119 results on '"Paduano, Francesco"'
Search Results
2. Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes.
- Author
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Paduano, Francesco, Fischetto, Rita, Moretti, Biagio, De Vito, Danila, and Tatullo, Marco
- Subjects
OSTEOGENESIS imperfecta ,POST-translational modification ,PATIENTS ,NUCLEOTIDE sequencing ,GENETIC counseling - Abstract
Introduction: Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder. The majority of affected cases are attributed to autosomal dominant pathogenic variants (PVs) found in the COL1A1 and COL1A2 genes, which encode type I collagen. However, PVs in other genes involved in collagen posttranslational modification, processing, crosslinking, osteoblast differentiation, and bone mineralization have also been associated with OI. Methods: In this study, we present the results of next-generation sequencing (NGS) analysis using a custom panel of 11 genes known to be associated with OI. This clinical study enrolled a total of 10 patients, comprising 7 male and 3 female patients from 7 families, all from the Puglia Region in South Italy, providing a detailed overview of their age, gender, family history, OI type, and non-skeletal features. Results: The genetic analysis revealed 5 PVs in the COL1A1 gene and 2 PVs in the COL1A2 gene. Importantly, three of these PVs have not been previously reported in the literature. These include two novel heterozygous frameshift PVs in COL1A1 (c.2890_2893del and c.3887del) and one novel heterozygous missense PV in COL1A2 (c.596G>T). Discussion: The identification of these previously unreported PVs expands the variant spectrum of the COL1A1 and COL1A2 genes and may have implications for accurate diagnosis, genetic counselling, and potential therapeutic interventions in affected individuals and their families. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. Human Periapical Cysts-Mesenchymal Stem Cells Cultured with Allogenic Human Serum are a “clinical-grade” construct alternative to bovine fetal serum and indicated in the regeneration of endo-periodontal tissues
- Author
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Tatullo, Marco, Marrelli, Massimo, Palmieri, Francesca, Rengo, Carlo, Paduano, Francesco, and Spagnuolo, Gianrico
- Published
- 2018
- Full Text
- View/download PDF
4. CD146 Expression Influences Periapical Cyst Mesenchymal Stem Cell Properties
- Author
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Paduano, Francesco, Marrelli, Massimo, Palmieri, Francesca, and Tatullo, Marco
- Published
- 2016
- Full Text
- View/download PDF
5. Heat shock protein 70 regulates Tcl1 expression in leukemia and lymphomas
- Author
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Gaudio, Eugenio, Paduano, Francesco, Ngankeu, Apollinaire, Lovat, Francesca, Fabbri, Muller, Sun, Hui-Lung, Gasparini, Pierluigi, Efanov, Alexey, Peng, Yong, Zanesi, Nicola, Shuaib, Mohammed A., Rassenti, Laura Z., Kipps, Thomas J., Li, Chenglong, Aqeilan, Rami I., Lesinski, Gregory B., Trapasso, Francesco, and Croce, Carlo M.
- Published
- 2013
- Full Text
- View/download PDF
6. Translational aspects of themodern genetics in head and neck cancers.
- Author
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PADUANO, FRANCESCO, ALTOMARE, EMANUELA, MARRELLI, BENEDETTA, DATTILO, VINCENZO, HUSSAINI, HAIZAL MOHD, COOPER, PAUL ROY, and TATULLO, MARCO
- Subjects
- *
TREATMENT of oral cancer , *SCIENTIFIC community , *SCIENTIFIC literature - Abstract
Oral cancer (OC) is one of the most recurrent cancers in the head and neck squamous cancer (SCCHN) category. Recently, the genome-wide association studies (GWAS) have gained growing interest in the scientific community. GWAS have identified several pathways involved in the interactions among general risk factors and genomic variants affecting SCCHN. This systematic overview aims to critically evaluate the latest data reported within the scientific literature. The aim was to investigate the impact of genetic aspects on SCCHN onset and prognosis, involving other clinical and systemic co-factors. PubMed, Google Scholar, and Cancer Genetics Web databases have been systematically investigated for original articles published in the last two years, reporting studies on the main queries addressed in this work. This review also comparatively describes the impact of environmental and pathological co-factors in different types of cancers, clarifying and updating the role of genetic factors in SCCHN onset and development. The main outcomes reported may be helpful to drive clinicians towards their clinical evaluations for the most appropriate therapeutic approach in SCCHN. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
7. Turner Syndrome Mosaicism 45,X/46,XY with Genital Ambiguity and Duchenne Muscular Dystrophy: Translational Approach of a Rare Italian Case.
- Author
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Lamanna, Bruno, Vinciguerra, Marina, Dellino, Miriam, Cascella, Gabriele, Cazzato, Gerardo, Macorano, Enrica, Malvasi, Antonio, Scacco, Salvatore, Cicinelli, Ettore, Loizzi, Vera, Vimercati, Antonella, Cormio, Gennaro, Paduano, Francesco, Cascardi, Eliano, and Tatullo, Marco
- Subjects
DUCHENNE muscular dystrophy ,TURNER'S syndrome ,MOSAICISM ,FRAGILE X syndrome ,Y chromosome ,GENETIC disorders ,PLANT chromosomes - Abstract
Turner syndrome (gonadal dysgenesis with short stature and sterility) is characterized by chromosomal karyotype 45,X in 50% of cases or by mosaicism (45,X/46,XX and 45,X/46,XY) in 30–40% or X structural defects (deletions, long arm isochromosome, ring chromosome). When mosaic Turner syndrome (TS) occurs with a Y chromosome, there may be ambiguous genitalia. Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disease with an X-Linked recessive pattern of inheritance that predominantly affects males, while females are usually asymptomatic. DMD has also been observed in groups of females affected by TS, not homozygous for the mutation. Here, we report a case of an Indian neonate born with ambiguous genitalia diagnosed prenatally by ultrasound who had a karyotype of 45,X/46,XY and who also had Duchenne muscular dystrophy caused by a de novo mutation in the DMD gene. Physical examination was normal without the typical dysmorphic features of TS with the exception of the genitourinary system showing ambiguous genitalia. Gender was assigned as female. At the age of three years, she had increasing difficulty walking, running, jumping and climbing stairs, proximal upper and lower extremity muscle weakness and a positive Gowers' sign. In addition, the serum creatine kinase (CK) value was over 30X the upper limit of normal. This study shows that DMD can occur in females with TS having 45,X/46,XY mosaicism and that this coexistence should be considered in women affected by TS who start to develop potential typical symptoms such as motor or developmental delay. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
8. Tcl1 interacts with Atm and enhances NF-κB activation in hematologic malignancies
- Author
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Gaudio, Eugenio, Spizzo, Riccardo, Paduano, Francesco, Luo, Zhenghua, Efanov, Alexey, Palamarchuk, Alexey, Leber, Amanda S., Kaou, Mohamed, Zanesi, Nicola, Bottoni, Arianna, Costinean, Stefan, Rassenti, Laura Z., Nakamura, Tatsuya, Kipps, Thomas J., Aqeilan, Rami I., Pekarsky, Yuri, Trapasso, Francesco, and Croce, Carlo M.
- Published
- 2012
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9. Design, synthesis, biophysical and biological studies of trisubstituted naphthalimides as G-quadruplex ligands
- Author
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Peduto, Antonella, Pagano, Bruno, Petronzi, Carmen, Massa, Antonio, Esposito, Veronica, Virgilio, Antonella, Paduano, Francesco, Trapasso, Francesco, Fiorito, Filomena, Florio, Salvatore, Giancola, Concetta, Galeone, Aldo, and Filosa, Rosanna
- Published
- 2011
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10. The Tumour Suppressor Fhit Protein Activates C-Raf Ubiquitination and Degradation in Human Melanoma Cells by Interacting with Hsp90.
- Author
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Paduano, Francesco, Gaudio, Eugenio, and Trapasso, Francesco
- Subjects
HEAT shock proteins ,MICROPHTHALMIA-associated transcription factor ,UBIQUITINATION ,PROTEINS ,MELANOMA - Abstract
Fhit protein expression is reduced in the majority of human tumors; moreover, its restoration both triggers apoptosis of cancer cells and suppresses tumor formation in a large number of preclinical models of cancers. In the following study, we observed that Fhit expression is significantly reduced in human melanoma cells, and their in vivo growth is blocked by a recombinant adenovirus carrying the FHIT gene. Importantly, we found here that Fhit physically interacts with Hsp90. Since Hsp90 is a chaperone with a crucial function in the conformational maturation and stabilization of C-Raf, we also investigated whether Fhit could interfere with the Hsp90/C-Raf protein complex in melanoma. Interestingly, the administration of the Hsp90 inhibitor 17-AAG, in combination with Fhit protein overexpression in melanoma cells, reacts synergistically to increase C-Raf ubiquitination and degradation. These data reveal Hsp90 as a novel interactor of Fhit and suggest that FHIT activity restoration could represent a helpful strategy for suppressing the oncogenic C-Raf pathway in the therapy of human melanoma. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. Translational aspects of the modern genetics in head and neck cancers.
- Author
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PADUANO, FRANCESCO, ALTOMARE, EMANUELA, MARRELLI, BENEDETTA, DATTILO, VINCENZO, HUSSAINI, HAIZAL MOHD, COOPER, PAUL ROY, and TATULLO, MARCO
- Subjects
HEAD & neck cancer ,SCIENTIFIC community ,SCIENTIFIC literature - Abstract
Oral cancer (OC) is one of the most recurrent cancers in the head and neck squamous cancer (SCCHN) category. Recently, the genome-wide association studies (GWAS) have gained growing interest in the scientific community. GWAS have identified several pathways involved in the interactions among general risk factors and genomic variants affecting SCCHN. This systematic overview aims to critically evaluate the latest data reported within the scientific literature. The aim was to investigate the impact of genetic aspects on SCCHN onset and prognosis, involving other clinical and systemic co-factors. PubMed, Google Scholar, and Cancer Genetics Web databases have been systematically investigated for original articles published in the last two years, reporting studies on the main queries addressed in this work. This review also comparatively describes the impact of environmental and pathological co-factors in different types of cancers, clarifying and updating the role of genetic factors in SCCHN onset and development. The main outcomes reported may be helpful to drive clinicians towards their clinical evaluations for the most appropriate therapeutic approach in SCCHN. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Germline Testing in a Cohort of Patients at High Risk of Hereditary Cancer Predisposition Syndromes: First Two-Year Results from South Italy.
- Author
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Paduano, Francesco, Colao, Emma, Fabiani, Fernanda, Rocca, Valentina, Dinatolo, Francesca, Dattola, Adele, D'Antona, Lucia, Amato, Rosario, Trapasso, Francesco, Baudi, Francesco, Perrotti, Nicola, and Iuliano, Rodolfo
- Subjects
- *
HEREDITARY cancer syndromes , *DISEASE risk factors , *BRCA genes , *GENETIC testing , *GERM cells , *TUMOR suppressor genes - Abstract
Germline pathogenic variants (PVs) in oncogenes and tumour suppressor genes are responsible for 5 to 10% of all diagnosed cancers, which are commonly known as hereditary cancer predisposition syndromes (HCPS). A total of 104 individuals at high risk of HCPS were selected by genetic counselling for genetic testing in the past 2 years. Most of them were subjects having a personal and family history of breast cancer (BC) selected according to current established criteria. Genes analysis involved in HCPS was assessed by next-generation sequencing (NGS) using a custom cancer panel with high- and moderate-risk susceptibility genes. Germline PVs were identified in 17 of 104 individuals (16.3%) analysed, while variants of uncertain significance (VUS) were identified in 21/104 (20.2%) cases. Concerning the germline PVs distribution among the 13 BC individuals with positive findings, 8/13 (61.5%) were in the BRCA1/2 genes, whereas 5/13 (38.4%) were in other high- or moderate-risk genes including PALB2, TP53, ATM and CHEK2. NGS genetic testing showed that 6/13 (46.1%) of the PVs observed in BC patients were detected in triple-negative BC. Interestingly, the likelihood of carrying the PVs in the moderate-to-high-risk genes calculated by the cancer risk model BOADICEA was significantly higher in pathogenic variant carriers than in negative subjects. Collectively, this study shows that multigene panel testing can offer an effective diagnostic approach for patients at high risk of hereditary cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
13. Protein tyrosine phosphatase PTPRJ is negatively regulated by microRNA-328
- Author
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Paduano, Francesco, Dattilo, Vincenzo, Narciso, Domenico, Bilotta, Anna, Gaudio, Eugenio, Menniti, Miranda, Agosti, Valter, Palmieri, Camillo, Perrotti, Nicola, Fusco, Alfredo, Trapasso, Francesco, and Iuliano, Rodolfo
- Published
- 2013
- Full Text
- View/download PDF
14. Case Report: Identification of a Novel Pathogenic Germline TP53 Variant in a Family With Li–Fraumeni Syndrome.
- Author
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Paduano, Francesco, Fabiani, Fernanda, Colao, Emma, Trapasso, Francesco, Perrotti, Nicola, Barbieri, Vito, Baudi, Francesco, and Iuliano, Rodolfo
- Subjects
LI-Fraumeni syndrome ,GERM cells ,GENETIC variation ,DISEASE susceptibility ,FAMILIES ,SONS - Abstract
Li–Fraumeni syndrome (LFS) is an inherited autosomal dominant disease characterized by a predisposition to many cancers. Germline pathogenic variants in TP53 are primarily responsible for LFS. By performing a targeted sequencing panel in a proband with liver carcinoma having a deceased son affected by osteosarcoma, we found the novel heterozygous frameshift variant c.645del (p.Ser215Argfs
* 32) in the TP53 gene. This variant co-segregated with typical LFS cancers in the family pedigree, consistent with the pathogenicity of this novel and previously undescribed TP53 variant. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
15. Mitochondria are primary targets in apoptosis induced by the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) in melanoma cell lines
- Author
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Caruso, Francesco, Villa, Raffaella, Rossi, Miriam, Pettinari, Claudio, Paduano, Francesco, Pennati, Marzia, Daidone, Maria Grazia, and Zaffaroni, Nadia
- Published
- 2007
- Full Text
- View/download PDF
16. Odontogenic Differentiation of Human Dental Pulp Stem Cells on Hydrogel Scaffolds Derived from Decellularized Bone Extracellular Matrix and Collagen Type I
- Author
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Marrelli, Massimo and Paduano, Francesco
- Abstract
The aim of this study was to evaluate the level of odontogenic differentiation of dental pulp stem cells (DPSCs) on hydrogel scaffolds derived from bone extracellular matrix (bECM) in comparison to those seeded on collagen I (Col-I), one of the main components of dental pulp ECM.
- Published
- 2016
17. Dental Pulp Stem Cell Mechanoresponsiveness: Effects of Mechanical Stimuli on Dental Pulp Stem Cell Behavior.
- Author
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Marrelli, Massimo, Codispoti, Bruna, Shelton, Richard M., Scheven, Ben A., Cooper, Paul R., Tatullo, Marco, and Paduano, Francesco
- Abstract
Dental pulp is known to be an accessible and important source of multipotent mesenchymal progenitor cells termed dental pulp stem cells (DPSCs). DPSCs can differentiate into odontoblast-like cells and maintain pulp homeostasis by the formation of new dentin which protects the underlying pulp. DPSCs similar to other mesenchymal stem cells (MSCs) reside in a niche, a complex microenvironment consisting of an extracellular matrix, other local cell types and biochemical stimuli that influence the decision between stem cell (SC) self-renewal and differentiation. In addition to biochemical factors, mechanical factors are increasingly recognized as key regulators in DPSC behavior and function. Thus, microenvironments can significantly influence the role and differentiation of DPSCs through a combination of factors which are biochemical, biomechanical and biophysical in nature. Under in vitro conditions, it has been shown that DPSCs are sensitive to different types of force, such as uniaxial mechanical stretch, cyclic tensile strain, pulsating fluid flow, low-intensity pulsed ultrasound as well as being responsive to biomechanical cues presented in the form of micro- and nano-scale surface topographies. To understand how DPSCs sense and respond to the mechanics of their microenvironments, it is essential to determine how these cells convert mechanical and physical stimuli into function, including lineage specification. This review therefore covers some aspects of DPSC mechanoresponsivity with an emphasis on the factors that influence their behavior. An in-depth understanding of the physical environment that influence DPSC fate is necessary to improve the outcome of their therapeutic application for tissue regeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
18. TCL1A interacts with TP63 and enhances the survival of Raji Burkitt lymphoma cell line.
- Author
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Gaudio, Eugenio, Paduano, Francesco, Pinton, Sandra, D'Agostino, Sabrina, Rocca, Roberta, Costa, Giosuè, Ngankeu, Apollinaire, Aqeilan, Rami I., Croce, Carlo M., Bertoni, Francesco, Alcaro, Stefano, and Trapasso, Francesco
- Subjects
- *
T-cell lymphoma , *TUMOR proteins , *LYMPHOMAS , *MASS spectrometry , *LYMPHOMA treatment - Abstract
The article highlights the interaction of T-cell leukemia/lymphoma protein 1A (TCL1A) with Tumor protein p63 (TP63) gene and enhances the survival of Raji Burkitt lymphoma cell line. Topics discussed include overexpression of TCL1A protein causes leukaemias and lymphomas; isolation of TCL1A-interacting proteins by using mass spectrometry; and information on treatment of lymphomas using different techniques.
- Published
- 2018
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- View/download PDF
19. Design, Synthesis, Biological Activity, and Structural Analysis of Lactam‐Constrained PTPRJ Agonist Peptides.
- Author
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Sala, Marina, Spensiero, Antonia, Scala, Maria Carmina, Pepe, Giacomo, Bilotta, Anna, Paduano, Francesco, D'Agostino, Sabrina, Lanzillotta, Delia, Bertamino, Alessia, Novellino, Ettore, Trapasso, Francesco, Gomez‐Monterrey, Isabel M., and Campiglia, Pietro
- Published
- 2018
- Full Text
- View/download PDF
20. T-Cell Leukemia/Lymphoma 1 (TCL1): An Oncogene Regulating Multiple Signaling Pathways.
- Author
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Paduano, Francesco, Gaudio, Eugenio, Mensah, Afua A., Pinton, Sandra, Bertoni, Francesco, and Trapasso, Francesco
- Subjects
HTLV-I ,JAK-STAT pathway ,LYMPHOCYTES - Abstract
Almost 30 years ago, Carlo Croce's group discovered the T-Cell Leukemia/Lymphoma 1A oncogene (TCL1A or TCL1). TCL1 protein is normally expressed in fetal tissues and early developmental stage lymphocytes. Its expression is deregulated in chronic lymphocytic leukemia (B-CLL) and most lymphomas. TCL1 plays a central role in lymphomagenesis as a co-activator of AKT kinases and other recently elucidated interacting protein partners. These include ATM, HSP70 and TP63, which were all confirmed as binding partners of TCL1 fromco-immunoprecipitation experiments utilizing endogenously expressed proteins. The nature of these interactions highlighted the role of TCL1 in enhancing multiple signaling pathways, including PI3K and NF-kB. Based on its role in the aforementioned pathways and, despite the lack of a well-defined enzymatic activity, TCL1 is considered a potential therapeutic target for TCL1-positive hematological malignancies. This perspective will provide an overview of TCL1A and its interacting partners. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
21. BranchingSets.
- Author
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Paduano, Francesco, Etemadpour, Ronak, and Forbes, Angus G.
- Published
- 2016
- Full Text
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22. Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications.
- Author
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Paduano, Francesco, Marrelli, Massimo, Amantea, Massimiliano, Rengo, Carlo, Rengo, Sandro, Goldberg, Michel, Spagnuolo, Gianrico, and Tatullo, Marco
- Subjects
- *
BONE regeneration , *CRANIOFACIAL abnormalities , *MESENCHYMAL stem cells , *ADIPOSE tissues , *CLINICAL trials , *THERAPEUTICS - Abstract
Bone regeneration in craniomaxillofacial surgery represents an issue that involves both surgical and aesthetic aspects. The most recent studies on bone tissue engineering involving adipose-derived stromal/stem cells (ASCs) have clearly demonstrated that such cells can play a crucial role in the treatment of craniomaxillofacial defects, given their strong commitment towards the osteogenic phenotype. A deeper knowledge of the molecular mechanisms underlying ASCs is crucial for a correct understanding of the potentialities of ASCs-based therapies in the most complex maxillofacial applications. In this topical review, we analyzed the molecular mechanisms of ASCs related to their support toward angiogenesis and osteogenesis, during bone regeneration. Moreover, we analyzed both case reports and clinical trials reporting the most promising clinical applications of ASCs in the treatment of craniomaxillofacial defects. Our study aimed to report the main molecular and clinical features shown by ASCs, used as a therapeutic support in bone engineering, as compared to the use of conventional autologous and allogeneic bone grafts. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
23. DSC-Differentiated Hepatocytes for Treatment of Liver Diseases.
- Author
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Paduano, Francesco, Marrelli, Massimo, Gaharwar, Akhilesh K., and Tatullo, Marco
- Published
- 2016
- Full Text
- View/download PDF
24. Decellularized bone extracellular matrix and human dental pulp stem cells as a construct for bone regeneration.
- Author
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Paduano, Francesco, Marrelli, Massimo, Alom, Noura, Amer, Mahetab, White, Lisa J., Shakesheff, Kevin M., and Tatullo, Marco
- Subjects
- *
EXTRACELLULAR matrix , *DENTAL pulp , *HUMAN stem cells , *BONE regeneration , *MESENCHYMAL stem cells , *CELL differentiation - Abstract
Dental pulp tissue represents a source of mesenchymal stem cells that have a strong differentiation potential towards the osteogenic lineage. The objective of the current study was to examinein vitroosteogenic induction of dental pulp stem cells (DPSCs) cultured on hydrogel scaffolds derived from decellularized bone extracellular matrix (bECM) compared to collagen type I (Col-I), the major component of bone matrix. DPSCs in combination with bECM hydrogels were cultured under three different conditions: basal medium, osteogenic medium and medium supplemented with growth factors (GFs) and cell growth, mineral deposition, gene and protein expression were investigated. The DPSCs/bECM hydrogel constructs cultured in basal medium showed that cells were viable after three weeks and that the expression of runt-related transcription factor 2 (RUNX-2) and bone sialoprotein (BSP) were significantly upregulated in the absence of extra osteogenic inducers compared to Col-I hydrogel scaffolds. In addition, the protein expression levels of BSP and osteocalcin were higher on bECM with respect to Col-I hydrogel scaffolds. Furthermore, DPSCs/bECM hydrogels cultured with osteogenic or GFs supplemented medium displayed a higher upregulation of the osteo-specific markers compared to Col-I hydrogels in identical media. Collectively, our results demonstrate that bECM hydrogels might be considered as suitable scaffolds to support osteogenic differentiation of DPSCs. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
25. Crosstalk between oral and general health status in e-smokers.
- Author
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Tatullo, Marco, Gentile, Stefano, Paduano, Francesco, Santacroce, Luigi, and Marrelli, Massimo
- Published
- 2016
- Full Text
- View/download PDF
26. Innovative approach for the in vitro research on biomedical scaffolds designed and customized with CAD-CAM technology.
- Author
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Marrelli, Massimo, Pujia, Antonella, Palmieri, Francesca, Gatto, Roberto, Falisi, Giovanni, Gargari, Marco, Caruso, Silvia, Apicella, Davide, Rastelli, Claudio, Nardi, Gianna Maria, Paduano, Francesco, and Tatullo, Marco
- Published
- 2016
- Full Text
- View/download PDF
27. Highly Efficient In Vitro Reparative Behaviour of Dental Pulp Stem Cells Cultured with Standardised Platelet Lysate Supplementation.
- Author
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Marrazzo, Pasquale, Paduano, Francesco, Palmieri, Francesca, Marrelli, Massimo, and Tatullo, Marco
- Subjects
- *
DENTAL pulp , *MESENCHYMAL stem cells , *CELL culture , *BLOOD platelets , *BLOOD serum analysis , *REGENERATIVE medicine - Abstract
Dental pulp is an accessible source of multipotent mesenchymal stromal cells (MSCs). The perspective role of dental pulp stem cells (DPSCs) in regenerative medicine demands an in vitro expansion and in vivo delivery which must deal with the safety issues about animal serum, usually required in cell culture practice. Human platelet lysate (PL) contains autologous growth factors and has been considered as valuable alternative to fetal bovine serum (FBS) in cell cultures. The optimum concentration to be added of such supplement is highly dependent on its preparation whose variability limits comparability of results. By in vitro experiments, we aimed to evaluate a standardised formulation of pooled PL. A low selected concentration of PL (1%) was able to support the growth and maintain the viability of the DPSCs. The use of PL in cell cultures did not impair cell surface signature typically expressed by MSCs and even upregulated the transcription of Sox2. Interestingly, DPSCs cultured in presence of PL exhibited a higher healing rate after injury and are less susceptible to toxicity mediated by exogenous H2O2 than those cultured with FBS. Moreover, PL addition was shown as a suitable option for protocols promoting osteogenic and chondrogenic differentiation of DPSCs. Taken together, our results indicated that PL is a valid substitute of FBS to culture and differentiate DPSCs for clinical-grade use. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
28. Danger-system: Exploring new ways to manage occupants safety in smart building.
- Author
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Piscitello, Andrea, Paduano, Francesco, Nacci, Alessandro A., Noferi, Danny, Santambrogio, Marco D., and Sciuto, Donatella
- Published
- 2015
- Full Text
- View/download PDF
29. Mechanical influence of tissue culture plates and extracellular matrix on mesenchymal stem cell behavior: A topical review.
- Author
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Tatullo, Marco, Marrelli, Massimo, Falisi, Giovanni, Rastelli, Claudio, Palmieri, Francesca, Gargari, Marco, Zavan, Barbara, Paduano, Francesco, and Benagiano, Vincenzo
- Published
- 2016
- Full Text
- View/download PDF
30. Odontogenic Differentiation of Human Dental Pulp Stem Cells on Hydrogel Scaffolds Derived from Decellularized Bone Extracellular Matrix and Collagen Type I.
- Author
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Paduano, Francesco, Marrelli, Massimo, White, Lisa J., Shakesheff, Kevin M., and Tatullo, Marco
- Subjects
- *
DENTAL pulp , *STEM cells , *HYDROGELS , *EXTRACELLULAR matrix , *COLLAGEN - Abstract
Objectives: The aim of this study was to evaluate the level of odontogenic differentiation of dental pulp stem cells (DPSCs) on hydrogel scaffolds derived from bone extracellular matrix (bECM) in comparison to those seeded on collagen I (Col-I), one of the main components of dental pulp ECM. Methods: DPSCs isolated from human third molars were characterized for surface marker expression and odontogenic potential prior to seeding into bECM or Col-I hydrogel scaffolds. The cells were then seeded onto bECM and Col-I hydrogel scaffolds and cultured under basal conditions or with odontogenic and growth factor (GF) supplements. DPSCs cultivated on tissue culture polystyrene (TCPS) with and without supplements were used as controls. Gene expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE) was evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and mineral deposition was observed by Von Kossa staining. Results: When DPSCs were cultured on bECM hydrogels, the mRNA expression levels of DSPP, DMP-1 and MEPE genes were significantly upregulated with respect to those cultured on Col-I scaffolds or TCPS in the absence of extra odontogenic inducers. In addition, more mineral deposition was observed on bECM hydrogel scaffolds as demonstrated by Von Kossa staining. Moreover, DSPP, DMP-1 and MEPE mRNA expressions of DPSCs cultured on bECM hydrogels were further upregulated by the addition of GFs or osteo/odontogenic medium compared to Col-I treated cells in the same culture conditions. Significance: These results demonstrate the potential of the bECM hydrogel scaffolds to stimulate odontogenic differentiation of DPSCs. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
31. Extended LineSets: a visualization technique for the interactive inspection of biological pathways.
- Author
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Paduano, Francesco and Forbes, Angus Graeme
- Subjects
- *
BIOLOGISTS , *BIOSYNTHESIS , *GENE expression , *MOLECULAR biology , *BIOMOLECULES - Abstract
Background: Biologists make use of pathway visualization tools for a range of tasks, including investigating inter-pathway connectivity and retrieving details about biological entities and interactions. Some of these tasks require an understanding of the hierarchical nature of elements within the pathway or the ability to make comparisons between multiple pathways. We introduce a technique inspired by LineSets that enables biologists to fulfill these tasks more effectively. Results: We introduce a novel technique, Extended LineSets, to facilitate new explorations of biological pathways. Our technique incorporates intuitive graphical representations of different levels of information and includes a well-designed set of user interactions for selecting, filtering, and organizing biological pathway data gathered from multiple databases. Conclusions: Based on interviews with domain experts and an analysis of two use cases, we show that our technique provides functionality not currently enabled by current techniques, and moreover that it helps biologists to better understand both inter-pathway connectivity and the hierarchical structure of biological elements within the pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
32. Correlation between Surgeon's Experience, Surgery Complexity and the Alteration of Stress Related Physiological Parameters.
- Author
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Marrelli, Massimo, Gentile, Stefano, Palmieri, Francesca, Paduano, Francesco, and Tatullo, Marco
- Subjects
ORAL medicine ,PHYSIOLOGICAL stress ,SURGEONS ,SURGICAL technology ,SURGICAL complications ,BIOMARKERS ,QUALITY of life - Abstract
Introduction: In the present work we analyzed the hormonal (salivary Cortisol; sC), immune (salivary Immunoglobulin A; sIgA) and cardiovascular (Heart rate, HR, and systolic blood pressure, SBP) responses induced by stress conditions in oral surgeons, randomly recruited according to their expertise level. Materials and methods: Each surgeon performed three different surgical procedures with increasing degrees of technical difficulty and under time-limited conditions, to assess whether these variants may influence the risks of stress-induced secondary hypertension among the involved health professionals. sC and sIgA samples and cardiovascular function measurements were taken up before, during, and two hours after every surgery. Salivary samples and cardiovascular measurements were taken also during non-surgical days, as baseline controls. Results: We observed that more experienced surgeons showed a higher stress management ability compared to those with less experience or, generally, younger, which are more exposed to the risks of developing secondary hypertension. Nevertheless, indipendently of sex and experience, oral surgeons are constantly exposed to high risks of developing stress-related diseases. Conclusions: On the basis of the issues addressed and the results obtained, we have highlighted the importance of the investigated stress biomarkers to monitor and to prevent stress-related pathologies among oral surgeons. This approach is aimed to emphasize the significance of these specific stress-biomarkers, which represent a powerful instrument to evaluate stress levels in oral surgeons, and that may help to reduce the most severe life-threatening risks to which they are daily exposed. In conclusion, final goal of this study is to suggest an useful guideline to monitor the stress levels of oral and maxillofacial surgeons in order to improve their quality of life, which is inevitably reflected on the quality of the performances provided and, finally, to prevent possible mistakes in their daily activities. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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33. Fhit Delocalizes Annexin A4 from Plasma Membrane to Cytosol and Sensitizes Lung Cancer Cells to Paclitaxel.
- Author
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Gaudio, Eugenio, Paduano, Francesco, Spizzo, Riccardo, Ngankeu, Apollinaire, Zanesi, Nicola, Gaspari, Marco, Ortuso, Francesco, Lovat, Francesca, Rock, Jonathan, Hill, Grace A., Kaou, Mohamed, Cuda, Giovanni, Aqeilan, Rami I., Alcaro, Stefano, Croce, Carlo M., and Trapasso, Francesco
- Subjects
- *
ANNEXINS , *CELL membranes , *CYTOSOL , *LUNG cancer , *CANCER cells , *PACLITAXEL , *IMMUNOPRECIPITATION , *CHEMOSENSITIZERS - Abstract
Fhit protein is lost or reduced in a large fraction of human tumors, and its restoration triggers apoptosis and suppresses tumor formation or progression in preclinical models. Here, we describe the identification of candidate Fhit-interacting proteins with cytosolic and plasma membrane localization. Among these, Annexin 4 (ANXA4) was validated by co-immunoprecipitation and confocal microscopy as a partner of this novel Fhit protein complex. Here we report that overexpression of Fhit prevents Annexin A4 translocation from cytosol to plasma membrane in A549 lung cancer cells treated with paclitaxel. Moreover, paclitaxel administration in combination with AdFHIT acts synergistically to increase the apoptotic rate of tumor cells both in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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34. Targeted Disruption of the Murine Homeodomain-Interacting Protein Kinase-2 Causes Growth Deficiency In Vivo and Cell Cycle Arrest In Vitro.
- Author
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Trapasso, Francesco, Aqeilan, Rami I., Iuliano, Rodolfo, Visone, Rosa, Gaudio, Eugenio, Ciuffini, Laura, Alder, Hansjuerg, Paduano, Francesco, Pierantoni, Giovanna Maria, Soddu, Silvia, Croce, Carlo M., and Fusco, Alfredo
- Subjects
PROTEIN kinases ,HOMEOBOX genes ,CELLULAR control mechanisms ,CELL cycle regulation ,CELL proliferation ,FIBROBLASTS - Abstract
The homeodomain-interacting protein kinase 2 (HIPK2) protein is a member of a recently identified family of nuclear protein kinases that are well conserved in various organisms. HIPK2 can bind to several homeotic factors and to a series of proteins involved in the regulation of cell survival and proliferation in response to morphogenetic and genotoxic signals. Here we report Hipk2-targeted disruption in mouse; Hipk2
−/− mice are viable and fertile but significantly smaller than their wild-type littermates. This feature is present at birth and retained throughout the mouse adulthood. Mouse embryo fibroblasts from Hipk2−/− mice show a reduced proliferation rate, compared to the wild-type counterparts, with accumulation in the G0/G1 phase of the cell cycle and altered levels of the cell cycle regulators cyclin D and CDK6. Restoration of wild-type HIPK2 expression in Hipk2−/− cells rescues the normal phenotype supporting a role for HIPK2 in the regulation of cell proliferation. [ABSTRACT FROM AUTHOR]- Published
- 2009
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35. A Familial Form of Epidermolysis Bullosa Simplex Associated with a Pathogenic Variant in KRT5.
- Author
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Paduano, Francesco, Colao, Emma, Grillone, Teresa, Vismara, Marco Flavio Michele, Amato, Rosario, Nisticò, Steven, Mignogna, Chiara, Dastoli, Stefano, Fabiani, Fernanda, Zucco, Rossella, Trapasso, Francesco, Perrotti, Nicola, and Iuliano, Rodolfo
- Subjects
- *
EPIDERMOLYSIS bullosa , *DNA sequencing , *BLISTERS , *HEREDITY , *EPITHELIAL cells - Abstract
Epidermolysis bullosa simplex is a disease that belongs to a group of genodermatoses characterised by the formation of superficial bullous lesions caused by minor mechanical trauma to the skin. The skin fragility observed in the EBS is mainly caused by pathogenic variants in the KRT5 and KRT14 genes that compromise the mechanical stability of epithelial cells. By performing DNA sequencing in a female patient with EBS, we found the pathogenic variant c.967G>A (p.Val323Met) in the KRT5 gene. This variant co-segregated with EBS in the family pedigree and was transmitted in an autosomal dominant inheritance manner. This is the first report showing a familial form of EBS due to this pathogenic variant. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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36. 7q35 Microdeletion and 15q13.3 and Xp22.33 Microduplications in a Patient with Severe Myoclonic Epilepsy, Microcephaly, Dysmorphisms, Severe Psychomotor Delay and Intellectual Disability.
- Author
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Paduano, Francesco, Colao, Emma, Loddo, Sara, Orlando, Valeria, Trapasso, Francesco, Novelli, Antonio, Perrotti, Nicola, and Iuliano, Rodolfo
- Subjects
- *
INTELLECTUAL disabilities , *NICOTINIC receptors , *PATHOLOGY , *MICROCEPHALY , *EPILEPSY , *ZIKA Virus Epidemic, 2015-2016 , *ZIKA virus infections - Abstract
Copy number variations (CNVs) play a key role in the pathogenesis of several diseases, including a wide range of neurodevelopmental disorders. Here, we describe the detection of three CNVs simultaneously in a female patient with evidence of severe myoclonic epilepsy, microcephaly, hypertelorism, dimorphisms as well as severe psychomotor delay and intellectual disability. Array-CGH analysis revealed a ~240 kb microdeletion at the 7q35 inherited from her father, a ∼538 kb microduplication at the 15q13.3 region and a ∼178 kb microduplication at Xp22.33 region, both transmitted from her mother. The microdeletion in 7q35 was included within an intragenic region of the contactin associated protein-like 2 (CNTNAP2) gene, whereas the microduplications at 15q13.3 and Xp22.33 involved the cholinergic receptor nicotinic α 7 subunit (CHRNA7) and the cytokine receptor-like factor 2 (CRLF2) genes, respectively. Here, we describe a female patient harbouring three CNVs whose additive contribution could be responsible for her clinical phenotypes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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37. Evaluation of Profile Changes in Class II Individuals Treated by Means of Herbst Miniscope Appliance.
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Martina, Stefano, Di Stefano, Maria Luisa, Paduano, Francesco Paolo, Aiello, Domenico, Valletta, Rosa, and Paduano, Sergio
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MAXILLA ,MANDIBLE ,MALOCCLUSION - Abstract
Background: To evaluate the profile changes following orthopedic/orthodontic treatment with the Herbst Miniscope
® appliance in subjects affected with Class II malocclusion with mandibular retrusion. Methods: A total of 44 patients presenting a skeletal Angle Class II malocclusion (ANB > 4°) due to mandibular retrusion and a cervical maturation stage between CS2 and CS3 were included in the study. Of these 44 patients, 22 (mean age 11.9 ± 1.3, HBT group) were treated using the Herbst appliance, while 22 (mean age 10.6 ± 1.3, CTR group) were followed for a 12-month observational period. A cephalometric tracing was performed at the beginning of treatment (T0) and after 12 months (T1). Results: In both groups there was a significant advancement of soft tissue pogonion (HBT = 3.5 ± 3.0 mm, p < 0.001; CTR = 2.2 ± 2.9 mm, p < 0.001), but the difference between the two groups was not significant (p = 0.172). On the contrary, both groups had a significant advancement of the mandibular sulcus (HBT = 3.7 ± 2.8 mm, p < 0.001; CTR = 1.2 ± 2.2 mm, p < 0.001) and a lower lip protrusion (HBT = 3.45 ± 2.51 mm, p < 0.001; CTR = 1.7 ± 2.7 mm, p = 0.008), but in both cases the HBT group showed a statistically significant greater increase in sulcus protrusion (p = 0.002) and lower lip protrusion (p = 0.029) than controls. There were no statistically significant effects on the upper jaw. Conclusions: The Herbst appliance advanced the lower jaw soft tissues. [ABSTRACT FROM AUTHOR]- Published
- 2020
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38. Strategic Tools in Regenerative and Translational Dentistry.
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Tatullo, Marco, Codispoti, Bruna, Paduano, Francesco, Nuzzolese, Manuel, and Makeeva, Irina
- Subjects
MESENCHYMAL stem cells ,TISSUE engineering ,REGENERATIVE medicine ,STEM cell research ,GINGIVA - Abstract
Human oral-derived stem cells can be easily obtained from several oral tissues, such as dental pulp, periodontal ligament, from gingiva, or periapical cysts. Due to their differentiation potential, oral-derived mesenchymal stem cells are promising for tissue engineering and regenerative medicine. The regenerative ability showed by some oral tissues strongly depends on their sleeping adult stem cell populations that are able to repair small defects and to manage local inflammation. To date, researchers are working on effective and efficient methods to ensure safe and predictable protocols to translate stem cell research into human models. In the last decades, the challenge has been to finally use oral-derived stem cells together with biomaterials or scaffold-free techniques, to obtain strategic tools for regenerative and translational dentistry. This paper aims to give a clear point of view on state of the art developments, with some exciting insights into future strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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39. Antisense oligonucleotide-mediated inhibition of hTERT, but not hTERC, induces rapid cell growth decline and apoptosis in the absence of telomere shortening in human prostate cancer cells
- Author
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Folini, Marco, Brambilla, Cinzia, Villa, Raffaella, Gandellini, Paolo, Vignati, Sara, Paduano, Francesco, Daidone, Maria Grazia, and Zaffaroni, Nadia
- Subjects
- *
DNA polymerases , *CANCER cells , *TELOMERASE , *CELL death - Abstract
Abstract: Recent evidence points to a novel function of human telomerase reverse transcriptase (hTERT) in promoting tumour cell survival, which might be independent of the telomere-elongating activity of the enzyme. To test this hypothesis, we evaluated comparatively the effects of telomerase inhibition, accomplished through antisense oligonucleotide-mediated interference with hTERT or human telomerase RNA component (hTERC), on the proliferative potential of DU145 human prostate cancer cells. Exposure of cells to a 2′-O-methyl-RNA phosphorothioate oligonucleotide targeting a splicing site within hTERT pre-mRNA induced almost complete inhibition of telomerase activity as a consequence of a marked reduction of the hTERT mRNA expression level, an early decline of DU145 cell growth and apoptotic cell death without any appreciable telomere shortening. Conversely, exposure of DU145 cells to a 2′-O-methyl-RNA phosphorothioate oligonucleotide targeting the template region of hTERC failed to interfere with cell proliferation in spite of the almost complete abrogation of telomerase activity. These results extend and corroborate earlier evidence in favour of an enzymatic activity-independent mechanism by which hTERT maintains tumour cell survival and proliferation. [Copyright &y& Elsevier]
- Published
- 2005
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40. Human periapical cysts-mesenchymal stem cells cultured with allogenic human serum are a ‘‘clinical-grade’’ construct alternative to bovine fetal serum and indicated in the regeneration of endo-periodontal tissues
- Author
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Massimo Marrelli, Francesco Paduano, Marco Tatullo, Carlo Rengo, Gianrico Spagnuolo, Francesca Palmieri, Tatullo, Marco, Marrelli, Massimo, Palmieri, Francesca, Rengo, Carlo, Paduano, Francesco, and Spagnuolo, Gianrico
- Subjects
0301 basic medicine ,Stem cell ,Regeneration (biology) ,Osteogenesi ,Mesenchymal stem cell ,Matrix (biology) ,Biology ,Translational research ,Human periapical cyst-MSC ,lcsh:RK1-715 ,Andrology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Downregulation and upregulation ,lcsh:Dentistry ,Gene expression ,Regenerative medicine ,Extracellular ,MEPE ,Dentistry (all) ,Von Kossa stain ,General Dentistry ,030215 immunology - Abstract
Aim: Our research investigated the use of human serum (HS) as a safe and clinical-grade culture medium, using a new cell-model: hPCy-MSCs. This article is aimed to concretely applicate the concept of “waste-based regenerative dentistry” to translate it in future endo-periodontal applications. Methodology: HPCy-MSCs were cultured in 2 different mediums, both containing α-MEM: the 1st with 10% FBS (Control group), and the 2nd with 10% human serum (Test group).Cell proliferation and stemness assays, gene expression, immunophenotypic analysis and osteogenic differentiation were performed to verify our hypothesis. cDNA samples were amplified with qPCR.Experiments were performed in triplicate and analysed with statistical software. Results: The hPCy-MSCs cultivated in a medium with HS were morphologically similar to those cultivated with FBS, and showed a significantly higher proliferation rate. Von Kossa's staining revealed that osteoblasts from hPCy-MSCs in HS implemented with osteogenic induction factors, showed a better osteogenic activity, also confirmed by a significant upregulation of osteopotin (OPN) and matrix extracellular phosphoglycoprotein (MEPE). Conclusions: HPCy-MSCs cultivated in HS showed phenotypic stability and a clear regenerative binding, thus, suggesting these two components as a clinically-grade construct for future endo-periodontal therapies. Riassunto: Obiettivi: La nostra ricerca ha analizzato l’utilizzo del siero umano (HS) come mezzo di coltura sicuro e “clinical-grade”, per uso clinico, utilizzando un nuovo modello cellulare: le hPC-MSCs. Questo articolo ha lo scopo di applicare concretamente il concetto di “odontoiatria rigenerativa basata sui rifiuti biologici”, al fine di tradurlo in future applicazioni endo-periodontali. Materiali e metodi: Le HPCy-MSCs sono state coltivate in 2 mezzi di coltura diversi, entrambi contenenti α-MEM: il primo con 10% di FBS (gruppo di controllo) e il secondo con il 10% di siero umano (gruppo di test).Sono stati eseguiti saggi di proliferazione cellulare e di staminalità, espressione genica, analisi immunofenotipica e differenziamento osteogenico per verificare la nostra ipotesi di partenza. Campioni di cDNA sono stati amplificati con qPCR.Gli esperimenti sono stati eseguiti in triplicato e analizzati con software statistici. Risultati: Le hPC-MSC coltivate in un terreno con HS erano morfologicamente simili a quelle coltivate con FBS e mostravano un tasso di proliferazione significativamente più alto. La colorazione di Von Kossa ha rivelato che gli osteoblasti da hPC-MSC coltivate in HS implementato con fattori di induzione osteogenica hanno mostrato una migliore attività osteogenica, confermata anche da una significativa up-regolazione di osteopotina (OPN) e fosfoglicoproteina della matrice extracellulare (MEPE). Conclusioni: Le HPCy-MSC coltivate in HS hanno mostrato stabilità fenotipica e un chiaro atteggiamento rigenerativo, suggerendo quindi questo protocollo come un approccio clinicamente valido per le future terapie endo-periodontali. Keywords: Regenerative medicine, Stem cells, Osteogenesis, Human periapical cyst-MSCs, Translational research, Parole chiave: Medicina rigenerativa, Cellule staminali, Osteogenesi, Human periapical cyst-MSCs, Ricerca traslazionale
- Published
- 2018
41. A novel splice variant of the protein tyrosine phosphatase PTPRJ that encodes for a soluble protein involved in angiogenesis
- Author
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Nicola Perrotti, Francesco Trapasso, Stefania Belviso, Alfredo Fusco, Eugenio Gaudio, Sabrina D'Agostino, Rodolfo Iuliano, Francesco Paduano, Anna Bilotta, Tullio Florio, Stefania Scalise, Mariaconcetta Bilotta, Vincenzo Dattilo, Bilotta, Anna, Dattilo, Vincenzo, D'Agostino, Sabrina, Belviso, Stefania, Scalise, Stefania, Bilotta, Mariaconcetta, Gaudio, Eugenio, Paduano, Francesco, Perrotti, Nicola, Florio, Tullio, Fusco, Alfredo, Iuliano, Rodolfo, and Trapasso, Francesco
- Subjects
0301 basic medicine ,Time Factors ,Glycosylation ,Angiogenesis ,Protein tyrosine phosphatase ,HeLa Cell ,0302 clinical medicine ,MCF-7 Cell ,HEK293 Cell ,Cell Movement ,Neoplasms ,Medicine ,Protein Isoforms ,Receptor ,Tube formation ,Neovascularization, Pathologic ,Cell adhesion molecule ,Receptor-Like Protein Tyrosine Phosphatases, Class 3 ,Gene Expression Regulation, Neoplastic ,Angiogenesi ,Ectodomain ,Oncology ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Research Paper ,Human ,Signal Transduction ,Gene isoform ,Time Factor ,Immunoprecipitation ,Human Umbilical Vein Endothelial Cell ,Neovascularization, Physiologic ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,Human Umbilical Vein Endothelial Cells ,Cell Adhesion ,Humans ,RNA, Messenger ,A549 Cell ,Cell Proliferation ,business.industry ,Protein Isoform ,Soluble isoform ,Molecular biology ,Angiogenic factor ,Glioblastoma ,030104 developmental biology ,HEK293 Cells ,Solubility ,A549 Cells ,Cell Adhesion Molecule ,Immunology ,Neoplasm ,Neoplasm Grading ,business ,Cell Adhesion Molecules ,HeLa Cells - Abstract
// Anna Bilotta 1 , Vincenzo Dattilo 2 , Sabrina D'Agostino 1 , Stefania Belviso 1 , Stefania Scalise 1 , Mariaconcetta Bilotta 1 , Eugenio Gaudio 1, 3 , Francesco Paduano 1, 4 , Nicola Perrotti 2 , Tullio Florio 5 , Alfredo Fusco 6 , Rodolfo Iuliano 1 , Francesco Trapasso 1 1 Department of Medicina Sperimentale e Clinica, University Magna Graecia of Catanzaro, Catanzaro, Italy 2 Department of Scienze della Salute, University Magna Graecia of Catanzaro, Catanzaro, Italy 3 Lymphoma and Genomics Research Program, Institute of Oncology Research (IOR), Bellinzona, Switzerland 4 Tecnologica Research Institute, Biomedical Section, Crotone, Italy 5 Laboratory of Pharmacology, Dept. of Internal Medicine, and Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy 6 Istituto di Endocrinologia e Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University Federico II of Napoli, Napoli, Italy Correspondence to: Rodolfo Iuliano, email: iuliano@unicz.it Francesco Trapasso, email: trapasso@unicz.it Keywords: protein tyrosine phosphatase, soluble isoform, angiogenesis, glioblastoma, angiogenic factor Received: September 20, 2016 Accepted: December 13, 2016 Published: December 29, 2016 ABSTRACT PTPRJ is a receptor protein tyrosine phosphatase with tumor suppressor activity. Very little is known about the role of PTPRJ ectodomain, although recently both physiological and synthetic PTPRJ ligands have been identified. A putative shorter spliced variant, coding for a 539 aa protein corresponding to the extracellular N-terminus of PTPRJ, is reported in several databases but, currently, no further information is available. Here, we confirmed that the PTPRJ short isoform (named sPTPRJ) is a soluble protein secreted into the supernatant of both endothelial and tumor cells. Like PTPRJ, also sPTPRJ undergoes post-translational modifications such as glycosylation, as assessed by sPTPRJ immunoprecipitation. To characterize its functional activity, we performed an endothelial cell tube formation assay and a wound healing assay on HUVEC cells overexpressing sPTPRJ and we found that sPTPRJ has a proangiogenic activity. We also showed that sPTPRJ expression down-regulates endothelial adhesion molecules, that is a hallmark of proangiogenic activity. Moreover, sPTPRJ mRNA levels in human high-grade glioma, one of the most angiogenic tumors, are higher in tumor samples compared to controls. Further studies will be helpful not only to clarify the way sPTPRJ works but also to supply clues to circumvent its activity in cancer therapy.
- Published
- 2017
42. The Human Periapical Cyst-Mesenchymal Stem Cells (hPCy-MSCs): The New Challenge of 'Waste Medicine' in Regenerative Dentistry
- Author
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Massimo Marrelli, Gianrico Spagnuolo, Francesco Paduano, Carlo Rengo, Marco Tatullo, Sandro Rengo, Marrelli, Massimo, Paduano, Francesco, Rengo, Carlo, Spagnuolo, Gianrico, Rengo, Sandro, and Tatullo, Marco
- Subjects
0301 basic medicine ,Periapical cyst ,business.industry ,Mesenchymal stem cell ,Dentistry ,medicine.disease ,Regenerative medicine ,Regenerative dentistry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Medicine ,030211 gastroenterology & hepatology ,Stem cell ,business ,Biomedicine - Abstract
Regenerative medicine is a modern branch of biomedicine that created the enormous therapeutic potential in the past decade.
- Published
- 2017
43. Adipose tissue as a strategic source of mesenchymal stem cells in bone regeneration: A topical review on the most promising craniomaxillofacial applications
- Author
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Massimo Marrelli, Gianrico Spagnuolo, Massimiliano Amantea, Carlo Rengo, Michel Goldberg, Marco Tatullo, Sandro Rengo, Francesco Paduano, Paduano, Francesco, Marrelli, Massimo, Amantea, Massimiliano, Rengo, Carlo, Rengo, Sandro, Goldberg, Michel, Spagnuolo, Gianrico, and Tatullo, Marco
- Subjects
0301 basic medicine ,Pathology ,Bone Regeneration ,Proteome ,Angiogenesis ,Adipose tissue ,Review ,Bioinformatics ,Bone tissue engineering ,Surgical reconstruction ,Catalysi ,lcsh:Chemistry ,Craniofacial Abnormalities ,Tissue engineering ,Osteogenesis ,lcsh:QH301-705.5 ,Spectroscopy ,Clinical Trials as Topic ,Tissue Scaffolds ,Computer Science Applications1707 Computer Vision and Pattern Recognition ,General Medicine ,Bone defect ,Computer Science Applications ,Topical review ,Clinical trial ,Adipose Tissue ,craniomaxillofacial bone defects ,Stem cell ,Adipose-derived stromal/stem cells (ASCs) ,medicine.medical_specialty ,Stromal cell ,Craniomaxillofacial bone defect ,bone defects ,Mesenchymal Stem Cell Transplantation ,Catalysis ,Molecular mechanism ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Bone regeneration ,Molecular Biology ,clinical trials ,Tissue Engineering ,business.industry ,Mesenchymal stem cell ,Organic Chemistry ,Mesenchymal Stem Cells ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,business ,Transcriptome - Abstract
Bone regeneration in craniomaxillofacial surgery represents an issue that involves both surgical and aesthetic aspects. The most recent studies on bone tissue engineering involving adipose-derived stromal/stem cells (ASCs) have clearly demonstrated that such cells can play a crucial role in the treatment of craniomaxillofacial defects, given their strong commitment towards the osteogenic phenotype. A deeper knowledge of the molecular mechanisms underlying ASCs is crucial for a correct understanding of the potentialities of ASCs-based therapies in the most complex maxillofacial applications. In this topical review, we analyzed the molecular mechanisms of ASCs related to their support toward angiogenesis and osteogenesis, during bone regeneration. Moreover, we analyzed both case reports and clinical trials reporting the most promising clinical applications of ASCs in the treatment of craniomaxillofacial defects. Our study aimed to report the main molecular and clinical features shown by ASCs, used as a therapeutic support in bone engineering, as compared to the use of conventional autologous and allogeneic bone grafts.
- Published
- 2017
44. Design, synthesis, biophysical and biological studies on trisubstituted naphthalimides as G-Quadruplex ligands
- Author
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Bruno Pagano, Antonella Peduto, Veronica Esposito, Francesco Paduano, Francesco Trapasso, Rosanna Filosa, Carmen Petronzi, Filomena Fiorito, Concetta Giancola, Antonella Virgilio, Aldo Galeone, Salvatore Florio, Antonio Massa, Peduto, A., Pagano, Bruno, Petronzi, C., Massa, A., Esposito, Veronica, Virgilio, Antonella, Paduano, F., Trapasso, F., Fiorito, Filomena, Florio, Salvatore, Giancola, Concetta, Galeone, Aldo, Filosa, R., Peduto, Antonella, Petronzi, Carmen, Massa, Antonio, Paduano, Francesco, Trapasso, Francesco, and Filosa, Rosanna
- Subjects
Circular dichroism ,Telomerase ,Lung Neoplasms ,Magnetic Resonance Spectroscopy ,Clinical Biochemistry ,Pharmaceutical Science ,Ligands ,Biochemistry ,chemistry.chemical_compound ,Mice ,Drug Discovery ,Enzyme Inhibitor ,heterocyclic compounds ,Enzyme Inhibitors ,NIH 3T3 Cell ,Melanoma ,Cancer ,G-quadruplex ,Molecular Structure ,Chemistry ,Circular Dichroism ,Nuclear magnetic resonance spectroscopy ,Naphthalimide ,Naphthalimides ,Molecular Medicine ,Human ,Stereochemistry ,Ligand ,Calorimetry ,Cell Line, Tumor ,G-Quadruplexe ,Animals ,Humans ,Molecular Biology ,Cell Proliferation ,Animal ,Cell growth ,Drug Discovery3003 Pharmaceutical Science ,Organic Chemistry ,Isothermal titration calorimetry ,Lung Neoplasm ,G-Quadruplexes ,Spectrometry, Fluorescence ,NIH 3T3 Cells ,Spectrophotometry, Ultraviolet ,DNA - Abstract
A series of trisubstituted naphthalimides have been synthesized and evaluated as telomeric G-quadruplex ligands by biophysical methods. Affinity for telomeric G-quadruplex AGGG(TTAGGG)(3) binding was first screened by fluorescence titrations. Subsequently, the interaction of the telomeric G-quadruplex with compounds showing the best affinity has been studied by isothermal titration calorimetry and UV-melting experiments. The two best compounds of the series tightly bind the telomeric quadruplex with a 2:1 drug/DNA stoichiometry. These derivatives have been further evaluated for their ability to inhibit telomerase by a TRAP assay and their pharmacological properties by treating melanoma (M14) and human lung cancer (A549) cell lines with increasing drug concentrations. A dose-dependent inhibition of cell proliferation was observed for all cellular lines during short-term treatment.
- Published
- 2011
45. A first-in-class Wiskott-Aldrich syndrome protein activator with anti-tumor activity in hematologic cancers.
- Author
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Spriano F, Sartori G, Sgrignani J, Barnabei L, Arribas AJ, Guala M, Del Amor AMC, Tomasso MR, Tarantelli C, Cascione L, Golino G, Riveiro ME, Bortolozzi R, Lupia A, Paduano F, Huguet S, Rezai K, Rinaldi A, Margheriti F, Ventura P, Guarda G, Costa G, Rocca R, Furlan A, Verdonk LM, Innocenti P, Martin NI, Viola G, Driessen C, Zucca E, Stathis A, Gahtory D, Van den Nieuwboer M, Bornhauser B, Alcaro S, Trapasso F, Cristobal S, Padrick SB, Pazzi N, Cavalli F, Cavalli A, Gaudio E, and Bertoni F
- Abstract
Hematological cancers are among the most common cancers in adults and children. Despite significant improvements in therapies, many patients still succumb to the disease. Therefore, novel therapies are needed. The Wiskott-Aldrich syndrome protein (WASp) family regulates actin assembly in conjunction with the Arp2/3 complex, a ubiquitous nucleation factor. WASp is expressed exclusively in hematopoietic cells and exists in two allosteric conformations: autoinhibited or activated. Here, we describe the development of EG-011, a first-in-class small molecule activator of the WASp auto-inhibited form. EG-011 possesses in vitro and in vivo anti-tumor activity as a single agent in lymphoma, leukemia, and multiple myeloma, including models of secondary resistance to PI3K, BTK, and proteasome inhibitors. The in vitro activity was confirmed in a lymphoma xenograft. Actin polymerization and WASp binding was demonstrated using multiple techniques. Transcriptome analysis highlighted homology with drugs-inducing actin polymerization.
- Published
- 2024
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46. A Dedifferentiation Strategy to Enhance the Osteogenic Potential of Dental Derived Stem Cells.
- Author
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Paduano F, Aiello E, Cooper PR, Marrelli B, Makeeva I, Islam M, Spagnuolo G, Maged D, De Vito D, and Tatullo M
- Abstract
Dental stem cells (DSCs) holds the ability to differentiate into numerous cell types. This property makes these cells particularly appropriate for therapeutic use in regenerative medicine. We report evidence that when DSCs undergo osteogenic differentiation, the osteoblast-like cells can be reverted back to a stem-like state and then further differentiated toward the osteogenic phenotype again, without gene manipulation. We have investigated two different MSCs types, both from dental tissues: dental follicle progenitor stem cells (DFPCs) and dental pulp stem cells (DPSCs). After osteogenic differentiation, both DFPCs and DPSCs can be reverted to a naïve stem cell-like status; importantly, dedifferentiated DSCs showed a greater potential to further differentiate toward the osteogenic phenotype. Our report aims to demonstrate for the first time that it is possible, under physiological conditions, to control the dedifferentiation of DSCs and that the rerouting of cell fate could potentially be used to enhance their osteogenic therapeutic potential. Significantly, this study first validates the use of dedifferentiated DSCs as an alternative source for bone tissue engineering., Competing Interests: DM was employed by company EMS—Elite Medical Service Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Paduano, Aiello, Cooper, Marrelli, Makeeva, Islam, Spagnuolo, Maged, De Vito and Tatullo.)
- Published
- 2021
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47. Exosomes from Human Periapical Cyst-MSCs: Theranostic Application in Parkinson's Disease.
- Author
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Tatullo M, Marrelli B, Zullo MJ, Codispoti B, Paduano F, Benincasa C, Fortunato F, Scacco S, Zavan B, and Cocco T
- Subjects
- Humans, Models, Biological, Precision Medicine, Circadian Rhythm, Exosomes, Mesenchymal Stem Cells, Parkinson Disease, Radicular Cyst
- Abstract
The scientific community continuously strives to get new disease models, to discover early markers or novel therapeutic approaches, improving the diagnosis and prognosis of several human pathologies. Parkinson's Disease (PD) is characterized by a long asymptomatic phase, characterized by a selective loss of dopaminergic neurons. Recently, the human Periapical Cyst-Mesenchymal Stem Cells (hPCy-MSCs) have been differentiated in functional dopaminergic neurons: such oral-derived MSCs and the hPCy-MSCs-derived exosomes may represent a strategic and useful in vitro study-model, as well as intriguing therapeutic carriers. Circadian rhythm (CR) alteration variously impacts on PD pathways: an interesting research target is represented by the analysis of the exosomes released by dopaminergic neurons, derived from neural-differentiated hPCy-MSCs, after having reproduced in-vitro PD-like conditions. This review aims to describe the crosstalk among some aspects of circadian rhythm related to the onset of PD and the exosomes released by cells of PD patients. More in detail: the first part of this article will describe the main characteristics of circadian rhythm and the involvement of the exosomes found to be effective in the pathogenesis of PD. Finally, the authors will suggest how those exosomes derived from dopaminergic neurons, obtained by oral-derived stem cells (hPCy-MSCs) may represent a smart model for the in vitro research on PD, to find new biomarkers, to test new drugs or, fatally, to find new pathways applicable in future therapeutic approaches., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2020
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48. Stem Cells-based and Molecular-based Approaches in Regenerative Dentistry: A Topical Review.
- Author
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Tatullo M, Codispoti B, Sied J, Makeeva I, Paduano F, Marrelli M, and Spagnuolo G
- Subjects
- Humans, Dental Pulp cytology, Dentistry, Regeneration, Stem Cell Transplantation, Stem Cells cytology, Tissue Engineering methods
- Abstract
Background: Regenerative medicine is a growing branch of medicine aimed to treat damaged or lost tissues, to promote tissue formation and to restore both aesthetics and function. In the last years, several scientific articles have been focused on the regenerative procedures aimed to increase the survival rate of compromised teeth; the most effective approaches have been based on molecularbased and on cellular-based protocols; however, to date, both these techniques have not been carefully analysed and discussed, to know in details the advantages of each of them., Methods: A literature search was undertaken on three electronic scientific databases: Medline via PubMed, EMBASE and Google Scholar. Authors aimed to select such articles published in the time span from January 1961 until December 2017. The authors screened the titles and the abstracts including the following keywords combinations: "Pulp AND Therapy", "Regenerative AND Endodontic", and "Endodontics AND Tissue engineering". After the exclusion of any not related articles, the full text of such papers related to the topics was included in this review., Results: Following the removal of duplicate articles and of other types of publications (such as erratum and corrigendum), 621 articles were selected to be included and analysed in our topical review. The articles were analysed into the following sections: cellular-based approaches for dental regeneration, molecular-based and combined cellular/molecular-based approaches for dental regeneration, and translational applications of regenerative dentistry., Conclusion: This topical review has been focused on the main, the most promising and the most innovative strategies for achieving the regeneration of dental pulp or dental tissues. The main and surprising "take-home message" is related to the great interest towards the dental-derived stem cells, characterized by a high angiogenic and neurogenic commitment. Future challenges will be focused on the development of biological-friendly regenerative strategies: the new approaches should overcome the current biological limitations, to promote the combined cellular and molecular-based treatments, able to ensure predictable clinical evidence, with the achievement of the regeneration/repairing of the compromised dental pulp and of the entire tooth structure., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2019
- Full Text
- View/download PDF
49. NANOmetric BIO-Banked MSC-Derived Exosome (NANOBIOME) as a Novel Approach to Regenerative Medicine.
- Author
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Codispoti B, Marrelli M, Paduano F, and Tatullo M
- Abstract
Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. In fact, MSCs can differentiate into several cell lineages and show paracrine behavior by releasing endogenous factors that stimulate tissue repair and modulate local immune response. Each MSC type is affected by specific biobanking issues-technical issues as well as regulatory and ethical concerns-thus making it quite tricky to safely and commonly use MSC banking for swift regenerative applications. Extracellular vesicles (EVs) include a group of 150⁻1000 nm vesicles that are released by budding from the plasma membrane into biological fluids and/or in the culture medium from varied and heterogenic cell types. EVs consist of various vesicle types that are defined with different nomenclature such as exosomes, shedding vesicles, nanoparticles, microvesicles and apoptotic bodies. Ectosomes, micro- and nanoparticles generally refer to the direct release of single vesicles from the plasma membrane. While many studies describe exosomes as deriving from multivesicular bodies, solid evidence about the origin of EVs is often lacking. Extracellular vesicles represent an important portion of the cell secretome. Their numerous properties can be used for diagnostic, prognostic, and therapeutic uses, so EVs are considered to be innovative and smart theranostic tools. The aim of this review is to investigate the usefulness of exosomes as carriers of the whole information panel characterizing the use of MSCs in regenerative medicine. Our purpose is to make a step forward in the development of the NANOmetric BIO-banked MSC-derived Exosome (NANOBIOME).
- Published
- 2018
- Full Text
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50. The receptor protein tyrosine phosphatase PTPRJ negatively modulates the CD98hc oncoprotein in lung cancer cells.
- Author
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D'Agostino S, Lanzillotta D, Varano M, Botta C, Baldrini A, Bilotta A, Scalise S, Dattilo V, Amato R, Gaudio E, Paduano F, Palmieri C, Iuliano R, Perrotti N, Indiveri C, Fusco A, Gaspari M, and Trapasso F
- Abstract
PTPRJ, a receptor protein tyrosine phosphatase strongly downregulated in human cancer, displays tumor suppressor activity by negatively modulating several proteins involved in proliferating signals. Here, through a proteomic-based approach, we identified a list of potential PTPRJ-interacting proteins and among them we focused on CD98hc, a type II glycosylated integral membrane protein encoded by SLC3A2 , corresponding to the heavy chain of a heterodimeric transmembrane amino-acid transporter, including LAT1. CD98hc is widely overexpressed in several types of cancers and contributes to the process of tumorigenesis by interfering with cell proliferation, adhesion, and migration. We first validated PTPRJ-CD98hc interaction, then demonstrated that PTPRJ overexpression dramatically reduces CD98hc protein levels in A549 lung cancer cells. In addition, following to the treatment of PTPRJ-transduced cells with MG132, a proteasome inhibitor, CD98hc levels did not decrease compared to controls, indicating that PTPRJ is involved in the regulation of CD98hc proteasomal degradation. Moreover, PTPRJ overexpression combined with CD98hc silencing consistently reduced cell proliferation and triggered apoptosis of lung cancer cells. Interestingly, by interrogating the can Evolve database, we observed an inverse correlation between PTPRJ and SLC3A2 gene expression. Indeed, the non-small cell lung cancers (NSCLCs) of patients showing a short survival rate express the lowest and the highest levels of PTPRJ and SLC3A2 , respectively. Therefore, the results reported here contribute to shed lights on PTPRJ signaling in cancer cells: moreover, our findings also support the development of a novel anticancer therapeutic approach by targeting the pathway of PTPRJ that is usually downregulated in highly malignant human neoplasias., Competing Interests: CONFLICTS OF INTEREST None.
- Published
- 2018
- Full Text
- View/download PDF
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