetics, Receptors, Transferrin metabolism, Receptors, Virus genetics, Receptors, Virus metabolism, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins metabolism, Substrate Specificity, Transferrin genetics, Transferrin metabolism, Viral Envelope Proteins genetics, Viral Envelope Proteins metabolism, Antigens, CD chemistry, Apoferritins chemistry, Protozoan Proteins chemistry, Receptors, Transferrin chemistry, Receptors, Virus chemistry, Transferrin chemistry, Viral Envelope Proteins chemistry
- Abstract
Human transferrin receptor 1 (CD71) guarantees iron supply by endocytosis upon binding of iron-loaded transferrin and ferritin. Arenaviruses and the malaria parasite exploit CD71 for cell invasion and epitopes on CD71 for interaction with transferrin and pathogenic hosts were identified. Here, we provide the molecular basis of the CD71 ectodomain-human ferritin interaction by determining the 3.9 Å resolution single-particle cryo-electron microscopy structure of their complex and by validating our structural findings in a cellular context. The contact surfaces between the heavy-chain ferritin and CD71 largely overlap with arenaviruses and Plasmodium vivax binding regions in the apical part of the receptor ectodomain. Our data account for transferrin-independent binding of ferritin to CD71 and suggest that select pathogens may have adapted to enter cells by mimicking the ferritin access gate.
- Published
- 2019
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- View/download PDF
36. Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells.
- Author
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Loria R, Giliberti C, Bedini A, Palomba R, Caracciolo G, Ceci P, Falvo E, Marconi R, Falcioni R, Bossi G, and Strigari L
- Subjects
- Antineoplastic Agents pharmacology, Cell Line, Tumor, Colonic Neoplasms pathology, Humans, Antineoplastic Agents therapeutic use, Colonic Neoplasms diagnostic imaging, Colonic Neoplasms drug therapy, Drug Delivery Systems methods, Nanoparticles metabolism, Ultrasonography methods
- Abstract
Background: The possibility to combine Low Intensity UltraSound (LIUS) and Nanoparticles (NP) could represent a promising strategy for drugs delivery in tumors difficult to treat overcoming resistance to therapies. On one side the NP can carry drugs that specifically target the tumors on the other the LIUS can facilitate and direct the delivery to the tumor cells. In this study, we investigated whether Very Low Intensity UltraSound (VLIUS), at intensities lower than 120 mW/cm
2 , might constitute a novel strategy to improve delivery to tumor cells. Thus, in order to verify the efficacy of this novel modality in terms of increase selective uptake in tumoral cells and translate speedily in clinical practice, we investigated VLIUS in three different in vitro experimental tumor models and normal cells adopting three different therapeutic strategies., Methods: VLIUS at different intensities and exposure time were applied to tumor and normal cells to evaluate the efficiency in uptake of labeled human ferritin (HFt)-based NP, the delivery of NP complexed Firefly luciferase reported gene (lipoplex-LUC), and the tumor-killing of chemotherapeutic agent., Results: Specifically, we found that specific VLIUS intensity (120 mW/cm2 ) increases tumor cell uptake of HFt-based NPs at specific concentration (0.5 mg/ml). Similarly, VLIUS treatments increase significantly tumor cells delivery of lipoplex-LUC cargos. Furthermore, of interest, VLIUS increases tumor killing of chemotherapy drug trabectedin in a time dependent fashion. Noteworthy, VLIUS treatments are well tolerated in normal cells with not significant effects on cell survival, NPs delivery and drug-induced toxicity, suggesting a tumor specific fashion., Conclusions: Our data shed novel lights on the potential application of VLIUS for the design and development of novel therapeutic strategies aiming to efficiently deliver NP loaded cargos or anticancer drugs into more aggressive and unresponsive tumors niche.- Published
- 2019
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- View/download PDF
37. Study of manganese binding to the ferroxidase centre of human H-type ferritin.
- Author
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Ardini M, Howes BD, Fiorillo A, Falvo E, Sottini S, Rovai D, Lantieri M, Ilari A, Gatteschi D, Spina G, Chiancone E, Stefanini S, and Fittipaldi M
- Subjects
- Electron Spin Resonance Spectroscopy, Humans, Protein Binding, Apoferritins chemistry, Apoferritins metabolism, Ceruloplasmin chemistry, Ceruloplasmin metabolism, Manganese chemistry, Manganese metabolism
- Abstract
Ferritins are ubiquitous and conserved proteins endowed with enzymatic ferroxidase activity, that oxidize Fe(II) ions at the dimetal ferroxidase centre to form a mineralized Fe(III) oxide core deposited within the apo-protein shell. Herein, the in vitro formation of a heterodimetal cofactor constituted by Fe and Mn ions has been investigated in human H ferritin (hHFt). Namely, Mn and Fe binding at the hHFt ferroxidase centre and its effects on Fe(II) oxidation have been investigated by UV-Vis ferroxidation kinetics, fluorimetric titrations, multifrequency EPR, and preliminary Mössbauer spectroscopy. Our results show that in hHFt, both Fe(II) and Mn(II) bind the ferroxidase centre forming a Fe-Mn cofactor. Moreover, molecular oxygen seems to favour Mn(II) binding and increases the ferroxidation activity of the Mn-loaded protein. The data suggest that Mn influences the Fe binding and the efficiency of the ferroxidation reaction. The higher efficiency of the Mn-Fe heterometallic centre may have a physiological relevance in specific cell types (i.e. glia cells), where the concentration of Mn is the same order of magnitude as iron., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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38. The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity.
- Author
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Falvo E, Malagrinò F, Arcovito A, Fazi F, Colotti G, Tremante E, Di Micco P, Braca A, Opri R, Giuffrè A, Fracasso G, and Ceci P
- Subjects
- Cell Line, Tumor, Humans, Tissue Distribution, Antineoplastic Agents administration & dosage, Apoferritins administration & dosage, Doxorubicin administration & dosage, Drug Carriers administration & dosage, Glutamic Acid administration & dosage, Mitoxantrone administration & dosage, Nanoparticles administration & dosage
- Abstract
A genetically engineered human ferritin heavy chain (HFt)-based construct has been recently shown by our group to efficiently entrap and deliver doxorubicin to cancer cells. This construct, named HFt-MP-PAS, contained a tumor-selective sequence (MP) responsive to proteolytic cleavage by tumor proteases (MMPs), located between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). HFt-MP-PAS displayed excellent therapeutic efficacy in xenogenic pancreatic and head and neck cancer models in vivo, leading to a significant increase in overall animal survivals. Here we report a new construct obtained by the genetic insertion of two glutamate residues in the PAS sequence of HFt-MP-PAS. Such new construct, named HFt-MP-PASE, is characterized by improved performances as drug biodistribution in a xenogenic pancreatic cancer model in vivo. Moreover, HFt-MP-PASE efficiently encapsulates the anti-cancer drug mitoxantrone (MIT), and the resulting MIT-loaded nanoparticles proved to be more soluble and monodispersed than the HFt-MP-PAS counterparts. Importantly, in vitro MIT-loaded HFt-MP-PASE kills several cancer cell lines of different origin (colon, breast, sarcoma and pancreas) at least as efficiently as the free drug. Finally, our MIT loaded protein nanocages allowed in vivo an impressive incrementing of the drug accumulation in the tumor with respect to the free drug., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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39. P1.20 CDX2 VDR Polymorphism Impinges on the Response of Cultured Breast Cancer Cell Lines to Vitamin D
- Author
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Pulito, C., primary, Terrenato, I., additional, Sacconi, A., additional, Biagioni, F., additional, Mottolese, M., additional, Blandino, G., additional, Muti, P., additional, Falvo, E., additional, and Strano, S., additional
- Published
- 2012
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- View/download PDF
40. Diagnostics
- Author
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Einert, T. R., primary, Schmidt, G., additional, Binnig, G., additional, Balacescu, O., additional, Balacescu, L., additional, Rus, M., additional, Buiga, R., additional, Tudoran, O., additional, Todor, N., additional, Nagy, V., additional, Irimie, A., additional, Neagoe, I., additional, Yacobi, R., additional, Ustaev, E., additional, Berger, R. R., additional, Barshack, I., additional, Kaur, K., additional, Henderson, S., additional, Cutts, A., additional, Domingo, E., additional, Woods, J., additional, Motley, C., additional, Dougherty, B., additional, Middleton, M., additional, Hassan, B., additional, Wang, Y., additional, Beasley, E., additional, Naley, M., additional, Schuh, A., additional, Tomlinson, I., additional, Taylor, J., additional, Planchard, D., additional, Lueza, B., additional, Rahal, A., additional, Lacroix, L., additional, Ngocamus, M., additional, Auger, N., additional, Saulnier, P., additional, Dorfmuller, P., additional, Le Chevalier, T., additional, Celebic, A., additional, Pignon, J. P., additional, Soria, J. C., additional, Besse, B., additional, Sun, Y. H., additional, Wang, R., additional, Li, C. G., additional, Pan, Y. J., additional, Chen, H. Q., additional, Chouchane, L., additional, Shan, J., additional, Kizhakayil, D., additional, Aigha, I., additional, Dsouza, S., additional, Noureddine, B., additional, Gabbouj, S., additional, Mathew, R., additional, Hassen, E., additional, Shan, S., additional, al-Rumaihi, K., additional, al-Bozom, I., additional, al-Said, S., additional, Rabah, D., additional, Farhat, K., additional, Jakobsen Falk, I. A., additional, Green, K. H. Z., additional, Lotfi, K., additional, Fyrberg, A., additional, Pejovic, T., additional, Li, H., additional, Mhawech-Fauceglia, P., additional, Hoatlin, M., additional, Guo, M. G., additional, Huang, M., additional, Ge, Y., additional, Hess, K., additional, Wei, C., additional, Zhang, W., additional, Bogush, T. A., additional, Dudko, E. A., additional, Nureev, M. V., additional, Kamensky, A. A., additional, Polotsky, B. E., additional, Tjulandin, S. A., additional, Davydov, M. I., additional, Caballero, M., additional, Hasmats, J., additional, Green, H., additional, Quanz, M., additional, Buhler, C., additional, Sun, J. S., additional, Dutreix, M., additional, Cebotaru, C. L., additional, Placintar, A. N., additional, Ghilezan, N., additional, Balogh, Z. B., additional, Reiniger, L., additional, Rajnai, H., additional, Csomor, J., additional, Szepesi, A., additional, Balogh, A., additional, Deak, L., additional, Gagyi, E., additional, Bodor, C., additional, Matolcsy, A., additional, Bozhenko, V. K., additional, Rozhkova, N. I., additional, Kudinova, E. A., additional, Bliznyukov, O. P., additional, Vaskevich, E. N., additional, Trotsenko, I. D., additional, Kharchenko, N. V., additional, Kiandarian, I. V., additional, Pulito, C., additional, Terrenato, I., additional, Sacconi, A., additional, Biagioni, F., additional, Mottolese, M., additional, Blandino, G., additional, Muti, P., additional, Falvo, E., additional, Strano, S., additional, Mori, F., additional, Ganci, F., additional, Covello, R., additional, Zoccali, C., additional, Biagini, R., additional, Palmer, G. A., additional, Wegdam, W., additional, Meijer, D., additional, Kramer, G., additional, Langridge, J., additional, Moerland, P. D., additional, de Jong, S. M., additional, Vissers, J. P., additional, Kenter, G. G., additional, Buist, M. R., additional, Aerts, J. M. F. G., additional, Milione, M., additional, de Braud, F., additional, Buzzoni, R., additional, Pusceddu, S., additional, Mazzaferro, V., additional, Damato, A., additional, Pelosi, G., additional, Garassino, M., additional, Broggini, M., additional, Marabese, M., additional, Veronese, S., additional, Ganzinelli, M., additional, Martelli, O., additional, Bossel, N., additional, Fontemaggi, G., additional, Manciocco, V., additional, Sperduti, I., additional, Strigari, L., additional, Spriano, G., additional, Domany, E., additional, Donzelli, S., additional, Bellissimo, T., additional, Alessandrini, G., additional, Carosi, M. A., additional, Pescarmona, E., additional, Facciolo, F., additional, Telera, S., additional, Pompili, A., additional, de Vriendt, V., additional, de Roock, W., additional, di Narzo, A. F., additional, Tian, S., additional, Biesmans, B., additional, Jacobs, B., additional, de Schutter, J., additional, Budzinska, E., additional, Sagaert, X., additional, Delorenzi, M., additional, Simon, I., additional, Tejpar, S., additional, Zhu, Y., additional, Wang, H. K., additional, Ye, D. W., additional, Denisov, E., additional, Tsyganov, M., additional, Tashireva, L., additional, Zavyalova, M., additional, Perelmuter, V., additional, Cherdyntseva, N., additional, Kim, Y. C., additional, Jang, T., additional, Oh, I. J., additional, Kim, K. S., additional, Ban, H., additional, Na, K. J., additional, Ahn, S. J., additional, Kang, H., additional, Kim, W. J., additional, Park, C., additional, Abousamra, N. K., additional, El-Din, M. S., additional, and Azmy, E. A., additional
- Published
- 2012
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- View/download PDF
41. P1.26 Micrornas' Expression Profile and their Correlation with Clinical Outcome in head and Neck Squamous Cell Carcinoma
- Author
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Ganci, F., primary, Bossel, N., additional, Sacconi, A., additional, Fontemaggi, G., additional, Manciocco, V., additional, Sperduti, I., additional, Falvo, E., additional, Strigari, L., additional, Covello, R., additional, Muti, P., additional, Strano, S., additional, Spriano, G., additional, Domany, E., additional, and Blandino, G., additional
- Published
- 2012
- Full Text
- View/download PDF
42. X-ray structure of Dps from Mycobacterium smegmatis
- Author
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Ilari, A., primary, Ceci, P., additional, Falvo, E., additional, and Chiancone, E., additional
- Published
- 2005
- Full Text
- View/download PDF
43. Therapeutic Efficacy of the Novel Stimuli-Sensitive Nano-Ferritins Containing Doxorubicin in a Head and Neck Cancer Model.
- Author
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Damiani V, Falvo E, Fracasso G, Federici L, Pitea M, De Laurenzi V, Sala G, and Ceci P
- Subjects
- Cell Line, Tumor, Cell Proliferation drug effects, Doxorubicin chemical synthesis, Doxorubicin chemistry, Doxorubicin pharmacology, Humans, Peptides chemistry, Receptors, Transferrin metabolism, Squamous Cell Carcinoma of Head and Neck, Treatment Outcome, Apoferritins chemistry, Carcinoma, Squamous Cell drug therapy, Doxorubicin therapeutic use, Head and Neck Neoplasms drug therapy, Nanoparticles chemistry
- Abstract
Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is a genetically engineered human ferritin heavy chain (HFt)-based construct able to efficiently entrap and deliver doxorubicin to cancer cells. HF-MP-PAS contains a short motif sequence (defined as MP) responsive to proteolytic cleavage by tumor matrix metalloproteases (MMPs), located between each HFt subunit and a masking polypeptide sequence rich in proline (P), alanine (A), and serine (S) residues (PAS). This carrier displayed excellent therapeutic efficacy in a xenogenic pancreatic cancer model in vivo, leading to a significant increase in overall animal survival in treated mice. Herein, we describe the HFt-MP-PAS40-Dox efficacy against squamous cell carcinomas of the head and neck (HNSCC) with the goal of validating the application of our nano-drug for the treatment of different solid tumors. In addition, a tolerability study in healthy mice was also performed. The results indicate that HFt-MP-PAS40-Dox produced increased anti-tumor effects both in vitro and in vivo in comparison to the free drug in several HNSCC cell lines. In the acute toxicity studies, the maximum tolerated dose (MTD) of HFt-MP-PAS40-Dox was about 3.5 higher than the free drug: 25 mg/kg versus 7 mg/kg doxorubicin equivalents. Importantly, evaluation of heart tissues provided evidence that doxorubicin is less cardio-toxic when encapsulated inside the ferritin carrier. In conclusion, HFt-MP-PAS40-Dox may be administered safely at higher doses compared with the free drug, resulting in superior efficacy to control HNSCC malignancies., Competing Interests: The authors declare no conflict of interest.
- Published
- 2017
- Full Text
- View/download PDF
44. Detection of soluble ERBB2 in breast cancer cell lysates using a combined label-free/fluorescence platform based on Bloch surface waves.
- Author
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Sinibaldi A, Sampaoli C, Danz N, Munzert P, Sibilio L, Sonntag F, Occhicone A, Falvo E, Tremante E, Giacomini P, and Michelotti F
- Subjects
- Antibodies, Monoclonal chemistry, Biomarkers, Tumor analysis, Cell Line, Tumor, Equipment Design, Female, Fluorescence, Humans, Lab-On-A-Chip Devices, Limit of Detection, Biosensing Techniques instrumentation, Breast pathology, Breast Neoplasms diagnosis, Receptor, ErbB-2 analysis
- Abstract
We report on the use of one-dimensional photonic crystals to detect clinically relevant concentrations of ERBB2/neu/Her2 in cell lysates. ERBB2 is a pivotal breast cancer biomarker and targetable oncogenic driver associated with aggressive breast cancer subtypes. To quantitate soluble ERBB2, we developed an optical platform that combines label-free and fluorescence detection modes. Such platform makes use of a sandwich assay in which the one-dimensional photonic crystals sustaining Bloch surface waves are tailored with a monoclonal antibody for highly specific biological recognition (BSW biochip). In a second step, a second antibody to ERBB2 quantitatively detects the bound analyte. The strategy of the present approach takes advantage of the combination of label-free and fluorescence techniques, making bio-recognition more robust and sensitive. In the fluorescence operation mode, the platform can attain the limit of detection 0.3ng/mL (1.5pM) for ERBB2 in cell lysates. Such resolution meets the international guidelines and recommendations (15ng/mL) for diagnostic ERBB2 assays that in the future may help to more precisely assign therapies counteracting cancer cell proliferation and metastatic spread., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
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45. Probing bulky ligand entry in engineered archaeal ferritins.
- Author
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Calisti L, Benni I, Cardoso Trabuco M, Baiocco P, Ruzicka B, Boffi A, Falvo E, Malatesta F, and Bonamore A
- Subjects
- Archaea genetics, Archaeoglobus fulgidus genetics, Archaeoglobus fulgidus metabolism, Cysteine metabolism, Ferritins genetics, Kinetics, Ligands, Mutation genetics, Pyrococcus furiosus genetics, Pyrococcus furiosus metabolism, Sulfhydryl Compounds metabolism, Archaea metabolism, Dithionitrobenzoic Acid metabolism, Ferritins metabolism
- Abstract
Background: A set of engineered ferritin mutants from Archaeoglobus fulgidus (Af-Ft) and Pyrococcus furiosus (Pf-Ft) bearing cysteine thiols in selected topological positions inside or outside the ferritin shell have been obtained. The two apo-proteins were taken as model systems for ferritin internal cavity accessibility in that Af-Ft is characterized by the presence of a 45Å wide aperture on the protein surface whereas Pf-Ft displays canonical (threefold) channels., Methods: Thiol reactivity has been probed in kinetic experiments in order to assess the protein matrix permeation properties towards the bulky thiol reactive DTNB (5,5'-dithiobis-2-nitrobenzoic acid) molecule., Results: Reaction of DTNB with thiols was observed in all ferritin mutants, including those bearing free cysteine thiols inside the ferritin cavity. As expected, a ferritin mutant from Pf-Ft, in which the cysteine thiol is on the outer surface displays the fastest binding kinetics. In turn, also the Pf-Ft mutant in which the cysteine thiol is placed within the internal cavity, is still capable of full stoichiometric DTNB binding albeit with an almost 200-fold slower rate. The behaviour of Af-Ft bearing a cysteine thiol in a topologically equivalent position in the internal cavity was intermediate among the two Pf-Ft mutants., Conclusions and General Significance: The data thus obtained indicate clearly that the protein matrix in archaea ferritins does not provide a significant barrier against bulky, negatively charged ligands such as DTNB, a finding of relevance in view of the multiple biotechnological applications of these ferritins that envisage ligand encapsulation within the internal cavity., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
46. Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness.
- Author
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Fracasso G, Falvo E, Colotti G, Fazi F, Ingegnere T, Amalfitano A, Doglietto GB, Alfieri S, Boffi A, Morea V, Conti G, Tremante E, Giacomini P, Arcovito A, and Ceci P
- Subjects
- Animals, Antibiotics, Antineoplastic administration & dosage, Cell Line, Tumor, Cell Proliferation drug effects, Drug Carriers administration & dosage, Female, Humans, Mice, Mice, Nude, Xenograft Model Antitumor Assays methods, Apoferritins administration & dosage, Doxorubicin administration & dosage, Drug Delivery Systems methods, Nanoparticles administration & dosage
- Abstract
Human ferritin heavy chain (HFt) has been demonstrated to possess considerable potential for targeted delivery of drugs and diagnostic agents to cancer cells. Here, we report the development of a novel HFt-based genetic construct (HFt-MP-PAS) containing a short peptide linker (MP) between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). The peptide linker contains a matrix-metalloproteinases (MMPs) cleavage site that permits the protective PAS shield to be removed by tumor-driven proteolytic cleavage within the tumor microenvironment. For the first time HFt-MP-PAS ability to deliver doxorubicin to cancer cells, subcellular localization, and therapeutic efficacy on a xenogeneic mouse model of a highly refractory to conventional chemotherapeutics type of cancer were evaluated. HFt-MP-PAS-DOXO performance was compared with the novel albumin-based drug delivery system INNO-206, currently in phase III clinical trials. The results of this work provide solid evidence indicating that the stimuli-sensitive, long-circulating HFt-MP-PAS nanocarriers described herein have the potential to be exploited in cancer therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
47. Improved Doxorubicin Encapsulation and Pharmacokinetics of Ferritin-Fusion Protein Nanocarriers Bearing Proline, Serine, and Alanine Elements.
- Author
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Falvo E, Tremante E, Arcovito A, Papi M, Elad N, Boffi A, Morea V, Conti G, Toffoli G, Fracasso G, Giacomini P, and Ceci P
- Subjects
- Alanine chemistry, Animals, Antibiotics, Antineoplastic pharmacokinetics, Antibiotics, Antineoplastic pharmacology, Cell Line, Tumor, Cell Survival drug effects, Doxorubicin pharmacokinetics, Doxorubicin pharmacology, Drug Screening Assays, Antitumor, Drug Stability, Ferritins chemistry, Half-Life, Humans, Mice, Inbred BALB C, Peptides chemistry, Polyethylene Glycols chemistry, Proline chemistry, Recombinant Fusion Proteins chemistry, Serine chemistry, Antibiotics, Antineoplastic chemistry, Doxorubicin chemistry, Nanocapsules chemistry
- Abstract
A novel human ferritin-based nanocarrier, composed of 24 modified monomers able to auto-assemble into a modified protein cage, was produced and used as selective carrier of anti-tumor payloads. Each modified monomer derives from the genetic fusion of two distinct modules, namely the heavy chain of human ferritin (HFt) and a stabilizing/protective PAS polypeptide sequence rich in proline (P), serine (S), and alanine (A) residues. Two genetically fused protein constructs containing PAS polymers with 40- and 75-residue lengths, respectively, were compared. They were produced and purified as recombinant proteins in Escherichia coli at high yields. Both preparations were highly soluble and stable in vitro as well as in mouse plasma. Size-exclusion chromatography, dynamic light scattering, and transmission electron microscopy results indicated that PASylated ferritins are fully assembled and highly monodispersed. In addition, yields and stability of encapsulated doxorubicin were significantly better for both HFt-PAS proteins than for wild-type HFt. Importantly, PAS sequences considerably prolonged the half-life of HFt in the mouse bloodstream. Finally, our doxorubicin-loaded nanocages preserved the pharmacological activity of the drug. Taken together, these results indicate that both of the developed HFt-PAS fusion proteins are promising nanocarriers for future applications in cancer therapy.
- Published
- 2016
- Full Text
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48. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.
- Author
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Pulito C, Terrenato I, Di Benedetto A, Korita E, Goeman F, Sacconi A, Biagioni F, Blandino G, Strano S, Muti P, Mottolese M, and Falvo E
- Subjects
- Breast Neoplasms metabolism, CDX2 Transcription Factor, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic drug effects, Homeodomain Proteins metabolism, Humans, MCF-7 Cells, Retrospective Studies, Vitamin D pharmacology, Breast Neoplasms genetics, Breast Neoplasms pathology, Homeodomain Proteins genetics, Polymorphism, Genetic, Receptors, Calcitriol genetics
- Abstract
Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.
- Published
- 2015
- Full Text
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49. In Vivo Targeting of Cutaneous Melanoma Using an Melanoma Stimulating Hormone-Engineered Human Protein Cage with Fluorophore and Magnetic Resonance Imaging Tracers.
- Author
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Vannucci L, Falvo E, Failla CM, Carbo M, Fornara M, Canese R, Cecchetti S, Rajsiglova L, Stakheev D, Krizan J, Boffi A, Carpinelli G, Morea V, and Ceci P
- Subjects
- Animals, Cell Line, Tumor, Contrast Media chemical synthesis, Fluorescent Dyes chemical synthesis, Melanoma metabolism, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence methods, Nanocapsules ultrastructure, Particle Size, Skin Neoplasms metabolism, Magnetic Resonance Imaging methods, Melanoma pathology, Nanocapsules chemistry, Skin Neoplasms pathology, alpha-MSH pharmacokinetics
- Abstract
Nanoparticle (NP)-based materials are promising agents for enhancing cancer diagnosis and treatment. Once functionalized for selective targeting of tumor-expressed molecules, they can specifically deliver drugs and diagnostic molecules inside tumor cells. In the present work, we evaluated the in vivo melanoma-targeting ability of a nanovector (HFt-MSH-PEG) based on human protein ferritin (HFt), functionalized with both melanoma-targeting melanoma stimulating hormone (α-MSH) and stabilizing poly(ethylene glycol) (PEG) molecules. Independent and complementary techniques, such as whole-specimen confocal microscopy and magnetic resonance imaging, were used to detect in vivo localization of NP constructs with suitable tracers (i.e., fluorophores or magnetic metals). Targeted HFt-MSH-PEG NPs accumulated persistently at the level of primary melanoma and with high selectivity with respect to other organs. Melanoma localization of untargeted HFt-PEG NPs, which lack the α-MSH moiety, was less pronounced. Furthermore, HFt-MSH-PEG NPs accumulated to a significantly lower extent and with a different distribution in a diverse type of tumor (TS/A adenocarcinoma), which does not express α-MSH receptors. Finally, in a spontaneous lung metastasis model, HFt-MSH-PEG NPs localized at the metastasis level as well. These results suggest that HFt-MSH-PEG NPs are suitable carriers for selective in vivo delivery of diagnostic or therapeutic agents to cutaneous melanoma.
- Published
- 2015
- Full Text
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50. A systematic review of steroid use in peripheral nerve pathologies and treatment.
- Author
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Couch, Brandon, Hayward, Dan, Baum, Gracie, Sakthiyendran, Naveen Arunachalam, Harder, Justin, Hernandez, Evan J., and MacKay, Brendan
- Abstract
Background: The use of corticosteroids has become a part of the standard of care in various pathologies but their use in peripheral nerve injury treatment is limited. Given corticosteroids' anti-inflammatory properties and their regulatory role in neuronal protein production and myelination, corticosteroids could serve as an adjunct therapy for peripheral nerve injuries. This review aims to systematically investigate the current use of corticosteroid treatment in peripheral nerve pathologies. Methods: The systematic search was performed on PubMed, MEDLINE, EMBASE, Scopus, Cochrane, and Web of Science using keywords such as "corticosteroid treatment," "peripheral nerve damage," "peripheral neuropathy," and "complications." The PRISMA guidelines were used to conduct the systematic review and all articles were reviewed by the corresponding author. After the initial search, individual study titles and abstracts were further screened and categorized using an inclusion and exclusion criteria followed by a final fulltext review. Results: Out of the total 27,922 identified records, 203 studies were included based on the selection criteria. These studies focused on the use and efficacy of steroids across a spectrum of compression and non-compression peripheral neuropathies such as cubital tunnel syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Various studies noted the promising role of steroids in offering pain relief, nerve block, and nerve regeneration effects. Additionally, safety considerations and potential complications regarding steroid use in peripheral nerve injuries were analyzed. Conclusion: While there is currently limited clinical utilization of corticosteroids in peripheral nerve pathologies, the anti-inflammatory and regenerative effects that steroids provide may be a beneficial tool in managing various peripheral neuropathies and their associated pain. Additional clinical trials and investigation into the mechanism of action could improve the reputation of steroid use as peripheral nerve injury treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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