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3. Impairment of circulating endothelial progenitors in Down syndrome

Author

Costa Valerio, Sommese Linda, Casamassimi Amelia, Colicchio Roberta, Angelini Claudia, Marchesano Valentina, Milone Lara, Farzati Bartolomeo, Giovane Alfonso, Fiorito Carmela, Rienzo Monica, Picardi Marco, Avallone Bice, Marco Corsi Massimiliano, Sarubbi Berardo, Calabrò Raffaele, Salvatore Paola, Ciccodicola Alfredo, and Napoli Claudio

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Methods Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. Results We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Conclusions Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.

Published
2010
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4. DDX11L: a novel transcript family emerging from human subtelomeric regions

Author

D'Urso Michele, Matarazzo Maria R, Gianfrancesco Fernando, Roberto Roberta, Casamassimi Amelia, Costa Valerio, D'Esposito Maurizio, Rocchi Mariano, and Ciccodicola Alfredo

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background The subtelomeric regions of human chromosomes exhibit an extraordinary plasticity. To date, due to the high GC content and to the presence of telomeric repeats, the subtelomeric sequences are underrepresented in the genomic libraries and consequently their sequences are incomplete in the finished human genome sequence, and still much remains to be learned about subtelomere organization, evolution and function. Indeed, only in recent years, several studies have disclosed, within human subtelomeres, novel gene family members. Results During a project aimed to analyze genes located in the telomeric region of the long arm of the human X chromosome, we have identified a novel transcript family, DDX11L, members of which map to 1pter, 2q13/14.1, 2qter, 3qter, 6pter, 9pter/9qter, 11pter, 12pter, 15qter, 16pter, 17pter, 19pter, 20pter/20qter, Xpter/Xqter and Yqter. Furthermore, we partially sequenced the underrepresented subtelomeres of human chromosomes showing a common evolutionary origin. Conclusion Our data indicate that an ancestral gene, originated as a rearranged portion of the primate DDX11 gene, and propagated along many subtelomeric locations, is emerging within subtelomeres of human chromosomes, defining a novel gene family. These findings support the possibility that the high plasticity of these regions, sites of DNA exchange among different chromosomes, could trigger the emergence of new genes.

Published
2009
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6. Multiple Sclerosis: From the Application of Oligoclonal Bands to Novel Potential Biomarkers.

Author

Maglio, Grazia, D'Agostino, Marina, Caronte, Francesco Pio, Pezone, Luciano, Casamassimi, Amelia, Rienzo, Monica, Di Zazzo, Erika, Nappo, Carmela, Medici, Nicola, Molinari, Anna Maria, and Abbondanza, Ciro

Subjects
IMMUNOGLOBULIN light chains, MULTIPLE sclerosis, CEREBROSPINAL fluid examination, CEREBROSPINAL fluid, BIOMARKERS, CENTRAL nervous system, NATALIZUMAB
Abstract

Multiple sclerosis is a chronic immune-mediated disorder of the central nervous system with a high heterogeneity among patients. In the clinical setting, one of the main challenges is a proper and early diagnosis for the prediction of disease activity. Current diagnosis is based on the integration of clinical, imaging, and laboratory results, with the latter based on the presence of intrathecal IgG oligoclonal bands in the cerebrospinal fluid whose detection via isoelectric focusing followed by immunoblotting represents the gold standard. Intrathecal synthesis can also be evidenced by the measurement of kappa free light chains in the cerebrospinal fluid, which has reached similar diagnostic accuracy compared to that of oligoclonal bands in the identification of patients with multiple sclerosis; moreover, recent studies have also highlighted its value for early disease activity prediction. This strategy has significant advantages as compared to using oligoclonal band detection, even though some issues remain open. Here, we discuss the current methods applied for cerebrospinal fluid analysis to achieve the most accurate diagnosis and for follow-up and prognosis evaluation. In addition, we describe new promising biomarkers, currently under investigation, that could contribute both to a better diagnosis of multiple sclerosis and to its monitoring of the therapeutic treatment response. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Transcriptional Regulation : Molecules, involved Mechanisms and Misregulation

Author

Casamassimi, Amelia and Ciccodicola, Alfredo

Abstract

Transcriptional regulation is a critical biological process involved in the response of a cell, a tissue or an organism to a variety of intra- and extra-cellular signals. Besides, it controls the establishment and maintenance of cell identity throughout developmental and differentiation programs. This highly complex and dynamic process is orchestrated by a huge number of molecules and protein networks and occurs through multiple temporal and functional steps. Of note, many human disorders are characterized by misregulation of global transcription since most of the signaling pathways ultimately target components of transcription machinery. This book includes a selection of papers that illustrate recent advances in our understanding of transcriptional regulation and focuses on many important topics, from cis-regulatory elements to transcription factors, chromatin regulators and non-coding RNAs, other than several transcriptome studies and computational analyses.

Published
2019

17. CXCR4/YY1 inhibition impairs VEGF network and angiogenesis during malignancy

Author

de Nigris, Filomena, Crudele, Valeria, Giovane, Alfonso, Casamassimi, Amelia, Giordano, Antonio, Garban, Hermes J., Cacciatore, Francesco, Pentimalli, Francesca, Marquez-Garban, Diana C., Petrillo, Antonella, Cito, Letizia, Sommese, Linda, Fiore, Andrea, Petrillo, Mario, Siani, Alfredo, Barbieri, Antonio, Arra, Claudio, Rengo, Franco, Hayashi, Toshio, Al-Omran, Mohammed, Ignarro, Louis J., and Napoli, Claudio

Published
2010

18. Detrimental Effects of Bartonella henselae Are Counteracted by L-Arginine and Nitric Oxide in Human Endothelial Progenitor Cells

Author

Salvatore, Paola, Casamassimi, Amelia, Sommese, Linda, Fiorito, Carmela, Ciccodicola, Alfredo, Rossiello, Raffaele, Avallone, Bice, Grimaldi, Vincenzo, Costa, Valerio, Rienzo, Monica, Colicchio, Roberta, Williams-Ignarro, Sharon, Pagliarulo, Caterina, Prudente, Maria Evelina, Abbondanza, Ciro, Lamberti, Florentia, Baroni, Adone, Buommino, Elisabetta, Farzati, Bartolomeo, Tufano, Maria Antonietta, Ignarro, Louis Joseph, and Napoli, Claudio

Published
2008
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19. Searching for a putative mechanism of tumor-promoting function of RIZ2 in cancer models

Author

Rienzo Monica, Sorrentino Anna, Di Zazzo Erika, Di Donato Marzia, Carafa Vincenzo, Marino Maria Michela, De Rosa Caterina, Gazzerro Patrizia, Castoria Gabriella, Altucci Lucia, Casamassimi Amelia, Abbondanza Ciro, Rienzo, Monica, Sorrentino, Anna, Di Zazzo, Erika, DI DONATO, Marzia, Carafa, Vincenzo, Marino Maria, Michela, De Rosa, Caterina, Gazzerro, Patrizia, Castoria, Gabriella, Altucci, Lucia, Casamassimi, Amelia, and Abbondanza, Ciro

Abstract

Positive Regulatory Domain (PRDM) gene family members commonly express two main molecular variants, the PR-plus isoform usually acting as tumor suppressor and the PR-minus one functioning as oncogene. Accordingly, PRDM2/RIZ encodes for RIZ1 (PR-plus) and RIZ2 (PR-minus). In human cancers, genetic or epigenetic modifications induce RIZ1 silencing with an expression level imbalance in favor of RIZ2 that could be relevant for tumorigenesis. Additionally, in estrogen target cells and tissues, estradiol increases RIZ2 expression level with concurrent increase of cell proliferation and survival. Several attempts to study RIZ2 function in HeLa or MCF-7 cells by its over-expression were unsuccessful. Thus, we over-expressed RIZ2 in HEK-293 cells, which are both RIZ1 and RIZ2 positive but unresponsive to estrogens. The forced RIZ2 expression increased cell viability and growth, prompted the G2-to-M phase transition and organoids formation. Accordingly, microarray analysis revealed that RIZ2 regulates several genes involved in mitosis. Consistently, RIZ silencing in both estrogen-responsive MCF-7 and –unresponsive MDA-MB-231 cells induced a reduction of cell proliferation and an increase of apoptosis rate. Our findings add novel insights on the putative RIZ2 tumor-promoting functions, although additional attempts are warranted to depict the underlying molecular mechanism.

Published
2021

23. PRDM12 in Health and Diseases

Author

Rienzo, Monica, primary, Di Zazzo, Erika, additional, Casamassimi, Amelia, additional, Gazzerro, Patrizia, additional, Perini, Giovanni, additional, Bifulco, Maurizio, additional, and Abbondanza, Ciro, additional

Published
2021
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30. Contributors

Author

Burdge, Graham C., primary, Carrell, Douglas T., additional, Casamassimi, Amelia, additional, Champagne, Frances A., additional, Chi, Tian, additional, Crews, David, additional, Cridge, Andrew G., additional, Csaba, György, additional, Dearden, Peter K., additional, Díaz, Rubén, additional, Dietert, Rodney R., additional, Ding, Yingwen, additional, Duncan, Elizabeth J., additional, Geoghegan, Jemma L., additional, Gore, Andrea C., additional, Grenfell, Leonie R., additional, Hanson, Mark A., additional, Hirasawa, Takae, additional, Ho, Dao H., additional, Hoile, Samuel P., additional, Ito, Hidetaka, additional, Jimenez-Chillaron, Josep C., additional, Kaundal, Ravinder, additional, Kellermayer, Richard, additional, Kosten, Therese A., additional, Kubota, Takeo, additional, Li, Jiong, additional, Lillycrop, Karen A., additional, Mancini, Francesco Paolo, additional, Mashoodh, Rahia, additional, Miyake, Kunio, additional, Murphy, Kristin E., additional, Murphy, Patrick J., additional, Napoli, Claudio, additional, Nielsen, David A., additional, Nilsson, Eric, additional, Nottoli, Timothy, additional, Osborne, Amy J., additional, Painter, Rebecca, additional, Paoloni-Giacobino, Ariane, additional, Ramón-Krauel, Marta, additional, Ribó, Sílvia, additional, Riddle, Nicole C., additional, Roseboom, Tessa, additional, Rosenfeld, Cheryl S., additional, Roeters van Lennep, Jeanine, additional, Sijbrands, Eric J.G., additional, Skinner, Michael K., additional, Tollefsbol, Trygve O., additional, Uller, Tobias, additional, Versmissen, Jorie, additional, Yang, Yan, additional, Zheng, Ling, additional, and Zullo, Alberto, additional

Published
2014
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35. Searching for a Putative Mechanism of RIZ2 Tumor-Promoting Function in Cancer Models

Author

Rienzo, Monica, primary, Sorrentino, Anna, additional, Di Zazzo, Erika, additional, Di Donato, Marzia, additional, Carafa, Vincenzo, additional, Marino, Maria Michela, additional, De Rosa, Caterina, additional, Gazzerro, Patrizia, additional, Castoria, Gabriella, additional, Altucci, Lucia, additional, Casamassimi, Amelia, additional, and Abbondanza, Ciro, additional

Published
2021
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36. Five Italian Families with Two Mutations in BRCA Genes

Author

Vietri, Maria Teresa, primary, Caliendo, Gemma, additional, D’Elia, Giovanna, additional, Resse, Marianna, additional, Casamassimi, Amelia, additional, Minucci, Pellegrino Biagio, additional, Dello Ioio, Concetta, additional, Cioffi, Michele, additional, and Molinari, Anna Maria, additional

Published
2020
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41. Double mutation of APC and BRCA1 in an Italian family

Author

Vietri, Maria Teresa, primary, D'Elia, Giovanna, additional, Caliendo, Gemma, additional, Casamassimi, Amelia, additional, Resse, Marianna, additional, Passariello, Luana, additional, Cioffi, Michele, additional, and Molinari, Anna Maria, additional

Published
2020
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42. Multifaceted Role of PRDM Proteins in Human Cancer

Author

Casamassimi, Amelia, primary, Rienzo, Monica, additional, Di Zazzo, Erika, additional, Sorrentino, Anna, additional, Fiore, Donatella, additional, Proto, Maria Chiara, additional, Moncharmont, Bruno, additional, Gazzerro, Patrizia, additional, Bifulco, Maurizio, additional, and Abbondanza, Ciro, additional

Published
2020
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43. Mobile Screening Units for the Early Detection of Breast Cancer and Cardiovascular Disease: A Pilot Telemedicine Study in Southern Italy

Author

Marino, Maria Michela, primary, Rienzo, Monica, additional, Serra, Nicola, additional, Marino, Nicola, additional, Ricciotti, Raffaella, additional, Mazzariello, Luigi, additional, Leonetti, Concetta Anna, additional, Ceraldi, Maria Palma, additional, Casamassimi, Amelia, additional, Capocelli, Francesca, additional, Martone, Gennaro, additional, and Caracciolo, Aniello Leonardo, additional

Published
2020
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48. Effects of polysaccharide A product by Bacteroides fragilis on endothelial progenitor cells

Author

CERCIELLO, RAIMONDO, Anna, Di Biase, COLICCHIO, ROBERTA, CASAMASSIMI, AMELIA, Claudio, Napoli, SALVATORE, PAOLA, AVALLONE, BICE, PAGEPress, Pavia, Italy, C. Pellicciari, Cerciello, Raimondo, Anna, Di Biase, Colicchio, Roberta, Casamassimi, Amelia, Claudio, Napoli, Salvatore, Paola, and Avallone, Bice

Subjects
Bacteroides, Tem, EPC
Abstract

Endothelial progenitor cells are produced in the bone marrow and have the hemangioblast as common precursor to hematopoietic stem cells. They have been identified in 1997 in the peripheral blood stream. The EPC are able to migrate, proliferate and differentiate into mature endothelial cells and to determine the formation of new blood vessels even in the postnatal period. These cells can be infected by Bartonella henselae, a Gram-negative pathogen, aetiological agent of a series of human diseases known as bartonellosis. Polysaccharide A pro-duced by Bacteroides fragilis, a human intestinal bacterium, has immunoregulatory properties, among which is proven in mice to provide protection from inflammation caused by B. henselae. We have infected the EPC with B. henselae, B. fragilis WT or B. fragilis PSA (not able to produce the polysaccharide A), or coinfected with B. henselae and B. fragilis, WT or PSA respectively, to assess whether the polysaccharide A had a role in the response of these cells to the infection. After the ultrastructural characterization of bacterial strains used in our experiments, Bacteroides ability to infect EPC was assessed by CLSM. Both bacterial strains are internalized already at 24h after infection and at a multiplicity of infection of 100. By TEM it was observed that Bacteroides in contrast to Bartonella, are internalized activating cytoplasmic lysosomes that digest them. B. henselae instead infects those cells forming invasomes in which they continues to proliferate. So polysaccharide A accentuates the macrophagic features that these cells have in their early differentiation stage. Analysis of genic expression using real time PCR from total RNA extracted by the cell cultures have shown the up-regulation of the gene coding for the IL-10 anti-inflammatory cytokine in cells co-infected with B. fragilis WT and B. henselae compared to the cells infected only with B. henselae. The main inflammatory cytokines secretion evaluated by ELISA has also evidenced an increase of IL-10 produced by cells coinfected with B. fragilis WT and B. henselae. These cells react to the co-infection in the same manner of macrophages. These data assert that the EPC does not play only a key role in vasculogenesis, but in an adult organism they could also play an essential role in the immune response. The EPC may collaborate with macrophages and T cells CD4+, to the inflammatory process triggered by the polysaccharide A after infection.

Published
2015

49. Seroprevalence of Bartonella henselae in patients awaiting heart transplant in Southern Italy

Author

Picascia A, Pagliuca C, Colicchio R, CASAMASSIMI, Amelia, Labonia F, Pastore G, Pagliarulo C, Cicatiello AG, Castaldo F, Schiano C, Maiello C, Mezza E, D'Armiento FP, Salvatore P, Napoli C., SOMMESE, Linda, Picascia, A, Pagliuca, C, Sommese, Linda, Colicchio, R, Casamassimi, Amelia, Labonia, F, Pastore, G, Pagliarulo, C, Cicatiello, Ag, Castaldo, F, Schiano, C, Maiello, C, Mezza, E, D'Armiento, Fp, Salvatore, P, and Napoli, C.

Published
2015

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