39 results on '"Cito, L."'
Search Results
2. URINARY P-IPG AS A MARKER FOR PREDICTION OF PREECLAMPSIA
- Author
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Scioscia, M, Paine, M A, Gumaa, K, Rodeck, C H, Cito, L, Monteduro, E, and Rademacher, T W
- Published
- 2007
3. pRb2/p130 localizes to the cytoplasm in diffuse gastric cancer
- Author
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Cito L., Indovina P., Forte I. M., Pentimalli F., Di Marzo D., Somma P., Barone D., Penon A., Penon D., Ceccherini E., Micheli P., Saragoni L., Di Domenico M., Feola A., Roviello F., Mattioli E., Giordano G. G., Giordano A., Cito, L., Indovina, P., Forte, I. M., Pentimalli, F., Di Marzo, D., Somma, P., Barone, D., Penon, A., Penon, D., Ceccherini, E., Micheli, P., Saragoni, L., Di Domenico, M., Feola, A., Roviello, F., Mattioli, E., Giordano, G. G., and Giordano, A.
- Subjects
Male ,Cytoplasm ,Retinoblastoma-Like Protein p130 ,Retinoblastoma Protein ,Crk-Associated Substrate Protein ,Salivary Proline-Rich Protein ,Stomach Neoplasm ,Phosphoprotein ,Cell Cycle Protein ,Female ,Genes, Tumor Suppressor ,Cell Division ,Human ,Transcription Factors - Published
- 2015
4. The inhibition of p85aPI3KSer83 phosphorylation prevents cell proliferation and invasion in prostate cancer cells
- Author
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Feola, A., Cimini, A., Migliucci, F., Iorio, R., Zuchegna, C., Rothenberger, R., Cito, L., Porcellini, A., Unteregger, G., Tombolini, Vincenzo, Giordano, A., Di Domenico, M., Feola, Antonia, Annamaria, Cimini, Francesca, Migliucci, Rosamaria, Iorio, Zuchegna, Candida, Rodger, Rothenberger, Letizia, Cito, Porcellini, Antonio, Gerhard, Unteregger, Vincenzo, Tombolini, Antonio, Giordano, Marina Di, Domenico, Feola, A, Cimini, A, Migliucci, F, Iorio, R, Zucchegna, C, Rothenberger, R, Cito, L, Porcellini, A, Unteregger, G, Tombolini, V, Giordano, A, and DI DOMENICO, Marina
- Subjects
Male ,Microscopy, Confocal ,Prostate cancer ,lncap ,regulatory subunit p85 ,prostate cancer ,phosphorylation ,Prostatic Neoplasms ,Apoptosis ,PI3K ,REGULATORY SUBUNIT p85 ,Phosphatidylinositol 3-Kinases ,Protein Subunits ,Cell Line, Tumor ,PROSTATE CANCER ,PHOSPHORYLATION ,LnCap ,Serine ,Humans ,metastasi ,Phosphorylation ,Cell Proliferation ,Signal Transduction - Abstract
Phosphoinositide 3‐kinase proteins are composed by a catalytic p110 subunit and a regulatory p85 subunit. There are three classes of PI3K, named class I–III, on the bases of the protein domain constituting and determining their specificity. The first one is the best characterized and includes a number of key elements for the integration of different cellular signals. Regulatory p85 subunit shares with the catalytic p110 subunit, a N‐terminal SH3 domain showing homology with the protein domain Rho‐GTP‐ase. After cell stimulation, all class I PI3Ks are recruited to the inner face of the plasma membrane, where they generate phosphatidylinositol‐3,4,5‐trisphosphate by direct phosphorylation of phosphatidylinositol‐4,5‐bisphosphate. All pathways trigger the control of different phenomena such as cell growth, proliferation, apoptosis, adhesion and migration through various downstream effectors. We have previously provided direct evidences that a Serine in position 83, adjacent to the N‐terminal SH3 domain of regulatory subunit of PI3K, is a substrate of PKA. The aim of this work is to confirm the role of p85aPI3KSer83 in regulating cell proliferation, migration and invasion in prostate cancer cells LNCaP. To this purpose cells were transfected with mutant forms of p85, where Serine was replaced by Alanine, where phosphorylation is prevented, or Aspartic Acid, to mimic the phosphorylated residue. The findings of this study suggest that identifying a peptide mimicking the sequence adjacent to Ser 83 may be used to produce antibodies against this residue that can be proposed as usefool tool for prognosis by correlating phosphorylation at Ser83 with tumor stage. J. Cell. Biochem. 114: 2114–2119, 2013.
- Published
- 2013
5. Novel findings about management of gastric cancer: A summary from 10thIGCC
- Author
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Penon, D., Cito, L., and Giordano, A.
- Subjects
Markers ,Gastric cancer ,Prognostic tools ,Therapy - Published
- 2014
6. Urokinase receptor activation by a novel interaction between connecting peptide region of Urokinase and αvβ5 Integrin Journal of Cell Science, 119, 3424-3434, 2006
- Author
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FRANCO, P, VOCCA, I, CARRIERO, M. V, ALFANO, D, CITO, L, LONGANESI CATTANI, I, P, OSSOWSKI, L, STOPPELLI, M. P., GRIECO, PAOLO, Franco, P, Vocca, I, Carriero, M. V, Alfano, D, Cito, L, Longanesi, Cattani, I, Grieco, Paolo, P, Ossowski, L, Stoppelli, and M., P.
- Subjects
Urokinase ,Peptide Synthesis - Abstract
The serine protease urokinase (uPA) binds to the urokinase receptor (uPAR) through its growth-factor domain (GFD, residues 1-49), affecting cell migration, adhesion and growth. Here, we show that uPA can promote cytoskeletal rearrangements and directional cell migration in a GFD-independent manner, through a new and specific interaction between an internal uPA domain coined 'connecting peptide' (residues 132-158) and cell-surface integrin alpha v beta 5. Remarkably, a peptide corresponding to this region (CPp, residues 135-158) retains the ability to bind to alpha v beta 5, eliciting cytoskeletal rearrangements and directing cell migration at a concentration as low as 1-10 pM. These effects are lost in cells not expressing uPAR, indicating that the uPAR is required for CPp-dependent signaling. Furthermore, the CPp-alpha v beta 5-integrin interaction enhances F-actin-enriched protrusions and cell migration induced by the well-established interaction between the uPAR-binding peptide (GFDp, residues 12-32) of uPA and uPAR. These results provide new insight into the function of uPA, which - through individual domains - can engage two different surface receptors (uPAR and alpha v beta 5 integrin), thus initiating and potentiating intracellular signaling and migration.
- Published
- 2006
7. Loss of tumour suppressor gene PTEN marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive germ cell tumors
- Author
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DI VIZIO D., CITO L., BOCCIA A., INSABATO L., PETTINATO G., MOTTI M. L., SCHEPIS F., D, AMICO W., FABIANI F., TAVERNISE B., VENUTA S., FUSCO A., VIGLIETTO G., CHIEFFI, Paolo, DI VIZIO, D., Cito, L., Boccia, A., Chieffi, Paolo, Insabato, L., Pettinato, G., Motti, M. L., Schepis, F., D, Amico, W., Fabiani, F., Tavernise, B., Venuta, S., Fusco, A., and Viglietto, G.
- Published
- 2005
8. Critical role of cyclin D3 in TSH-dependent growth of thyreocytes and in hyperproliferative disorders of the thyroid gland
- Author
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MOTTI M. L, BOCCIA A, BELETTI B, BRUNI P, CITO L, MONACO M, CHIAPPETTA G, BALDASSARE G, PALOMBINI L, FUSCO, ALFREDO, VIGLIETTO G., TRONCONE, GIANCARLO, MOTTI M., L, Boccia, A, Beletti, B, Bruni, P, Troncone, Giancarlo, Cito, L, Monaco, M, Chiappetta, G, Baldassare, G, Palombini, L, Fusco, Alfredo, and Viglietto, G.
- Published
- 2003
9. Cytokines and VEGF Induction in Orthodontic Movement in Animal Models
- Author
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Di Domenico, M., D'apuzzo, F., Feola, A., Cito, L., Monsurrò, A., Pierantoni, G. M., Berrino, L., De Rosa, A., Polimeni, A., and Perillo, L.
- Subjects
stomatognathic diseases ,stomatognathic system ,Article Subject - Abstract
Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1β and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor.
- Published
- 2012
- Full Text
- View/download PDF
10. Epigenetics, MicroRNAs, and Cancer: An Update
- Author
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Russo, G., Puca, A., Masulli, F., Rovetta, S., Cito, L., Muresu, D., Rizzolio, F., and Giordano, A.
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Epigenetic alterations and miRNAs - biological importance of miRNAs ,epi-miRNAs ,NEW GROUP of miRNAs ,not fully understood ,Epigenetics ,and cancer - microRNAs or miRNA ,as negative protein-encoded gene regulators ,small noncoding molecules ,indirect - epigenetic mechanisms ,gene expression regulation in human cancer development ,Epigenetic alterations and miRNAs - biological importance of miRNAs, regulation of miRNA expression, not fully understood ,Epigenetics, microRNAs, and cancer - microRNAs or miRNA, small noncoding molecules, as negative protein-encoded gene regulators ,NEW GROUP of miRNAs, epi-miRNAs, indirect - epigenetic mechanisms, gene expression regulation in human cancer development ,regulation of miRNA expression ,microRNAs - Published
- 2011
11. Rb family proteins in gastric cancer
- Author
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Cito, L., Pentimalli, F., Forte, I., Mattioli, E., and Antonio Giordano
- Published
- 2010
12. Suppression of HMGA2 Protein Synthesis Could Be a Tool for the Therapy of Well Differentiated Liposarcomas Overexpressing HMGA2
- Author
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Pentimalli, F., Dentice, M., Fedele, M., Pierantoni, G. M., Cito, L., Pallante, P., Santoro, M., Viglietto, G., Dal Cin, P., and Alfredo Fusco
- Abstract
Atypical lipomatous tumors (ALTs)/well-differentiated liposarcomas represent a distinctive subset of mesenchymal neoplasms featuring mature adipocytic proliferation. These tumors are characterized cytogenetically by the presence of supernumerary ring and/or long marker chromosomes that contain several copies of the chromosomal region 12q13-15, in which the HMGA2 gene is located. Deregulation of the HMGA2 gene is a common molecular alteration implicated in the development of a variety of benign tumors, such as lipomas, uterine leiomyomas, and pulmonary chondroid hamartomas. In this study, we observed HMGA2 overexpression in 7 of 12 ALT primary cell cultures examined. Subsequently, we generated an adenovirus containing the HMGA2 gene in the antisense orientation (Ad-A2as) to study the effect of HMGA2 protein suppression in ALT cells. The infection of six ALT cells, three of which were positive for HMGA2 expression, resulted in growth inhibition coupled with a significant increase in apoptosis. In addition, the growth of the ALT cells negative for HMGA2 expression was not affected by the infection with either the Ad-A2as or the control virus. On the basis of these findings, the targeting of the HMGA2 protein expression may represent a promising approach for treating the well-differentiated liposarcomas resistant to conventional therapies.
13. Dual role of parathyroid hormone in endothelial progenitor cells and marrow stromal mesenchymal stem cells
- Author
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Umberto Galderisi, Giovanni Di Bernardo, Marilena Cipollaro, Claudio Napoli, Antonio Giordano, Carmela Fiorito, Letizia Cito, Tiziana Squillaro, DI BERNARDO, Giovanni, Galderisi, Umberto, Fiorito, C, Squillaro, T, Cito, L, Cipollaro, Marilena, Giordano, A, Napoli, Claudio, Di Bernardo, G., Galderisi, U., Fiorito, C., Squillaro, T., Cito, L., Cipollaro, M., Giordano, A., Napoli, C., Di Bernardo, Giovanni, Fiorito, Carmela, Squillaro, Tiziana, Cito, Letizia, and Giordano, Antonio
- Subjects
Time Factors ,Physiology ,Clinical Biochemistry ,Parathyroid hormone ,Apoptosis ,Retinoblastoma Protein ,Cells, Cultured ,Cellular Senescence ,Endothelial Cell ,Stem Cells ,Cell Differentiation ,Endothelial stem cell ,Haematopoiesis ,medicine.anatomical_structure ,Mesenchymal Stem Cell ,8-Hydroxy-2'-Deoxyguanosine ,Parathyroid Hormone ,cardiovascular system ,Bone Marrow Cell ,Stem cell ,hormones, hormone substitutes, and hormone antagonists ,circulatory and respiratory physiology ,Human ,medicine.medical_specialty ,endocrine system ,Stromal cell ,Time Factor ,Bone Marrow Cells ,Biology ,Stem Cell ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,Progenitor cell ,Cell Proliferation ,Mesenchymal stem cell ,Stromal Cell ,Endothelial Cells ,Apoptosi ,Deoxyguanosine ,Mesenchymal Stem Cells ,Cell Biology ,Endocrinology ,Gene Expression Regulation ,Cancer research ,Receptors, Parathyroid Hormone ,Bone marrow ,Stromal Cells ,Tumor Suppressor Protein p53 ,DNA Damage - Abstract
Hematopoietic stem cells derive regulatory information also from parathyroid hormone (PTH). To explore the possibility that PTH may have a role in regulation of other stem cells residing in bone marrow, such as mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) we assessed the effect of this hormone on the in vitro behavior of MSCs and EPCs. Weevidenced that MSCs were much more responsive to PTH than EPCs. PTH increased the proliferation rate of MSCs with a diminution of senescence and apoptosis. Taken together, our results may suggest a protective effect of PTH on MSCs that reduces stress phenomena and preserve genome integrity. At the opposite, PTH did not modify the fate of EPCs in culture. © 2009 Wiley-Liss, Inc.
- Published
- 2010
14. Translational Research and Plasma Proteomic in Cancer
- Author
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Annamaria Chiara Santini, Adelaide Auletta, Carlo Astarita, Angelina Di Carlo, Antonio Giordano, Antonia Feola, Letizia Cito, Roberto Alfano, Alfonso Fiorelli, Marina Di Domenico, Giancarlo Giovane, Santini, A. C., Giovane, G., Auletta, A., Di Carlo, A., Fiorelli, A., Cito, L., Astarita, C., Giordano, A., Alfano, R., Feola, A., Di Domenico, M., Santini, Annamaria Chiara, Giovane, Giancarlo, Auletta, Adelaide, Di Carlo, Angelina, Fiorelli, Alfonso, Cito, Letizia, Astarita, Carlo, Giordano, Antonio, Alfano, Roberto, Feola, Antonia, and DI DOMENICO, Marina
- Subjects
0301 basic medicine ,Male ,Proteomics ,PLASMA PROTEOMIC ,Lung Neoplasms ,BIOMARKERS ,Reproducibility of Result ,Gene Expression ,Translational research ,Disease ,Biology ,Bioinformatics ,Tumor heterogeneity ,Biochemistry ,Sensitivity and Specificity ,Neoplasm Protein ,Translational Research, Biomedical ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Biomarkers, Tumor ,Humans ,Tumor growth ,Translational Medical Research ,Molecular Biology ,Ovarian Neoplasms ,biomarkers ,cancer ,plasma proteomic ,Ovarian Neoplasm ,Pancreatic Neoplasm ,Cancer ,Proteomic ,Reproducibility of Results ,Cell Biology ,medicine.disease ,CANCER ,Neoplasm Proteins ,Lung Neoplasm ,Pancreatic Neoplasms ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer biomarkers ,Female ,Human - Abstract
Proteomics is a recent field of research in molecular biology that can help in the fight against cancer through the search for biomarkers that can detect this disease in the early stages of its development. Proteomic is a speedily growing technology, also thanks to the development of even more sensitive and fast mass spectrometry analysis. Although this technique is the most widespread for the discovery of new cancer biomarkers, it still suffers of a poor sensitivity and insufficient reproducibility, essentially due to the tumor heterogeneity. Common technical shortcomings include limitations in the sensitivity of detecting low abundant biomarkers and possible systematic biases in the observed data. Current research attempts are trying to develop high-resolution proteomic instrumentation for high-throughput monitoring of protein changes that occur in cancer. In this review, we describe the basic features of the proteomic tools which have proven to be useful in cancer research, showing their advantages and disadvantages. The application of these proteomic tools could provide early biomarkers detection in various cancer types and could improve the understanding the mechanisms of tumor growth and dissemination.
- Published
- 2015
15. pRb2/p130 localizes to the cytoplasm in diffuse gastric cancer
- Author
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Letizia, Cito, Paola, Indovina, Iris Maria, Forte, Francesca, Pentimalli, Domenico, Di Marzo, Pasquale, Somma, Daniela, Barone, Antonella, Penon, Danila, Penon, Elisa, Ceccherini, Pietro, Micheli, Luca, Saragoni, Marina, Di Domenico, Antonia, Feola, Franco, Roviello, Eliseo, Mattioli, Giovan Giacomo, Giordano, Antonio, Giordano, 1., Cito L, Indovina, P, Forte, I. M., Marzo, D. D., Somma, P, Barone, D, Penon, A, Penon, D, Ceccherini, E, Micheli, P, Saragoni, L, DI DOMENICO, Marina, Feola, A, Roviello, F, Mattioli, E, Giordano, G. G., and Giordano, A.
- Subjects
Male ,Cytoplasm ,Transcription Factor ,Physiology ,Clinical Biochemistry ,Cell Cycle Proteins ,Cell Division ,Crk-Associated Substrate Protein ,Female ,Genes, Tumor Suppressor ,Humans ,Phosphoproteins ,Retinoblastoma Protein ,Retinoblastoma-Like Protein p130 ,Salivary Proline-Rich Proteins ,Stomach Neoplasms ,Transcription Factors ,Stomach Neoplasm ,Cell Cycle Protein ,Cell Biology ,Salivary Proline-Rich Protein ,Genes ,Phosphoprotein ,Tumor Suppressor ,Human - Abstract
pRb2/p130 is a key tumor suppressor, whose oncosuppressive activity has mainly been attributed to its ability to negatively regulate cell cycle by interacting with the E2F4 and E2F5 transcription factors. Indeed, pRb2/p130 has been found altered in various cancer types in which it functions as a valuable prognostic marker. Here, we analyzed pRb2/p130 expression in gastric cancer tissue samples of diffuse histotype, in comparison with their normal counterparts. We found a cytoplasmic localization of pRb2/p130 in cancer tissue samples, whereas, in normal counterparts, we observed the expected nuclear localization. pRb2/p130 cytoplasmic delocalization can lead to cell cycle deregulation, but considering the emerging involvement of pRb2/p130 in other key cellular processes, it could contribute to gastric tumorigenesis also through other mechanisms. Our data support the necessity of further investigations to verify the possibility of using pRb2/p130 as a biomarker or potential therapeutic target for diffuse gastric cancer.
- Published
- 2015
16. Cytokines and VEGF induction in orthodontic movement in animal models
- Author
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L. Berrino, Fabrizia d’Apuzzo, A. De Rosa, M. Di Domenico, Letizia Cito, Antonia Feola, Giovanna Maria Pierantoni, A. Monsurrò, Letizia Perillo, Antonella Polimeni, DI DOMENICO, Marina, D'Apuzzo, F, Feola, A, Cito, L, Monsurrò, A, Pierantoni, Gm, Berrino, Liberato, DE ROSA, Alfredo, Polimeni, A, Perillo, Letizia, Di Domenico, M, Pierantoni, GIOVANNA MARIA, Berrino, L, De Rosa, A, and Perillo, L.
- Subjects
Vascular Endothelial Growth Factor A ,Macrophage colony-stimulating factor ,Tooth Movement Techniques ,Health, Toxicology and Mutagenesis ,lcsh:Biotechnology ,Osteoclasts ,Dentistry ,lcsh:Medicine ,Review Article ,Bone resorption ,Proinflammatory cytokine ,chemistry.chemical_compound ,stomatognathic system ,lcsh:TP248.13-248.65 ,Genetics ,medicine ,Animals ,Periodontal fiber ,Molecular Biology ,Dental alveolus ,Orthodontics ,Osteoblasts ,business.industry ,lcsh:R ,General Medicine ,Periodontium ,medicine.disease ,Rats ,Vascular endothelial growth factor ,Disease Models, Animal ,stomatognathic diseases ,chemistry ,Cytokines ,Molecular Medicine ,Malocclusion ,business ,Biotechnology - Abstract
Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1βand vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor.
- Published
- 2012
17. CXCR4/YY1 inhibition impairs VEGF network and angiogenesis during malignancy
- Author
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Antonio Giordano, Mario Petrillo, Diana C. Márquez-Garbán, Toshio Hayashi, Alfonso Giovane, Valeria Crudele, Louis J. Ignarro, Letizia Cito, Amelia Casamassimi, Hermes Garban, Antonella Petrillo, Linda Sommese, Alfredo Siani, Claudio Arra, Franco Rengo, Antonio Barbieri, Filomena de Nigris, Andrea Fiore, Claudio Napoli, Francesco Cacciatore, Francesca Pentimalli, Mohammed Al-Omran, de Nigris, F, Crudele, V, Giovane, A, Casamassimi, A, Giordano, A, Garban, Hj, Cacciatore, F, Pentimalli, F, Marquez Garban, Dc, Petrillo, A, Cito, L, Sommese, L, Fiore, A, Petrillo, M, Siani, A, Barbieri, A, Arra, C, Rengo, Franco, Hayashi, T, Al Omran, M, Ignarro, Lj, Napoli, C., de NIGRIS, Filomena, Giovane, Alfonso, Casamassimi, Amelia, MARQUEZ GARBAN, Dc, Sommese, Linda, Rengo, F, AL OMRAN, M, and Napoli, Claudio
- Subjects
Multidisciplinary ,Oncogene ,CXCR4/SDF-1 inhibitor ,Angiogenesis ,medicine.medical_treatment ,Biology ,Biological Sciences ,VEGF ,Vascular endothelial growth factor B ,Chemokine receptor ,Cytokine ,embryonic structures ,medicine ,Cancer research ,neoangiogenesi ,Gene silencing ,Transcription factor ,Protein kinase B - Abstract
Tumor growth requires neoangiogenesis. VEGF is the most potent proangiogenic factor. Dysregulation of hypoxia-inducible factor (HIF) or cytokine stimuli such as those involving the chemokine receptor 4/stromal-derived cell factor 1 (CXCR4/SDF-1) axis are the major cause of ectopic overexpression of VEGF in tumors. Although the CXCR4/SDF-1 pathway is well characterized, the transcription factors executing the effector function of this signaling are poorly understood. The multifunctional Yin Yang 1 (YY1) protein is highly expressed in different types of cancers and may regulate some cancer-related genes. The network involving CXCR4/YY1 and neoangiogenesis could play a major role in cancer progression. In this study we have shown that YY1 forms an active complex with HIF-1α at VEGF gene promoters and increases VEGF transcription and expression observed by RT-PCR, ELISA, and Western blot using two different antibodies against VEGFB. Long-term treatment with T22 peptide (a CXCR4/SDF-1 inhibitor) and YY1 silencing can reduce in vivo systemic neoangiogenesis ( P < 0.01 and P < 0.05 vs. control, respectively) during metastasis. Moreover, using an in vitro angiogenesis assay, we observed that YY1 silencing led to a 60% reduction in branches ( P < 0.01) and tube length ( P < 0.02) and a 75% reduction in tube area ( P < 0.001) compared with control cells. A similar reduction was observed using T22 peptide. We demonstrated that T22 peptide determines YY1 cytoplasmic accumulation by reducing its phosphorylation via down-regulation of AKT, identifying a crosstalk mechanism involving CXCR4/YY1. Thus, YY1 may represent a crucial molecular target for antiangiogenic therapy during cancer progression.
- Published
- 2010
18. Loss of the tumor suppressor gene PTEN marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive germ cell tumors
- Author
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Alfredo Fusco, Wanda D'Amico, Barbara Tavernise, Luigi Insabato, Filippo Schepis, Guido Pettinato, Dolores Di Vizio, Maria Letizia Motti, Paolo Chieffi, Fernanda Fabiani, Letizia Cito, Salvatore Venuta, Angelo Boccia, Giuseppe Viglietto, Di Vizio, D., Cito, L., Boccia, A., Chieffi, P., Insabato, Luigi, Pettinato, Guido, Motti, M. L., Schepis, F., D'Amico, W., Fabiani, F., Tavernise, B., Venuta, S., Fusco, Alfredo, and Viglietto, G.
- Subjects
Male ,PTEN ,Cancer Research ,Animals ,Breast Neoplasms ,Cell Line ,Tumor ,Cell Transformation ,Neoplastic ,Chromosomes ,Human ,Pair 10 ,Female ,Flow Cytometry ,Genes ,Tumor Suppressor ,Germinoma ,Humans ,In Situ Hybridization ,Loss of Heterozygosity ,Mice ,PTEN Phosphohydrolase ,Phosphoric Monoester Hydrolases ,RNA ,Messenger ,Testicular Neoplasms ,Testis ,Tumor Suppressor Proteins ,endocrine system diseases ,Genes, Tumor Suppressor ,Cell Transformation, Neoplastic ,Teratoma ,Tumor suppressor gene ,Biology ,Embryonal carcinoma ,Cell Line, Tumor ,Genetics ,medicine ,RNA, Messenger ,Molecular Biology ,PI3K/AKT/mTOR pathway ,ITGCN ,Chromosomes, Human, Pair 10 ,germ cell tumor ,Seminoma ,medicine.disease ,Cancer research ,biology.protein ,Germ cell tumors ,p27kip1 - Abstract
PTEN/MMAC1/TEP1: (hereafter PTEN) is a tumor suppressor gene (located at 10q23) that is frequently mutated or deleted in sporadic human tumors. PTEN encodes a multifunctional phosphatase, which negatively regulates cell growth, migration and survival via the phosphatidylinositol 3'-kinase/AKT signalling pathway. Accordingly, Pten+/- mice develop various types of tumors including teratocarcinomas and teratomas. We have investigated PTEN expression in 60 bioptic specimens of germ cell tumors (32 seminomas, 22 embryonal carcinomas and six teratomas) and 22 intratubular germ cell neoplasias (ITGCN) adjacent to the tumors for PTEN protein and mRNA expression. In total, 10 testicular biopsies were used as controls. In the testis, PTEN was abundantly expressed in germ cells whereas it was virtually absent from 56% of seminomas as well as from 86% of embryonal carcinomas and virtually all teratomas. On the contrary, ITGCN intensely expressed PTEN, indicating that loss of PTEN expression is not an early event in testicular tumor development. The loss of PTEN expression occurs mainly at the RNA level as determined by in situ hybridization of cellular mRNA (17/22) but also it may involve some kind of post-transcriptional mechanisms in the remaining 25% of cases. Analysis of microsatellites D10S551, D10S541 and D10S1765 in GCTs (n=22) showed LOH at the PTEN locus at 10q23 in at least 36% of GCTs (three embryonal carcinoma, three seminoma, two teratoma); one seminoma and one embryonal (9%) carcinoma presented an inactivating mutation in the PTEN gene (2/22). Finally, we demonstrated that the phosphatidylinositol 3'-kinase/AKT pathway, which is regulated by the PTEN phosphatase, is crucial in regulating the proliferation of the NT2/D1 embryonal carcinoma cells, and that the cyclin-dependent kinase inhibitor p27(kip1) is a key downstream target of this pathway.
- Published
- 2005
19. Critical role of cyclin D3 in TSH-dependent growth of thyrocytes and in hyperproliferative diseases of the thyroid gland
- Author
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Giancarlo Troncone, Barbara Belletti, Lucio Palombini, Gustavo Baldassarre, Gennaro Chiappetta, Mario Monaco, Alfredo Fusco, Letizia Cito, Paola Bruni, Giuseppe Viglietto, Angelo Boccia, Maria Letizia Motti, Motti, Ml, Boccia, A, Belletti, B, Bruni, P, Troncone, Giancarlo, Cito, L, Monaco, M, Chiappetta, G, Baldassarre, G, Palombini, Lucio, Fusco, A, and Viglietto, G.
- Subjects
endocrine system ,Cancer Research ,endocrine system diseases ,Cyclin D ,Thyroid Gland ,Cyclin B ,Thyrotropin ,Cell Line ,Thyroid-stimulating hormone ,Cyclins ,Cyclin E ,Genetics ,medicine ,Animals ,Humans ,Cyclin D3 ,Molecular Biology ,Cyclin ,biology ,Thyroid ,Contact inhibition ,Thyroid Diseases ,Cyclin-Dependent Kinases ,Rats ,medicine.anatomical_structure ,Gene Expression Regulation ,biology.protein ,Cancer research ,Protein Kinases ,Cell Division ,Cyclin A2 - Abstract
We report that cyclin D3 is rate limiting for G1 progression in thyroid follicular cells and that its constitutive upregulation by chronic stimulation of the TSH/cAMP pathway plays a role in human and experimental hyperproliferative diseases of the thyroid gland. These conclusions are supported by in vitro and in vivo studies. In rat thyrocytes (PC Cl 3 cells), cyclin D3 expression is enhanced in response to activation of the TSH/cAMP pathway. Interference with the expression of G1 cyclins (in particular cyclin D3) by the antisense methodology strongly reduced TSH-dependent proliferation of PC Cl 3 cells, indicating that proper progression through G1 requires cyclin D3. Accordingly, PC Cl 3 cells engineered to overexpress cyclin D3 (PC-D3 cells) show enhanced growth rate and elude hormone-dependence and contact inhibition. Using an animal experimental model of thyroid stimulation, we demonstrate that cyclin D3 is a key mediator of TSH-dependent proliferation of thyroid follicular cells also in vivo. Cyclin D3 protein levels were higher in the thyrocytes from glands of propylthiouracil-treated rats compared with control animals. The increase in cyclin D3 expression occurred after the propylthiouracil-induced increase in TSH levels and preceded the burst of cell proliferation. Finally, we found that cyclin D3 protein is expressed in a fraction of human goiters but it is strongly overexpressed in most follicular adenomas.
- Published
- 2003
20. Lack of voluntary interest and difficulty making eye contact are the most discriminative behaviors of the ASQ:SE and might suggest delays: Results from a large-scale assessment.
- Author
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Anunciação L, Cito L, Pessoa L, Squires J, Murphy K, and Landeira-Fernandez J
- Subjects
- Humans, Infant, Female, Male, Child, Preschool, Child Development physiology, Psychometrics standards, Surveys and Questionnaires, Social Behavior, Developmental Disabilities
- Abstract
Background: Every child is unique, but development tends to occur in predictable steps and stages. The early identification of infants who face developmental delays is critical, boosting the use of screening tools to determine risks for delays. The city of Rio de Janeiro conducted a large-scale assessment of children who were enrolled in educational facilities using the Ages & Stages Questionnaires: Social-Emotional (ASQ:SE)., Objectives: We examined the internal structure of the ASQ:SE and its most discriminative items of risks of delays in development among 12- to 60-month-old children. The trajectory of the discrimination parameter of eight anchor items was used to check how well they inform the risk of social-emotional competence delays throughout development., Methods: Data from 79,332 children (1-5 years) were analyzed via Samejima Graded Response model of Item Response Theory (IRT). The discrimination ( a ) and threshold ( b ) parameters were computed, and errors were achieved via maximum likelihood. Data/codes are available at https://osf.io/by6sf/., Results: (a) Item Response Theory analyses supported the unidimensionality of data via the root mean square error of approximation and standardized root mean square residual results (RMSEA). (b) The lack of voluntary interest was the most discriminative risk behavior in the first 5 years. (c) Lack of interest was the most persistent risk behavior. (d) Difficulty making eye contact was nearly as informative as lack of interest., Conclusion: Lack of voluntary interest in things should be considered a critical risk-related behavior, and making eye contact is a vital aspect of typical development. Both behaviors may be predictors of children's delays.MAIN OUTCOMESThe ASQ:SE is a valid and reliable tool to measure child development.The internal structure of the ASQ:SE is well-fitted with a unidimensional solution.A child's age is a vital aspect of the discrimination parameter of the IRT model.Lack of interest in things and difficulty making eye contact are critical risk-related behaviors.
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- 2024
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21. Retraction: Suppression of HMGA2 Protein Synthesis Could Be a Tool for the Therapy of Well Differentiated Liposarcomas Overexpressing HMGA2 .
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Pentimalli F, Dentice M, Fedele M, Pierantoni GM, Cito L, Pallante P, Santoro M, Viglietto G, Cin PD, and Fusco A
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- 2018
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22. Antitumoral potential, antioxidant activity and carotenoid content of two Southern Italy tomato cultivars extracts: San Marzano and Corbarino.
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Barone D, Cito L, Tommonaro G, Abate AA, Penon D, De Prisco R, Penon A, Forte IM, Benedetti E, Cimini A, Indovina P, Nicolaus B, Pentimalli F, and Giordano A
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- Antineoplastic Agents, Phytogenic isolation & purification, Antioxidants isolation & purification, Apoptosis drug effects, Carotenoids isolation & purification, Cell Cycle drug effects, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Fruit chemistry, Humans, Italy, Neoplasm Invasiveness, Phytotherapy, Plants, Medicinal, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Time Factors, Antineoplastic Agents, Phytogenic pharmacology, Antioxidants pharmacology, Carotenoids pharmacology, Solanum lycopersicum chemistry, Stomach Neoplasms drug therapy
- Abstract
Gastric cancer represents a diffuse and aggressive neoplasm, whose mortality index is among the highest in the world. Predisposing factors are E-cadherin mutations, Helicobacter pylori infection, and a diet rich in salted and smoked food, with a low intake of fresh fruits and vegetables. Here, we analyzed the effect of total lipophilic extracts of two Southern Italy tomato varieties, San Marzano and Corbarino, on an in vitro model of gastric cancer, YCC-1, YCC-2 and YCC-3 cell lines, characterized by different aggressiveness. Our results showed a possible role of these two varieties of tomatoes against typical neoplastic features. The treatment with tomato extracts affected cancer cell ability to grow both in adherence and in semisolid medium, reducing also cell migration ability. No toxic effects were observed on non-tumoral cells. We found, on gastric cancer cell lines, effects on both cell cycle progression and apoptosis modulation. The extent of antineoplastic effects, however, did not seem to correlate with the carotenoid content and antioxidant activity of the two tomato varieties. Our data indicate that San Marzano and Corbarino intake might be further considered as nutritional support not only in cancer prevention, but also for cancer patient diet., (© 2017 Wiley Periodicals, Inc.)
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- 2018
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23. Translational Research and Plasma Proteomic in Cancer.
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Santini AC, Giovane G, Auletta A, Di Carlo A, Fiorelli A, Cito L, Astarita C, Giordano A, Alfano R, Feola A, and Di Domenico M
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- Biomarkers, Tumor blood, Female, Gene Expression, Humans, Lung Neoplasms blood, Lung Neoplasms genetics, Lung Neoplasms pathology, Male, Neoplasm Proteins blood, Ovarian Neoplasms blood, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology, Pancreatic Neoplasms blood, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Proteomics instrumentation, Reproducibility of Results, Sensitivity and Specificity, Translational Research, Biomedical, Biomarkers, Tumor genetics, Lung Neoplasms diagnosis, Neoplasm Proteins genetics, Ovarian Neoplasms diagnosis, Pancreatic Neoplasms diagnosis, Proteomics methods
- Abstract
Proteomics is a recent field of research in molecular biology that can help in the fight against cancer through the search for biomarkers that can detect this disease in the early stages of its development. Proteomic is a speedily growing technology, also thanks to the development of even more sensitive and fast mass spectrometry analysis. Although this technique is the most widespread for the discovery of new cancer biomarkers, it still suffers of a poor sensitivity and insufficient reproducibility, essentially due to the tumor heterogeneity. Common technical shortcomings include limitations in the sensitivity of detecting low abundant biomarkers and possible systematic biases in the observed data. Current research attempts are trying to develop high-resolution proteomic instrumentation for high-throughput monitoring of protein changes that occur in cancer. In this review, we describe the basic features of the proteomic tools which have proven to be useful in cancer research, showing their advantages and disadvantages. The application of these proteomic tools could provide early biomarkers detection in various cancer types and could improve the understanding the mechanisms of tumor growth and dissemination., (© 2015 Wiley Periodicals, Inc.)
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- 2016
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24. pRb2/p130 localizes to the cytoplasm in diffuse gastric cancer.
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Cito L, Indovina P, Forte IM, Pentimalli F, Di Marzo D, Somma P, Barone D, Penon A, Penon D, Ceccherini E, Micheli P, Saragoni L, Di Domenico M, Feola A, Roviello F, Mattioli E, Giordano GG, and Giordano A
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- Cell Cycle Proteins metabolism, Cell Division genetics, Cell Division physiology, Female, Genes, Tumor Suppressor physiology, Humans, Male, Phosphoproteins physiology, Retinoblastoma Protein metabolism, Retinoblastoma-Like Protein p130 metabolism, Stomach Neoplasms genetics, Crk-Associated Substrate Protein metabolism, Cytoplasm metabolism, Salivary Proline-Rich Proteins metabolism, Stomach Neoplasms metabolism, Transcription Factors metabolism
- Abstract
pRb2/p130 is a key tumor suppressor, whose oncosuppressive activity has mainly been attributed to its ability to negatively regulate cell cycle by interacting with the E2F4 and E2F5 transcription factors. Indeed, pRb2/p130 has been found altered in various cancer types in which it functions as a valuable prognostic marker. Here, we analyzed pRb2/p130 expression in gastric cancer tissue samples of diffuse histotype, in comparison with their normal counterparts. We found a cytoplasmic localization of pRb2/p130 in cancer tissue samples, whereas, in normal counterparts, we observed the expected nuclear localization. pRb2/p130 cytoplasmic delocalization can lead to cell cycle deregulation, but considering the emerging involvement of pRb2/p130 in other key cellular processes, it could contribute to gastric tumorigenesis also through other mechanisms. Our data support the necessity of further investigations to verify the possibility of using pRb2/p130 as a biomarker or potential therapeutic target for diffuse gastric cancer., (© 2014 Wiley Periodicals, Inc.)
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- 2015
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25. Novel findings about management of gastric cancer: a summary from 10th IGCC.
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Penon D, Cito L, and Giordano A
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- Animals, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Cadherins genetics, Cadherins metabolism, Humans, Microsatellite Instability, Molecular Targeted Therapy, Patient Selection, Precision Medicine, Predictive Value of Tests, Prognosis, Risk Factors, Signal Transduction, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Vascular Endothelial Growth Factors metabolism, Stomach Neoplasms therapy
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The Tenth International Gastric Cancer Congress (IGCC) was held in Verona, Italy, from June 19 to 22, 2013. The meeting enclosed various aspects of stomach tumor management, including both tightly clinical approaches, and topics more related to basic research. Moreover, an overview on gastrointestinal stromal tumors was provided too, although here not discussed. Here we will discuss some topics related to molecular biology of gastric cancer (GC), inherent to prognostic, diagnostic and therapeutic tools shown at the conference. Results about well known subjects, such as E-cadherin loss of expression/function, were presented. They revealed that other mutations of the gene were identified, showing a continuous research to improve diagnosis and prognosis of stomach tumor. Simultaneously, new possible molecular markers with an established role for other neoplasms, were discussed, such as mesothelin, stomatin-like protein 2 and Notch-1. Hence, a wide overview including both old and new diagnostic/prognostic tools was offered. Great attention was also dedicated to possible drugs to be used against GC. They included monoclonal antibodies, such as MS57-2.1, drugs used in other pathologies, such as maraviroc, and natural extracts from plants such as biflorin. We would like to contribute to summarize the most impressive studies presented at the IGCC, concerning novel findings about molecular biology of gastric cancer. Although further investigations will be necessary, it can be inferred that more and more tools were developed, so as to better face stomach neoplasms.
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- 2014
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26. The inhibition of p85αPI3KSer83 phosphorylation prevents cell proliferation and invasion in prostate cancer cells.
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Feola A, Cimini A, Migliucci F, Iorio R, Zuchegna C, Rothenberger R, Cito L, Porcellini A, Unteregger G, Tombolini V, Giordano A, and Di Domenico M
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- Apoptosis genetics, Apoptosis physiology, Cell Line, Tumor, Cell Proliferation, Humans, Male, Microscopy, Confocal, Phosphatidylinositol 3-Kinases genetics, Phosphorylation, Prostatic Neoplasms genetics, Protein Subunits chemistry, Protein Subunits genetics, Signal Transduction genetics, Signal Transduction physiology, Phosphatidylinositol 3-Kinases chemistry, Phosphatidylinositol 3-Kinases metabolism, Prostatic Neoplasms metabolism, Protein Subunits metabolism, Serine metabolism
- Abstract
Phosphoinositide 3-kinase proteins are composed by a catalytic p110 subunit and a regulatory p85 subunit. There are three classes of PI3K, named class I-III, on the bases of the protein domain constituting and determining their specificity. The first one is the best characterized and includes a number of key elements for the integration of different cellular signals. Regulatory p85 subunit shares with the catalytic p110 subunit, a N-terminal SH3 domain showing homology with the protein domain Rho-GTP-ase. After cell stimulation, all class I PI3Ks are recruited to the inner face of the plasma membrane, where they generate phosphatidylinositol-3,4,5-trisphosphate by direct phosphorylation of phosphatidylinositol-4,5-bisphosphate. All pathways trigger the control of different phenomena such as cell growth, proliferation, apoptosis, adhesion and migration through various downstream effectors. We have previously provided direct evidences that a Serine in position 83, adjacent to the N-terminal SH3 domain of regulatory subunit of PI3K, is a substrate of PKA. The aim of this work is to confirm the role of p85αPI3KSer83 in regulating cell proliferation, migration and invasion in prostate cancer cells LNCaP. To this purpose cells were transfected with mutant forms of p85, where Serine was replaced by Alanine, where phosphorylation is prevented, or Aspartic Acid, to mimic the phosphorylated residue. The findings of this study suggest that identifying a peptide mimicking the sequence adjacent to Ser 83 may be used to produce antibodies against this residue that can be proposed as usefool tool for prognosis by correlating phosphorylation at Ser83 with tumor stage., (Copyright © 2013 Wiley Periodicals, Inc.)
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- 2013
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27. Advances in gastric cancer prevention.
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Giordano A and Cito L
- Abstract
Gastric cancer is a multifactorial neoplastic pathology numbering among its causes both environmental and genetic predisposing factors. It is mainly diffused in South America and South-East Asia, where it shows the highest morbility percentages and it is relatively scarcely diffused in Western countries and North America. Although molecular mechanisms leading to gastric cancer development are only partially known, three main causes are well characterized: Helicobacter pylori (H. pylori) infection, diet rich in salted and/or smoked food and red meat, and epithelial cadherin (E-cadherin) mutations. Unhealthy diet and H. pylori infection are able to induce in stomach cancer cells genotypic and phenotypic transformation, but their effects may be crossed by a diet rich in vegetables and fresh fruits. Various authors have recently focused their attention on the importance of a well balanced diet, suggesting a necessary dietary education starting from childhood. A constant surveillance will be necessary in people carrying E-cadherin mutations, since they are highly prone in developing gastric cancer, also within the inner stomach layers. Above all in the United States, several carriers decided to undergo a gastrectomy, preferring changing their lifestyle than living with the awareness of the development of a possible gastric cancer. This kind of choice is strictly personal, hence a decision cannot be suggested within the clinical management. Here we summarize the key points of gastric cancer prevention analyzing possible strategies referred to the different predisposing factors. We will discuss about the effects of diet, H. pylori infection and E-cadherin mutations and how each of them can be handled.
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- 2012
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28. Rb family proteins in gastric cancer (review).
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Cito L, Pentimalli F, Forte I, Mattioli E, and Giordano A
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- Animals, Biomarkers, Tumor genetics, Biomarkers, Tumor physiology, Carcinoma diagnosis, Carcinoma pathology, Carcinoma therapy, Disease Progression, Gene Expression Regulation, Neoplastic, Humans, Multigene Family physiology, Prognosis, Retinoblastoma Protein genetics, Stomach Neoplasms diagnosis, Stomach Neoplasms pathology, Stomach Neoplasms therapy, Carcinoma genetics, Retinoblastoma Protein physiology, Stomach Neoplasms genetics
- Abstract
Gastric cancer is one of the most diffuse neoplastic pathologies in the world whose environmental and molecular causes, although deeply investigated, have not been completely clarified. Besides some well-established etiological factors, such as Helicobacter pylori and E-cadherin mutations, investigations on other possible causes gave contrasting results. Rb family proteins (including pRb/p105, pRb2/p130 and p107) are involved in cell cycle regulation and their function and/or expression is often lost in various kinds of tumours such as lung, bladder, breast and brain cancer. The consequences of RB inactivation in tumours can be very different depending on the context and the type of cancer. Recent evidence indicates that Rb status correlates with a different therapeutic response according to the tumour type and the therapeutic agent. Studies performed on Rb family proteins in gastrointestinal tract tumours suggest that these proteins have an important role in these cancer types. However, owing to contrasting results, further investigation is required to assess whether the expression of Rb family proteins can potentially be used as a prognostic or predictive factor in gastric cancer.
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- 2010
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29. CXCR4/YY1 inhibition impairs VEGF network and angiogenesis during malignancy.
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de Nigris F, Crudele V, Giovane A, Casamassimi A, Giordano A, Garban HJ, Cacciatore F, Pentimalli F, Marquez-Garban DC, Petrillo A, Cito L, Sommese L, Fiore A, Petrillo M, Siani A, Barbieri A, Arra C, Rengo F, Hayashi T, Al-Omran M, Ignarro LJ, and Napoli C
- Subjects
- Animals, Cell Line, Tumor, Humans, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Neoplasm Transplantation, Neoplasms metabolism, Peptides pharmacology, Rats, Receptor Cross-Talk physiology, Receptors, CXCR4 metabolism, Transcription Factors, Transplantation, Heterologous, YY1 Transcription Factor physiology, Neoplasms blood supply, Neovascularization, Pathologic, Receptors, CXCR4 antagonists & inhibitors, Vascular Endothelial Growth Factors genetics, YY1 Transcription Factor metabolism
- Abstract
Tumor growth requires neoangiogenesis. VEGF is the most potent proangiogenic factor. Dysregulation of hypoxia-inducible factor (HIF) or cytokine stimuli such as those involving the chemokine receptor 4/stromal-derived cell factor 1 (CXCR4/SDF-1) axis are the major cause of ectopic overexpression of VEGF in tumors. Although the CXCR4/SDF-1 pathway is well characterized, the transcription factors executing the effector function of this signaling are poorly understood. The multifunctional Yin Yang 1 (YY1) protein is highly expressed in different types of cancers and may regulate some cancer-related genes. The network involving CXCR4/YY1 and neoangiogenesis could play a major role in cancer progression. In this study we have shown that YY1 forms an active complex with HIF-1alpha at VEGF gene promoters and increases VEGF transcription and expression observed by RT-PCR, ELISA, and Western blot using two different antibodies against VEGFB. Long-term treatment with T22 peptide (a CXCR4/SDF-1 inhibitor) and YY1 silencing can reduce in vivo systemic neoangiogenesis (P < 0.01 and P < 0.05 vs. control, respectively) during metastasis. Moreover, using an in vitro angiogenesis assay, we observed that YY1 silencing led to a 60% reduction in branches (P < 0.01) and tube length (P < 0.02) and a 75% reduction in tube area (P < 0.001) compared with control cells. A similar reduction was observed using T22 peptide. We demonstrated that T22 peptide determines YY1 cytoplasmic accumulation by reducing its phosphorylation via down-regulation of AKT, identifying a crosstalk mechanism involving CXCR4/YY1. Thus, YY1 may represent a crucial molecular target for antiangiogenic therapy during cancer progression.
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- 2010
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30. Dual role of parathyroid hormone in endothelial progenitor cells and marrow stromal mesenchymal stem cells.
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Di Bernardo G, Galderisi U, Fiorito C, Squillaro T, Cito L, Cipollaro M, Giordano A, and Napoli C
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine, Apoptosis, Bone Marrow Cells pathology, Cell Differentiation, Cell Proliferation, Cells, Cultured, Cellular Senescence, DNA Damage, Deoxyguanosine analogs & derivatives, Deoxyguanosine metabolism, Endothelial Cells pathology, Gene Expression Regulation, Humans, Mesenchymal Stem Cells pathology, RNA, Messenger metabolism, Receptors, Parathyroid Hormone metabolism, Retinoblastoma Protein metabolism, Stem Cells pathology, Stromal Cells pathology, Time Factors, Tumor Suppressor Protein p53 metabolism, Bone Marrow Cells metabolism, Endothelial Cells metabolism, Mesenchymal Stem Cells metabolism, Parathyroid Hormone metabolism, Stem Cells metabolism, Stromal Cells metabolism
- Abstract
Hematopoietic stem cells derive regulatory information also from parathyroid hormone (PTH). To explore the possibility that PTH may have a role in regulation of other stem cells residing in bone marrow, such as mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) we assessed the effect of this hormone on the in vitro behavior of MSCs and EPCs. We evidenced that MSCs were much more responsive to PTH than EPCs. PTH increased the proliferation rate of MSCs with a diminution of senescence and apoptosis. Taken together, our results may suggest a protective effect of PTH on MSCs that reduces stress phenomena and preserve genome integrity. At the opposite, PTH did not modify the fate of EPCs in culture., ((c) 2009 Wiley-Liss, Inc.)
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- 2010
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31. The retinoblastoma family member pRb2/p130 is an independent predictor of survival in human soft tissue sarcomas.
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Masciullo V, Berardengo E, Boglione A, Sgambato A, Bernardi A, Forni M, Linari A, Cito L, Scambia G, Comandone A, and Giordano A
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- Adult, Aged, Aged, 80 and over, Disease-Free Survival, Humans, Immunohistochemistry, Middle Aged, Models, Biological, Multivariate Analysis, Prognosis, Sarcoma genetics, Soft Tissue Neoplasms genetics, Treatment Outcome, Gene Expression Regulation, Neoplastic, Retinoblastoma-Like Protein p130 biosynthesis, Retinoblastoma-Like Protein p130 physiology, Sarcoma metabolism, Sarcoma mortality, Soft Tissue Neoplasms metabolism, Soft Tissue Neoplasms mortality
- Abstract
Purpose: pRb2/p130, a member of the Retinoblastoma gene family, has been shown to be a powerful prognostic factor in several malignancies. We sought to evaluate pRb2/p130 protein expression and its clinical effect in patients affected with soft tissue sarcomas (STS)., Experimental Design: Expression of pRb2/p130 was evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded sections in 41 STSs. Results obtained were correlated with clinicopathologic variables and disease-free and overall survival (OS) in univariate and multivariate analysis., Results: Expression of pRb2/p130 was diminished in 25 (61%) tumors, whereas the remaining ones (39%) were classified as high expressors. No correlation between pRb2/p130 expression and clinicopathologic variables was observed. However, a direct relationship between pRb2/p130 expression and clinical outcome of the patients was found in the subgroup of nonmetastatic tumors (n = 31). In univariate analysis, reduced pRb2/p130 expression was a negative prognostic factor and correlated with shorter disease-free survival (P = 0.021) and OS (P = 0.017) survival. In multivariate analysis, reduced pRb2/p130 expression was confirmed to be an independent predictor of shorter OS when considered together with tumor stage and grading (risk ratio, 7.893; confidence interval, 1.618-38.509; P = 0.011)., Conclusions: This study shows for the first time the potential prognostic value of pRb2/130 expression evaluated on formalin-fixed, paraffin-embedded sections in STSs patients. pRb2/p130 immunoreactivity can be used to predict OS in patients with nonmetastatic STSs and, therefore, may represent a new prognostic marker.
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- 2008
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32. Social determinants of the increasing caesarean section rate in Italy.
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Scioscia M, Vimercati A, Cito L, Chironna E, Scattarella D, and Selvaggi LE
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- Female, Humans, Italy epidemiology, Liability, Legal, Pregnancy, Psychology, Social Responsibility, Socioeconomic Factors, Cesarean Section statistics & numerical data
- Abstract
Aim: Consistent modifications of socio-economic factors may represent crucial non-clinical determinants for the rising rate of caesarean section among primiparae. This increasing trend has been reported in many countries and its relationship with social modifications is widely accepted, though poorly supported by published data., Methods: Population-based social and economic data were analyzed between two study periods 30 years apart (1971 vs 2001)., Results: The number of births dropped dramatically within the study period (about -40%). Italian women tend to delay childbearing (25.1 vs 28.8 years of age at first delivery) to pursue a career and a later marriage and motherhood lead to a contraction of the number of members of the family. Older mothers are at higher risk of caesarean (treble over 40 years of age), especially those with high career position. Health expenditures increased significantly between 1971 and 2001. A progressive contraction of the number of women in reproductive age is expected in the next 50 years in Italy., Conclusion: Many determinants are involved in the choice of a caesarean section and most of these are not strictly medical. The rapidly mounting number of legal claims may indeed lead to defensive practices. Given these data, a reduction of caesarean section rate seems unlikely to be achieved at present.
- Published
- 2008
33. Overexpression of the S-phase kinase-associated protein 2 in thyroid cancer.
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Chiappetta G, De Marco C, Quintiero A, Califano D, Gherardi S, Malanga D, Scrima M, Montero-Conde C, Cito L, Monaco M, Motti ML, Pasquinelli R, Agosti V, Robledo M, Fusco A, and Viglietto G
- Subjects
- Carcinoma chemistry, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p27 analysis, Cyclin-Dependent Kinase Inhibitor p27 metabolism, Gene Amplification, Humans, RNA, Messenger analysis, RNA, Messenger metabolism, S-Phase Kinase-Associated Proteins analysis, S-Phase Kinase-Associated Proteins genetics, Thyroid Neoplasms chemistry, Carcinoma metabolism, Carcinoma pathology, S-Phase Kinase-Associated Proteins metabolism, Thyroid Neoplasms metabolism, Thyroid Neoplasms pathology
- Abstract
Loss of expression of the cyclin-dependent kinase inhibitor p27 through enhanced protein degradation frequently occurs in human cancer. Degradation of p27 requires ubiquitination by the S-phase kinase-associated protein 2 (Skp2), a member of the F-box family of Skp1-Cullin-F-box protein ubiquitin ligases. In the present study, we have investigated the role of Skp2 in human thyroid tumours. Immunohistochemistry analysis showed that Skp2 was overexpressed significantly in thyroid carcinomas (26 out of 51) compared with goitres (0 out of 12, P<0.001) or adenomas (1 out of 10, P<0.05), and that high Skp2 expression was detected more often in anaplastic thyroid (ATC; 83%, n=12) than follicular thyroid (FTC; 40%, n=20) or papillary thyroid (PTC; 42%, n=19) carcinomas (P<0.05). Thyroid cancer cell lines and tissues with high levels of Skp2 protein presented high p27 degradation activity and there was an inverse correlation between Skp2 and p27 expression in thyroid cancer tissues (n=68; P<0.05). In most cases, the observed overexpression of Skp2 protein was paralleled by an increase in the levels of Skp2 mRNA, and we observed Skp2 gene amplification at 5p13 in 2 out of 6 cell lines and in 9 out of 23 primary tumours (six out of eight ATCs, two out of nine PTCs and one out of six FTCs) using Q-PCR and/or fluorescence in situ hybridization analysis. Finally, in vitro experiments demonstrated that suppression of Skp2 expression drastically reduced proliferation of thyroid cancer cells and, conversely, forced expression of Skp2 circumvented serum dependency and contact inhibition in Skp2-negative cells by promoting p27 degradation. These findings indicate that Skp2 plays an important role for the development of thyroid cancer.
- Published
- 2007
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34. AZD3409 inhibits the growth of breast cancer cells with intrinsic resistance to the EGFR tyrosine kinase inhibitor gefitinib.
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Maiello MR, D'Alessio A, De Luca A, Carotenuto A, Rachiglio AM, Napolitano M, Cito L, Guzzo A, and Normanno N
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- Antineoplastic Combined Chemotherapy Protocols pharmacology, Blotting, Western, Cell Line, Tumor, Drug Resistance, Neoplasm, Enzyme Inhibitors pharmacology, Epidermal Growth Factor drug effects, Female, Flow Cytometry, Gefitinib, Humans, Protein-Tyrosine Kinases antagonists & inhibitors, Antineoplastic Agents pharmacology, Breast Neoplasms metabolism, Cell Proliferation drug effects, Quinazolines pharmacology
- Abstract
AKT and MAPK signaling are involved in the resistance of breast cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. RAS proteins are upstream mediators that transfer messages from surface receptors to intracellular signal transducers including MAPK and AKT pathways. AZD3409 is a novel prenyl inhibitor that has shown activity against both farnesyl transferase and geranylgeranyl transferase in isolated enzyme studies. We explored the activity of AZD3409 on breast cancer cell lines with high (SK-Br-3), intermediate (MDA-MB-361) or low (MDA-MB-468) sensitivity to gefitinib. We found that AZD3409 inhibits the growth of breast cancer cells in a dose-dependent manner, with the MDA-MB-468 and MDA-MB-361 cell lines showing higher sensitivity as compared with SK-Br-3 cells. Treatment with AZD3409 produced a significant reduction in the levels of activation of AKT in the three cell lines. AZD3409 also induced an increase in the expression of p27kip-1 and of hypophosphorylated forms of pRb2 in MDA-MB-468 cells that was associated with accumulation of cells in G0/G1 and the appearance of a sub-G1 peak suggestive of apoptosis. In contrast, AZD3409 produced a G2 arrest associated with reduced expression of pRb2 in MDA-MB-361 cells. A synergistic anti-tumor effect was observed when MDA-MB-468 or MDA-MB-361 cells were treated with both AZD3409 and gefitinib, whereas this combination was only additive in SK-Br-3 cells. However, treatment of breast cancer cells with AZD3409 and gefitinib did not produce a more significant blockade of AKT signaling as compared with gefitinib alone. These data suggest that AZD3409 might be active in gefitinib-resistant breast carcinoma.
- Published
- 2007
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35. Activation of urokinase receptor by a novel interaction between the connecting peptide region of urokinase and alpha v beta 5 integrin.
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Franco P, Vocca I, Carriero MV, Alfano D, Cito L, Longanesi-Cattani I, Grieco P, Ossowski L, and Stoppelli MP
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- Actins metabolism, Animals, Cells, Cultured, Chemotaxis, Humans, Kidney metabolism, Mice, Receptors, Urokinase Plasminogen Activator, Signal Transduction, U937 Cells, Cell Movement, Integrins metabolism, Peptide Fragments metabolism, Receptors, Cell Surface metabolism, Receptors, Vitronectin metabolism, Urokinase-Type Plasminogen Activator metabolism
- Abstract
The serine protease urokinase (uPA) binds to the urokinase receptor (uPAR) through its growth-factor domain (GFD, residues 1-49), affecting cell migration, adhesion and growth. Here, we show that uPA can promote cytoskeletal rearrangements and directional cell migration in a GFD-independent manner, through a new and specific interaction between an internal uPA domain coined ;connecting peptide' (residues 132-158) and cell-surface integrin alpha v beta 5. Remarkably, a peptide corresponding to this region (CPp, residues 135-158) retains the ability to bind to alpha v beta 5, eliciting cytoskeletal rearrangements and directing cell migration at a concentration as low as 1-10 pM. These effects are lost in cells not expressing uPAR, indicating that the uPAR is required for CPp-dependent signaling. Furthermore, the CPp-alpha v beta 5-integrin interaction enhances F-actin-enriched protrusions and cell migration induced by the well-established interaction between the uPAR-binding peptide (GFDp, residues 12-32) of uPA and uPAR. These results provide new insight into the function of uPA, which--through individual domains--can engage two different surface receptors (uPAR and alpha v beta 5 integrin), thus initiating and potentiating intracellular signaling and migration.
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- 2006
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36. Loss of the tumor suppressor gene PTEN marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive germ cell tumors.
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Di Vizio D, Cito L, Boccia A, Chieffi P, Insabato L, Pettinato G, Motti ML, Schepis F, D'Amico W, Fabiani F, Tavernise B, Venuta S, Fusco A, and Viglietto G
- Subjects
- Animals, Breast Neoplasms, Cell Line, Tumor, Chromosomes, Human, Pair 10, Female, Flow Cytometry, Humans, In Situ Hybridization, Loss of Heterozygosity, Male, Mice, PTEN Phosphohydrolase, RNA, Messenger genetics, Testis cytology, Testis embryology, Testis pathology, Cell Transformation, Neoplastic, Genes, Tumor Suppressor, Germinoma genetics, Phosphoric Monoester Hydrolases genetics, Testicular Neoplasms genetics, Tumor Suppressor Proteins genetics
- Abstract
PTEN/MMAC1/TEP1: (hereafter PTEN) is a tumor suppressor gene (located at 10q23) that is frequently mutated or deleted in sporadic human tumors. PTEN encodes a multifunctional phosphatase, which negatively regulates cell growth, migration and survival via the phosphatidylinositol 3'-kinase/AKT signalling pathway. Accordingly, Pten+/- mice develop various types of tumors including teratocarcinomas and teratomas. We have investigated PTEN expression in 60 bioptic specimens of germ cell tumors (32 seminomas, 22 embryonal carcinomas and six teratomas) and 22 intratubular germ cell neoplasias (ITGCN) adjacent to the tumors for PTEN protein and mRNA expression. In total, 10 testicular biopsies were used as controls. In the testis, PTEN was abundantly expressed in germ cells whereas it was virtually absent from 56% of seminomas as well as from 86% of embryonal carcinomas and virtually all teratomas. On the contrary, ITGCN intensely expressed PTEN, indicating that loss of PTEN expression is not an early event in testicular tumor development. The loss of PTEN expression occurs mainly at the RNA level as determined by in situ hybridization of cellular mRNA (17/22) but also it may involve some kind of post-transcriptional mechanisms in the remaining 25% of cases. Analysis of microsatellites D10S551, D10S541 and D10S1765 in GCTs (n=22) showed LOH at the PTEN locus at 10q23 in at least 36% of GCTs (three embryonal carcinoma, three seminoma, two teratoma); one seminoma and one embryonal (9%) carcinoma presented an inactivating mutation in the PTEN gene (2/22). Finally, we demonstrated that the phosphatidylinositol 3'-kinase/AKT pathway, which is regulated by the PTEN phosphatase, is crucial in regulating the proliferation of the NT2/D1 embryonal carcinoma cells, and that the cyclin-dependent kinase inhibitor p27(kip1) is a key downstream target of this pathway.
- Published
- 2005
- Full Text
- View/download PDF
37. Suppression of HMGA2 protein synthesis could be a tool for the therapy of well differentiated liposarcomas overexpressing HMGA2.
- Author
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Pentimalli F, Dentice M, Fedele M, Pierantoni GM, Cito L, Pallante P, Santoro M, Viglietto G, Dal Cin P, and Fusco A
- Subjects
- Adenoviruses, Human genetics, Apoptosis genetics, Cell Division genetics, DNA, Antisense administration & dosage, DNA, Antisense genetics, Genetic Therapy methods, HMGA2 Protein biosynthesis, HMGA2 Protein genetics, Humans, Liposarcoma genetics, Liposarcoma pathology, Reverse Transcriptase Polymerase Chain Reaction, Transduction, Genetic, Tumor Cells, Cultured, HMGA2 Protein antagonists & inhibitors, Liposarcoma metabolism, Liposarcoma therapy
- Abstract
Atypical lipomatous tumors (ALTs)/well-differentiated liposarcomas represent a distinctive subset of mesenchymal neoplasms featuring mature adipocytic proliferation. These tumors are characterized cytogenetically by the presence of supernumerary ring and/or long marker chromosomes that contain several copies of the chromosomal region 12q13-15, in which the HMGA2 gene is located. Deregulation of the HMGA2 gene is a common molecular alteration implicated in the development of a variety of benign tumors, such as lipomas, uterine leiomyomas, and pulmonary chondroid hamartomas. In this study, we observed HMGA2 overexpression in 7 of 12 ALT primary cell cultures examined. Subsequently, we generated an adenovirus containing the HMGA2 gene in the antisense orientation (Ad-A2as) to study the effect of HMGA2 protein suppression in ALT cells. The infection of six ALT cells, three of which were positive for HMGA2 expression, resulted in growth inhibition coupled with a significant increase in apoptosis. In addition, the growth of the ALT cells negative for HMGA2 expression was not affected by the infection with either the Ad-A2as or the control virus. On the basis of these findings, the targeting of the HMGA2 protein expression may represent a promising approach for treating the well-differentiated liposarcomas resistant to conventional therapies.
- Published
- 2003
38. Critical role of cyclin D3 in TSH-dependent growth of thyrocytes and in hyperproliferative diseases of the thyroid gland.
- Author
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Motti ML, Boccia A, Belletti B, Bruni P, Troncone G, Cito L, Monaco M, Chiappetta G, Baldassarre G, Palombini L, Fusco A, and Viglietto G
- Subjects
- Animals, Cell Division drug effects, Cell Line, Cyclin D3, Cyclin E, Cyclin-Dependent Kinases metabolism, Gene Expression Regulation drug effects, Humans, Protein Kinases metabolism, Rats, Thyroid Gland metabolism, Thyroid Gland pathology, Cyclins metabolism, Thyroid Diseases metabolism, Thyroid Diseases pathology, Thyroid Gland cytology, Thyroid Gland drug effects, Thyrotropin pharmacology
- Abstract
We report that cyclin D3 is rate limiting for G1 progression in thyroid follicular cells and that its constitutive upregulation by chronic stimulation of the TSH/cAMP pathway plays a role in human and experimental hyperproliferative diseases of the thyroid gland. These conclusions are supported by in vitro and in vivo studies. In rat thyrocytes (PC Cl 3 cells), cyclin D3 expression is enhanced in response to activation of the TSH/cAMP pathway. Interference with the expression of G1 cyclins (in particular cyclin D3) by the antisense methodology strongly reduced TSH-dependent proliferation of PC Cl 3 cells, indicating that proper progression through G1 requires cyclin D3. Accordingly, PC Cl 3 cells engineered to overexpress cyclin D3 (PC-D3 cells) show enhanced growth rate and elude hormone-dependence and contact inhibition. Using an animal experimental model of thyroid stimulation, we demonstrate that cyclin D3 is a key mediator of TSH-dependent proliferation of thyroid follicular cells also in vivo. Cyclin D3 protein levels were higher in the thyrocytes from glands of propylthiouracil-treated rats compared with control animals. The increase in cyclin D3 expression occurred after the propylthiouracil-induced increase in TSH levels and preceded the burst of cell proliferation. Finally, we found that cyclin D3 protein is expressed in a fraction of human goiters but it is strongly overexpressed in most follicular adenomas.
- Published
- 2003
- Full Text
- View/download PDF
39. Inhibition of receptor-dependent urokinase signaling by specific Ser to Glu substitutions.
- Author
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Carriero MV, Franco P, Gargiulo L, Vocca I, Cito L, Fontana L, Iaccarino C, Del Pozzo G, Guardiola J, and Stoppelli MP
- Subjects
- Amino Acid Substitution, Animals, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes drug effects, Cell Movement drug effects, Cytoskeletal Proteins metabolism, Enzyme Activation drug effects, Female, Glutamic Acid, Humans, Mice, Oncogene Proteins, Viral metabolism, Paxillin, Phosphoproteins metabolism, Protein Binding, Receptors, Cell Surface metabolism, Receptors, Urokinase Plasminogen Activator, Receptors, Vitronectin metabolism, Serine, Tumor Cells, Cultured, Urokinase-Type Plasminogen Activator genetics, Urokinase-Type Plasminogen Activator metabolism, src-Family Kinases, Proto-Oncogene Proteins, Receptors, Cell Surface physiology, Signal Transduction, Urokinase-Type Plasminogen Activator physiology
- Abstract
We have previously reported that phosphorylation of human urokinase on Ser138/303 abolishes its catalytic-independent motogen and proadhesive abilities, whereas receptor binding is not affected. Here we show that substitution of the two relevant serines with glutamic acid residues impairs the ability of urokinase to mobilize a variety of human and mouse cell lines as well as human primary T lymphocytes. Accordingly, urokinase receptor-dependent signaling, leading to cytoskeletal rearrangements and paxillin re-distribution, does not occur in MCF-7 breast carcinoma cells exposed to 'phosphorylation-like' urokinase. Unlike the wild-type form, di-substituted urokinase is unable to induce the physical association of urokinase receptor with alphavbeta5 vitronectin receptor, which is required for MCF-7 urokinase-dependent cell migration. Finally, the di-substituted variant fails to activate p55fgr, a member of the Src tyrosine kinase family, which mediates cell migration and adhesion of U937 myelomonocytic cells. In conclusion, the finding that specific amino acid substitutions strongly interfere with the ability of urokinase to stimulate cell migration, and the associated intracellular events uncover a novel way to regulate urokinase receptor-dependent signaling.
- Published
- 2002
- Full Text
- View/download PDF
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