165 results on '"Rigolio R"'
Search Results
2. Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency
- Author
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Ceccon, M, Merlo, M E Boggio, Mologni, L, Poggio, T, Varesio, L M, Menotti, M, Bombelli, S, Rigolio, R, Manazza, A D, Di Giacomo, F, Ambrogio, C, Giudici, G, Casati, C, Mastini, C, Compagno, M, Turner, S D, Gambacorti-Passerini, C, Chiarle, R, and Voena, C
- Published
- 2016
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3. Neuroprotective Effects of Progesterone in Chronic Experimental Autoimmune Encephalomyelitis
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Giatti, S., Caruso, D., Boraso, M., Abbiati, F., Ballarini, E., Calabrese, D., Pesaresi, M., Rigolio, R., Santos-Galindo, M., Viviani, B., Cavaletti, G., Garcia-Segura, L. M., and Melcangi, R. C.
- Published
- 2012
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4. Sex dimorphism in an animal model of multiple sclerosis: Focus on pregnenolone synthesis
- Author
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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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5. Resveratrol interference with the cell cycle protects human neuroblastoma SH-SY5Y cell from paclitaxel-induced apoptosis
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Rigolio, R., Miloso, M., Nicolini, G., Villa, D., Scuteri, A., Simone, M., and Tredici, G.
- Published
- 2005
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6. PERIPHERAL NERVOUS SYSTEM INVOLVEMENT IN NIEMANN-PICK DISEASE TYPE A
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Rigolio, R, Vercelli, A, Gilardini, A, Bossi, M, Avezza, F, Tredici, G, Marmiroli, P, and Cavaletti, G
- Published
- 2005
7. Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis
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Cavaletti, G, Cavalletti, E, Crippa, L, Di Luccio, E, Oggioni, N, Mazzanti, B, Biagioli, T, Sala, F, Sala, V, Frigo, M, Rota, S, Tagliabue, E, Stanzani, L, Galbiati, S, Rigolio, R, Zoia, C, Tredici, G, Perseghin, P, Dassi, M, Riccio, P, and Lolli, F
- Published
- 2004
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8. Effect of trans-resveratrol on signal transduction pathways involved in paclitaxel-induced apoptosis in human neuroblastoma SH-SY5Y cells
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Nicolini, G., Rigolio, R., Scuteri, A., Miloso, M., Saccomanno, D., Cavaletti, G., and Tredici, G.
- Published
- 2003
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9. Evaluation of in vitro antitumoral activity and neurotoxicity of a Hibiscus Sabdariffa ethyl acetate fraction against human multiple myeloma cells
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Malacrida, A, Rigolio, R, Nicolini, G, Cassetti, A, Cavaletti, G, Miloso, M, Malacrida, A, Rigolio, R, Nicolini, G, Cassetti, A, Cavaletti, G, and Miloso, M
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BIO/16 - ANATOMIA UMANA ,Hibiscus Sabdariffa, proliferation, neurotoxicity, multiple myeloma - Abstract
Background: Hibiscus Sabdariffa is a plant of the Malvacee family commonly used in Asian and African folk medicine and for Karkadè preparation. In our laboratory, we previously demonstrated that Hibiscus Sabdariffa total extract (HSE) exerted against human multiple myeloma cells a reversible cytostatic effect and reduced cell motility/invasiveness. In order to identify the molecule/s involved in HSE effects, in this study we evaluated the antitumoral activity of a fraction of HSE obtained after ethyl acetate separation (HEF). Material and methods: Human multiple myelomacell s RPMI8226 were treated with different HEF concentrations and cell viability was evaluated by MTT and Trypan blue vital count assays. Apoptosis cell death was evaluated by AnnexinV assay and Caspase3 western blot. Cells migration/invasion was assessed using Boyden Chamber assay. Rat embryo dorsal root ganglia cultures were used to assess HEF neurotoxicity in vitro. HEF and HSE activity was compared. Results: HEF was effective in reducing RPMI8226 cell viability in a dose and time dependent manner. HEF enhanced cell mortality, AnnexinV positive cells and Caspase3 activation. Moreover, HEF was effective in reducing cells migration/invasion and it was not neurotoxic in vitro. Conclusions: In this study we evaluated the in vitro effects of HEF against human multiple myeloma cells RPMI8226. Our results demonstrated that HEF treatment showed an increased effectiveness and Caspase3-dependent apoptosis, but not an increased neurotoxicity, compared to HSE. Considering evident anticancer properties of HEF, it can provide the basis for a further fractionation in order to isolate molecules responsible for Hibiscus sabdariffa effects.
- Published
- 2016
10. Size and specimen-dependent strategy for x-ray micro-ct and tem correlative analysis of nervous system samples
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Parlanti, P., primary, Cappello, V., additional, Brun, F., additional, Tromba, G., additional, Rigolio, R., additional, Tonazzini, I., additional, Cecchini, M., additional, Piazza, V., additional, and Gemmi, M., additional
- Published
- 2017
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11. Neutrophil contribution and immunoglobulin effect in Dark Agouti Experimental Autoimmune Encephalomyelitis
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Ballarini, E, Carozzi, V, Canta, A, Chiorazzi, A, Meregalli, C, Avezza, F, Crippa, L, Oggioni, N, Cavaletti, G, Rigolio, R, Ballarini, E, Carozzi, V, Canta, A, Chiorazzi, A, Meregalli, C, Avezza, F, Crippa, L, Oggioni, N, Cavaletti, G, and Rigolio, R
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Experimental autoimmune encephalomyelitis, innate immunity, neutrophils ,BIO/16 - ANATOMIA UMANA - Published
- 2010
12. Granulocytes in actively induced Lewis rat EAE
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Rigolio, R, Rodriguez-Menendez, V, Chiorazzi, A, Meregalli, C, Donzelli, E, Oggioni, N, Cavaletti, G, Rigolio, R, Rodriguez-Menendez, V, Chiorazzi, A, Meregalli, C, Donzelli, E, Oggioni, N, and Cavaletti, G
- Subjects
Granulocytes, Lewis rat, induced EAE ,BIO/16 - ANATOMIA UMANA - Published
- 2008
13. Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency
- Author
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Ceccon, M, primary, Merlo, M E Boggio, additional, Mologni, L, additional, Poggio, T, additional, Varesio, L M, additional, Menotti, M, additional, Bombelli, S, additional, Rigolio, R, additional, Manazza, A D, additional, Di Giacomo, F, additional, Ambrogio, C, additional, Giudici, G, additional, Casati, C, additional, Mastini, C, additional, Compagno, M, additional, Turner, S D, additional, Gambacorti-Passerini, C, additional, Chiarle, R, additional, and Voena, C, additional
- Published
- 2015
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14. Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodeling
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Tambalo, S., primary, Peruzzotti-Jametti, L., additional, Rigolio, R., additional, Fiorini, S., additional, Bontempi, P., additional, Mallucci, G., additional, Balzarotti, B., additional, Marmiroli, P., additional, Sbarbati, A., additional, Cavaletti, G., additional, Pluchino, S., additional, and Marzola, P., additional
- Published
- 2015
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15. Peripheral nervous system involvement in Niemann-Pick disease type A
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Rigolio, R., Vercelli, Alessandro, Gilardini, A., Bossi, M., Avezza, F., Tredici, G., and Marmiroli, P. Cavaletti G.
- Published
- 2004
16. Functionalized Mesoporous Silica Nanoparticles: A Possible Strategy to Target Cancer Cells Reducing Peripheral Nervous System Uptake
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Ceresa, C., primary, Nicolini, G., additional, Rigolio, R., additional, Bossi, M., additional, Pasqua, L., additional, and Cavaletti, G., additional
- Published
- 2013
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17. ChemInform Abstract: A Reliable and Efficient Synthesis of SR 142801.
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GIARDINA, G. A. M., primary, GRUGNI, M., additional, RIGOLIO, R., additional, VASSALLO, M., additional, ERHARD, K., additional, and FARINA, C., additional
- Published
- 2010
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18. Targeting Cells With MR Imaging Probes: Cellular Interaction And Intracellular Magnetic Iron Oxide Nanoparticles Uptake In Brain Capillary Endothelial and Choroidal Plexus Epithelial Cells
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Cambianica, I., primary, Bossi, M., additional, Gasco, P., additional, Gonzalez, W., additional, Idee, J. M., additional, Miserocchi, G., additional, Rigolio, R., additional, Chanana, M., additional, Morjan, I., additional, Wang, D., additional, Sancini, G., additional, and Borsella, Elisabetta, additional
- Published
- 2010
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19. Targeting Cells With MR Imaging Probes: Cellular Interaction And Intracellular Magnetic Iron Oxide Nanoparticles Uptake In Brain Capillary Endothelial and Choroidal Plexus Epithelial Cells.
- Author
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Cambianica, I., Bossi, M., Gasco, P., Gonzalez, W., Idee, J. M., Miserocchi, G., Rigolio, R., Chanana, M., Morjan, I., Wang, D., and Sancini, G.
- Subjects
MAGNETIC resonance imaging ,IRON oxides ,NANOPARTICLES ,EPITHELIAL cells ,CONFOCAL microscopy ,ENDOCYTOSIS ,NYSTATIN ,CONTRAST media - Abstract
Magnetic iron oxide nanoparticles (NPs) are considered for various diagnostic and therapeutic applications in brain including their use as contrast agent for magnetic resonance imaging. In delivery application, the critical step is the transport across cell layers and the internalization of NPs into specific cells, a process often limited by poor targeting specificity and low internalization efficiency. The development of the models of brain endothelial cells and choroidal plexus epithelial cells in culture has allowed us to investigate into these mechanisms. Our strategy is aimed at exploring different routes to the entrapment of iron oxide NPs in these brain related cells. Here we demonstrated that not only cells endowed with a good phagocytic activity like activated macrophages but also endothelial brain capillary and choroidal plexus epithelial cells do internalize iron oxide NPs. Our study of the intracellular trafficking of NPs by TEM, and confocal microscopy revealed that NPs are mainly internalized by the endocytic pathway. Iron oxide NPs were dispersed in water and coated with 3,4-dihydroxyl-L-phenylalanine (L-DOPA) using standard procedures. Magnetic lipid NPs were prepared by NANOVECTOR: water in oil in water (W/O/W) microemulsion process has been applied to directly coat different iron based NPs by lipid layer or to encapsulate them into Solid Lipid Nanoparticles (SLNs). By these coating/loading the colloidal stability was improved without strong alteration of the particle size distribution. Magnetic lipid NPs could be reconstituted after freeze drying without appreciable changes in stability. L-DOPA coated NPs are stable in PBS and in MEM (Modified Eagle Medium) medium. The magnetic properties of these NPs were not altered by the coating processes. We investigated the cellular uptake, cytotoxicity, and interaction of these NPs with rat brain capillary endothelial (REB4) and choroidal plexus epithelial (Z310) cells. By means of widefield, confocal microscopy and flow cytometry we studied the cell uptake of magnetic SLNs derivatized with a fluorescent reporter molecule and of L-DOPA-TRITC coated NPs. Inhibition of the caveolae-mediated pathway by preincubation with filipin and nystatin did not modify the cellular uptake of these NPs in both cell lines. Furthermore a mild decrease of the NPs cell uptake was obtained after chlorpromazine and NaN
3 pretreatment, which interferes with clathrin and energy-dependent endocytosis, and cytochalasin and amiloride pretreatment which interfere with macropinocytosis. NPs particle size as such can strongly affect the efficiency of cellular uptake and the mode of endocytosis. Considering that our L-DOPA and magnetic SLNs display a medium hydrodynamic size of 120 nm with a polydispersity index of 0.3, we can assume that the cell uptake process of these NPs may develop, depending the particle size, both via clathrin mediated endocytosis and macropinocytosis and only to less extent via the pathway of caveolae-mediated endocytosis. Taken together these results let us to conclude that SLNs iron loaded and iron based L-DOPA coated NPs are internalized into brain endothelial and choroidal plexus epithelial cells and this might provide the first step of an intracellular trafficking to transport these NPs between blood and brain. [ABSTRACT FROM AUTHOR]- Published
- 2010
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20. Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 25
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Piatti, M, primary, Tagliabue, E, additional, Tredici, G, additional, Marmiroli, P, additional, Zoia, C, additional, Galbiati, S, additional, Rigolio, R, additional, Nicolini, G, additional, Villa, P, additional, Rotondi, A, additional, Ferraro, R, additional, Resta, G, additional, Buda, A, additional, Lissoni, A, additional, Cundari, S, additional, Zanna, C, additional, and Cavaletti, G, additional
- Published
- 2003
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21. PACLITAXEL NEUROTOXICITY: ANTI‐APOPTOTIC EFFECT OF RESVERATROL
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Miloso, M., primary, Rigolio, R., additional, Nicolini, G., additional, Crimi, M., additional, Donzelli, E., additional, Di Silvestro, A., additional, Cavaletti, G., additional, and Tredici, G, additional
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- 2000
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22. Replacement of the quinoline system in 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonists
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Giardina, G.A.M, primary, Artico, M, additional, Cavagnera, S, additional, Cerri, A, additional, Consolandi, E, additional, Gagliardi, S, additional, Graziani, D, additional, Grugni, M, additional, Hay, D.W.P, additional, Luttmann, M.A, additional, Mena, R, additional, Raveglia, L.F, additional, Rigolio, R, additional, Sarau, H.M, additional, Schmidt, D.B, additional, Zanoni, G, additional, and Farina, C, additional
- Published
- 1999
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23. ChemInform Abstract: A Novel Synthesis of 3‐Halo‐2‐phenylquinoline‐4‐carboxylic Acids.
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RAVEGLIA, L. F., primary, GIARDINA, G. A. M., additional, GRUGNI, M., additional, RIGOLIO, R., additional, and FARINA, C., additional
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- 1997
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24. Anti-apoptotic effect of trans-resveratrol on paclitaxel-induced apoptosis in the human neuroblastoma SH-SY5Y cell line
- Author
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Nicolini, G., Rigolio, R., Miloso, M., Bertelli, A. A., and Tredici, G.
- Published
- 2001
- Full Text
- View/download PDF
25. Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 2. Identification of (S)-N-(1-Phenylpropyl)-3-hydroxy-2- phenylquinoline-4-carboxamide (SB 223412)
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Giardina, G. A. M., Raveglia, L. F., Grugni, M., Sarau, H. M., Farina, C., Medhurst, A. D., Graziani, D., Schmidt, D. B., Rigolio, R., Luttmann, M., Cavagnera, S., Foley, J. J., Vecchietti, V., and Hay, D. W. P.
- Abstract
Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist
14 , with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31 ) or by lower alkyl groups (Et,21 , or n-Pr,24 ). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds53 (3-OH, SB 223412, hNK-3-CHO binding Ki = 1.4 nM) and55 (3-NH2 , hNK-3-CHO binding Ki = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 μM. In vitro studies demonstrated that53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (53 , SB 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.- Published
- 1999
26. 2-Phenyl-4-quinolinecarboxamides: A Novel Class of Potent and Selective Non-Peptide Competitive Antagonists for the Human Neurokinin-3 Receptor
- Author
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Giardina, G. A. M., Sarau, H. M., Farina, C., Medhurst, A. D., Grugni, M., Foley, J. J., Raveglia, L. F., Schmidt, D. B., Rigolio, R., Vassallo, M., Vecchietti, V., and Hay, D. W. P.
- Published
- 1996
27. Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 1. Identification of the 4-Quinolinecarboxamide Framework
- Author
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Giardina, G. A. M., Sarau, H. M., Farina, C., Medhurst, A. D., Grugni, M., Raveglia, L. F., Schmidt, D. B., Rigolio, R., Luttmann, M., Vecchietti, V., and Hay, D. W. P.
- Abstract
A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor antagonists, featuring the 4-quinolinecarboxamide framework, has been designed based upon chemically diverse NK-1 receptor antagonists. The novel compounds
33 −76 , prompted by chemical modifications of the prototype4 , have been characterized by binding analysis using a membrane preparation of chinese hamster ovary (CHO) cells expressing the human neurokinin-3 receptors (hNK-3-CHO), and clear structure−activity relationships (SARs) have been established. From SARs, (R)-N-[α-(methoxycarbonyl)benzyl]-2-phenylquinoline-4-carboxamide (65 , SB 218795, hNK-3-CHO binding Ki = 13 nM) emerged as one of the most potent compounds of this novel class. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that65 is about 90-fold selective for hNK-3 versus hNK-2 receptors (hNK-2-CHO binding Ki = 1221 nM) and over 7000-fold selective versus hNK-1 receptors (hNK-1-CHO binding Ki = >100 μM). In vitro functional studies in rabbit isolated iris sphincter muscle preparation demonstrated that65 is a competitive antagonist of the contractile response induced by the potent and selective NK-3 receptor agonist senktide with a Kb = 43 nM. Overall, the data indicate that65 is a potent and selective hNK-3 receptor antagonist and a useful lead for further chemical optimization.- Published
- 1997
28. Neuropathological changes in the peripheral nervous system and spinal cord in a transgenic mouse model of Niemann-Pick disease type A
- Author
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Marmiroli P, Rodriguez-Menendez V, Rigamonti L, Tonoli E, Rigolio R, Cavaletti G, Tredici G, Alessandro Vercelli, Marmiroli, P, RODRIGUEZ MENENDEZ, V, Rigamonti, L, Tonoli, E, Rigolio, R, Cavaletti, G, Tredici, G, and Vercelli, A
- Subjects
Animal ,Mice, Transgenic ,Niemann-Pick Disease, Type A ,Fluoresceins ,ASM ,sphingomyelinase ,peripheral nerve ,Disease Models, Animal ,Mice ,Sphingomyelin Phosphodiesterase ,Spinal Cord ,Peripheral Nervous System ,Animals ,Organic Chemical ,Organic Chemicals - Abstract
OBJECTIVE: Type A Niemann-Pick is a severe neurological disease, caused by a mutation of the gene of acid sphingomyelinase (ASM) and reduced enzyme activity. Some studies reported neuropathological changes occurring in the central nervous system of ASM deficient transgenic (ASMKO) mice, while a detailed study on the peripheral nervous system (PNS) at different ages is currently lacking. The aim of our study was to examine the pathological changes occurring in the PNS and in the spinal cord in an AMSKO model of Niemann-Pick disease (NPD) Type A. MATERIAL AND METHOD: Dorsal root ganglia (DRG), peripheral nerves and spinal cord specimens were obtained from ASMKO mice and age-matched wild type animals (age range = 1-7 months). They were observed at the light and electron microscope. Behavioral testing was performed to assess motor coordination and reactivity. Fluoro-Jade B was used as a high affinity fluorescent marker for degenerating neurons. RESULTS: Typical NPD cytoplasmic inclusions were observed in DRG neurons and satellite cells, in peripheral nerve Schwann cells, in spinal cord neurons and in endothelial cells. All these inclusions were present from the age of 1 month and increased with aging. By Fluoro-Jade B staining we demonstrated the occurrence of neuronal degeneration starting from 5 months of age. CONCLUSION: Despite the fact that a definite diagnosis of NPD Type A depends on enzymatic assays and/or molecular analysis, morphological investigation remains an important diagnostic procedure. Well-defined and complete neuropathological information about the ASMKO mouse model, inclusive of PNS examination, may be crucial in the pre-clinical evaluation of new therapies.
29. Circulating nerve growth factor level changes during oxaliplatin treatment-induced neurotoxicity in the rat
- Author
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guido cavaletti, Petruccioli, M. G., Marmiroli, P., Rigolio, R., Galbiati, S., Zoia, C., Ferrarese, C., Tagliabue, E., Dolci, C., Bayssas, M., Etienne, G., Tredici, G., Cavaletti, G, Petruccioli, M, Marmiroli, P, Rigolio, R, Galbiati, S, Zoia, C, Ferrarese, C, Tagliabue, E, Dolci, C, Bayssas, M, Griffon Etienne, G, and Tredici, G
- Subjects
Tail ,Organoplatinum Compounds ,Animal ,Organoplatinum Compound ,Neural Conduction ,Peripheral Nervous System Diseases ,Antineoplastic Agents ,Sciatic Nerve ,Rats ,Antineoplastic Agent ,Oxaliplatin ,Ganglia, Spinal ,Nerve Growth Factor ,Rat ,Animals ,Female ,Nerve Growth Factors ,Neurons, Afferent ,Peripheral Nervous System Disease ,Rats, Wistar - Abstract
BACKGROUND: Oxaliplatin neurotoxicity represents a clinically-relevant problem and its etio-pathogenesis is still unknown. We explored the possible role of some neuronal growth factors ("neurotrophins") during the course of oxaliplatin sensory neuronopathy. MATERIALS AND METHODS: In our rat model two different doses of oxaliplatin were used (2 and 3 mg/kg i.v. twice weekly for 9 times). The neurotoxicity of the treatment was assessed with neurophysiological and pathological methods and serum neurotrophin levels were measured by ELISA. RESULTS: Both oxaliplatin-treated groups showed the neurophysiological and neuropathological changes which mimic the chronic effects of oxaliplatin administration in humans, e.g. reversible sensory impairment due to dorsal root ganglia neuron damage. These changes were associated with a significant and dose-dependent reduction only in the circulating level of nerve growth factor (NGF), which returned to normal values after neurophysiological and pathological recovery. CONCLUSION: This specific association between neurological impairment and NGF modulation indicates that NGF impairment has a role in the neurotoxicity of oxaliplatin
30. Erratum: Evaluation of brain activity changes occurring in an animal model for multiple sclerosis: A functional magnetic resonance imaging study (Italian Journal of Anatomy and Embryology (2012) 117:2 (161))
- Author
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Rigolio, R., Marmiroli, P., Cavaletti, G., Rodriguez-Menendez, V., Fiorini, S., Tambalo, S., and Pasquina MARZOLA
31. ChemInform Abstract: A Reliable and Efficient Synthesis of SR 142801.
- Author
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GIARDINA, G. A. M., GRUGNI, M., RIGOLIO, R., VASSALLO, M., ERHARD, K., and FARINA, C.
- Published
- 1997
- Full Text
- View/download PDF
32. Size and specimen-dependent strategy for x-ray micro-ct and tem correlative analysis of nervous system samples
- Author
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Francesco Brun, Ilaria Tonazzini, Vincenzo Piazza, Paola Parlanti, Mauro Gemmi, Marco Cecchini, Roberta Rigolio, Valentina Cappello, Giuliana Tromba, Parlanti, P, Cappello, V, Brun, F, Tromba, G, Rigolio, R, Tonazzini, I, Cecchini, M, Piazza, V, Gemmi, M, Parlanti, P., Cappello, V., Brun, F., Tromba, G., Rigolio, R., Tonazzini, I., Cecchini, M., Piazza, V., and Gemmi, M.
- Subjects
0301 basic medicine ,Correlative ,Nervous system ,Pathology ,medicine.medical_specialty ,Science ,Biology ,x-ray micro-ct, TEM, nervous system ,Nervous System ,Article ,law.invention ,03 medical and health sciences ,Mice ,Imaging, Three-Dimensional ,Microscopy, Electron, Transmission ,law ,Microscopy ,medicine ,Animals ,Multidisciplinary ,Animal ,Resolution (electron density) ,X-ray ,X-Ray Microtomography ,Synchrotron ,Characterization (materials science) ,Leukodystrophy, Globoid Cell ,Rats ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Spinal Cord ,Transmission electron microscopy ,Rat ,Medicine ,Biomedical engineering - Abstract
Correlative approaches are a powerful tool in the investigation of biological samples, but require specific preparation procedures to maintain the strength of the employed methods. Here we report the optimization of the embedding protocol of nervous system samples for a correlative synchrotron X-ray computed microtomography (micro-CT) and transmission electron microscopy (TEM) approach. We demonstrate that it is possible to locate, with the micrometric resolution of micro-CT, specific volumes of interest for a further ultrastructural characterization to be performed with TEM. This approach can be applied to samples of different size and morphology up to several cm. Our optimized method represents an invaluable tool for investigating those pathologies in which microscopic alterations are localized in few confined regions, rather than diffused in entire tissues, organs or systems. We present a proof of concept of our method in a mouse model of Globoid Cells Leukodistrophy.
- Published
- 2017
33. Artificial apolipoprotein corona enables nanoparticle brain targeting
- Author
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Maurizio Ricci, Roberta Dal Magro, Barbara Albertini, Paolo Blasi, Elisabetta Donzelli, Giulio Sancini, Silvia Beretta, Roberta Rigolio, Alessia Chiorazzi, Dal Magro, R, Albertini, B, Beretta, S, Rigolio, R, Donzelli, E, Chiorazzi, A, Ricci, M, Blasi, P, Sancini, G, Dal Magro R., Albertini B., Beretta S., Rigolio R., Donzelli E., Chiorazzi A., Ricci M., Blasi P., and Sancini G.
- Subjects
0301 basic medicine ,Male ,Apolipoprotein B ,Endothelium ,Apolipoprotein E4 ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Nanoparticle ,Lipid nanoparticle ,Bioengineering ,Nanotechnology ,Protein Corona ,02 engineering and technology ,Blood–brain barrier ,03 medical and health sciences ,Blood brain barrier ,Brain targeting ,Lipid nanoparticles ,Protein corona ,Animals ,Apolipoproteins ,Biological Transport ,Blood-Brain Barrier ,Brain ,Mice ,Mice, Inbred BALB C ,Nanoparticles ,Drug Delivery Systems ,BIO/09 - FISIOLOGIA ,Parenchyma ,medicine ,General Materials Science ,Apolipoprotein e4 ,Inbred BALB C ,biology ,Animal ,Chemistry ,021001 nanoscience & nanotechnology ,Apolipoprotein ,030104 developmental biology ,medicine.anatomical_structure ,Biophysics ,biology.protein ,Molecular Medicine ,0210 nano-technology - Abstract
Many potential therapeutic compounds for brain diseases fail to reach their molecular targets due to the impermeability of the blood-brain barrier, limiting their clinical development. Nanotechnology-based approaches might improve compounds pharmacokinetics by enhancing binding to the cerebrovascular endothelium and translocation into the brain. Adsorption of apolipoprotein E4 onto polysorbate 80-stabilized nanoparticles to produce a protein corona allows the specific targeting of cerebrovascular endothelium. This strategy increased nanoparticle translocation into brain parenchyma, and improved brain nanoparticle accumulation 3-fold compared to undecorated particles (119.8 vs 40.5 picomoles). Apolipoprotein decorated nanoparticles have high clinical translational potential and may improve the development of nanotechnology-based medicine for a variety of neurological diseases. (C) 2017 Elsevier Inc. All rights reserved.
- Published
- 2018
34. Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent
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Alessio Malacrida, Marie Deschamps-Wright, Roberta Rigolio, Guido Cavaletti, Mariarosaria Miloso, Malacrida, A, Deschamps-Wright, M, Rigolio, R, Cavaletti, G, and Miloso, M
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p53 ,Inorganic Chemistry ,lung cancer ,rigosertib ,Organic Chemistry ,glioblastoma ,cell cycle ,General Medicine ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Catalysis ,Computer Science Applications - Abstract
Rigosertib is a small molecule in preclinical development that, due to its characteristics as a dual PLK1 and PI3K inhibitor, is particularly effective in counteracting the advance of different types of tumors. In this work, we evaluated the efficacy of Rigosertib and the expression of p53 in five different human tumor cell lines in vitro, A549 (lung adenocarcinoma), MCF-7 and MDA-MB231 (breast cancer cells), RPMI 8226 (multiple myeloma), and U87-MG (glioblastoma). We demonstrated that in all cell lines, the effect was dose- and time-dependent, but A549 cells were the most sensible to the treatment while higher concentrations were required for the most resistant cell line U87-MG. Moreover, the highest and lowest p53 levels have been observed, respectively, in A459 and U87-MG cells. The alterations in the cell cycle and in cell-cycle-related proteins were observed in A549 at lower concentrations than U87-MG. In conclusion, with this article we have demonstrated that Rigosertib has different efficacy depending on the cell line considered and that it could be a potential antineoplastic agent against lung cancer in humans.
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- 2023
35. Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy
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Giulia Fumagalli, Laura Monza, Guido Cavaletti, Roberta Rigolio, Cristina Meregalli, Fumagalli, G, Monza, L, Cavaletti, G, Rigolio, R, and Meregalli, C
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0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Neuroimmunomodulation ,Immunology ,Axonal loss ,Antineoplastic Agents ,Review ,Blood–brain barrier ,neuroinflammation ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,Humans ,Immunology and Allergy ,Cognitive Dysfunction ,immune cell activation ,Vinca Alkaloids ,Neuroinflammation ,Inflammation ,neuropathic pain ,immune modulation ,Microglia ,business.industry ,Neurotoxicity ,Peripheral Nervous System Diseases ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Peripheral neuropathy ,Chemotherapy-induced peripheral neuropathy ,nervous system ,Peripheral nervous system ,Quality of Life ,Cytokines ,Neuralgia ,Taxoids ,Chemokines ,Cisplatin ,business ,lcsh:RC581-607 ,Neuroscience ,Proteasome Inhibitors ,030217 neurology & neurosurgery ,Signal Transduction ,chemotherapy-induced peripheral neuropathy - Abstract
Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) neurons cell body (neuronopathy/ganglionopathy). In addition, antineoplastic treatments may affect the blood brain barrier integrity, leading to cognitive impairment that may be severe and long-lasting. CIPN may affect patient quality of life leading to modification or discontinuation of the anticancer therapy. Although the mechanisms of the damage are not completely understood, several hypotheses have been proposed, among which neuroinflammation is now emerging to be relevant in CIPN pathophysiology. In this review, we consider different aspects of neuro-immune interactions in several CIPN preclinical studies which suggest a critical connection between chemotherapeutic agents and neurotoxicity. The features of the neuroinflammatory processes may be different depending on the type of drug (platinum derivatives, taxanes, vinca alkaloids and proteasome inhibitors). In particular, recent studies have demonstrated an involvement of the immune response (both innate and adaptive) and the stimulation and secretion of mediators (cytokines and chemokines) that may be responsible for the painful symptoms, whereas glial cells such as satellite and Schwann cells might contribute to the maintenance of the neuroinflammatory process in DRG and axons respectively. Moreover, neuroinflammatory components have also been shown in the spinal cord with microglia and astrocytes playing an important role in CIPN development. Taking together, better understanding of these aspects would permit the development of possible strategies in order to improve the management of CIPN.
- Published
- 2021
36. Sex dimorphism in an animal model of multiple sclerosis: Focus on pregnenolone synthesis
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Luis M. Garcia-Segura, Roberta Rigolio, Silvia Giatti, Roberto Cosimo Melcangi, Eva Falvo, Guido Cavaletti, Silvia Diviccaro, Donatella Caruso, Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (España), Instituto de Salud Carlos III, European Commission, Giatti, S, Rigolio, R, Diviccaro, S, Falvo, E, Caruso, D, Garcia-Segura, L, Cavaletti, G, and Melcangi, R
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0301 basic medicine ,Nervous system ,Male ,medicine.medical_specialty ,Neuroactive steroid ,Encephalomyelitis, Autoimmune, Experimental ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biochemistry ,Substrate Specificity ,Multiple sclerosis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Oxysterol ,Internal medicine ,medicine ,Animals ,Humans ,Multiple sclerosi ,Molecular Biology ,Sex Characteristics ,Spinal cord ,business.industry ,Cholesterol ,Experimental autoimmune encephalomyelitis ,Cell Biology ,Oxysterols ,medicine.disease ,Rats ,Sexual dimorphism ,Disease Models, Animal ,Kinetics ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Pregnenolone ,Molecular Medicine ,Female ,business ,Neurosteroids ,medicine.drug - Abstract
Neuroactive steroids, molecules produced from cholesterol in steroidogenic cells (i.e., peripheral glands and nervous system) are physiological modulators and protective agents of nervous function. A possible role for neuroactive steroids in the sex-dimorphic clinical manifestation, onset and progression of Multiple Sclerosis (MS) has been recently suggested. To explore this possibility, we assessed the synthesis of the first steroidogenic product (pregnenolone; PREG) in the spinal cord of experimental autoimmune encephalomyelitis rats, a MS model. Data obtained indicate that the synthesis of PREG in the spinal cord is altered by the pathology in a sex-dimorphic way and depending on the pathological progression. Indeed, in male spinal cord the synthesis was already decreased at the acute phase of the disease (i.e., 14 days post induction - dpi) and maintained low during the chronic phase (i.e., 45 dpi), while in females this effect was observed only at the chronic phase. Substrate availability had also a role in the sex-dimorphic kinetics. Indeed, at the chronic phase, male animals showed a reduction in the levels of free cholesterol coupled to alteration of cholesterol metabolism into oxysterols; these effects were not observed in female animals. These findings suggest that the comprehension of the neurosteroidogenic processes could be relevant to better understand the sexual dimorphism of MS and to possibly design sex-oriented therapeutic strategies based on neuroactive steroids., 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
37. Oxaliplatin-induced neuropathy occurs through impairment of haemoglobin proton buffering and is reversed by carbonic anhydrase inhibitors
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Armando A. Genazzani, Elisa Ballarini, Alberto Potenzieri, Alessia Chiorazzi, Beatrice Riva, Guido Cavaletti, Eleonora Pozzi, Roberta Rigolio, Potenzieri, A, Riva, B, Rigolio, R, Chiorazzi, A, Pozzi, E, Ballarini, E, Cavaletti, G, and Genazzani, A
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Intracellular pH ,Primary Cell Culture ,TRPV1 ,Antineoplastic Agents ,Pharmacology ,Buffers ,03 medical and health sciences ,Hemoglobins ,Mice ,0302 clinical medicine ,Transient Receptor Potential Channels ,030202 anesthesiology ,Topiramate ,Carbonic anhydrase ,Ganglia, Spinal ,medicine ,Animals ,Humans ,Carbonic Anhydrase Inhibitors ,Neurons ,Mice, Inbred BALB C ,biology ,Chemistry ,Neurotoxicity ,Peripheral Nervous System Diseases ,Hydrogen-Ion Concentration ,medicine.disease ,digestive system diseases ,Oxaliplatin ,Acetazolamide ,Anesthesiology and Pain Medicine ,Allodynia ,HEK293 Cells ,Neurology ,Hyperalgesia ,biology.protein ,oxaliplatin, carbonic anhydrase, neurotoxicity, peripheral nerve, DRG ,Neurology (clinical) ,medicine.symptom ,Protons ,030217 neurology & neurosurgery ,Homeostasis ,medicine.drug - Abstract
Oxaliplatin is a cornerstone chemotherapeutic used in the treatment of colorectal cancer, the third leading cause of death in Western countries. Most side effects of this platinum-containing drug are adequately managed in the clinic, although acute and long-term neurotoxicity still severely compromises the quality of life of patients treated with oxaliplatin. We have previously demonstrated that therapeutically relevant concentrations/doses of oxaliplatin lead to a reduction in intracellular pH in mouse dorsal root ganglion (DRG) neurons in vitro and in vivo and that this alteration sensitizes TRPA1 and TRPV1 channels, which most likely mediate the allodynia associated with treatment. In this study, we show that oxaliplatin leads to a reduction of intracellular pH by forming adducts with neuronal haemoglobin, which acts in this setting as a proton buffer. Furthermore, we show that FDA-approved drugs that inhibit carbonic anhydrase (an enzyme that is linked to haemoglobin in intracellular pH homeostasis), ie, topiramate and acetazolamide, revert (1) oxaliplatin-induced cytosolic acidification and TRPA1 and TRPV1 modulation in DRG neurons in culture, (2) oxaliplatin-induced cytosolic acidification of DRG of treated animals, and (3) oxaliplatin-induced acute cold allodynia in mice while not affecting OHP-induced cytotoxicity on cancer cells. Our data would therefore suggest that reversal of oxaliplatin-induced cytosolic acidification is a viable strategy to minimize acute oxaliplatin-induced symptoms.
- Published
- 2019
38. In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells
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Luigi Celio, Vincenzo Mazzaferro, Alessio Malacrida, Guido Cavaletti, Roberta Rigolio, Silvia Damian, Mariarosaria Miloso, Malacrida, A, Rigolio, R, Celio, L, Damian, S, Cavaletti, G, Mazzaferro, V, and Miloso, M
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0301 basic medicine ,Radiation-Sensitizing Agents ,cell migration ,medicine.medical_treatment ,chemotherapy ,Deoxycytidine ,0302 clinical medicine ,Cell Movement ,Sulfones ,Biology (General) ,Spectroscopy ,Rigosertib ,General Medicine ,Cell cycle ,Computer Science Applications ,Chemistry ,030220 oncology & carcinogenesis ,cell cycle ,Fluorouracil ,cholangiocarcinoma ,medicine.drug ,autophagy ,Radiosensitizer ,QH301-705.5 ,Glycine ,Antineoplastic Agents ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Humans ,Physical and Theoretical Chemistry ,mitotic catastrophe ,QD1-999 ,Molecular Biology ,Survival rate ,radiotherapy ,Chemotherapy ,business.industry ,Organic Chemistry ,Cancer ,medicine.disease ,Gemcitabine ,Radiation therapy ,proteasome ,030104 developmental biology ,Bile Duct Neoplasms ,Cancer research ,business - Abstract
Cholangiocarcinoma is the first most common cancer of the biliary tract. To date, surgical resection is the only potentially curative option, but it is possible only for a limited percentage of patients, and in any case survival rate is quite low. Moreover, cholangiocarcinoma is often chemotherapy-resistant, and the only drug with a significant benefit for patient’s survival is Gemcitabine. It is necessary to find new drugs or combination therapies to treat nonresectable cholangiocarcinoma and improve the overall survival rate of patients. In this work, we evaluate in vitro the antitumoral effects of Rigosertib, a multi-kinase inhibitor in clinical development, against cholangiocarcinoma EGI-1 cell lines. Rigosertib impairs EGI-1 cell viability in a dose- and time-dependent manner, reversibility is dose-dependent, and significant morphological and nuclear alterations occur. Moreover, Rigosertib induces the arrest of the cell cycle in the G2/M phase, increases autophagy, and inhibits proteasome, cell migration, and invasion. Lastly, Rigosertib shows to be a stronger radiosensitizer than Gemcitabine and 5-Fluorouracil. In conclusion, Rigosertib could be a potential therapeutic option, alone or in combination with radiations, for nonresectable patients with cholangiocarcinoma.
- Published
- 2021
39. Anti-Multiple Myeloma Potential of Secondary Metabolites from Hibiscus sabdariffa
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Francesca Vasile, Mariarosaria Miloso, Valeria Cavalloro, Marcello Di Giacomo, Simona Collina, Arianna Cassetti, Gabriella Nicolini, Guido Cavaletti, Alessio Malacrida, Emanuela Martino, Barbara Mannucci, Roberta Rigolio, Malacrida, A, Cavalloro, V, Martino, E, Cassetti, A, Nicolini, G, Rigolio, R, Cavaletti, G, Mannucci, B, Vasile, F, Di Giacomo, M, Collina, S, and Miloso, M
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Hibiscu ,Pharmaceutical Science ,Secondary Metabolism ,Pharmacology ,Chemical Fractionation ,Mass Spectrometry ,Analytical Chemistry ,0302 clinical medicine ,Multiple myeloma ,Drug Discovery ,Chromatography, High Pressure Liquid ,0303 health sciences ,biology ,Molecular Structure ,Hibiscus sabdariffa ,In vitro toxicology ,Cell migration ,Hibiscus ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,nature-aided drug discovery ,Molecular Medicine ,Human ,bioguided assay fractionation ,Spectrometry, Mass, Electrospray Ionization ,Article ,Plant Extract ,lcsh:QD241-441 ,03 medical and health sciences ,lcsh:Organic chemistry ,Cell Line, Tumor ,medicine ,Humans ,Viability assay ,Physical and Theoretical Chemistry ,Hib-ester ,030304 developmental biology ,business.industry ,Plant Extracts ,Hib-carbaldehyde ,Organic Chemistry ,Neurotoxicity ,medicine.disease ,biology.organism_classification ,Antineoplastic Agents, Phytogenic ,Cell culture ,business - Abstract
Multiple myeloma (MM) belongs to hematological cancers and its incidence is increasing worldwide. Despite recent advances in its therapy, MM still causes many deaths every year. In fact, current therapies sometimes fail and are associated with severe adverse effects, including neurotoxicity. As a part of our ongoing efforts to discover new potential therapies against MM, we prepared Hibiscus sabdariffa extracts obtained by a microwave-assisted solvent extraction and investigate their activity by in vitro assays on the RPMI-8226 cell line. The bioguided fractionation of the crude ethanolic extract allowed the identification of HsFC as the most effective extract. We assessed cell viability (MTT and Tripan blue test), cell migration (Boyden chamber assay), and neurotoxicity (DRG neurotoxicity assay). The promising results prompted us to further fractionate HsFC and we obtained two molecules effective against RPMI-8226 cells without neurotoxic effects at their active concentrations. Moreover, both compounds are able to significantly reduce cell migration.
- Published
- 2019
40. De novo UBE2A mutations are recurrently acquired during chronic myeloid leukemia progression and interfere with myeloid differentiation pathways
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Caterina Mezzatesta, David T Yeung, Miriam Nava, Alessandro Morotti, Carlo Gambacorti-Passerini, Jacqueline Boultwood, Deborah D'Aliberti, Roberta Rigolio, Luca Massimino, Wendy T Parker, Rocco Piazza, Diletta Fontana, Alessandra Pirola, Sara Readelli, Dong-Wook Kim, Nitesh Sharma, Andreas W. Schreiber, Mario Mauri, Ilaria Crespiatico, Susan Branford, Vera Magistroni, Giuseppe Saglio, R Perego, Praveen Khandelwal, Michela Viltadi, Paul Wang, Silvia Bombelli, Stefania Citterio, Magistroni, V, Mauri, M, D'Aliberti, D, Mezzatesta, C, Crespiatico, I, Nava, M, Fontana, D, Sharma, N, Parker, W, Schreiber, A, Yeung, D, Pirola, A, Redaelli, S, Massimino, L, Wang, P, Khandelwal, P, Citterio, S, Viltadi, M, Bombelli, S, Rigolio, R, Perego, R, Boultwood, J, Morotti, A, Saglio, G, Dong-Wook, K, Branford, S, Gambacorti Passerini, C, Piazza, R, Magistroni, Vera, Mauri, Mario, D'Aliberti, Deborah, Mezzatesta, Caterina, Branford, Susan, and Piazza, Rocco
- Subjects
Myeloid ,Blast Crisis progression ,kinase ,bcr-abl ,Chronic Myeloid Leukemia ,Article ,gene ube2a cause ,Molecular Genetics ,03 medical and health sciences ,Myelogenous ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,medicine ,Humans ,Chronic Myelogenous Leukemia ,business.industry ,Ubiquitination ,Myeloid leukemia ,Imatinib ,Hematology ,organization ,medicine.disease ,blast crisis ,3. Good health ,Hematopoiesis ,Ematologia, leucemia mieloide cronica, crisi blastica, mutazioni ,inhibitor ,Leukemia ,chronic myelogenous leukemia ,enzyme ,medicine.anatomical_structure ,resistant ,Leukemia, Myeloid ,repair ,Mutation ,Atypical chronic myeloid leukemia ,Cancer research ,business ,030215 immunology ,K562 cells ,Chronic myelogenous leukemia ,medicine.drug - Abstract
Despite the advent of tyrosine kinase inhibitors, a proportion of chronic myeloid leukemia patients in chronic phase fails to respond to Imatinib or to second generation inhibitors and progress to blast crisis. Limited improvements in the understanding of the molecular mechanisms responsible for chronic myeloid leukemia transformation from chronic phase to the aggressive blast crisis were achieved until now. We present here a massive parallel sequencing analysis of 10 blast crisis samples and of the corresponding autologous chronic phase controls which reveals, for the first time, recurrent mutations affecting the ubiquitin-conjugating enzyme E2A gene (UBE2A, formerly RAD6A). Additional analyses on a cohort of 24 blast crisis, 41 chronic phase as well as 40 acute myeloid leukemia and 38 atypical chronic myeloid leukemia patients at onset confirmed that UBE2A mutations are specifically acquired during chronic myeloid leukemia progression with a frequency of 16.7% in advanced phases. In vitro studies show that the mutations here described cause a decrease in UBE2A activity, leading to an impairment of myeloid differentiation in chronic myeloid leukemia cells.
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- 2019
41. Differential Exchange of Multifunctional Liposomes Between Glioblastoma Cells and Healthy Astrocytes via Tunneling Nanotubes
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Beatrice Formicola, Francesca Re, Simone Stucchi, Roberta Rigolio, Alessia D’Aloia, Michela Ceriani, Roberta Dal Magro, Formicola, B, D'Aloia, A, Dal Magro, R, Stucchi, S, Rigolio, R, Ceriani, M, and Re, F
- Subjects
0301 basic medicine ,liposomes ,Histology ,lcsh:Biotechnology ,Biomedical Engineering ,Brain tumor ,Bioengineering ,02 engineering and technology ,doxorubicin ,Metastasis ,tunneling nanotubes ,03 medical and health sciences ,chemistry.chemical_compound ,tunneling nanotube ,lcsh:TP248.13-248.65 ,medicine ,Doxorubicin ,Original Research ,Liposome ,Vesicle ,nanoparticle ,glioblastoma ,Bioengineering and Biotechnology ,021001 nanoscience & nanotechnology ,medicine.disease ,BIO/11 - BIOLOGIA MOLECOLARE ,nanomedicine ,BIO/10 - BIOCHIMICA ,Cell biology ,030104 developmental biology ,Chlorotoxin ,chemistry ,glioblastoma, liposomes, tunneling nanotubes, doxorubicin, nanoparticles, nanomedicine ,Tumor progression ,liposome ,Nanomedicine ,nanoparticles ,0210 nano-technology ,Biotechnology ,medicine.drug - Abstract
Despite advances in cancer therapies, nanomedicine approaches including the treatment of glioblastoma (GBM), the most common, aggressive brain tumor, remains inefficient. These failures are likely attributable to the complex and not yet completely known biology of this tumor, which is responsible for its strong invasiveness, high degree of metastasis, high proliferation potential, and resistance to radiation and chemotherapy. The intimate connection through which the cells communicate between them plays an important role in these biological processes. In this scenario, tunneling nanotubes (TnTs) are recently gaining importance as a key feature in tumor progression and in particular in the re-growth of GBM after surgery. In this context, we firstly identified structural differences of TnTs formed by U87-MG cells, as model of GBM cells, in comparison with those formed by normal human astrocytes (NHA), used as a model of healthy cells. Successively, we have studied the possibility to exploit U87-MG TnTs as drug-delivery channels in cancer therapy, using liposomes composed of cholesterol/sphingomyelin and surface functionalized with mApoE and chlorotoxin peptides (Mf-LIP) as nanovehicle model. The results showed that U87-MG cells formed almost exclusively thick and long protrusions, whereas NHA formed more thin and short TnTs. Considering that thick TnTs are more efficient in transport of vesicles and organelles, we showed that fluorescent-labeled Mf-LIP can be transported via TnTs between U87-MG cells and with less extent through the protrusions formed by NHA cells. Our results demonstrate that nanotubes are potentially useful as drug-delivery channels for cancer therapy, facilitating the intercellular redistribution of this drug in close and far away cells, thus reaching isolated tumor niches that are hardly targeted by simple drug diffusion in the brain parenchyma. Moreover, the differences identified in TnTs formed by GBM and NHA cells can be exploited to increase treatment precision and specificity.
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- 2019
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42. Oxaliplatin induces pH acidification in dorsal root ganglia neurons
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Valentina Alda Carozzi, Roberta Rigolio, Armando A. Genazzani, Celia Cordero-Sanchez, Alessia Chiorazzi, Alberto Potenzieri, Beatrice Riva, Dmitry Lim, Paola Marmiroli, Guido Cavaletti, Marianna Dionisi, Carla Distasi, Riva, B, Dionisi, M, Potenzieri, A, Chiorazzi, A, Cordero-Sanchez, C, Rigolio, R, Carozzi, V, Lim, D, Cavaletti, G, Marmiroli, P, Distasi, C, and Genazzani, A
- Subjects
0301 basic medicine ,Dorsum ,Sensory Receptor Cells ,Intracellular Space ,lcsh:Medicine ,Action Potentials ,Antineoplastic Agents ,Pharmacology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,Ganglia, Spinal ,medicine ,Animals ,Humans ,lcsh:Science ,TRPA1 Cation Channel ,Sensitization ,Multidisciplinary ,Chemistry ,Oxalic Acid ,lcsh:R ,Neurotoxicity ,Hydrogen-Ion Concentration ,medicine.disease ,Peripheral ,Oxaliplatin ,Electrophysiological Phenomena ,Cytosol ,030104 developmental biology ,medicine.anatomical_structure ,Toxicity ,lcsh:Q ,oxaliplatin, side effects, pH ,Cisplatin ,030217 neurology & neurosurgery ,Biomarkers ,medicine.drug - Abstract
Oxaliplatin induced peripheral neurotoxicity is characterized by an acute cold-induced syndrome characterized by cramps, paresthesias/dysesthesias in the distal limbs and perioral region, that develops rapidly and lasts up to one week affecting nearly all the patients as well as by long-lasting symptoms. It has been previously shown that pharmacological or genetic ablation of TRPA1 responses reduces oxaliplatin-induced peripheral neurotoxicity in mouse models. In the present report, we show that treatment with concentrations of oxaliplatin similar to those found in plasma of treated patients leads to an acidification of the cytosol of mouse dorsal root ganglia neurons in culture and this in turn is responsible for sensitization of TRPA1 channels, thereby providing a mechanistic explanation to toxicity of oxaliplatin. Reversal of the acidification indeed leads to a significantly reduced activity of TRPA1 channels. Last, acidification occurs also in vivo after a single injection of therapeutically-relevant doses of oxaliplatin.
- Published
- 2018
43. Synergistic activity of ALK and mTOR inhibitors for the treatment of NPM-ALK positive lymphoma
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Marco Peronaci, Luca Mologni, Alessandra Pirola, Carlo Gambacorti-Passerini, Monica Ceccon, Sara Redaelli, Roberta Rigolio, Laura Antolini, Redaelli, S, Ceccon, M, Antolini, L, Rigolio, R, Pirola, A, Peronaci, M, GAMBACORTI PASSERINI, C, and Mologni, L
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0301 basic medicine ,Lymphoma ,medicine.medical_treatment ,synergy ,Pharmacology ,Targeted therapy ,Mice ,0302 clinical medicine ,Recurrence ,hemic and lymphatic diseases ,Anaplastic Lymphoma Kinase ,Anaplastic large-cell lymphoma ,ALK/ALCL, synergy, TKI, targeted therapy, resistance ,TOR Serine-Threonine Kinases ,Cell Cycle ,Drug Synergism ,Protein-Tyrosine Kinases ,targeted therapy ,TKI ,Temsirolimus ,Tumor Burden ,Oncology ,030220 oncology & carcinogenesis ,Female ,Signal Transduction ,Research Paper ,medicine.drug ,medicine.drug_class ,Antineoplastic Agents ,resistance ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Crizotinib ,business.industry ,Receptor Protein-Tyrosine Kinases ,ALK/ALCL ,medicine.disease ,Xenograft Model Antitumor Assays ,Lorlatinib ,ALK inhibitor ,Disease Models, Animal ,030104 developmental biology ,business - Abstract
ALK-positive Anaplastic Large Cell Lymphoma (ALCL) represents a subset of Non-Hodgkin Lymphoma whose treatment benefited from crizotinib development, a dual ALK/MET inhibitor. Crizotinib blocks ALK-triggered pathways such as PI3K/AKT/ mTOR, indispensable for survival of ALK-driven tumors. Despite the positive impact of targeted treatment in ALCL, resistant clones are often selected during therapy. Strategies to overcome resistance include the design of second generation drugs and the use of combined therapies that simultaneously target multiple nodes essential for cells survival. We investigated the effects of combined ALK/mTOR inhibition. We observed a specific synergistic effect of combining ALK inhibitors with an mTOR inhibitor (temsirolimus), in ALK+ lymphoma cells. The positive cooperation resulted in an increased inhibition of mTOR effectors, compared to single treatments, a block in G0/G1 phase and induction of apoptosis. The combination was able to prevent the selection of resistant clones, while longterm exposure to single agents led to the establishment of resistant cell lines, with either ALK inhibitor or temsirolimus. In vivo, mice injected with Karpas 299 cells and treated with low dose combination showed complete regression of tumors, while only partial inhibition was obtained in single agents-treated mice. Upon treatment stop the combination was able to significantly delay tumor relapses. Re-challenge of relapsed tumors at a higher dose led to full regression of xenografts in the combination group, but not in mice treated with lorlatinib alone. In conclusion, our data suggest that the combination of ALK and mTOR inhibitors could be a valuable therapeutic option for ALK+ ALCL patients.
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- 2016
44. Animal Models for the Study of Human Central and Peripheral Nervous System Diseases
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MONZA, LAURA, FUMAGALLI, GIULIA, POZZI, ELEONORA, ALBERTI, PAOLA, CANTA, ANNALISA ROSANNA, CHIORAZZI, ALESSIA, MEREGALLI, CRISTINA, CAROZZI, VALENTINA ALDA, RIGOLIO, ROBERTA, OGGIONI, NORBERTO, MARMIROLI, PAOLA LORENA, CAVALETTI, GUIDO ANGELO, Monza, L, Fumagalli, G, Pozzi, E, Alberti, P, Canta, A, Chiorazzi, A, Meregalli, C, Carozzi, V, Rigolio, R, Oggioni, N, Marmiroli, P, and Cavaletti, G
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anima models, peripheral and central nervous diseases - Published
- 2017
45. Multimodal experimental approach to the study of human neurological diseases
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CHIORAZZI, ALESSIA, MEREGALLI, CRISTINA, CANTA, ANNALISA ROSANNA, CAROZZI, VALENTINA ALDA, OGGIONI, NORBERTO, RIGOLIO, ROBERTA, POZZI, ELEONORA, MONZA, LAURA, FUMAGALLI, GIULIA, MARMIROLI, PAOLA LORENA, CAVALETTI, GUIDO ANGELO, Alberti, A, Chiorazzi, A, Meregalli, C, Canta, A, Carozzi, V, Oggioni, N, Rigolio, R, Pozzi, E, Monza, L, Fumagalli, G, Alberti, A, Marmiroli, P, and Cavaletti, G
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experimental approach to human neurological diseases - Published
- 2017
46. ApoE-modified solid lipid nanoparticles: A feasible strategy to cross the blood-brain barrier
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Giulio Sancini, P Gasco, Roberta Rigolio, C Musicanti, R Dal Magro, Francesca Re, Elisabetta Donzelli, Elisa Ballarini, Guido Cavaletti, F Ornaghi, Annalisa Canta, Ilaria Cambianica, S Beretta, DAL MAGRO, R, Ornaghi, F, Cambianica, I, Beretta, S, Re, F, Musicanti, C, Rigolio, R, Donzelli, E, Canta, A, Ballarini, E, Cavaletti, G, Gasco, P, and Sancini, G
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0301 basic medicine ,Apolipoprotein E ,Male ,BALB 3T3 Cells ,Surface Properties ,Pharmaceutical Science ,Peptide ,02 engineering and technology ,Pharmacology ,Blood–brain barrier ,Cell Line ,Capillary Permeability ,03 medical and health sciences ,Mice ,Apolipoproteins E ,Drug Delivery Systems ,BIO/09 - FISIOLOGIA ,Solid lipid nanoparticle ,medicine ,Animals ,chemistry.chemical_classification ,Drug Carriers ,Chemistry ,021001 nanoscience & nanotechnology ,Solid lipid nanoparticles, ApoE-derived peptide, pulmonary administration, brain targeting, blood-brain barrier ,Lipid Metabolism ,Lipids ,Bioavailability ,030104 developmental biology ,medicine.anatomical_structure ,Blood-Brain Barrier ,Drug delivery ,Surface modification ,Nanoparticles ,Nanocarriers ,0210 nano-technology - Abstract
Solid lipid nanoparticles (SLN) are colloidal drug delivery systems characterized by higher entrapment efficiency, good scalability of the preparation process and increased sustained prolonged release of the payload compared to other nanocarriers. The possibility to functionalize the surface of SLN with ligands to achieve a site specific targeting makes them attractive to overcome the limited blood-brain barrier (BBB) penetration of therapeutic compounds. SLN are prepared for brain targeting by exploiting the adaptability of warm microemulsion process for the covalent surface modification with an Apolipoprotein E-derived peptide (SLN-mApoE). Furthermore, the influence of the administration route on SLN-mApoE brain bioavailability is here evaluated. SLN-mApoE are able to cross intact a BBB in vitro model. The pulmonary administration of SLN-mApoE is related to a higher confinement in the brain of Balb/c mice compared to the intravenous and intraperitoneal administration routes, without inducing any acute inflammatory reaction in the lungs. These results promote the pulmonary administration of brain-targeted SLN as a feasible strategy for improving brain delivery of therapeutics.
- Published
- 2016
47. Functionalized Mesoporous Silica Nanoparticles: A Possible Strategy to Target Cancer Cells Reducing Peripheral Nervous System Uptake
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Cecilia Ceresa, Roberta Rigolio, M Bossi, Luigi Pasqua, Gabriella Nicolini, Guido Cavaletti, Ceresa, C, Nicolini, G, Rigolio, R, Bossi, M, Pasqua, L, and Cavaletti, G
- Subjects
Mesoporous silica materials, drugs, nanoparticles ,Drug ,Cell Survival ,media_common.quotation_subject ,Antineoplastic Agents ,Pharmacology ,Biochemistry ,Rats, Sprague-Dawley ,Ganglia, Spinal ,Drug Discovery ,medicine ,Animals ,Humans ,Folate Receptor 1 ,Cytotoxicity ,Cells, Cultured ,media_common ,Neurons ,Cisplatin ,Drug Carriers ,Microscopy, Confocal ,Chemistry ,Organic Chemistry ,Neurotoxicity ,Mesoporous silica ,Silicon Dioxide ,medicine.disease ,Rats ,Drug delivery ,Cancer cell ,Nanoparticles ,Molecular Medicine ,Drug carrier ,Porosity ,Fluorescein-5-isothiocyanate ,medicine.drug - Abstract
Mesoporous silica materials (MSM) have been proposed as promising tools for cell specific drug delivery or fluorescent cell tracking. In cancer therapy there is an urgent need to develop a cancer cell specific drug carrier able to limit the non-specific uptake of the drug by normal cells thereby reducing serious side effects. Chemotherapy induced peripheral neurotoxicity (CIPN) is one of the most clinically relevant side effects linked to the use of several antineoplastic drugs. In this study we showed that the uptake of MSM (synthesized using a PEG surfactant-based interfacial synthesis procedure), functionalised with folic acid (MSM-FOL) after 1, 6 and 24 hours is very limited in neuronal-like cellular systems such as differentiated SH-SY5Y human neuroblastoma cells and rat embryonic dorsal root ganglia sensory neurons. By contrast, the nanoparticles are highly internalized in A549 and IGROV-1 cancer cells. The 6 hour-treatment of A549 and IGROV-1 cells with nanoparticles loaded with the antineoplastic drug cisplatin (CP) induced significant cytotoxicity with respect to CP alone. These results were observed treating IGROV-1 cells with 25 and 50 μg/ml nanoparticles doses (corresponding respectively to CP 6.25 and 12.5 μM) and treating A549 with 50 μg/ml.Our results demonstrated a selective uptake of functionalized MSM suggesting them as promising tools for targeted antineoplastic therapy. Further studies will be necessary in order to confirm if this approach may be useful in reducing neurotocity of anticancer drugs.
- Published
- 2013
48. Multiple Sclerosis Drug Therapy: From the Classical Pharmaceutical Down to Cellular and Molecular Approach
- Author
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Roberta Rigolio, Elisa Ballarini, Maria Grimoldi, Margherita Gardinetti, Gabriele Di Sante, Atta-ur-Rahman, Rigolio, R, Ballarini, E, Gabriele, D, Gardinetti, M, and Grimoldi, M
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Anti-Lingo-1 antibody, Alemtuzumab, Daclizumab, disease-modifying drugs, ethiopathology, helminthes, histopathology, immune system, Masinitib mesylate, monoclonal antibodies, MOR103, Multiple Sclerosis, Ofatumumab, Ocrelizumab, remyelination strategies, Rituximab, Secukinumab, stem cells, Tabalumab, tolerogenic vaccines, vitamin D ,MED/26 - NEUROLOGIA ,MED/05 - PATOLOGIA CLINICA - Abstract
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting over 2.000.000 individuals around the world. Although MS etiopathogenesis is still not completely defined environmental factor exposure and genetic background are relevant in disease development. Moreover, MS shows heterogeneous onset and course so that different disease forms can be described which are all characterized by motor and/or sensory and even cognitive impairment. Two steps in the disease progression can be described. First MS lesions are originated by the activated immune system which recognizes CNS myelin as a foreign element thus leading to the formation of demyelinated plaques that evolve into axonal damage and subsequent neurodegeneration over the time. Since the beginning MS therapy has been focused on counteracting immune system action. Nevertheless, besides the immunosuppressive/immunomodulating drugs such as Glatiramer Acetate, Beta-interferons and steroids, the advance in the comprehension of the immune-mediated mechanisms has sustained the development and use of molecular and cellular-focused approaches, e.g. monoclonal antibodies and stem cells. At the same time very few weapons are specifically available for fighting MS neurodegenerative progression. We report an overview on MS and both old and new therapeutic approaches to the disease
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- 2016
49. Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency
- Author
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C Casati, Roberta Rigolio, Giovanni Giudici, Lydia Varesio, M E Boggio Merlo, Luca Mologni, Andrea D. Manazza, Roberto Chiarle, Silvia Bombelli, F Di Giacomo, Carlo Gambacorti-Passerini, Monica Ceccon, Mara Compagno, Claudia Voena, Matteo Menotti, Suzanne D. Turner, Chiara Ambrogio, Cristina Mastini, Teresa Poggio, Ceccon, M, Merlo, M, Mologni, L, Poggio, T, Varesio, L, Menotti, M, Bombelli, S, Rigolio, R, Manazza, A, Di Giacomo, F, Ambrogio, C, Giudici, G, Casati, C, Mastini, C, Compagno, M, Turner, S, GAMBACORTI PASSERINI, C, Chiarle, R, Voena, C, Turner, Suzanne [0000-0002-8439-4507], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Cancer Research ,Oncogene Proteins, Fusion ,Pyridines ,Apoptosis ,Mice, SCID ,Histones ,0302 clinical medicine ,Mice, Inbred NOD ,hemic and lymphatic diseases ,Extracellular Signal-Regulated MAP Kinases ,Cells, Cultured ,Mice, Knockout ,Microscopy, Confocal ,integumentary system ,Kinase ,Drug Synergism ,Cell cycle ,Protein-Tyrosine Kinases ,Hydrazines ,030220 oncology & carcinogenesis ,Lymphoma, Large-Cell, Anaplastic ,RNA Interference ,Signal transduction ,Tyrosine kinase ,Nucleophosmin ,medicine.drug ,Signal Transduction ,Programmed cell death ,Cell Survival ,Blotting, Western ,Transplantation, Heterologous ,Biology ,Article ,03 medical and health sciences ,Molecular Biology ,Genetics ,Crizotinib ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Kinase activity ,Protein Kinase Inhibitors ,Dose-Response Relationship, Drug ,Triazoles ,030104 developmental biology ,Cytoplasm ,Immunology ,Cancer research ,Pyrazoles - Abstract
Most of the anaplastic large-cell lymphoma (ALCL) cases carry the t(2;5; p23;q35) that produces the fusion protein NPM-ALK (nucleophosmin-anaplastic lymphoma kinase). NPM-ALK-deregulated kinase activity drives several pathways that support malignant transformation of lymphoma cells. We found that in ALK-rearranged ALCL cell lines, NPM-ALK was distributed in equal amounts between the cytoplasm and the nucleus. Only the cytoplasmic portion was catalytically active in both cell lines and primary ALCL, whereas the nuclear portion was inactive because of heterodimerization with NPM1. Thus, about 50% of the NPM-ALK is not active and sequestered as NPM-ALK/NPM1 heterodimers in the nucleus. Overexpression or relocalization of NPM-ALK to the cytoplasm by NPM genetic knockout or knockdown caused ERK1/2 (extracellular signal-regulated protein kinases 1 and 2) increased phosphorylation and cell death through the engagement of an ATM/Chk2- and γH2AX (phosphorylated H2A histone family member X)-mediated DNA-damage response. Remarkably, human NPM-ALK-amplified cell lines resistant to ALK tyrosine kinase inhibitors (TKIs) underwent apoptosis upon drug withdrawal as a consequence of ERK1/2 hyperactivation. Altogether, these findings indicate that an excess of NPM-ALK activation and signaling induces apoptosis via oncogenic stress responses. A 'drug holiday' where the ALK TKI treatment is suspended could represent a therapeutic option in cells that become resistant by NPM-ALK amplification.
- Published
- 2016
50. Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model
- Author
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Francesco Nicotra, Giulio Sancini, Barbara La Ferla, Francesca Re, Silvia Sesana, Alfredo Cagnotto, Mario Salmona, Massimo Masserini, Cristiano Zona, Gianluigi Forloni, Maria Gregori, Ilaria Cambianica, Roberta Rigolio, Re, F, Cambianica, I, Zona, C, Sesana, M, Gregori, M, Rigolio, R, LA FERLA, B, Nicotra, F, Forloni, G, Cagnotto, A, Salmona, M, Masserini, M, and Sancini, G
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Pharmaceutical Science ,Medicine (miscellaneous) ,Peptide ,02 engineering and technology ,environment and public health ,law.invention ,Drug Delivery Systems ,law ,BIO/09 - FISIOLOGIA ,CHIM/06 - CHIMICA ORGANICA ,General Materials Science ,chemistry.chemical_classification ,0303 health sciences ,Liposome ,Microscopy, Confocal ,medicine.diagnostic_test ,Brain ,Cell sorting ,021001 nanoscience & nanotechnology ,Flow Cytometry ,brain endothelial cell ,medicine.anatomical_structure ,Biochemistry ,Blood-Brain Barrier ,Molecular Medicine ,0210 nano-technology ,Materials science ,Curcumin ,nanoliposome ,Biomedical Engineering ,Bioengineering ,Blood–brain barrier ,Permeability ,Flow cytometry ,Cell Line ,03 medical and health sciences ,Apolipoproteins E ,Confocal microscopy ,medicine ,NLS ,Animals ,Humans ,ApoE-peptide ,030304 developmental biology ,Endothelial Cells ,Biological Transport ,Rats ,chemistry ,Liposomes ,Biophysics ,Nanoparticles ,Nanocarriers - Abstract
A promising strategy to enhance blood-brain barrier penetration by drugs is the functionalization of nanocarriers with uptake-facilitating ligands. We studied the cellular uptake, by cultured RBE4 brain capillary endothelial cells, of nanoliposomes (NLs) covalently coupled with monomer or tandem dimer of apolipoprotein E (ApoE)-derived peptides (residues 141-150), at various densities. NLs without functionalization did not show either relevant membrane accumulation or cellular uptake, as monitored by confocal microscopy and quantified by fluorescence-activated cell sorting. Functionalization with peptides mediated an efficient NLs uptake that increased with peptide density; NLs carrying monomeric peptide performed the best. Moreover, we studied the ability of ApoE-NLs to enhance the transport of a drug payload through a RBE4 cell monolayer. The permeability of a tritiated curcumin derivative was enhanced after its entrapment into ApoE-NLs, in particular those functionalized with the dimer (+83% with respect to free drug, P < 0.01). Thus, these NLs appear particularly suitable for implementing further strategies for drug brain targeting. From the Clinical Editor: Re and her collaborators present a method for delivering nanoliposomes via the blood brain barrier by utilizing peptide fragments including monomers or tandem dimers ApoE. This method may enable enhanced nanoliposome associated drug delivery via the blood-brain barrier, which would have enormous significance in neurodegenerative and other CNS disorders
- Published
- 2011
- Full Text
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