571 results on '"Lavitrano, M."'
Search Results
2. EPTRI - European Paediatric Translational Research Infrastructure. Bridging the gaps of the paediatric excellence medicine
- Author
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Bonifazi, D, Lupo, M, Pignataro, V, Toni, I, Kubova, H, Tuleu, C, Lavitrano, M, and Ceci, A
- Published
- 2019
3. Olfactory receptor genes and chromosome 11 structural aberrations: Players or spectators?
- Author
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Redaelli, S, Grati, F, Tritto, V, Giannuzzi, G, Recalcati, M, Sala, E, Villa, N, Crosti, F, Roversi, G, Malvestiti, F, Zanatta, V, Repetti, E, Rodeschini, O, Valtorta, C, Catusi, I, Romitti, L, Martinoli, E, Conconi, D, Dalprà, L, Lavitrano, M, Riva, P, Bentivegna, A, Redaelli, Serena, Grati, Francesca Romana, Tritto, Viviana, Giannuzzi, Giuliana, Recalcati, Maria Paola, Sala, Elena, Villa, Nicoletta, Crosti, Francesca, Roversi, Gaia, Malvestiti, Francesca, Zanatta, Valentina, Repetti, Elena, Rodeschini, Ornella, Valtorta, Chiara, Catusi, Ilaria, Romitti, Lorenza, Martinoli, Emanuela, Conconi, Donatella, Dalprà, Leda, Lavitrano, Marialuisa, Riva, Paola, Bentivegna, Angela, Redaelli, S, Grati, F, Tritto, V, Giannuzzi, G, Recalcati, M, Sala, E, Villa, N, Crosti, F, Roversi, G, Malvestiti, F, Zanatta, V, Repetti, E, Rodeschini, O, Valtorta, C, Catusi, I, Romitti, L, Martinoli, E, Conconi, D, Dalprà, L, Lavitrano, M, Riva, P, Bentivegna, A, Redaelli, Serena, Grati, Francesca Romana, Tritto, Viviana, Giannuzzi, Giuliana, Recalcati, Maria Paola, Sala, Elena, Villa, Nicoletta, Crosti, Francesca, Roversi, Gaia, Malvestiti, Francesca, Zanatta, Valentina, Repetti, Elena, Rodeschini, Ornella, Valtorta, Chiara, Catusi, Ilaria, Romitti, Lorenza, Martinoli, Emanuela, Conconi, Donatella, Dalprà, Leda, Lavitrano, Marialuisa, Riva, Paola, and Bentivegna, Angela
- Abstract
The largest multi-gene family in metazoans is the family of olfactory receptor (OR) genes. Human ORs are organized in clusters over most chromosomes and seem to include >0.1% the human genome. Because 369 out of 856 OR genes are mapped on chromosome 11 (HSA11), we sought to determine whether they mediate structural rearrangements involving this chromosome. To this aim, we analyzed 220 specimens collected during diagnostic procedures involving structural rearrangements of chromosome 11. A total of 222 chromosomal abnormalities were included, consisting of inversions, deletions, translocations, duplications, and one insertion, detected by conventional chromosome analysis and/or fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (array-CGH). We verified by bioinformatics and statistical approaches the occurrence of breakpoints in cytobands with or without OR genes. We found that OR genes are not involved in chromosome 11 reciprocal translocations, suggesting that different DNA motifs and mechanisms based on homology or non-homology recombination can cause chromosome 11 structural alterations. We also considered the proximity between the chromosomal territories of chromosome 11 and its partner chromosomes involved in the translocations by using the deposited Hi-C data concerning the possible occurrence of chromosome interactions. Interestingly, most of the breakpoints are located in regions highly involved in chromosome interactions. Further studies should be carried out to confirm the potential role of chromosome territories’ proximity in promoting genome structural variation, so fundamental in our understanding of the molecular basis of medical genetics and evolutionary genetics.
- Published
- 2024
4. Differential Expression of NOTCH-1 and Its Molecular Targets in Response to Metronomic Followed by Conventional Therapy in a Patient with Advanced Triple-Negative Breast Cancer
- Author
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Ilari, A, Cogliati, V, Sherif, N, Grassilli, E, Ramazzotti, D, Cordani, N, Cazzaniga, G, Di Bella, C, Lavitrano, M, Cazzaniga, M, Cerrito, M, Ilari, Alice, Cogliati, Viola, Sherif, Noorhan, Grassilli, Emanuela, Ramazzotti, Daniele, Cordani, Nicoletta, Cazzaniga, Giorgio, Di Bella, Camillo, Lavitrano, Marialuisa, Cazzaniga, Marina Elena, Cerrito, Maria Grazia, Ilari, A, Cogliati, V, Sherif, N, Grassilli, E, Ramazzotti, D, Cordani, N, Cazzaniga, G, Di Bella, C, Lavitrano, M, Cazzaniga, M, Cerrito, M, Ilari, Alice, Cogliati, Viola, Sherif, Noorhan, Grassilli, Emanuela, Ramazzotti, Daniele, Cordani, Nicoletta, Cazzaniga, Giorgio, Di Bella, Camillo, Lavitrano, Marialuisa, Cazzaniga, Marina Elena, and Cerrito, Maria Grazia
- Abstract
A group of 27 patients diagnosed with metastatic triple-negative breast cancer (mTNBC) was randomly distributed into two groups and underwent different lines of metronomic treatment (mCHT). The former group (N 14) received first-line mCHT and showed a higher overall survival rate than the second group (N 13), which underwent second-line mCHT. Analysis of one patient still alive from the first group, diagnosed with mTNBC in 2019, showed a complete metabolic response (CMR) after a composite approach implicating first-line mCHT followed by second-line epirubicin and third-line nab-paclitaxel, and was chosen for subsequent molecular characterization. We found altered expression in the cancer stemness-associated gene NOTCH-1 and its corresponding protein. Additionally, we found changes in the expression of oncogenes, such as MYC and AKT, along with their respective proteins. Overall, our data suggest that a first-line treatment with mCHT followed by MTD might be effective by negatively regulating stemness traits usually associated with the emergence of drug resistance.
- Published
- 2024
5. Vacuolar Proton-Translocating ATPase May Take Part in the Drug Resistance Phenotype of Glioma Stem Cells
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Giambra, M, Di Cristofori, A, Raimondo, F, Rigolio, R, Conconi, D, Chiarello, G, Tabano, S, Antolini, L, Nicolini, G, Bua, M, Ferlito, D, Carrabba, G, Giussani, C, Lavitrano, M, Bentivegna, A, Giambra, Martina, Di Cristofori, Andrea, Raimondo, Francesca, Rigolio, Roberta, Conconi, Donatella, Chiarello, Gaia, Tabano, Silvia Maria, Antolini, Laura, Nicolini, Gabriella, Bua, Miriam, Ferlito, Davide, Carrabba, Giorgio, Giussani, Carlo Giorgio, Lavitrano, Marialuisa, Bentivegna, Angela, Giambra, M, Di Cristofori, A, Raimondo, F, Rigolio, R, Conconi, D, Chiarello, G, Tabano, S, Antolini, L, Nicolini, G, Bua, M, Ferlito, D, Carrabba, G, Giussani, C, Lavitrano, M, Bentivegna, A, Giambra, Martina, Di Cristofori, Andrea, Raimondo, Francesca, Rigolio, Roberta, Conconi, Donatella, Chiarello, Gaia, Tabano, Silvia Maria, Antolini, Laura, Nicolini, Gabriella, Bua, Miriam, Ferlito, Davide, Carrabba, Giorgio, Giussani, Carlo Giorgio, Lavitrano, Marialuisa, and Bentivegna, Angela
- Abstract
The vacuolar proton-translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism underlying carcinogenesis is mainly based on anaerobic glycolytic reactions. Moreover, neoplastic cells use the V-ATPase to extrude chemotherapy drugs into the extra-cellular compartment as a drug resistance mechanism. In glioblastoma (GBM), the most malignant and incurable primary brain tumor, the expression of this pump is upregulated, making it a new possible therapeutic target. In this work, the bafilomycin A1-induced inhibition of V-ATPase in patient-derived glioma stem cell (GSC) lines was evaluated together with temozolomide, the first-line therapy against GBM. In contrast with previous published data, the proposed treatment did not overcome resistance to the standard therapy. In addition, our data showed that nanomolar dosages of bafilomycin A1 led to the blockage of the autophagy process and cellular necrosis, making the drug unusable in models which are more complex. Nevertheless, the increased expression of V-ATPase following bafilomycin A1 suggests a critical role of the proton pump in GBM stem components, encouraging the search for novel strategies to limit its activity in order to circumvent resistance to conventional therapy.
- Published
- 2024
6. Insights into the Peritumoural Brain Zone of Glioblastoma: CDK4 and EXT2 May Be Potential Drivers of Malignancy
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Giambra, M, Di Cristofori, A, Conconi, D, Marzorati, M, Redaelli, S, Zambuto, M, Rocca, A, Roumy, L, Carrabba, G, Lavitrano, M, Roversi, G, Giussani, C, Bentivegna, A, Giambra M., Di Cristofori A., Conconi D., Marzorati M., Redaelli S., Zambuto M., Rocca A., Roumy L., Carrabba G., Lavitrano M., Roversi G., Giussani C., Bentivegna A., Giambra, M, Di Cristofori, A, Conconi, D, Marzorati, M, Redaelli, S, Zambuto, M, Rocca, A, Roumy, L, Carrabba, G, Lavitrano, M, Roversi, G, Giussani, C, Bentivegna, A, Giambra M., Di Cristofori A., Conconi D., Marzorati M., Redaelli S., Zambuto M., Rocca A., Roumy L., Carrabba G., Lavitrano M., Roversi G., Giussani C., and Bentivegna A.
- Abstract
Despite the efforts made in recent decades, glioblastoma is still the deadliest primary brain cancer without cure. The potential role in tumour maintenance and progression of the peritumoural brain zone (PBZ), the apparently normal area surrounding the tumour, has emerged. Little is known about this area due to a lack of common definition and due to difficult sampling related to the functional role of peritumoural healthy brain. The aim of this work was to better characterize the PBZ and to identify genes that may have role in its malignant transformation. Starting from our previous study on the comparison of the genomic profiles of matched tumour core and PBZ biopsies, we selected CDK4 and EXT2 as putative malignant drivers of PBZ. The gene expression analysis confirmed their over-expression in PBZ, similarly to what happens in low-grade glioma and glioblastoma, and CDK4 high levels seem to negatively influence patient overall survival. The prognostic role of CDK4 and EXT2 was further confirmed by analysing the TCGA cohort and bioinformatics prediction on their gene networks and protein–protein interactions. These preliminary data constitute a good premise for future investigations on the possible role of CDK4 and EXT2 in the malignant transformation of PBZ.
- Published
- 2023
7. Evaluating [18F]FDG and [18F]FLT Radiotracers as Biomarkers of Response for Combined Therapy Outcome in Triple-Negative and Estrogen-Receptor-Positive Breast Cancer Models
- Author
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Rainone, P, Valtorta, S, Villa, C, Todde, S, Cadamuro, M, Bertoli, G, Conconi, D, Lavitrano, M, Moresco, R, Rainone P., Valtorta S., Villa C., Todde S., Cadamuro M., Bertoli G., Conconi D., Lavitrano M., Moresco R. M., Rainone, P, Valtorta, S, Villa, C, Todde, S, Cadamuro, M, Bertoli, G, Conconi, D, Lavitrano, M, Moresco, R, Rainone P., Valtorta S., Villa C., Todde S., Cadamuro M., Bertoli G., Conconi D., Lavitrano M., and Moresco R. M.
- Abstract
Breast cancer (BC) is the most frequent cancer and the second leading cause of death in women. A typical feature of BC cells is the metabolic shift toward increased glycolysis, which has become an interesting therapeutic target for metabolic drugs such as metformin (MET). Recently, the administration of the antihypertensive syrosingopine (SYRO) in combination with MET has shown a synergistic effect toward a variety of cancers. However, a fundamental need remains, which is the development of in vivo biomarkers that are able to detect early clinical response. In this study, we exploited a triple-negative murine BC cell line (4T1) and a metastatic ER+ murine BC cell line (TS/A) in order to investigate, in vivo, the early response to treatment, based on MET and/or SYRO administration, evaluating [18F]FDG and [18F]FLT as potential biomarkers via PET/CT. The study provides evidence that SYRO plus MET has a synergistic effect on tumor growth inhibition in both 4T1 and TS/A experimental models and has showed the highest efficacy on the TNBC xenograft mice (4T1) via the expression reduction in the lactate transporter MCT4 and in the epithelial–mesenchymal transition biomarker Snail, promoting its potential application in therapy settings. In addition, the selective reduction in the [18F]FLT tumor uptake (at 7 dd), observed in the SYRO plus MET treated mice in comparison with the vehicle group, suggests that this radiotracer could be potentially used as a biomarker for the early detection of therapy response, in both evaluated xenografts models.
- Published
- 2023
8. Genomic Complexity and Complex Chromosomal Rearrangements in Genetic Diagnosis: Two Illustrative Cases on Chromosome 7
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Villa, N, Redaelli, S, Farina, S, Conconi, D, Sala, E, Crosti, F, Mariani, S, Colombo, C, Dalprà, L, Lavitrano, M, Bentivegna, A, Roversi, G, Villa N., Redaelli S., Farina S., Conconi D., Sala E. M., Crosti F., Mariani S., Colombo C. M., Dalprà L., Lavitrano M., Bentivegna A., Roversi G., Villa, N, Redaelli, S, Farina, S, Conconi, D, Sala, E, Crosti, F, Mariani, S, Colombo, C, Dalprà, L, Lavitrano, M, Bentivegna, A, Roversi, G, Villa N., Redaelli S., Farina S., Conconi D., Sala E. M., Crosti F., Mariani S., Colombo C. M., Dalprà L., Lavitrano M., Bentivegna A., and Roversi G.
- Abstract
Complex chromosomal rearrangements are rare events compatible with survival, consisting of an imbalance and/or position effect of one or more genes, that contribute to a range of clinical presentations. The investigation and diagnosis of these cases are often difficult. The interpretation of the pattern of pairing and segregation of these chromosomes during meiosis is important for the assessment of the risk and the type of imbalance in the offspring. Here, we investigated two unrelated pediatric carriers of complex rearrangements of chromosome 7. The first case was a 2-year-old girl with a severe phenotype. Conventional cytogenetics evidenced a duplication of part of the short arm of chromosome 7. By array-CGH analysis, we found a complex rearrangement with three discontinuous trisomy regions (7p22.1p21.3, 7p21.3, and 7p21.3p15.3). The second case was a newborn investigated for hypodevelopment and dimorphisms. The karyotype analysis promptly revealed a structurally altered chromosome 7. The array-CGH analysis identified an even more complex rearrangement consisting of a trisomic region at 7q11.23q22 and a tetrasomic region of 4.5 Mb spanning 7q21.3 to q22.1. The mother’s karyotype examination revealed a complex rearrangement of chromosome 7: the 7q11.23q22 region was inserted in the short arm at 7p15.3. Finally, array-CGH analysis showed a trisomic region that corresponds to the tetrasomic region of the son. Our work proved that the integration of several technical solutions is often required to appropriately analyze complex chromosomal rearrangements in order to understand their implications and offer appropriate genetic counseling.
- Published
- 2023
9. Characterization of Chromosomal Breakpoints in 12 Cases with 8p Rearrangements Defines a Continuum of Fragility of the Region
- Author
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Redaelli, S, Conconi, D, Sala, E, Villa, N, Crosti, F, Roversi, G, Catusi, I, Valtorta, C, Recalcati, M, Dalpra, L, Lavitrano, M, Bentivegna, A, Redaelli S., Conconi D., Sala E., Villa N., Crosti F., Roversi G., Catusi I., Valtorta C., Recalcati M. P., Dalpra L., Lavitrano M., Bentivegna A., Redaelli, S, Conconi, D, Sala, E, Villa, N, Crosti, F, Roversi, G, Catusi, I, Valtorta, C, Recalcati, M, Dalpra, L, Lavitrano, M, Bentivegna, A, Redaelli S., Conconi D., Sala E., Villa N., Crosti F., Roversi G., Catusi I., Valtorta C., Recalcati M. P., Dalpra L., Lavitrano M., and Bentivegna A.
- Abstract
Improvements in microarray-based comparative genomic hybridization technology have allowed for high-resolution detection of genome wide copy number alterations, leading to a better definition of rearrangements and supporting the study of pathogenesis mechanisms. In this study, we focused our attention on chromosome 8p. We report 12 cases of 8p rearrangements, analyzed by molecular karyotype, evidencing a continuum of fragility that involves the entire short arm. The breakpoints seem more concentrated in three intervals: one at the telomeric end, the others at 8p23.1, close to the beta-defensin gene cluster and olfactory receptor low-copy repeats. Hypothetical mechanisms for all cases are described. Our data extend the cohort of published patients with 8p aberrations and highlight the need to pay special attention to these sequences due to the risk of formation of new chromosomal aberrations with pathological effects.
- Published
- 2022
10. Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma
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Virtuoso, A, De Luca, C, Cirillo, G, Riva, M, Romano, G, Bentivegna, A, Lavitrano, M, Papa, M, Giovannoni, R, Virtuoso A., De Luca C., Cirillo G., Riva M., Romano G., Bentivegna A., Lavitrano M., Papa M., Giovannoni R., Virtuoso, A, De Luca, C, Cirillo, G, Riva, M, Romano, G, Bentivegna, A, Lavitrano, M, Papa, M, Giovannoni, R, Virtuoso A., De Luca C., Cirillo G., Riva M., Romano G., Bentivegna A., Lavitrano M., Papa M., and Giovannoni R.
- Abstract
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a malignant prognosis. GBM is characterized by high cellular heterogeneity and its progression relies on the interaction with the central nervous system, which ensures the immune-escape and tumor promotion. This interplay induces metabolic, (epi)-genetic and molecular rewiring in both domains. In the present study, we aim to characterize the time-related changes in the GBM landscape, using a syngeneic mouse model of primary GBM. GL261 glioma cells were injected in the right striatum of immuno-competent C57Bl/6 mice and animals were sacrificed after 7, 14, and 21 days (7D, 14D, 21D). The tumor development was assessed through 3D tomographic imaging and brains were processed for immunohistochemistry, immunofluorescence, and western blotting. A human transcriptomic database was inquired to support the translational value of the experimental data. Our results showed the dynamic of the tumor progression, being established as a bulk at 14D and surrounded by a dense scar of reactive astrocytes. The GBM growth was paralleled by the impairment in the microglial/macrophagic recruitment and antigen-presenting functions, while the invasive phase was characterized by changes in the extracellular matrix, as shown by the analysis of tenascin C and metalloproteinase-9. The present study emphasizes the role of the molecular changes in the microenvironment during the GBM progression, fostering the development of novel multi-targeted, time-dependent therapies in an experimental model similar to the human disease.
- Published
- 2022
11. Paediatric biobanking for health: The ethical, legal, and societal landscape
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Casati, S, Ellul, B, Mayrhofer, M, Lavitrano, M, Caboux, E, Kozlakidis, Z, Casati S., Ellul B., Mayrhofer M. T., Lavitrano M., Caboux E., Kozlakidis Z., Casati, S, Ellul, B, Mayrhofer, M, Lavitrano, M, Caboux, E, Kozlakidis, Z, Casati S., Ellul B., Mayrhofer M. T., Lavitrano M., Caboux E., and Kozlakidis Z.
- Abstract
Biobanks play a central role in pediatric translational research, which deals primarily with genetic data from sample-based research. However, participation of children in biobanking has received only limited attention in the literature, even though research in general and in clinical trials in particular have a long history in involving minors. So, we resolved to explore specific challenging ethical, legal, and societal issues (ELSI) in the current pediatric biobanking landscape to propose a way forward for biobanking with children as partners in research. Methodologically, we first established the accessibility and utilization of pediatric biobanks, mainly in Europe. This was supported by a literature review related to children's participation, taking into account not only academic papers but also relevant guidelines and best-practices. Our findings are discussed under five themes: general vulnerability; ethical issues-balancing risks and benefits, right to an open future, return of results including secondary findings; legal issues-capacity and legal majority; societal issues-public awareness and empowerment; and responsible research with children. Ultimately, we observed an on-going shift from the parents'/guardians' consent being a sine-qua-non condition to the positive minor's agreement: confirming that the minor is the participant, not the parent(s)/guardian(s). This ethical rethinking is paving the way toward age-appropriate, dynamic and participatory models of involving minors in decision-making. However, we identified a requirement for dynamic tools to assess maturity, a lack of co-produced engagement tools and paucity of shared best practices. We highlight the need to provide empowerment and capability settings to support researchers and biobankers, and back this with practical examples. In conclusion, equipping children and adults with appropriate tools, and ensuring children's participation is at the forefront of responsible pediatric biobanking, is an
- Published
- 2022
12. Co-targeting triple-negative breast cancer cells and endothelial cells by metronomic chemotherapy inhibits cell regrowth and migration via downregulation of the FAK/VEGFR2/VEGF axis and autophagy/apoptosis activation
- Author
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Scagliotti, A, Capizzi, L, Cazzaniga, M, Ilari, A, De Giorgi, M, Cordani, N, Gallazzi, M, Bruno, A, Pelosi, G, Albini, A, Lavitrano, M, Grassilli, E, Cerrito, M, Scagliotti A., Capizzi L., Cazzaniga M. E., Ilari A., De Giorgi M., Cordani N., Gallazzi M., Bruno A., Pelosi G., Albini A., Lavitrano M., Grassilli E., Cerrito M. G., Scagliotti, A, Capizzi, L, Cazzaniga, M, Ilari, A, De Giorgi, M, Cordani, N, Gallazzi, M, Bruno, A, Pelosi, G, Albini, A, Lavitrano, M, Grassilli, E, Cerrito, M, Scagliotti A., Capizzi L., Cazzaniga M. E., Ilari A., De Giorgi M., Cordani N., Gallazzi M., Bruno A., Pelosi G., Albini A., Lavitrano M., Grassilli E., and Cerrito M. G.
- Abstract
High-dose standard-of-care chemotherapy is the only option for triple-negative breast cancer (TNBC) patients, which eventually die due to metastatic tumors. Recently, metronomic chemotherapy (mCHT) showed advantages in treating TNBCs leading us to investigate the anti-metastatic and anti-angiogenic potential of metronomic 5-Fluorouracil plus Vinorelbine (5-FU+VNR) on endothelial cells (ECs) and TNBCs in comparison to standard treatment (STD). We found that 10-fold lower doses of 5-FU+VNR given mCHT vs. STD inhibits cell proliferation and survival of ECs and TNBC cells. Both schedules strongly affect ECs migration and invasion, but in TNBC cells mCHT is significantly more effective than STD in impairing cell migration and invasion. The two treatments disrupt FAK/VEGFR/VEGF signaling in both ECs and TNBC cells. mCHT, and to a much lesser extent STD treatment, induces apoptosis in ECs, whereas it switches the route of cell death from apoptosis (as induced by STD) to autophagy in TNBC cells. mCHT-treated TNBCs-derived conditioned medium also strongly affects ECs’ migration, modulates different angiogenesis-associated proteins, and hampers angiogenesis in matrix sponge in vivo. In conclusion, mCHT administration of 5-FU+VNR is more effective than STD schedule in controlling cell proliferation/survival and migration/invasion of both ECs and TNBC cells and has a strong anti-angiogenic effect. Our data suggest that the stabilization of tumor growth observed in TNBC patients treated with mCHT therapy schedule is likely due not only to direct cytotoxic effects but also to anti-metastatic and anti-angiogenic effects.
- Published
- 2022
13. Matrix metalloproteinases, purinergic signaling, and epigenetics: hubs in the spinal neuroglial network following peripheral nerve injury
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De Luca, C, Virtuoso, A, Cerasuolo, M, Gargano, F, Colangelo, A, Lavitrano, M, Cirillo, G, Papa, M, De Luca C., Virtuoso A., Cerasuolo M., Gargano F., Colangelo A. M., Lavitrano M., Cirillo G., Papa M., De Luca, C, Virtuoso, A, Cerasuolo, M, Gargano, F, Colangelo, A, Lavitrano, M, Cirillo, G, Papa, M, De Luca C., Virtuoso A., Cerasuolo M., Gargano F., Colangelo A. M., Lavitrano M., Cirillo G., and Papa M.
- Abstract
Activation of glial cells (reactive gliosis) and the purinergic pathway, together with metalloproteinase (MMP)-induced remodeling of the neural extracellular matrix (nECM), drive maladaptive changes in the spinal cord following peripheral nerve injury (PNI). We evaluated the effects on spinal maladaptive plasticity through administration of oxidized ATP (oxATP), an antagonist of P2X receptors (P2XR), and/or GM6001, an inhibitor of MMPs, in rats following spared nerve injury (SNI) of the sciatic nerve. With morpho-molecular techniques, we demonstrated a reduction in spinal reactive gliosis and changes in the neuro-glial-nECM crosstalk via expression remodeling of P2XR, nerve growth factor (NGF) receptors (TrkA and p75), and histone deacetylase 2 (HDAC2) after treatments with oxATP/GM6001. Altogether, our data suggest that MMPs and purinergic inhibition have a modulatory impact on key proteins in the neuro-glial-nECM network, acting at different levels from intracellular signaling to epigenetic modifications.
- Published
- 2022
14. Can SARS-CoV-2 Infection Exacerbate Alzheimer’s Disease? An Overview of Shared Risk Factors and Pathogenetic Mechanisms
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Villa, C, Rivellini, E, Lavitrano, M, Combi, R, Villa C., Rivellini E., Lavitrano M., Combi R., Villa, C, Rivellini, E, Lavitrano, M, Combi, R, Villa C., Rivellini E., Lavitrano M., and Combi R.
- Abstract
The current coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, is affecting every aspect of global society, including public healthcare systems, medical care access, and the economy. Although the respiratory tract is primarily affected by SARS-CoV-2, emerging evidence suggests that the virus may also reach the central nervous system (CNS), leading to several neurological issues. In particular, people with a diagnosis of Alzheimer’s disease (AD) are a vulnerable group at high risk of contracting COVID-19, and develop more severe forms and worse outcomes, including death. Therefore, understanding shared links between COVID-19 and AD could aid the development of therapeutic strategies against both. Herein, we reviewed common risk factors and potential pathogenetic mechanisms that might contribute to the acceleration of neurodegenerative processes in AD patients infected by SARS-CoV-2.
- Published
- 2022
15. 19q12q13.2 duplication syndrome: neuropsychiatric long-term follow-up of a new case and literature update
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Nacinovich R, Villa N, Broggi F, Tavaniello C, Bomba M, Conconi D, Redaelli S, Sala E, Lavitrano M, and Neri F
- Subjects
19q duplication ,neuropsychiatric follow-up ,array-CGH ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Renata Nacinovich,1,2 Nicoletta Villa,3 Fiorenza Broggi,1,2 Cristina Tavaniello,1 Monica Bomba,1 Donatella Conconi,2 Serena Redaelli,2 Elena Sala,3 Marialuisa Lavitrano,2 Francesca Neri1,2 1Childhood and Adolescence Neuropsychiatric Unit, San Gerardo Hospital, 2School of Medicine and Surgery, University of Milano Bicocca, 3Medical Genetics Laboratory, Clinical Pathology Department, San Gerardo Hospital, Monza, Italy Abstract: Genetic syndromes are well characterized by the phenotypic point of view, but little is known about their progression and patients’ quality of life. We report a 10-year neuropsychiatric follow-up of a boy with duplication of chromosome 19. Cytogenetic investigation was requested at the age of 5 years for psychomotor and speech delay. The genomic study identified an 8.17 Mb duplication on chromosome 19q12q13.2. We propose that the long-term follow-up of our patient would help to delineate the neuropsychiatric phenotype associated with 19q duplication. This study could be a model for further long-term research in the neuropsychiatric follow-up of patients with 19q duplication syndrome. Keywords: 19q duplication, neuropsychiatric follow-up, array-CGH
- Published
- 2017
16. Pathologist Validation of a Machine Learning-Derived Feature for Colon Cancer Risk Stratification
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L'Imperio, V, Wulczyn, E, Plass, M, Müller, H, Tamini, N, Gianotti, L, Zucchini, N, Reihs, R, Corrado, G, Webster, D, Peng, L, Chen, P, Lavitrano, M, Liu, Y, Steiner, D, Zatloukal, K, Pagni, F, L'Imperio, Vincenzo, Wulczyn, Ellery, Plass, Markus, Müller, Heimo, Tamini, Nicolò, Gianotti, Luca, Zucchini, Nicola, Reihs, Robert, Corrado, Greg S, Webster, Dale R, Peng, Lily H, Chen, Po-Hsuan Cameron, Lavitrano, Marialuisa, Liu, Yun, Steiner, David F, Zatloukal, Kurt, Pagni, Fabio, L'Imperio, V, Wulczyn, E, Plass, M, Müller, H, Tamini, N, Gianotti, L, Zucchini, N, Reihs, R, Corrado, G, Webster, D, Peng, L, Chen, P, Lavitrano, M, Liu, Y, Steiner, D, Zatloukal, K, Pagni, F, L'Imperio, Vincenzo, Wulczyn, Ellery, Plass, Markus, Müller, Heimo, Tamini, Nicolò, Gianotti, Luca, Zucchini, Nicola, Reihs, Robert, Corrado, Greg S, Webster, Dale R, Peng, Lily H, Chen, Po-Hsuan Cameron, Lavitrano, Marialuisa, Liu, Yun, Steiner, David F, Zatloukal, Kurt, and Pagni, Fabio
- Abstract
Importance: Identifying new prognostic features in colon cancer has the potential to refine histopathologic review and inform patient care. Although prognostic artificial intelligence systems have recently demonstrated significant risk stratification for several cancer types, studies have not yet shown that the machine learning-derived features associated with these prognostic artificial intelligence systems are both interpretable and usable by pathologists. Objective: To evaluate whether pathologist scoring of a histopathologic feature previously identified by machine learning is associated with survival among patients with colon cancer. Design, Setting, and Participants: This prognostic study used deidentified, archived colorectal cancer cases from January 2013 to December 2015 from the University of Milano-Bicocca. All available histologic slides from 258 consecutive colon adenocarcinoma cases were reviewed from December 2021 to February 2022 by 2 pathologists, who conducted semiquantitative scoring for tumor adipose feature (TAF), which was previously identified via a prognostic deep learning model developed with an independent colorectal cancer cohort. Main Outcomes and Measures: Prognostic value of TAF for overall survival and disease-specific survival as measured by univariable and multivariable regression analyses. Interpathologist agreement in TAF scoring was also evaluated. Results: A total of 258 colon adenocarcinoma histopathologic cases from 258 patients (138 men [53%]; median age, 67 years [IQR, 65-81 years]) with stage II (n = 119) or stage III (n = 139) cancer were included. Tumor adipose feature was identified in 120 cases (widespread in 63 cases, multifocal in 31, and unifocal in 26). For overall survival analysis after adjustment for tumor stage, TAF was independently prognostic in 2 ways: TAF as a binary feature (presence vs absence: hazard ratio [HR] for presence of TAF, 1.55 [95% CI, 1.07-2.25]; P = .02) and TAF as a semiquantitative categorica
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- 2023
17. Loss of CDKN2B expression as a potential marker of resistance to CDK4/6 inhibitor in Luminal Breast Cancer cells
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Cordani, N, Mologni, L, Piazza, R, Cogliati, V, Pepe, F, Capici, S, DI BELLA, C, Jaconi, M, Cerrito, M, Villa, M, Tettamanti, P, Cavaletti, G, Lavitrano, M, Cazzaniga, M, Nicoletta Cordani, Luca Mologni, Rocco Piazza, Viola Cogliati, Francesca Pepe, Serena Capici, Camillo Di Bella, Marta Jaconi, Maria Grazia Cerrito, Matteo Villa, Pietro Tettamanti, Guido Cavaletti, Marialuisa Lavitrano, Marina Elena Cazzaniga, Cordani, N, Mologni, L, Piazza, R, Cogliati, V, Pepe, F, Capici, S, DI BELLA, C, Jaconi, M, Cerrito, M, Villa, M, Tettamanti, P, Cavaletti, G, Lavitrano, M, Cazzaniga, M, Nicoletta Cordani, Luca Mologni, Rocco Piazza, Viola Cogliati, Francesca Pepe, Serena Capici, Camillo Di Bella, Marta Jaconi, Maria Grazia Cerrito, Matteo Villa, Pietro Tettamanti, Guido Cavaletti, Marialuisa Lavitrano, and Marina Elena Cazzaniga
- Abstract
Background Cyclin-Dependent Kinase (CDK) 4/6 inhibitors have significantly improved progression-free survival of Hormone Receptor positive (HR+), Human Epidermal Growth Factor Receptor type 2 negative (HER2-) luminal breast cancers (LBC). Several studies demonstrated that the addition of CDK4/6 inhibitors to endocrine therapy results in a significant prolongation of progression-free survival in patients with endocrine-sensitive or endocrine-resistant LBCs. However, the percentage of patients unresponsive or refractory to these therapies is as high as 40%, and no reliable and reproducible biomarkers able to select a priori responder or resistant patients have been validated till now. The main cause of resistance is the selection of mutant clones in the target oncoprotein. Other mechanisms, like oncogene amplification/overexpression or mutations in other pathways, have been described in several models. Here, we focused on palbociclib, a selective inhibitor of CDK4/6. Methods: We generated and characterized human luminal breast cancer MCF-7 and T47D derived cell lines, able to survive and proliferate at different palbociclib concentrations, which also shows cross-resistance to abemaciclib. The resistant MCF7 cell line was characterized by RNA sequencing. Results: To confirm resistance, we performed cell viability assays in MCF-7 and T47D palbociclib sensitive cells (MCF-7pS and T47pS) versus MCF-7 and T47D palbociclib resistant cells (MCF-7pR5), showing a 10-fold increase of IC50 in MCF-7pR5 compared to parental MCF-7pS cells (16.7 vs 1.8 µM) and a 3-fold increase of IC50 in T47DpR5 vs parental T47DpS. We also confirmed a significant cross resistance using abemaciclib in MCF-7pR5 with an IC50 equal to 6.8 vs 0.35 µM and in T47DpR with an IC50 of 10.72 vs 0.5 µM. RNA sequencing, qRT-qPCR and Western blot results demonstrated a dramatic downregulation of the CDK4 inhibitor CDKN2B in both cell lines and we found upregulation of an miR-31, a putative regulator of CDKN2B. T
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- 2023
18. TWIST1 Upregulation Is a Potential Target for Reversing Resistance to the CDK4/6 Inhibitor in Metastatic Luminal Breast Cancer Cells
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Cordani, N, Mologni, L, Piazza, R, Tettamanti, P, Cogliati, V, Mauri, M, Villa, M, Malighetti, F, DI BELLA, C, Jaconi, M, Cerrito, M, Cavaletti, G, Lavitrano, M, Cazzaniga, M, Nicoletta Cordani, Luca Mologni, Rocco Piazza, Pietro Tettamanti, Viola Cogliati, Mario Mauri, Matteo Villa, Federica Malighetti, Camillo Di Bella, Marta Jaconi, Maria Grazia Cerrito, Guido Cavaletti, Marialuisa Lavitrano, Marina Elena Cazzaniga, Cordani, N, Mologni, L, Piazza, R, Tettamanti, P, Cogliati, V, Mauri, M, Villa, M, Malighetti, F, DI BELLA, C, Jaconi, M, Cerrito, M, Cavaletti, G, Lavitrano, M, Cazzaniga, M, Nicoletta Cordani, Luca Mologni, Rocco Piazza, Pietro Tettamanti, Viola Cogliati, Mario Mauri, Matteo Villa, Federica Malighetti, Camillo Di Bella, Marta Jaconi, Maria Grazia Cerrito, Guido Cavaletti, Marialuisa Lavitrano, and Marina Elena Cazzaniga
- Abstract
Cyclin-dependent kinase (CDK) 4/6 inhibitors have significantly improved progression-free survival in hormone-receptor-positive (HR+), human-epidermal-growth-factor-receptor-type-2-negative (HER2−) metastatic luminal breast cancer (mLBC). Several studies have shown that in patients with endocrine-sensitive or endocrine-resistant LBC, the addition of CDK4/6 inhibitors to endocrine therapy significantly prolongs progression-free survival. However, the percentage of patients who are unresponsive or refractory to these therapies is as high as 40%, and no reliable and reproducible biomarkers have been validated to select a priori responders or refractory patients. The selection of mutant clones in the target oncoprotein is the main cause of resistance. Other mechanisms such as oncogene amplification/overexpression or mutations in other pathways have been described in several models. In this study, we focused on palbociclib, a selective CDK4/6 inhibitor. We generated a human MCF-7 luminal breast cancer cell line that was able to survive and proliferate at different concentrations of palbociclib and also showed cross-resistance to abemaciclib. The resistant cell line was characterized via RNA sequencing and was found to strongly activate the epithelial-to-mesenchymal transition. Among the top deregulated genes, we found a dramatic downregulation of the CDK4 inhibitor CDKN2B and an upregulation of the TWIST1 transcription factor. TWIST1 was further validated as a target for the reversal of palbociclib resistance. This study provides new relevant information about the mechanisms of resistance to CDK4/6 inhibitors and suggests potential new markers for patients’ follow-up care during treatment.
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- 2023
19. AhRR and PPP1R3C: Potential Prognostic Biomarkers for Serous Ovarian Cancer
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Ardizzoia, A, Jemma, A, Redaelli, S, Silva, M, Bentivegna, A, Lavitrano, M, Conconi, D, Ardizzoia, Alessandra, Jemma, Andrea, Redaelli, Serena, Silva, Marco, Bentivegna, Angela, Lavitrano, Marialuisa, Conconi, Donatella, Ardizzoia, A, Jemma, A, Redaelli, S, Silva, M, Bentivegna, A, Lavitrano, M, Conconi, D, Ardizzoia, Alessandra, Jemma, Andrea, Redaelli, Serena, Silva, Marco, Bentivegna, Angela, Lavitrano, Marialuisa, and Conconi, Donatella
- Abstract
The lack of effective screening and successful treatment contributes to high ovarian cancer mortality, making it the second most common cause of gynecologic cancer death. Development of chemoresistance in up to 75% of patients is the cause of a poor treatment response and reduced survival. Therefore, identifying potential and effective biomarkers for its diagnosis and prognosis is a strong critical need. Copy number alterations are frequent in cancer, and relevant for molecular tumor stratification and patients’ prognoses. In this study, array-CGH analysis was performed in three cell lines and derived cancer stem cells (CSCs) to identify genes potentially predictive for ovarian cancer patients’ prognoses. Bioinformatic analyses of genes involved in copy number gains revealed that AhRR and PPP1R3C expression negatively correlated with ovarian cancer patients’ overall and progression-free survival. These results, together with a significant association between AhRR and PPP1R3C expression and ovarian cancer stemness markers, suggested their potential role in CSCs. Furthermore, AhRR and PPP1R3C’s increased expression was maintained in some CSC subpopulations, reinforcing their potential role in ovarian cancer. In conclusion, we reported for the first time, to the best of our knowledge, a prognostic role of AhRR and PPP1R3C expression in serous ovarian cancer.
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- 2023
20. BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression
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Betzler, A, Strobel, H, Abou Kors, T, Ezić, J, Lesakova, K, Pscheid, R, Azoitei, N, Sporleder, J, Staufenberg, A, Drees, R, Weissinger, S, Greve, J, Doescher, J, Theodoraki, M, Schuler, P, Laban, S, Kibe, T, Kishida, M, Kishida, S, Idel, C, Hoffmann, T, Lavitrano, M, Grassilli, E, Brunner, C, Betzler, Annika C, Strobel, Hannah, Abou Kors, Tsima, Ezić, Jasmin, Lesakova, Kristina, Pscheid, Ronja, Azoitei, Ninel, Sporleder, Johanna, Staufenberg, Anna-Rebekka, Drees, Robert, Weissinger, Stephanie E, Greve, Jens, Doescher, Johannes, Theodoraki, Marie-Nicole, Schuler, Patrick J, Laban, Simon, Kibe, Toshiro, Kishida, Michiko, Kishida, Shosei, Idel, Christian, Hoffmann, Thomas K, Lavitrano, Marialuisa, Grassilli, Emanuela, Brunner, Cornelia, Betzler, A, Strobel, H, Abou Kors, T, Ezić, J, Lesakova, K, Pscheid, R, Azoitei, N, Sporleder, J, Staufenberg, A, Drees, R, Weissinger, S, Greve, J, Doescher, J, Theodoraki, M, Schuler, P, Laban, S, Kibe, T, Kishida, M, Kishida, S, Idel, C, Hoffmann, T, Lavitrano, M, Grassilli, E, Brunner, C, Betzler, Annika C, Strobel, Hannah, Abou Kors, Tsima, Ezić, Jasmin, Lesakova, Kristina, Pscheid, Ronja, Azoitei, Ninel, Sporleder, Johanna, Staufenberg, Anna-Rebekka, Drees, Robert, Weissinger, Stephanie E, Greve, Jens, Doescher, Johannes, Theodoraki, Marie-Nicole, Schuler, Patrick J, Laban, Simon, Kibe, Toshiro, Kishida, Michiko, Kishida, Shosei, Idel, Christian, Hoffmann, Thomas K, Lavitrano, Marialuisa, Grassilli, Emanuela, and Brunner, Cornelia
- Abstract
Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients.
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- 2023
21. Carotid Plaque Echolucency Measured by Grayscale Median Identifies Patients at Increased Risk of Stroke during Carotid Stenting. The Imaging in Carotid Angioplasty and Risk of Stroke Study
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Froio, A., Deleo, G., Piazzoni, C., Camesasca, V., Liloia, A., Lavitrano, M., Biasi, G. M., AbuRahma, Ali F., editor, and Bergan, John J., editor
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- 2010
- Full Text
- View/download PDF
22. p65BTK Is a Novel Biomarker and Therapeutic Target in Solid Tumors
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Grassilli, E, Cerrito, M, Bonomo, S, Giovannoni, R, Conconi, D, Lavitrano, M, Grassilli E., Cerrito M. G., Bonomo S., Giovannoni R., Conconi D., Lavitrano M., Grassilli, E, Cerrito, M, Bonomo, S, Giovannoni, R, Conconi, D, Lavitrano, M, Grassilli E., Cerrito M. G., Bonomo S., Giovannoni R., Conconi D., and Lavitrano M.
- Abstract
Bruton’s tyrosine kinase (BTK) is a non-receptor intracellular kinase playing a key role in the proliferation and survival of normal and malignant B-lymphocytes. Its targeting by Ibrutinib, the first specific inhibitor, represented a turning point for the therapy of certain types of B-cell leukemias/lymphomas and several more BTK inhibitors are today in the clinic or advanced clinical trials. BTK expression was successively found to occur also outside of the hematopoietic compartment. In fact, we identified p65BTK, a novel 65 kDa isoform lacking an N-term stretch of 86 amino acids (compared to the 77 kDa protein expressed in B cells) as highly expressed in colon cancer patients. We demonstrated that p65BTK is a powerful oncogene acting downstream of the RAS/MAPK pathway and necessary for RAS-mediated transformation. Notably, the kinase domain is conserved and therefore inhibited by the available BTK-targeting drugs (Ibrutinib, Spebrutinib, etc.) which we used to demonstrate that p65BTK is an actionable target in drug-resistant colorectal carcinomas. We found p65BTK expressed also in >50% non-small cell lung cancers (NSCLC) and demonstrated that it is an actionable target in KRAS-mutated/EGFR-wild type drug-resistant NSCLC models (for which no targeted therapy is available). We also reported a significant correlation between p65BTK expression and low-grade tumors and overall survival of patients with grade III gliomas and showed that its targeting induced a significant decrease in the viability of in glioma stem cells. Finally, in ovarian cancer patients, p65BTK expression levels correlate with early relapse and shorter progression-free survival, both indicators of resistance to therapy. Remarkably, Ibrutinib is more effective than standard of care (SOC) therapeutics in in vitro and ex vivo settings. On the whole, our preclinical data indicate that, depending on the tumor type, BTK inhibitors used alone can induce cytotoxicity (gliomas), be more effective than SOC
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- 2021
23. Novel cytotoxic chemotherapies in small cell lung carcinoma
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Cortinovis, D, Bidoli, P, Canova, S, Colonese, F, Gemelli, M, Lavitrano, M, Banna, G, Liu, S, Morabito, A, Cortinovis D., Bidoli P., Canova S., Colonese F., Gemelli M., Lavitrano M. L., Banna G. L., Liu S. V., Morabito A., Cortinovis, D, Bidoli, P, Canova, S, Colonese, F, Gemelli, M, Lavitrano, M, Banna, G, Liu, S, Morabito, A, Cortinovis D., Bidoli P., Canova S., Colonese F., Gemelli M., Lavitrano M. L., Banna G. L., Liu S. V., and Morabito A.
- Abstract
Small cell lung cancer (SCLC) is one of the deadliest thoracic neoplasms, in part due to its fast doubling time and early metastatic spread. Historically, cytotoxic chemotherapy consisting of platinum–etoposide or anthracycline-based regimens has demonstrated a high response rate, but early chemoresistance leads to a poor prognosis in advanced SCLC. Only a fraction of patients with limited-disease can be cured by chemo-radiotherapy. Given the disappointing survival rates in advanced SCLC, new cytotoxic agents are eagerly awaited. Unfortunately, few novel chemotherapy drugs have been developed in the latest decades. This review describes the results and potential application in the clinical practice of novel chemotherapy agents for SCLC.
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- 2021
24. The glioblastoma microenvironment: Morphology, metabolism, and molecular signature of glial dynamics to discover metabolic rewiring sequence
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Virtuoso, A, Giovannoni, R, De Luca, C, Gargano, F, Cerasuolo, M, Maggio, N, Lavitrano, M, Papa, M, Virtuoso A., Giovannoni R., De Luca C., Gargano F., Cerasuolo M., Maggio N., Lavitrano M., Papa M., Virtuoso, A, Giovannoni, R, De Luca, C, Gargano, F, Cerasuolo, M, Maggio, N, Lavitrano, M, Papa, M, Virtuoso A., Giovannoni R., De Luca C., Gargano F., Cerasuolo M., Maggio N., Lavitrano M., and Papa M.
- Abstract
Different functional states determine glioblastoma (GBM) heterogeneity. Brain cancer cells coexist with the glial cells in a functional syncytium based on a continuous metabolic rewiring. However, standard glioma therapies do not account for the effects of the glial cells within the tumor microenvironment. This may be a possible reason for the lack of improvements in patients with high-grade gliomas therapies. Cell metabolism and bioenergetic fitness depend on the availability of nutrients and interactions in the microenvironment. It is strictly related to the cell location in the tumor mass, proximity to blood vessels, biochemical gradients, and tumor evolution, underlying the influence of the context and the timeline in anti-tumor therapeutic approaches. Besides the cancer metabolic strategies, here we review the modifications found in the GBM-associated glia, focusing on morphological, molecular, and metabolic features. We propose to analyze the GBM metabolic rewiring processes from a systems biology perspective. We aim at defining the crosstalk between GBM and the glial cells as modules. The complex networking may be expressed by metabolic modules corresponding to the GBM growth and spreading phases. Variation in the oxidative phosphorylation (OXPHOS) rate and regulation appears to be the most important part of the metabolic and functional heterogeneity, correlating with glycolysis and response to hypoxia. Integrated metabolic modules along with molecular and morphological features could allow the identification of key factors for controlling the GBM-stroma metabolism in multi-targeted, time-dependent therapies.
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- 2021
25. Human chromosome 18 and acrocentrics: A dangerous liaison
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Villa, N, Redaelli, S, Sala, E, Conconi, D, Romitti, L, Manfredini, E, Crosti, F, Roversi, G, Lavitrano, M, Rodeschini, O, Recalcati, M, Piazza, R, Dalpra, L, Riva, P, Bentivegna, A, Villa N., Redaelli S., Sala E., Conconi D., Romitti L., Manfredini E., Crosti F., Roversi G., Lavitrano M., Rodeschini O., Recalcati M. P., Piazza R., Dalpra L., Riva P., Bentivegna A., Villa, N, Redaelli, S, Sala, E, Conconi, D, Romitti, L, Manfredini, E, Crosti, F, Roversi, G, Lavitrano, M, Rodeschini, O, Recalcati, M, Piazza, R, Dalpra, L, Riva, P, Bentivegna, A, Villa N., Redaelli S., Sala E., Conconi D., Romitti L., Manfredini E., Crosti F., Roversi G., Lavitrano M., Rodeschini O., Recalcati M. P., Piazza R., Dalpra L., Riva P., and Bentivegna A.
- Abstract
The presence of thousands of repetitive sequences makes the centromere a fragile region subject to breakage. In this study we collected 31 cases of rearrangements of chromosome 18, of which 16 involved an acrocentric chromosome, during genetic screening done in three centers. We noticed a significant enrichment of reciprocal translocations between the centromere of chromosome 18 and the centromeric or pericentromeric regions of the acrocentrics. We describe five cases with translocation between chromosome 18 and an acrocentric chromosome, and one case involving the common telomere regions of chromosomes 18p and 22p. In addition, we bring evidence to support the hypothesis that chromosome 18 preferentially recombines with acrocentrics: (i) the presence on 18p11.21 of segmental duplications highly homologous to acrocentrics, that can justify a NAHR mechanism; (ii) the observation by 2D-FISH of the behavior of the centromeric regions of 18 respect to the centromeric regions of acrocentrics in the nuclei of normal subjects; (iii) the contact analysis among these regions on published Hi-C data from the human lymphoblastoid cell line (GM12878).
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- 2021
26. BCU Imaging Biobank, an Innovative Digital Resource for Biomedical Research Collecting Imaging and Clinical Data from Human Healthy and Pathological Subjects
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Esposito, G, Pagliari, G, Randon, M, Mirabelli, P, Lavitrano, M, Aiello, M, Salvatore, M, Esposito G., Pagliari G., Randon M., Mirabelli P., Lavitrano M., Aiello M., Salvatore M., Esposito, G, Pagliari, G, Randon, M, Mirabelli, P, Lavitrano, M, Aiello, M, Salvatore, M, Esposito G., Pagliari G., Randon M., Mirabelli P., Lavitrano M., Aiello M., and Salvatore M.
- Abstract
BCU Imaging Biobank (BCU-IB) is a non-profit biorepository aimed at the collection, storage and retrieval of diagnostic images, derived descriptors and clinical data. The main scope of BCU-IB is to foster scientific advances in imaging and analysis, opening up new ways for biomedical research to diagnose, treat and potentially prevent diseases. BCU-IB collects a vast amount of images of the human body, including healthy and pathological subjects. Diagnostic images, clinical, anamnestic and demographic data are made available to study the associations between imaging phenotypes, diagnostic and prognostic factors. Curated datasets are stored and organized in a secure and reliable dedicated information systems based on the Extensible Neuroimaging Archive Toolkit (XNAT), hosted by Bio Check Up Srl.
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- 2021
27. The CORBEL matrix on informed consent in clinical studies: a multidisciplinary approach of Research Infrastructures Building Enduring Life-science Services
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Colombo, C, Mayrhofer, M, Kubiak, C, Battaglia, S, Matei, M, Lavitrano, M, Casati, S, Chico, V, Schluender, I, Carapina, T, Mosconi, P, Colombo C., Mayrhofer M. T., Kubiak C., Battaglia S., Matei M., Lavitrano M., Casati S., Chico V., Schluender I., Carapina T., Mosconi P., Colombo, C, Mayrhofer, M, Kubiak, C, Battaglia, S, Matei, M, Lavitrano, M, Casati, S, Chico, V, Schluender, I, Carapina, T, Mosconi, P, Colombo C., Mayrhofer M. T., Kubiak C., Battaglia S., Matei M., Lavitrano M., Casati S., Chico V., Schluender I., Carapina T., and Mosconi P.
- Abstract
Background: Informed consent forms for clinical research are several and variable at international, national and local levels. According to the literature, they are often unclear and poorly understood by participants. Within the H2020 project CORBEL—Coordinated Research Infrastructures Building Enduring Life-science Services—clinical researchers, researchers in ethical, social, and legal issues, experts in planning and management of clinical studies, clinicians, researchers in citizen involvement and public engagement worked together to provide a minimum set of requirements for informed consent in clinical studies. Methods: The template was based on a literature review including systematic reviews and guidelines searched on PubMed, Embase, Cochrane Library, NICE, SIGN, GIN, and Clearinghouse databases, and on comparison of templates gathered through an extensive search on the websites of research institutes, national and international agencies, and international initiatives. We discussed the draft versions step-by-step and then we referred to it as the “matrix” to underline its modular character and indicate that it allows adaptation to the context in which it will be used. The matrix was revised by representatives of two international patient groups. Results: The matrix covers the process of ensuring that the appropriate information, context and setting are provided so that the participant can give truly informed consent. It addresses the key topics and proposes wording on how to clarify the meaning of placebo and of non-inferiority studies, the importance of individual participants’ data sharing, and the impossibility of knowing in advance how the data might be used in future studies. Finally, it presents general suggestions on wording, format, and length of the information sheet. Conclusions: The matrix underlines the importance of improving the process of communication, its proper conditions (space, time, setting), and addresses the participants’ lack of knowled
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- 2021
28. Genomic and epigenomic profile of uterine smooth muscle tumors of uncertain malignant potential (Stumps) revealed similarities and differences with leiomyomas and leiomyosarcomas
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Conconi, D, Redaelli, S, Lissoni, A, Cilibrasi, C, Perego, P, Gautiero, E, Sala, E, Paderno, M, Dalpra, L, Landoni, F, Lavitrano, M, Roversi, G, Bentivegna, A, Conconi D., Redaelli S., Lissoni A. A., Cilibrasi C., Perego P., Gautiero E., Sala E., Paderno M., Dalpra L., Landoni F., Lavitrano M., Roversi G., Bentivegna A., Conconi, D, Redaelli, S, Lissoni, A, Cilibrasi, C, Perego, P, Gautiero, E, Sala, E, Paderno, M, Dalpra, L, Landoni, F, Lavitrano, M, Roversi, G, Bentivegna, A, Conconi D., Redaelli S., Lissoni A. A., Cilibrasi C., Perego P., Gautiero E., Sala E., Paderno M., Dalpra L., Landoni F., Lavitrano M., Roversi G., and Bentivegna A.
- Abstract
Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) represent a heterogeneous group of tumors that cannot be histologically diagnosed as unequivocally benign or malignant. For this reason, many authors are working to obtain a better definition of diagnostic and prognostic criteria. In this work, we analyzed the genomic and epigenomic profile of uterine smooth muscle tumors (USMTs) in order to find similarities and differences between STUMPs, leiomyosarcomas (LMSs) and leiomyomas (LMs), and possibly identify prognostic factors in this group of tumors. Array-CGH data on 23 USMTs demonstrated the presence of a more similar genomic profile between STUMPs and LMSs. Some genes, such as PRKDC and PUM2, with a potential prognostic value, were never previously associated with STUMP. The methylation data appears to be very promising, especially with regards to the divergent profile found in the sample that relapsed, characterized by an overall CGI hypomethylation. Finally, the Gene Ontology analysis highlighted some cancer genes that could play a pivotal role in the unexpected aggressive behavior that can be found in some of these tumors. These genes could prove to be prognostic markers in the future.
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- 2021
29. Carotid Plaque Echolucency Measured by Grayscale Median Identifies Patients at Increased Risk of Stroke during Carotid Stenting. The Imaging in Carotid Angioplasty and Risk of Stroke Study
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Froio, A., Deleo, G., Piazzoni, C., Camesasca, V., Liloia, A., Lavitrano, M., Biasi, G. M., AbuRahma, Ali F., editor, and Bergan, John J., editor
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- 2007
- Full Text
- View/download PDF
30. A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation
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Grassilli, E, Pisano, F, Cialdella, A, Bonomo, S, Missaglia, C, Cerrito, M G, Masiero, L, Ianzano, L, Giordano, F, Cicirelli, V, Narloch, R, D’Amato, F, Noli, B, Ferri, G L, Leone, B E, Stanta, G, Bonin, S, Helin, K, Giovannoni, R, and Lavitrano, M
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- 2016
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31. Persistence of Anti-SARS-CoV-2 Antibodies in Non-Hospitalized COVID-19 Convalescent Health Care Workers
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Bruni, M, Cecatiello, V, Diaz-Basabe, A, Lattanzi, G, Mileti, E, Monzani, S, Pirovano, L, Rizzelli, F, Visintin, C, Bonizzi, G, Giani, M, Lavitrano, M, Faravelli, S, Forneris, F, Caprioli, F, Pelicci, P, Natoli, G, Pasqualato, S, Mapelli, M, Facciotti, F, Bruni M, Cecatiello V, Diaz-Basabe A, Lattanzi G, Mileti E, Monzani S, Pirovano L, Rizzelli F, Visintin C, Bonizzi G, Giani M, Lavitrano M, Faravelli S, Forneris F, Caprioli F, Pelicci PG, Natoli G, Pasqualato S, Mapelli M, Facciotti F, Bruni, M, Cecatiello, V, Diaz-Basabe, A, Lattanzi, G, Mileti, E, Monzani, S, Pirovano, L, Rizzelli, F, Visintin, C, Bonizzi, G, Giani, M, Lavitrano, M, Faravelli, S, Forneris, F, Caprioli, F, Pelicci, P, Natoli, G, Pasqualato, S, Mapelli, M, Facciotti, F, Bruni M, Cecatiello V, Diaz-Basabe A, Lattanzi G, Mileti E, Monzani S, Pirovano L, Rizzelli F, Visintin C, Bonizzi G, Giani M, Lavitrano M, Faravelli S, Forneris F, Caprioli F, Pelicci PG, Natoli G, Pasqualato S, Mapelli M, and Facciotti F
- Abstract
Although antibody response to SARS-CoV-2 can be detected early during the infection, several outstanding questions remain to be addressed regarding the magnitude and persistence of antibody titer against different viral proteins and their correlation with the strength of the immune response. An ELISA assay has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length Nucleocapsid protein (N). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies as well as soluble pro-inflammatory mediators in the sera. Non-hospitalized subjects showed lower antibody titers and blood pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested. Noteworthy, in non-severe COVID-19 infections, antibody titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Thus, rapid decline in antibody titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection, suggesting that antibody-mediated protection against re-infection with SARS-CoV-2 is of short duration. These results suggest caution in using serological testing to estimate the prevalence of SARS-CoV-2 infection in the general population.
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- 2020
32. The antiangiogenic effect of the metronomic combination of 5-Fluorouracil plus vinorelbine is mediated by FAK/AKT pathway downregulation and apoptosis activation
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Scagliotti, A, Grassilli, E, Cazzaniga, M, Capizzi, L, Lavitrano, M, Cerrito, M, Scagliotti A., Grassilli E., Cazzaniga M. E., Capizzi L., Lavitrano M., Cerrito M. G., Scagliotti, A, Grassilli, E, Cazzaniga, M, Capizzi, L, Lavitrano, M, Cerrito, M, Scagliotti A., Grassilli E., Cazzaniga M. E., Capizzi L., Lavitrano M., and Cerrito M. G.
- Published
- 2020
33. Instability of short arm of acrocentric chromosomes: Lesson from non-acrocentric satellited chromosomes. report of 24 unrelated cases
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Redaelli, S, Conconi, D, Villa, N, Sala, E, Crosti, F, Corti, C, Catusi, I, Garzo, M, Romitti, L, Martinoli, E, Patrizi, A, Malgara, R, Recalcati, M, Dalpra, L, Lavitrano, M, Riva, P, Roversi, G, Bentivegna, A, Redaelli S., Conconi D., Villa N., Sala E., Crosti F., Corti C., Catusi I., Garzo M., Romitti L., Martinoli E., Patrizi A., Malgara R., Recalcati M. P., Dalpra L., Lavitrano M., Riva P., Roversi G., Bentivegna A., Redaelli, S, Conconi, D, Villa, N, Sala, E, Crosti, F, Corti, C, Catusi, I, Garzo, M, Romitti, L, Martinoli, E, Patrizi, A, Malgara, R, Recalcati, M, Dalpra, L, Lavitrano, M, Riva, P, Roversi, G, Bentivegna, A, Redaelli S., Conconi D., Villa N., Sala E., Crosti F., Corti C., Catusi I., Garzo M., Romitti L., Martinoli E., Patrizi A., Malgara R., Recalcati M. P., Dalpra L., Lavitrano M., Riva P., Roversi G., and Bentivegna A.
- Abstract
Satellited non-acrocentric autosomal chromosomes (ps–qs-chromosomes) are the result of an interchange between sub-or telomeric regions of autosomes and the p arm of acrocentrics. The sequence homology at the rearrangement breakpoints appears to be, among others, the most frequent mechanism generating these variant chromosomes. The unbalanced carriers of this type of translocation may or may not display phenotypic abnormalities. With the aim to understand the causative mechanism, we revised all the ps–qs-chromosomes identified in five medical genetics laboratories, which used the same procedures for karyotype analysis, reporting 24 unrelated cases involving eight chromosomes. In conclusion, we observed three different scenarios: true translocation, benign variant and complex rearrangement. The detection of translocation partners is essential to evaluate possible euchromatic unbalances and to infer their effect on phenotype. Moreover, we emphasize the importance to perform both, molecular and conventional cytogenetics methods, to better understand the behavior of our genome.
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- 2020
34. Analysis of copy number alterations in bladder cancer stem cells revealed a prognostic role of LRP1B
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Conconi, D, Jemma, A, Giambra, M, Redaelli, S, Croci, G, Dalprà, L, Lavitrano, M, Bentivegna, A, Conconi, Donatella, Jemma, Andrea, Giambra, Martina, Redaelli, Serena, Croci, Giorgio Alberto, Dalprà, Leda, Lavitrano, Marialuisa, Bentivegna, Angela, Conconi, D, Jemma, A, Giambra, M, Redaelli, S, Croci, G, Dalprà, L, Lavitrano, M, Bentivegna, A, Conconi, Donatella, Jemma, Andrea, Giambra, Martina, Redaelli, Serena, Croci, Giorgio Alberto, Dalprà, Leda, Lavitrano, Marialuisa, and Bentivegna, Angela
- Abstract
Purpose: Bladder cancer is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. It represents a spectrum of diseases, from recurrent non-invasive tumors (NMIBCs) managed chronically, to muscle infiltrating and advanced-stage disease (MIBC) that requires multimodal and invasive treatment. Multiple studies have underlined the complexity of bladder tumors genome, highlighting many specific genetic lesions and genome-wide occurrences of copy-number alterations (CNAs). In this study, we analyzed CNAs of selected genes in our cohorts of cancer stem cells (CSCs) and in The Cancer Genome Atlas (TCGA-BLCA) cohort with the aim to correlate their frequency with patients’ prognosis. Methods: CNAs have been verified on our array-CGH data previously reported on 19 bladder cancer biopsies (10 NMIBCs and 9 MIBCs) and 16 matched isolated CSC cultures. In addition, CNAs data have been consulted on the TCGA database, to search correlations with patients’ follow-up. Finally, mRNA expression levels of LRP1B in TGCA cohort were obtained from The Human Protein Atlas. Results: We firstly identified CNAs differentially represented between TGCA data and CSCs derived from NMIBCs and MIBCs, and we correlated the presence of these CNAs with patients’ follow-up. LRP1B loss was significantly increased in CSCs and linked to short-term poor prognosis, both at genomic and transcriptomic level, confirming its pivotal role in bladder cancer tumorigenesis. Conclusion: Our study allowed us to identify potential "predictive" prognostic CNAs for bladder cancer, implementing knowledge for the ultimate goal of personalized medicine.
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- 2022
35. Exome Sequencing in an ADSHE Family: VUS Identification and Limits
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Villa, C, Arrigoni, F, Rivellini, E, Lavitrano, M, De Gioia, L, Ferini-Strambi, L, Combi, R, Villa, Chiara, Arrigoni, Federica, Rivellini, Eleonora, Lavitrano, Marialuisa, De Gioia, Luca, Ferini-Strambi, Luigi, Combi, Romina, Villa, C, Arrigoni, F, Rivellini, E, Lavitrano, M, De Gioia, L, Ferini-Strambi, L, Combi, R, Villa, Chiara, Arrigoni, Federica, Rivellini, Eleonora, Lavitrano, Marialuisa, De Gioia, Luca, Ferini-Strambi, Luigi, and Combi, Romina
- Abstract
Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is the familial form of a focal epilepsy characterized by hyperkinetic focal seizures, mainly arising during non-rapid eye movements (NREM) sleep. Mutations associated with ADSHE account for a small proportion of the genetically determined cases, suggesting the existence of other disease-causing genes. Here, we reported the results obtained by performing trio-based whole-exome sequencing (WES) in an Italian family showing ADSHE and investigated the structural impact of putative variants by in silico modeling analysis. We identified a p.(Trp276Gly) variant in MOXD1 gene encoding the monooxigenase DBH like 1 protein, cosegregating with the disease and annotated as VUS under the ACMG recommendations. Structural bioinformatic analysis predicted a high destabilizing effect of this variant, due to the loss of important hydrophilic bonds and an expansion of cavity volume in the protein hydrophobic core. Although our data support a functional effect of the p.(Trp276Gly) variant, we highlight the need to identify additional families carrying MOXD1 mutations or functional analyses in suitable models to clarify its role in ADSHE pathogenesis. Moreover, we discuss the importance of VUS reporting due to the low rate of pathogenic variant identification by NGS in epilepsy and for future reinterpretation studies.
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- 2022
36. BTK, the new kid on the (oncology) block?
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Grassilli, E, Cerrito, M, Lavitrano, M, Grassilli, Emanuela, Cerrito, Maria Grazia, Lavitrano, Marialuisa, Grassilli, E, Cerrito, M, Lavitrano, M, Grassilli, Emanuela, Cerrito, Maria Grazia, and Lavitrano, Marialuisa
- Abstract
In the last decade data piled up indicating that BTK – for twenty years considered as a “private matter” of bone marrow-derived cells – it is expressed and plays important and different roles also outside of the hematopoietic compartment and, most notably, in tumor cells. Initial evidence that BTK plays a critical role in B cell-derived malignancies prompted the chase for specific inhibitors, the forefather of which entered the clinic in a record time and paved the way for an ever increasing number of new molecules to be trialed. The growing interests in BTK also led to the discovery that, in solid tumors, two novel isoforms are mainly expressed and actionable liabilities for target therapy. Remarkably, the different isoforms appear to be involved in different signaling pathways which will have to be attentively specified in order to define the area of therapeutic intervention. In this perspective we briefly summarize the progress made in the last decade in studying BTK and its isoforms in cancer cells and define the open questions to be addressed in order to get the most benefits from its targeting for therapeutic purposes.
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- 2022
37. Referee report. For: Making European performance and impact assessment frameworks glocal [version 1; peer review: 1 approved, 1 approved with reservations]
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Enrico Guarini, Guarini, E, Lavitrano, M, Enrico Guarini, Marialuisa Lavitrano, Enrico Guarini, Guarini, E, Lavitrano, M, Enrico Guarini, and Marialuisa Lavitrano
- Published
- 2022
38. Data in question: A survey of European biobank professionals on ethical, legal and societal challenges of biobank research
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Goisauf, M, Martin, G, Bentzen, H, Budin-Ljosne, I, Ursin, L, Durnova, A, Leitsalu, L, Smith, K, Casati, S, Lavitrano, M, Mascalzoni, D, Boeckhout, M, Mayrhofer, M, Goisauf M., Martin G., Bentzen H. B., Budin-Ljosne I., Ursin L., Durnova A., Leitsalu L., Smith K., Casati S., Lavitrano M., Mascalzoni D., Boeckhout M., Mayrhofer M. Th., Goisauf, M, Martin, G, Bentzen, H, Budin-Ljosne, I, Ursin, L, Durnova, A, Leitsalu, L, Smith, K, Casati, S, Lavitrano, M, Mascalzoni, D, Boeckhout, M, Mayrhofer, M, Goisauf M., Martin G., Bentzen H. B., Budin-Ljosne I., Ursin L., Durnova A., Leitsalu L., Smith K., Casati S., Lavitrano M., Mascalzoni D., Boeckhout M., and Mayrhofer M. Th.
- Abstract
Biobanks have evolved, and their governance procedures have undergone important transformations. Our paper examines this issue by focusing on the perspective of the professionals working in management or scientific roles in research-based biobanks, who have an important impact on shaping these transformations. In particular, it highlights that recent advances in molecular medicine and genomic research have raised a range of ethical, legal and societal implications (ELSI) related to biobank-based research, impacting directly on regulations and local practices of informed consent (IC), private-public partnerships (PPPs), and engagement of participants. In our study, we investigate the ways that these concerns influence biobanking practices and assess the level of satisfaction of the cross-national biobanking research communities with the ELSI related procedures that are currently in place. We conducted an online survey among biobankers and researchers to investigate secondary use of data, informing and/or re-contacting participants, sharing of data with third parties from industry, participant engagement, and collaboration with industrial partners. Findings highlight the need for a more inclusive and transparent biobanking practice where biobanks are seen in a more active role in providing information and communicating with participants; the need to improve the current IC procedures and the role of biobanks in sharing of samples and data with industry partners and different countries, and the need for practical, tangible and hands-on ethical and legal guidance.
- Published
- 2019
39. Erratum: Correction: Data in question: A survey of European biobank professionals on ethical, legal and societal challenges of biobank research (PloS one (2019) 14 9 (e0221496))
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Goisauf M., Goisauf, M, Martin, G, Bentzen, H, Budin-Ljosne, I, Ursin, L, Durnova, A, Leitsalu, L, Smith, K, Casati, S, Lavitrano, M, Mascalzoni, D, Boeckhout, M, Mayrhofer, M, Goisauf M., Martin G., Bentzen H. B., Budin-Ljosne I., Ursin L., Durnova A., Leitsalu L., Smith K., Casati S., Lavitrano M., Mascalzoni D., Boeckhout M., Mayrhofer M. T., Goisauf M., Goisauf, M, Martin, G, Bentzen, H, Budin-Ljosne, I, Ursin, L, Durnova, A, Leitsalu, L, Smith, K, Casati, S, Lavitrano, M, Mascalzoni, D, Boeckhout, M, Mayrhofer, M, Goisauf M., Martin G., Bentzen H. B., Budin-Ljosne I., Ursin L., Durnova A., Leitsalu L., Smith K., Casati S., Lavitrano M., Mascalzoni D., Boeckhout M., and Mayrhofer M. T.
- Abstract
[This corrects the article DOI: 10.1371/journal.pone.0221496.].
- Published
- 2019
40. Carotid Artery Disease: Novel Pathophysiological Mechanisms Identified by Gene-expression Profiling of Peripheral Blood
- Author
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Rossi, L., Lapini, I., Magi, A., Pratesi, G., Lavitrano, M., Biasi, G.M., Pulli, R., Pratesi, C., Abbate, R., and Giusti, B.
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- 2010
- Full Text
- View/download PDF
41. Gene Expression Profiling of Peripheral Blood in Patients with Abdominal Aortic Aneurysm
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Giusti, B., Rossi, L., Lapini, I., Magi, A., Pratesi, G., Lavitrano, M., Biasi, G.M., Pulli, R., Pratesi, C., and Abbate, R.
- Published
- 2009
- Full Text
- View/download PDF
42. Sperm-mediated gene transfer–treated spermatozoa maintain good quality parameters and in vitro fertilization ability in swine
- Author
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Bacci, M.L., Zannoni, A., De Cecco, M., Fantinati, P., Bernardini, C., Galeati, G., Spinaci, M., R.Giovannoni, Lavitrano, M., Seren, E., and Forni, M.
- Published
- 2009
- Full Text
- View/download PDF
43. Inhibition of plasminogen/plasmin system retrieves endogenous nerve growth factor and adaptive spinal synaptic plasticity following peripheral nerve injury
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Virtuoso, A, Colangelo, A, Korai, S, Izzo, S, Todisco, A, Giovannoni, R, Lavitrano, M, Papa, M, Cirillo, G, Virtuoso, Assunta, Colangelo, Anna Maria, Korai, Sohaib Ali, Izzo, Sara, Todisco, Antonio, Giovannoni, Roberto, Lavitrano, Marialuisa, Papa, Michele, Cirillo, Giovanni, Virtuoso, A, Colangelo, A, Korai, S, Izzo, S, Todisco, A, Giovannoni, R, Lavitrano, M, Papa, M, Cirillo, G, Virtuoso, Assunta, Colangelo, Anna Maria, Korai, Sohaib Ali, Izzo, Sara, Todisco, Antonio, Giovannoni, Roberto, Lavitrano, Marialuisa, Papa, Michele, and Cirillo, Giovanni
- Abstract
Dysfunctions of the neuronal-glial crosstalk and/or impaired signaling of neurotrophic factors represent key features of the maladaptive changes in the central nervous system (CNS) in neuroinflammatory as neurodegenerative disorders. Tissue plasminogen activator (tPA)/plasminogen (PA)/plasmin system has been involved in either process of maturation and degradation of nerve growth factor (NGF), highlighting multiple potential targets for new therapeutic strategies. We here investigated the role of intrathecal (i.t.) delivery of neuroserpin (NS), an endogenous inhibitor of plasminogen activators, on neuropathic behavior and maladaptive synaptic plasticity in the rat spinal cord following spared nerve injury (SNI) of the sciatic nerve. We demonstrated that SNI reduced spinal NGF expression, induced spinal reactive gliosis, altering the expression of glial and neuronal glutamate and GABA transporters, reduced glutathione (GSH) levels and is associated to neuropathic behavior. Beside the increase of NGF expression, i.t. NS administration reduced reactive gliosis, restored synaptic homeostasis, GSH levels and reduced neuropathic behavior. Our results hereby highlight the essential role of tPA/PA system in the synaptic homeostasis and mechanisms of maladaptive plasticity, sustaining the beneficial effects of NGF-based approach in neurological disorders.
- Published
- 2021
44. Patient-Derived Induced Pluripotent Stem Cells (iPSCs) and Cerebral Organoids for Drug Screening and Development in Autism Spectrum Disorder: Opportunities and Challenges
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Villa, C, Combi, R, Conconi, D, Lavitrano, M, Villa, Chiara, Combi, Romina, Conconi, Donatella, Lavitrano, Marialuisa, Villa, C, Combi, R, Conconi, D, Lavitrano, M, Villa, Chiara, Combi, Romina, Conconi, Donatella, and Lavitrano, Marialuisa
- Abstract
Autism spectrum disorder (ASD) represents a group of neurodevelopmental diseases characterized by persistent deficits in social communication, interaction, and repetitive patterns of behaviors, interests, and activities. The etiopathogenesis is multifactorial with complex interactions between genetic and environmental factors. The clinical heterogeneity and complex etiology of this pediatric disorder have limited the development of pharmacological therapies. The major limit to ASD research remains a lack of relevant human disease models which can faithfully recapitulate key features of the human pathology and represent its genetic heterogeneity. Recent advances in induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of patients into all types of patient-specific neural cells, have provided a promising cellular tool for disease modeling and development of novel drug treatments. The iPSCs technology allowed not only a better investigation of the disease etiopathogenesis but also opened up the potential for personalized therapies and offered new opportunities for drug discovery, pharmacological screening, and toxicity assessment. Moreover, iPSCs can be differentiated and organized into three-dimensional (3D) organoids, providing a model which mimics the complexity of the brain's architecture and more accurately recapitulates tissue- and organ-level disease pathophysiology. The aims of this review were to describe the current state of the art of the use of human patient-derived iPSCs and brain organoids in modeling ASD and developing novel therapeutic strategies and to discuss the opportunities and major challenges in this rapidly moving field.
- Published
- 2021
45. Sperm-Mediated Genetic Modifications
- Author
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Larson, Melissa, Lavitrano, M, Farina, L, Cerrito, M, Giovannoni, R, Cerrito, MG, Larson, Melissa, Lavitrano, M, Farina, L, Cerrito, M, Giovannoni, R, and Cerrito, MG
- Abstract
The ability to introduce controlled modifications of the genome of animals represents an important tool for biomedical and veterinary research. Among transgenic techniques, we describe here the sperm-mediated gene transfer method that is based on the spontaneous ability of sperm cells to bind and internalize exogenous DNA and to carry it to the oocyte during fertilization, producing genetically modified animals.
- Published
- 2020
46. BTK inhibitors synergise with 5-FU to treat drug-resistant TP53-null colon cancers
- Author
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Lavitrano, M, Ianzano, L, Bonomo, S, Cialdella, A, Cerrito, M, Pisano, F, Missaglia, C, Giovannoni, R, Romano, G, Mclean, C, Voest, E, D'Amato, F, Noli, B, Ferri, G, Agostini, M, Pucciarelli, S, Helin, K, Leone, B, Canzonieri, V, Grassilli, E, Lavitrano, Marialuisa, Ianzano, Leonarda, Bonomo, Sara, Cialdella, Annamaria, Cerrito, Maria Grazia, Pisano, Fabio, Missaglia, Carola, Giovannoni, Roberto, Romano, Gabriele, McLean, Chelsea M, Voest, Emile E, D'Amato, Filomena, NOLI, BARBARA, Ferri, Gian Luca, Agostini, Marco, Pucciarelli, Salvatore, Helin, Kristian, Leone, Biagio Eugenio, Canzonieri, Vincenzo, Grassilli, Emanuela, Lavitrano, M, Ianzano, L, Bonomo, S, Cialdella, A, Cerrito, M, Pisano, F, Missaglia, C, Giovannoni, R, Romano, G, Mclean, C, Voest, E, D'Amato, F, Noli, B, Ferri, G, Agostini, M, Pucciarelli, S, Helin, K, Leone, B, Canzonieri, V, Grassilli, E, Lavitrano, Marialuisa, Ianzano, Leonarda, Bonomo, Sara, Cialdella, Annamaria, Cerrito, Maria Grazia, Pisano, Fabio, Missaglia, Carola, Giovannoni, Roberto, Romano, Gabriele, McLean, Chelsea M, Voest, Emile E, D'Amato, Filomena, NOLI, BARBARA, Ferri, Gian Luca, Agostini, Marco, Pucciarelli, Salvatore, Helin, Kristian, Leone, Biagio Eugenio, Canzonieri, Vincenzo, and Grassilli, Emanuela
- Abstract
Colorectal cancer (CRC) is the fourth cause of death from cancer worldwide mainly due to the high incidence of drug-resistance. During a screen for new actionable targets in drug-resistant tumours we recently identified p65BTK – a novel oncogenic isoform of Bruton's tyrosine kinase. Studying three different cohorts of patients here we show that p65BTK expression correlates with histotype and cancer progression. Using drug-resistant TP53-null colon cancer cells as a model we demonstrated that p65BTK silencing or chemical inhibition overcame the 5-fluorouracil resistance of CRC cell lines and patient-derived organoids and significantly reduced the growth of xenografted tumours. Mechanistically, we show that blocking p65BTK in drug-resistant cells abolished a 5-FU-elicited TGFB1 protective response and triggered E2F-dependent apoptosis. Taken together, our data demonstrated that targeting p65BTK restores the apoptotic response to chemotherapy of drug-resistant CRCs and gives a proof-of-concept for suggesting the use of BTK inhibitors in combination with 5-FU as a novel therapeutic approach in CRC patients. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Published
- 2020
47. Inhaled Carbon Monoxide (CO) Prevents Lung Oedema Induced by Endotoxic Shock
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Mazzola, S., Forni, M., Albertini, M., Bacci, M.L., Ciminaghi, B., Lavitrano, M., Seren, E., and Clement, M.G.
- Published
- 2004
- Full Text
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48. ‘Advanced’ generation lentiviruses as efficient vectors for cardiomyocyte gene transduction in vitro and in vivo
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Bonci, D, Cittadini, A, Latronico, M V G, Borello, U, Aycock, J K, Drusco, A, Innocenzi, A, Follenzi, A, Lavitrano, M, Monti, M G, Ross, Jr, J, Naldini, L, Peschle, C, Cossu, G, and Condorelli, G
- Published
- 2003
- Full Text
- View/download PDF
49. Transfected human dendritic cells to induce antitumor immunity
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Rughetti, A, Biffoni, M, Sabbatucci, M, Rahimi, H, Pellicciotta, I, Fattorossi, A, Pierelli, L, Scambia, G, Lavitrano, M, Frati, L, and Nuti, M
- Published
- 2000
- Full Text
- View/download PDF
50. AAV-mediated photoreceptor transduction of the pig cone-enriched retina
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Mussolino, C, della Corte, M, Rossi, S, Viola, F, Di Vicino, U, Marrocco, E, Neglia, S, Doria, M, Testa, F, Giovannoni, R, Crasta, M, Giunti, M, Villani, E, Lavitrano, M, Bacci, M L, Ratiglia, R, Simonelli, F, Auricchio, A, and Surace, E M
- Published
- 2011
- Full Text
- View/download PDF
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