114 results on '"Solmi R"'
Search Results
2. Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer
- Author
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Li, Y, Lauriola, M, Kim, D, Francesconi, M, D’Uva, G, Shibata, D, Malafa, M P, Yeatman, T J, Coppola, D, Solmi, R, and Cheng, J Q
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- 2016
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- View/download PDF
3. Ceramic support for cell cultures
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Krajewski, A., Ravaglioli, A., Kirsch, M., Biagini, G., Solmi, R., Belmonte, M., Zucchini, C., Gandolfi, M. G., Castaldini, C., Rodriguez, L., Giardino, R., Mongiorgi, R., Roncari, E., and Orlandi, L.
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- 1996
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- View/download PDF
4. Interactions of fibroblasts with soldered and laser-welded joints
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Solmi, R., Martini, D., Zanarini, M., Isaza Penco, S., Rimondini, L., Carinci, P., Borea, G., and Ruggeri, A.
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- 2004
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- View/download PDF
5. Gingival fibroblasts “in vitro” and Down's Syndrome
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Solmi R., Rossetti A., Talassi O., Tomasini G. L., Fato R., Estornell E., Lucarini G., Lenaz G., Simonelli L., Brunelli M. A., and Biagini G.
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- 1993
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- View/download PDF
6. AHAs and derivatives: an in vitro study of their effect on cell proliferation and morphology
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Tucci, M.G., Belmonte, M. Mattioli, Biagini, G., Vellucci, E., Morganti, P., Talassi, O., Solmi, R., and Ricotti, G.
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Organic acids -- Physiological aspects ,Dermatologic agents -- Physiological aspects ,Cell proliferation -- Physiological aspects ,Cells -- Morphology ,Business ,Pharmaceuticals and cosmetics industries - Abstract
An in vitro study of their effect on cell proliferation and morphology This study reports on a biological model based on cutaneous fibroblasts cultured in the presence of glycolic acid, [...]
- Published
- 1998
7. CDH1 POLYMORPHISMS AND LOW EXPRESSION OF E-CADHERIN AND β-CATENIN IN COLORECTAL CANCER PATIENTS
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Martinelli, M., Palmieri, A., Rodia, M. T., Cura, F., Luca Scapoli, Ugolini, G., Montroni, I., Sanctis, P., Solmi, R., Martinelli, M, Palmieri, A, Rodia, M T, Cura, F, Scapoli, L, Ugolini, G, Montroni, I, De Sanctis, P, and Solmi, R
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embryonic structures ,colorectal cancer, E-cadherin, β-catenin, association, expression analysis - Abstract
Epithelial-mesenchymal transition (EMT) process has a central role in tumor progression and metastases. Loss of cell-to-cell adhesiveness is a key step in EMT. In particular, E-cadherin and β-catenin, components of the adherens junctions, play a strategic role. Accumulation of β-catenin at cytoplasmic level following adherens junctions disruption, induces its translocation into the nucleus, where it binds to members of the TCF/LEF family of transcription factors. In particular, Lymphoid Enhancer-Binding factor 1 (LEF1) product can target genes involved in EMT. The aim of the present study was to evaluate the influence of CDH1 and CTNNB1 genes, coding for E-cadherin and β-catenin respectively and LEF1 in a sample study of 140 Italian patients affected by colorectal cancer. An association study between four single nucleotide polymorphisms (rs11865026, rs11642413, rs13689, and rs10431923) of CDH1 and the disease did not provide statistically significant results. The gene expression analysis carried out for CDH1, CTNNB1 and LEF1 in 54 paired specimens from 27 patients provided evidence of a reduced expression of the first two in cancer tissues. We believe there may be a sort of cross regulation between the products of these two genes which closely interact in EMT activation and that such hypothesis should be further investigated in a greater number of cases.
- Published
- 2015
8. In vitro growth of periodontal fibroblasts on treated cementum.
- Author
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Biagini, G., Checchi, L., Pelliccioni, G. A., and Solmi, R.
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DENTAL pathology ,CEMENTUM ,DENTAL cements ,FIBROBLASTS ,CONNECTIVE tissue cells ,PERIODONTIUM ,CITRIC acid ,PERIODONTICS ,PHOSPHORIC acid - Abstract
The aim of the present study was to assess the ability in vitro of phosphoric and citric acids, applied on human root cementum, to neutralize noxious plaque and calculus and to allow the growth of human gingival fibroblasts. Fibroblasts grown on cementum treated with phosphoric acid appeared typically elongated and aligned parallel to the root surface. Fibroblasts grown on cementum treated with citric acid, in both normal and periodontally diseased teeth, lost their elongated shape, acquiring polygonal borders with irregular cytoplasmic extrusions, and the cell density was significantly lower. These findings suggest that phosphoric acid cleaning of both normal and diseased root surfaces may result in an oriented, high rate of fibroblastic growth with more effective periodontal cellular proliferation than that observed after citric acid treatment. [ABSTRACT FROM AUTHOR]
- Published
- 1992
9. Evaluating and comparing language workbenches: Existing results and benchmarks for the future
- Author
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Erdweg, S. (Sebastian), Storm, T. (Tijs) van der, Voelter, M., Tratt, L., Bosman, R., Cook, W.R., Gerritsen, A., Hulshout, A., Kelly, S., Loh, A., Konat, G., Molina, P.J., Palatnik, M., Pohjonen, R., Schindler, E., Schindler, K., Solmi, R., Vergu, V., Visser, E., Vlist, K.B. (Kevin) van der, Wachsmuth, G., Woning, J.M. (Jimi) van der, Erdweg, S. (Sebastian), Storm, T. (Tijs) van der, Voelter, M., Tratt, L., Bosman, R., Cook, W.R., Gerritsen, A., Hulshout, A., Kelly, S., Loh, A., Konat, G., Molina, P.J., Palatnik, M., Pohjonen, R., Schindler, E., Schindler, K., Solmi, R., Vergu, V., Visser, E., Vlist, K.B. (Kevin) van der, Wachsmuth, G., and Woning, J.M. (Jimi) van der
- Abstract
Language workbenches are environments for simplifying the creation and use of computer languages. The annual Language Workbench Challenge (LWC) was launched in 2011 to allow the many academic and industrial researchers in this area an opportunity to quantitatively and qualitatively compare their approaches. We first describe all four LWCs to date, before focussing on the approaches used, and results generated, during the third LWC. We give various empirical data for ten approaches from the third LWC. We present a generic feature model within which the approaches can be understood and contrasted. Finally, based on our experiences of the existing LWCs, we propose a number of benchmark problems for future LWCs.
- Published
- 2015
- Full Text
- View/download PDF
10. The State Of The Art In Language Workbenches. Conclusions From The Language Workbench Challenge
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Storm, Tijs, Erdweg, Sebastian, Voelter, M., Boersma, M., Bosman, R., Cook, W.R., Gerritsen, A., Hulshout, A., Kelly, S., Loh, A., Konat, G., Molina, P.J., Patatnik, M., Pohjonen, R., Schindler, Eugen, Schindler, K., Solmi, R., Vergu, V., Vlist, Kevin, Wachsmuth, G., Woning, Jimi, Technische Universität Darmstadt (TU Darmstadt), Centrum Wiskunde & Informatica (CWI), Analysis and Transformation based on rEliAble tool coMpositionS (ATEAMS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centrum Wiskunde & Informatica (CWI), Voelter [Stuttgart ], DSL Consultancy [Leiden], Sioux [Eindhoven], University of Texas at Austin [Austin], Delphino Consultancy [Best], MetaCase [Jyväskylä], Delft University of Technology (TU Delft), Icinetic [Sevilla], Independent Author, Universiteit van Amsterdam (UvA), Technische Universität Darmstadt - Technical University of Darmstadt (TU Darmstadt), Software Analysis and Transformation, and Evolutionary Intelligence
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Software_GENERAL ,domain-specific languages ,tools ,[INFO.INFO-SE]Computer Science [cs]/Software Engineering [cs.SE] ,language workbenches - Abstract
International audience; Language workbenches are tools that provide high-level mechanisms for the implementation of (domain-specific) languages. Language workbenches are an active area of research that also receives many contributions from industry. To compare and discuss existing language workbenches, the annual Language Workbench Challenge was launched in 2011. Each year, participants are challenged to realize a given domain-specific language with their workbenches as a basis for discussion and comparison. In this paper, we describe the state of the art of language workbenches as observed in the previous editions of the Language Workbench Challenge. In particular, we capture the design space of language workbenches in a feature model and show where in this design space the participants of the 2013 Language Workbench Challenge reside. We compare these workbenches based on a DSL for questionnaires that was realized in all workbenches.
- Published
- 2013
11. The State of the Art in Language Workbenches. Conclusions from the Language Workbench Challenge
- Author
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Storm, T. (Tijs) van der, Erdweg, S. (Sebastian), Voelter, M., Boersma, M., Bosman, R., Cook, W.R., Gerritsen, A., Hulshout, A., Kelly, S., Loh, A., Konat, G., Molina, P.J., Patatnik, M., Pohjonen, R., Schindler, E., Schindler, K., Solmi, R., Vergu, V., Vlist, K.B. (Kevin) van der, Wachsmuth, G., Woning, J.M. (Jimi) van der, Storm, T. (Tijs) van der, Erdweg, S. (Sebastian), Voelter, M., Boersma, M., Bosman, R., Cook, W.R., Gerritsen, A., Hulshout, A., Kelly, S., Loh, A., Konat, G., Molina, P.J., Patatnik, M., Pohjonen, R., Schindler, E., Schindler, K., Solmi, R., Vergu, V., Vlist, K.B. (Kevin) van der, Wachsmuth, G., and Woning, J.M. (Jimi) van der
- Abstract
Language workbenches are tools that provide high-level mechanisms for the implementation of (domain-specific) languages. Language workbenches are an active area of research that also receives many contributions from industry. To compare and discuss existing language workbenches, the annual Language Workbench Challenge was launched in 2011. Each year, participants are challenged to realize a given domain-specific language with their workbenches as a basis for discussion and comparison. In this paper, we describe the state of the art of language workbenches as observed in the previous editions of the Language Workbench Challenge. In particular, we capture the design space of language workbenches in a feature model and show where in this design space the participants of the 2013 Language Workbench Challenge reside. We compare these workbenches based on a DSL for questionnaires that was realized in all workbenches.
- Published
- 2013
- Full Text
- View/download PDF
12. Human skeletal muscle mitochondria in aging: lack of detectable morphological and enzymatic defects
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Zucchini, C., Pugnaloni, A., Pallotti, F., Solmi, R., Crimi, Massimo, Castaldini, C., and Lenaz, G. BIAGINI E. G.
- Published
- 1995
13. Gene Expression Profile of Human Colon Cancer Cells Treated with Cross-Reacting Material 197, a Diphtheria Toxin Non-Toxic Mutant
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Rivetti, S., primary, Lauriola, M., additional, Voltattorni, M., additional, Bianchini, M., additional, Martini, D., additional, Ceccarelli, C., additional, Palmieri, A., additional, Mattei, G., additional, Franchi, M., additional, Ugolini, G., additional, Rosati, G., additional, Montroni, I., additional, Taffurelli, M., additional, and Solmi, R., additional
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- 2011
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14. Expression profile of epidermal differentiation complex genes in normal and anal cancer cells
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Zucchini, C., primary, Biolchi, A., additional, Strippoli, P., additional, Solmi, R., additional, Rosati, G., additional, Del Governatore, M., additional, Milano, E., additional, Ugolini, G., additional, Salfi, N., additional, Farina, A., additional, Caira, A., additional, Zanotti, S., additional, Carinci, P., additional, and Valvassori, L., additional
- Published
- 2001
- Full Text
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15. Expression analysis and mutational screening of the epithelium-specific ets gene-1 (ESE-1) in patients with squamous anal cancer.
- Author
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Zucchini, C, primary, Strippoli, P, additional, Rosati, G, additional, Del Governatore, M, additional, Milano, E, additional, Ugolini, G, additional, Solmi, R, additional, Mattei, G, additional, Caira, A, additional, Zanotti, S, additional, Carinci, P, additional, and Valvassori, L, additional
- Published
- 2000
- Full Text
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16. Evaluation of Some Microenvironmental Inflences on the Regenerative Mechanisms of the Periodontium: An in Vitro Study
- Author
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Belmonte, M. Mattioli, primary, Amati, S., additional, Tesei, M., additional, Biagini, G., additional, Solmi, R., additional, Talassi, O., additional, De Florio, L., additional, and Muzzarelli, Raa., additional
- Published
- 1998
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- View/download PDF
17. Osteoinduction by Chitosan-Complexed BMP: Morpho-Structural Responses in an Osteoporotic Model
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Muzzarelli, R. A. A., primary, Biagini, G., additional, Belmonte, M. Mattioli, additional, Talassi, O., additional, Gandolfi, M. G., additional, Solmi, R., additional, Carraro, S., additional, Giardino, R., additional, Fini, M., additional, and Nicoli-Aldini, N., additional
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- 1997
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18. Cell growth on cordierite: an approach to the identification of reliable supports for continuous-flow solid-bed reactors
- Author
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Orlandi, L., primary, Solmi, R., additional, Krajewski, A., additional, Bearzatto, A., additional, Biagini, G., additional, Ciccopiedi, E., additional, and Ravaglioli, A., additional
- Published
- 1997
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19. Fibroblast proliferation over dialysis membrane: an experimental model for “tissue” biocompatibility evaluation
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Biagini, G., primary, Stefoni, S., additional, Solmi, R., additional, Castaldini, C., additional, Buttazzi, R., additional, Rossetti, A., additional, Belmonte, M. Mattioli, additional, Costa, A. Nanni, additional, Lannelli, S., additional, Borgnino, L.C., additional, and De Sanctis, L., additional
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- 1994
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20. In vitro study of gingival fibroblasts from normal and inflamed tissue: age-related responsiveness
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Solmi, R., Tietz, C., Zucchini, C., Gualandi, G., Pugnaloni, A., Talassi, O., Castaldini, C., Simonelli, L., and Biagini, G.
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- 1996
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21. Search for epithelial-specific mRNAs in peripheral blood of patients with colon cancer by RT-PCR
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Solmi, R., Sanctis, P., Zucchini, C., Ugolini, G., Giancarlo Rosati, Del Governatore, M., Coppola, D., Yeatman, T. J., Lenzi, L., Caira, A., Zanotti, S., Taffurelli, M., Carinci, P., Valvassori, L., Strippoli, P., SOLMI R, DE SANCTIS P, ZUCCHINI C, UGOLINI G, ROSATI G, DEL GOVERNATORE M, COPPOLA D, YEATMAN TJ, LENZI L, CAIRA A, ZANOTTI S, TAFFURELLI M, CARINCI P., VALVASSORI L, and STRIPPOLI P.
- Subjects
BLOOD ,MARKERS OF MALIGNANCY ,RT-PCR ASSAY ,COLON CANCER ,MRNA EXPRESSION - Abstract
Research has widely supported the efficacy of screening for colorectal cancer in reducing mortality. A blood-based assay potentially represents a more accessible early detection tool for the identification of solid tumor cells originating from a primary tumor site in the body. We demonstrate a relatively easy and highly reproducible technique for the detection of mRNA expression of genes as markers of malignancy in blood samples of patients with colon cancer. The present study aims to identify a set of specific mRNAs expressed in epithelial cells but not in blood cells, which may be useful as markers for early detection of circulating colon cancer cells by a simple, qualitative RT-PCR assay following semi-automated RNA extraction from peripheral blood samples. Our approach includes a systematic search for candidate markers using digital differential display, search on UniGene colon EST libraries and analysis of published data on colon cancer gene expression. A final list included the following genes: bone morphogenetic protein 4 (BMP4), cyclin D (CycD), family with sequence similarity 3, member D (FAM3D), gastrin (GAS), glycoprotein A33 transmembrane (GPA33), glutathione peroxidase 2 gastrointestinal (GPX2), galactoside-binding, soluble, 4 (galectin 4) (LGALS4), non-SMC, structural maintenance of chromosomes, element 1 protein (NSE1), tumor-associated calcium signal transducer 1 (TACSTD1), telomerase reverse transcriptase (hTERT), trefoil factor 3 intestinal (TFF3), transmembrane 4 superfamily member 3 (TM4SF3), UDP glycosyltransferase 1 family, polypeptide A9 (UGT1A9), villin 1 (VIL1), and the novel gene FLJ20127. The mRNA expression of these genes was evaluated in a pool of 16 samples from subjects diagnosed with colon cancer and from 16 normal-controls. We observed expression in 13 of the 15 investigated genes from the blood samples of the vast majority of patients considered, but also in a certain percentage of the controls (from 14.3 to 100%). This finding confirms that the extreme sensitivity of RT-PCR is able to detect minimal amounts of mRNA expressed in a non tissue-specific manner ('illegitimate transcription'). On the contrary, NSE1 and GAS mRNAs were not detected either in patient or in control blood samples; however, they were abundantly expressed in normal and cancerous colon mucosa, encouraging further search for useful markers able to detect epithelial cells in peripheral blood.
22. CDH1 POLYMORPHISMS AND LOW EXPRESSION OF E-CADHERIN AND beta-CATENIN IN COLORECTAL CANCER PATIENTS
- Author
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Martinelli, M., Palmieri, A., Rodia, M. T., Cura, F., Luca Scapoli, Ugolini, G., Montroni, I., Sanctis, P., and Solmi, R.
23. RDF and Topic Maps interoperability: A model-driven approach
- Author
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Di Dorio, A., Duca, S., VALENTINA PRESUTTI, Solmi, R., and Vitali, F.
24. Lack of major mitochondrial bioenergetic changes in cultured skin fibroblasts from aged individuals
- Author
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Solmi, R., Pallotti, F., Michela Rugolo, Genova, M. L., Estornell, E., Ghetti, P., Pugnaloni, A., Biagini, G., Rizzoli, C., and Lenaz, G.
25. In vitro structural aspects of the human trophoblastic cell | Aspetti strutturali 'in vitro' delle cellule trofoblastiche umane
- Author
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Pugnaloni, A., Faloia, E., Franca Saccucci, Mazzanti, L., Solmi, R., Cester, N., Romanini, C., Pirro, R., and Biagini, G.
26. Cultured hepatocytes are contaminated by Ito cells: Relevance for studies of extracellular matrix synthesis
- Author
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Lenzi, M., primary, Solmi, R., additional, Ballardini, G., additional, Croff, P., additional, Giostra, F., additional, Biagini, G., additional, and Bianchi, F.B., additional
- Published
- 1989
- Full Text
- View/download PDF
27. Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines
- Author
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Pezzetti Furio, Santini Donatella, Taffurelli Mario, Mattei Gabriella, Montroni Isacco, Zanotti Simone, Rosati Giancarlo, Ugolini Giampaolo, Ceccarelli Claudio, Voltattorni Manuela, Martini Désirée, Francesconi Mirko, Lauriola Mattia, Solmi Rossella, Ruggeri Alessandro, Castellani Gastone, Guidotti Lia, Coppola Domenico, and Strippoli Pierluigi
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. Methods Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. Results Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. Conclusion This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an expression pattern that inversely correlates with EGF treatment. We found interesting cyto-morphological features closely relating to gene expression profile. Both drugs have an effect on differentiation towards cellular death.
- Published
- 2008
- Full Text
- View/download PDF
28. Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer
- Author
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Coppola Domenico, Santini Donatella, Taffurelli Mario, Caira Antonello, del Governatore Marco, Montroni Isacco, Lauriola Mattia, Zanotti Simone, Rosati Giancarlo, Ugolini Giampaolo, Solmi Rossella, Guidotti Lia, Carinci Paolo, and Strippoli Pierluigi
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. Methods In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22) that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription – polymerase chain reaction (RT-PCR). Results Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. Conclusion The design of new approaches to identify such markers is warranted.
- Published
- 2006
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- View/download PDF
29. Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines.
- Author
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Solmi R, Lauriola M, Francesconi M, Martini D, Voltattorni M, Ceccarelli C, Ugolini G, Rosati G, Zanotti S, Montroni I, Mattei G, Taffurelli M, Santini D, Pezzetti F, Ruggeri A, Castellani G, Guidotti L, Coppola D, Strippoli P, and Solmi, Rossella
- Abstract
Background: EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF.Methods: Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A.Results: Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases.Conclusion: This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an expression pattern that inversely correlates with EGF treatment. We found interesting cyto-morphological features closely relating to gene expression profile. Both drugs have an effect on differentiation towards cellular death. [ABSTRACT FROM AUTHOR]- Published
- 2008
- Full Text
- View/download PDF
30. Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer
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Rossella Solmi, Jin Q. Cheng, Domenico Coppola, Donghwa Kim, Yajuan Li, Mattia Lauriola, Dave Shibata, Timothy J. Yeatman, Gabriele D'Uva, Mokenge P. Malafa, Mirko Francesconi, Li, Y, Lauriola, M., Kim, D., Francesconi, M., D’Uva, G., Shibata, D., Malafa, M.P., Yeatman, T.J., Coppola, D., Solmi, R., and Cheng, J.Q.
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Beta-catenin ,Colorectal cancer ,Adenomatous polyposis coli ,Adenomatous Polyposis Coli Protein ,Adenomatous Polyposis Coli (APC) ,Article ,03 medical and health sciences ,Genetics ,medicine ,Humans ,miRNA-17-92 ,Promoter Regions, Genetic ,Genetics, microRNA ,Molecular Biology ,Wnt Signaling Pathway ,beta Catenin ,biology ,Wnt signaling pathway ,Cancer ,β-catenin ,medicine.disease ,3. Good health ,CRC ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Tumor progression ,Tissue Array Analysis ,Catenin ,Cancer cell ,Immunology ,Mutation ,Cancer research ,biology.protein ,Female ,Colorectal Neoplasms ,transcription regulation - Abstract
Adenomatous polyposis coli (APC) mutation is the most common genetic change in sporadic colorectal cancer (CRC). Although deregulations of miRNAs have been frequently reported in this malignancy, APC-regulated miRNAs have not been extensively documented. Here, by using an APC-inducible cell line and array analysis, we identified a total of 26 deregulated miRNAs. Among them, members of miR-17-92 cluster were dramatically inhibited by APC and induced by enforced expression of β-catenin. Furthermore, we demonstrate that activated β-catenin resulted from APC loss binds to and activates the miR-17-92 promoter. Notably, enforced expression of miR-19a overrides APC tumor suppressor activity, and knockdown of miR-19a in cancer cells with compromised APC function reduced their aggressive features in vitro. Finally, we observed that expression of miR-19a significantly correlates with β-catenin levels in colorectal cancer specimens, and it is associated to the aggressive stage of tumor progression. Thus, our study reveals that miR-17-92 cluster is directly regulated by APC/β-catenin pathway and could be a potential therapeutic target in colon cancers with aberrant APC/β-catenin signaling.Oncogene advance online publication, 25 January 2016; doi:10.1038/onc.2015.522.
- Published
- 2015
31. Interactions of fibroblasts with soldered and laser-welded joints
- Author
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Rossella Solmi, S. Isaza Penco, M. Zanarini, Alessandra Ruggeri, Desiree Martini, Paolo Carinci, G. Borea, Lia Rimondini, SOLMI R, MARTINI D, ZANARINI M., ISAZA PENCO S, RIMONDINI L, CARINCI P, BOREA G, and RUGGERI A.
- Subjects
Adult ,Male ,Materials science ,Biocompatibility ,Cell Survival ,Orthodontic Brackets ,Scanning electron microscope ,Gingiva ,Biophysics ,Dental appliances ,Dentistry ,Bioengineering ,Welding ,law.invention ,Dental Soldering/adverse effects, Equipment Failure Analysis, Fibroblasts pathology, Fibroblasts physiology, Foreign-Body Reaction etiology, Foreign-Body Reaction pathology, Gingiva pathology, Gingiva physiopathology, Orthodontic Brackets adverse effects ,Biomaterials ,law ,Materials Testing ,Microscopy ,Cell Adhesion ,medicine ,Humans ,Cell adhesion ,Fibroblast ,Cells, Cultured ,Cell Size ,business.industry ,Foreign-Body Reaction ,technology, industry, and agriculture ,Fibroblasts ,respiratory system ,Equipment Failure Analysis ,medicine.anatomical_structure ,Mechanics of Materials ,Soldering ,Ceramics and Composites ,Dental Soldering ,business ,Cell Division ,Biomedical engineering - Abstract
Relatively little is known about the biocompatibility of the soldered or laser-welded joints of dental appliances. We investigated the reaction of human gingival fibroblasts cultured in vitro in direct contact with samples of soldered and laser-welded joints from orthodontic lingual arches. Contrast phase light microscopy was used to evaluate cell adhesion, morphology and proliferation after 6 and 24h and after 7 and 16 days. Scanning electron microscopy (SEM) was performed at 16 days. Our in vitro findings provide evidence that laser-welded orthodontic appliances have superior fibroblast biocompatibility.
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- 2004
32. Colorectal cancer susceptibility: apparent gender-related modulation by ABCB1 gene polymorphisms
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Rossella Solmi, Giampaolo Ugolini, Isacco Montroni, Maria Teresa Rodia, Francesca Cura, Luca Scapoli, Marcella Martinelli, Martinelli, M, Scapoli, L, Cura, F, Rodia, Mt, Ugolini, G, Montroni, I, and Solmi, R
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Male ,ATP Binding Cassette Transporter, Subfamily B ,Colorectal cancer ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Locus (genetics) ,Single-nucleotide polymorphism ,Biology ,Association analysis ,Polymorphism, Single Nucleotide ,ABCB1 gene ,Risk Factors ,Carcinoma ,medicine ,Humans ,Pharmacology (medical) ,Genetic Predisposition to Disease ,Allele ,Polymorphism ,Molecular Biology ,Genetic association ,Aged ,Biochemistry, medical ,Genetics ,Aged, 80 and over ,Research ,Biochemistry (medical) ,Haplotype ,Case-control study ,Cell Biology ,General Medicine ,Middle Aged ,medicine.disease ,digestive system diseases ,Haplotypes ,Italy ,Case-Control Studies ,Colorectal cancer, ABCB1 gene, Polymorphism, Association analysis ,Cancer research ,Female ,Colorectal Neoplasms - Abstract
Background The ATP-binding cassette transporter B1 (ABCB1) gene codes for a membrane efflux pump localized in epithelial cells. Together with other Permeability-glycoproteins in the small and large intestine, its product represents a barrier against xenobiotics, bacterial toxins, drugs and other substances introduced with diet, including carcinogens. The aim of this investigation was to verify the possible contribution of ABCB1 single nucleotide polymorphisms (SNPs) to the genetic risk of colorectal cancer (CRC). Results DNA obtained from the peripheral blood of 98 CRC patients and 100 healthy controls was genotyped for the three selected SNPs: 1236C > T (rs1128503), 2677G > T/A (rs2032582), and 3435C > T (rs1045642). Molecular data were analyzed to asses allele and haplotype association with CRC. No evidence of an association between ABCB1 alleles and CRC occurrence as a whole was found. However, ABCB1 showed either association with carcinoma of the sigmoid colon, and appeared able to influence the sex ratio among CRC patients. These two effects seemed to act independently based on multivariate analysis. We showed that ABCB1 polymorphisms were able to influence CRC susceptibility related to tumor localization and patient gender. Conclusions We suggest that sensitivity to undetermined risk factors could depend on the genetic background of ABCB1 locus, with a mechanism that also depends on patient gender. Electronic supplementary material The online version of this article (doi:10.1186/s12929-014-0089-8) contains supplementary material, which is available to authorized users.
- Published
- 2014
33. Diurnal suppression of EGFR signalling by glucocorticoids and implications for tumour progression and treatment
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Morris E. Feldman, Lee Roth, Hadas Cohen-Dvashi, Moshit Lindzen, Fernando Schmitt, Rossella Solmi, Michal Sharon-Sevilla, Amit Zeisel, Stefan Wiemann, Yehoshua Enuka, Gabriele D'Uva, Mattia Lauriola, Nir Ben-Chetrit, Yosef Yarden, Nava Nevo, Eytan Domany, Silvia Carvalho, Alon Chen, Kirti Sharma, Merav Kedmi, Lauriola M, Enuka Y, Zeisel A, D'Uva G, Roth L, Sharon-Sevilla M, Lindzen M, Sharma K, Nevo N, Feldman M, Carvalho S, Cohen-Dvashi H, Kedmi M, Ben-Chetrit N, Chen A, Solmi R, Wiemann S, Schmitt F, Domany E, and Yarden Y.
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medicine.medical_specialty ,MAP Kinase Signaling System ,EGFR ,Circadian clock ,General Physics and Astronomy ,Biology ,Ligands ,Article ,General Biochemistry, Genetics and Molecular Biology ,Receptor tyrosine kinase ,Mice ,Receptors, Glucocorticoid ,Cell Movement ,Cell Line, Tumor ,Neoplasms ,Oscillometry ,Internal medicine ,Negative feedback ,medicine ,Animals ,Humans ,Receptor ,Glucocorticoids ,Mice, Knockout ,Multidisciplinary ,Kinase ,General Chemistry ,Circadian Rhythm ,ErbB Receptors ,Mice, Inbred C57BL ,Treatment Outcome ,Endocrinology ,Nuclear receptor ,Disease Progression ,Cancer research ,biology.protein ,Female ,Signal transduction ,Signal Transduction ,Hormone - Abstract
Signal transduction by receptor tyrosine kinases (RTKs) and nuclear receptors for steroid hormones is essential for body homeostasis, but the cross-talk between these receptor families is poorly understood. We observed that glucocorticoids inhibit signalling downstream of EGFR, an RTK. The underlying mechanism entails suppression of EGFR’s positive feedback loops and simultaneous triggering of negative feedback loops that normally restrain EGFR. Our studies in mice reveal that the regulation of EGFR’s feedback loops by glucocorticoids translates to circadian control of EGFR signalling: EGFR signals are suppressed by high glucocorticoids during the active phase (night-time in rodents), while EGFR signals are enhanced during the resting phase. Consistent with this pattern, treatment of animals bearing EGFR-driven tumours with a specific kinase inhibitor was more effective if administered during the resting phase of the day, when glucocorticoids are low. These findings support a circadian clock-based paradigm in cancer therapy., Glucocorticoids are released in a diurnal pattern. Here, the authors show that EGF receptor (EGFR) signalling is negatively regulated by glucocorticoids, and that EGFR inhibitor has stronger antitumour effects when administered during the resting phase, when glucocorticoids are low, offering potential optimization of cancer therapy regimens.
- Published
- 2014
34. Idiopathic pulmonary fibrosis and polymorphisms of the folate pathway genes
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Marcella Martinelli, Ambra Girardi, Angela Maria Grazia Pacilli, Gabriella Mattei, Ilaria Valentini, Stefano Nava, Luca Scapoli, Paolo Carbonara, Rossella Solmi, Luca Fasano, Francesca Farinella, Martinelli M, Scapoli L, Carbonara P, Valentini I, Girardi A, Farinella F, Mattei G, Pacilli AM, Fasano L, Nava S, and Solmi R
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Male ,Pathology ,medicine.medical_specialty ,Clinical Biochemistry ,Single-nucleotide polymorphism ,5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ,Polymorphism, Single Nucleotide ,Idiopathic pulmonary fibrosis, Polymorphisms, Folate pathway ,Minor Histocompatibility Antigens ,Idiopathic pulmonary fibrosis ,Folic Acid ,Genotype ,Medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Gene ,Genetic association ,Aged ,Methylenetetrahydrofolate Dehydrogenase (NADP) ,Pregnancy ,Transcobalamins ,business.industry ,Haplotype ,General Medicine ,Middle Aged ,medicine.disease ,Idiopathic Pulmonary Fibrosis ,Tetrahydrofolate Dehydrogenase ,Haplotypes ,Case-Control Studies ,Immunology ,Female ,business - Abstract
Objectives This study aims to determine the possible association between folate pathway gene polymorphisms and idiopathic pulmonary fibrosis. This represents the first study carried out on folate pathway gene polymorphisms as possible risk factors in this kind of pathology. The premise is that several polymorphisms mapping on genes responsible for folate uptake are associated with the risk of numerous diseases occurring between pregnancy and old age, and that too little is currently known about idiopathic pulmonary fibrosis. Design and methods We genotyped 9 single nucleotide polymorphisms and 1 polymorphic insertion in 7 essential genes belonging to the folate pathway in 32 Italian idiopathic pulmonary fibrosis patients and 81 control subjects. This was done by PCR and restriction analysis. Results Allelic and genotypic association tests indicated that for all the analysed polymorphisms there were no significant differences between patients and controls. Nevertheless, the haplotype association analysis revealed a significant association between idiopathic pulmonary fibrosis and transcobalamin II gene polymorphisms: specifically the haplotype 776G (rs1801198)–c.1026-394G (rs7286680)–444C (rs10418) (OR = 2.84; 95% C.I. 1.36–5.93, P value = 0.004). Conclusions This small-scale preliminary study would suggest the importance of further research focusing on the role of folate in the onset of idiopathic pulmonary fibrosis.
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- 2013
35. A candidate gene study of one-carbon metabolism pathway genes and colorectal cancer risk
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Isacco Montroni, Giampaolo Ugolini, Gabriella Mattei, Rossella Solmi, Marcella Martinelli, Davide Zattoni, Luca Scapoli, Giancarlo Rosati, Martinelli M, Scapoli L, Mattei G, Ugolini G, Montroni I, Zattoni D, Rosati G, and Solmi R
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Male ,Candidate gene ,Genotype ,Colorectal cancer ,METHYLENETETRAHYDROFOLATE REDUCTASE, FOLATE METABOLISM, COLON-CANCER, MTHFR C677T, POLYMORPHISMS, TRANSCOBALAMIN, ADENOMA, METAANALYSIS, ASSOCIATION ,Medicine (miscellaneous) ,Biology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Folic Acid ,Methionine ,Gene Frequency ,medicine ,SNP ,Humans ,Genetic Predisposition to Disease ,Gene ,Genotyping ,Genetic Association Studies ,Genetic association ,Aged ,One-Carbon Group Transferases ,Genetics ,Transcobalamins ,Nutrition and Dietetics ,Nucleotides ,Cancer ,medicine.disease ,Carbon ,Diet ,Mutagenesis, Insertional ,Vitamin B 12 ,Methylenetetrahydrofolate reductase ,Case-Control Studies ,biology.protein ,Female ,Colorectal Neoplasms - Abstract
The risk of colorectal cancer (CRC) may be influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by impaired dietary folate intake as well as by polymorphic variants in one-carbon metabolism genes. A case–control study using seventy-one CRC patients and eighty unrelated healthy controls was carried out to assess the genetic association of fifteen SNP and one insertion in nine genes belonging to the folate pathway. Polymorphism selection was based on literature data, and included those which have a known or suspected functional impact on cancer and missense polymorphisms that are most likely to alter protein function. Genotyping was performed by real-time PCR and PCR followed by restriction analysis. The likelihood ratio statistic indicated that most of the polymorphisms were not associated with the risk of CRC. However, an increased risk of CRC was observed for two variant alleles of SNP mapping on the transcobalamin 2 gene (TCN2): C776G (rs1801198) and c.1026-394T>G (rs7286680). Considering the crucial biological function played by one-carbon metabolism genes, further investigations with larger cohorts of CRC patients are needed in order to confirm our preliminary results. These preliminary results indicate that TCN2 polymorphisms can be a susceptibility factor for CRC.
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- 2012
36. The EGFR R521K polymorphism influences the risk to develop colorectal cancer
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Marcella Martinelli, Giampaolo Ugolini, Mario Taffurelli, Stefano Rivetti, Alessio Manaresi, Davide Zattoni, Giancarlo Rosati, Mattia Lauriola, Gabriella Mattei, Luca Scapoli, Rossella Solmi, Isacco Montroni, Martinelli M, Ugolini G, Scapoli L, Rivetti S, Lauriola M, Mattei G, Rosati G, Montroni I, Manaresi A, Zattoni D, Taffurelli M, and Solmi R
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Oncology ,Adult ,Risk ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,Single-nucleotide polymorphism ,Arginine ,Polymorphism, Single Nucleotide ,Internal medicine ,Genotype ,Genetics ,medicine ,SNP ,Humans ,Genetic Predisposition to Disease ,Epidermal growth factor receptor ,Kinase activity ,Genetic Association Studies ,Genetic association ,EGFR inhibitors ,Aged ,Aged, 80 and over ,biology ,Lysine ,Colorectal cancer, EGFR, HER2, HER3, polymorphisms ,General Medicine ,Middle Aged ,medicine.disease ,ErbB Receptors ,Amino Acid Substitution ,biology.protein ,Female ,Colorectal Neoplasms - Abstract
Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been extensively investigated for its possible involvement in cancer development and progression. In colorectal cancer (CRC) EGFR family has been found frequently over-expressed, thus therapy targeting EGFR has been developed. Interestingly, it has been observed that genetic variants in these receptors may alter the therapeutic efficacy of EGFR inhibitors. Polymorphic variants in members of the EGFR family could influence different biologic activities, such as ligands affinity, dimerization efficiency, kinase activity, expression levels, with a consequent impact in signalling pathways and cell behaviour. This study aimed to verify whether single nucleotide polymorphisms (SNPs) of EGFR family members could represent susceptibility factors able to influence the risk to develop CRC. Peripheral blood of 70 Italian colon cancer patients and 72 healthy controls was used as a source of genomic DNA to investigate EGFR, HER2 and HER3 common non-synonymous SNPs. Genetic association tests were performed to verify a possible relationship with CRC. Evidence of genotype association was found for the R521K EGFR polymorphism under a dominant mode of inheritance (Mid-P=0.031). Genotypes with the variant allele of EGFR R521K SNP confer a risk reduction to develop CRC.
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- 2011
37. Gene expression profile of human colon cancer cells treated with cross-reacting material 197, a diphtheria toxin non-toxic mutant
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Giampaolo Ugolini, Giancarlo Rosati, Mario Taffurelli, Manuela Voltattorni, Mattia Lauriola, Gabriella Mattei, Isacco Montroni, Stefano Rivetti, Annalisa Palmieri, Desiree Martini, Marco Franchi, Claudio Ceccarelli, Rossella Solmi, Michele Bianchini, Rivetti S, Lauriola M, Voltattorni M, Bianchini M, Martini D, Ceccarelli C, Palmieri A, Mattei G, Franchi M, Ugolini G, Rosati G, Montroni I, Taffurelli M, and Solmi R.
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DNA, Complementary ,Receptor, ErbB-4 ,Cell Survival ,Heparin-binding EGF-like growth factor ,Immunology ,CRM197 ,GNAI1 ,Bacterial Proteins ,MICROARRAY ,Epidermal growth factor ,Colon cancer ,Microarray ,Humans ,Immunology and Allergy ,RNA, Neoplasm ,Epidermal growth factor receptor ,Coloring Agents ,In Situ Hybridization ,Pharmacology ,Regulation of gene expression ,Diphtheria toxin ,COLORECTAL CANCER ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Microarray analysis techniques ,Chemistry ,Gene Expression Profiling ,Cell Cycle ,Trypan Blue ,Flow Cytometry ,Microarray Analysis ,Immunohistochemistry ,Molecular biology ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,HB-EGF ,Enterocytes ,Colonic Neoplasms ,Cancer cell ,Microscopy, Electron, Scanning ,biology.protein ,Intercellular Signaling Peptides and Proteins ,sense organs ,HT29 Cells ,Heparin-binding EGF-like Growth Factor - Abstract
Cross-Reacting Material 197 (CRM197) is a diphtheria toxin non-toxic mutant that has shown antitumor activity in mice and humans. It is still unclear whether this anti-tumorigenic effect depends on its strong inflammatory-immunological property, its ability to inhibit heparin-binding epidermal growth factor (HB-EGF), or even its possible weak toxicity. CRM197 is utilized as a specific inhibitor of HB-EGF that competes for the epidermal growth factor receptor (EGFR), overexpressed in colorectal cancer and implicated in its progression. In this study we evaluate the effects of CRM197 on HT-29 human colon cancer cell line behaviour and, for CRM197 recognized ability to inhibit HB-EGF, its possible influence on EGFR activation. In particular, while HT-29 does not show any reduction of viability after CRM197 treatment (MTT modified assay), or changes in cell cycle distribution (flow cytometry), in EGFR localization, phospho-EGFR detected signals (immunohistochemistry) or in morphology (scanning electron microscopy, SEM) they show a change in the gene expression profile by microarray analysis (cDNA microarray SS-H19k8). The overexpression of genes like protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA), guanine nucleotide-binding protein G subunit alpha-1(GNAIl) and butyrophilin, subfamily 2, member A1 (BTN2A1) has been confirmed with real-time-qPCR. This is the first study where the CRM197 treatment on HT-29 shows a possible scarce implication of endogenous HB-EGF on EGFR expression and cancer cell development. At the same time, our results show the alteration of a specific and selected number of genes.
- Published
- 2011
38. IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes
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Alessio Manaresi, Simone Zanotti, Mario Taffurelli, Sara Nanì, Giancarlo Rosati, Stefano Rivetti, Gabriele D'Uva, Isacco Montroni, Davide Zattoni, Gabriella Mattei, Lucia Castellani, Andrea Belluzzi, Pierluigi Strippoli, Mattia Lauriola, Giampaolo Ugolini, Rossella Solmi, Lauriola M, Ugolini G, Rivetti S, Nanì S, Rosati G, Zanotti S, Montroni I, Manaresi A, Zattoni D, Belluzzi A, Castellani L, D'Uva G, Mattei G, Taffurelli M, Strippoli P, and Solmi R.
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Adult ,Male ,Heterozygote ,single nucleotide polymorphism, genotype, Crohn's disease, genetic susceptibility ,Adolescent ,Nod2 Signaling Adaptor Protein ,Autophagy-Related Proteins ,ATG16L1 ,Crohn's Disease ,Single-nucleotide polymorphism ,Biology ,PHOX2B ,Models, Biological ,polymorphism ,Crohn Disease ,IL23R ,Risk Factors ,NOD2 ,Genotype ,Genetics ,Genetic predisposition ,Humans ,SNP ,Allele ,Child ,Alleles ,Homeodomain Proteins ,NOD2/CARD15 ,Polymorphism, Genetic ,Homozygote ,Smoking ,Infant ,Receptors, Interleukin ,General Medicine ,Odds ratio ,Middle Aged ,Child, Preschool ,Immunology ,Female ,Carrier Proteins ,Transcription Factors - Abstract
Recent genomic research has identified interleukin-23 receptor (IL23R), nucleotide-binding oligomerization domain containing 2 caspase-activation recruitment domain 15 (NOD2/CARD15), autophagy related 16-like 1 (ATG16L1) and paired-like homeobox 2b (PHOX2B) as susceptibility loci for Crohn's Disease (CD). Our aim was to investigate these gene variants in a group of CD patients and to analyse the correlation to sub-phenotypes such as gender, smoking habits, disease behaviour at diagnosis, severity of disease and extra-intestinal manifestations. Nineteen patients with CD and 20 healthy controls were included in the study. The gene variants IL23R rs7517847 and rs11209026, NOD2/CARD15 rs2066845, PHOX2B rs16853571, ATG16L1 rs2241879 and rs2241880 were genotyped by PCR followed by sequencing. The frequency of the G risk allele of IL23R rs7517847 was found to be increased in patients with CD (42%) compared to that in control subjects (20%) [odds ratio (OR), 2.9; 95% confidence interval [CI], 1.06-7.9; P=0.03]. In addition, the homozygous condition GG was also associated with CD (OR, 8.70; 95% CI, 0.9-81.6; P=0.038). The analysis of correlation of genotype to sub-phenotypes showed an association of ATG16L1 rs2241879 with the lack of extra-intestinal manifestations (OR, 0.03; 95% CI, 0.002-0.45; P=0.006), and the patients defined as non-smokers displayed an increased frequency of the risk allele C (P=0.03). The present study confirms the association of the heterozygous and homozygous IL23R rs7517847 variant with CD and suggests an additive effect of smoking to the ATG16L1 rs2241879 C risk allele SNP, in the context of the multifactorial model established for the development of CD and a protective effect of the same allele against extra-intestinal manifestations.
- Published
- 2011
39. Identification by a Digital Gene Expression Displayer (DGED) and test by RT-PCR analysis of new mRNA candidate markers for colorectal cancer in peripheral blood
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Stefano Rivetti, Domenico Coppola, Rossella Solmi, Mario Taffurelli, Mattia Lauriola, Davide Zattoni, Simone Zanotti, Isacco Montroni, Gabriella Mattei, Giampaolo Ugolini, Giancarlo Rosati, Alessio Manaresi, Pierluigi Strippoli, LAURIOLA M., UGOLINI G., ROSATI G., ZANOTTI S., MONTRONI I., MANARESI A., ZATTONI D., RIVETTI S., MATTEI G., COPPOLA D., STRIPPOLI P., TAFFURELLI M., and SOLMI R.
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Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Colorectal cancer ,Biology ,CIRCULATING TUMOR CELLS ,Complementary DNA ,Gene expression ,medicine ,Biomarkers, Tumor ,Image Processing, Computer-Assisted ,Humans ,Serial analysis of gene expression ,RNA, Messenger ,DIGITAL GENE EXPRESSION DISPLAY ,Cancer Genome Anatomy Project ,Genetic Association Studies ,Aged ,Aged, 80 and over ,COLORECTAL CANCER ,cDNA library ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Carcinoma ,Cancer ,Signal Processing, Computer-Assisted ,Middle Aged ,medicine.disease ,Neoplastic Cells, Circulating ,Molecular biology ,Gene expression profiling ,Oncology ,Case-Control Studies ,Female ,Colorectal Neoplasms - Abstract
Evidence from the literature widely supports the efficacy of screening for colorectal cancer (CRC) in reducing mortality. A blood-based assay, potentially, represents a more accessible early detection tool for the identification of circulating tumour cells originating from a primary tumour site in the body. The present work aimed at identifying a set of specific mRNAs expressed in colon tissue but not in blood cells. These mRNAs may represent useful markers for early detection of circulating colon cancer cells by a simple, qualitative RT-PCR assay, following RNA extraction from peripheral blood samples. Using a data-mining tool called cDNA digital gene expression displayer (DGED), based on serial analysis of gene expression (SAGE) from the Cancer Genome Anatomy Project (CGAP) database, 4-colon and 14-blood cDNA libraries were analyzed. We selected 7 genes expressed in colon tissue but not in blood and were able to test 6 of them by RT-PCR in peripheral blood of CRC patients and healthy controls. We present a relatively easy and highly reproducible technique for the detection of mRNA expression of genes as candidate markers of malignancy in blood samples of patients with colon cancer. SAGE DGED provided a list of the best candidate mRNAs predicted to detect colon cells in the blood, namely those encoding the following proteins: hypothetical protein LOC644844 (LOC644844, whose cDNA was not amplifiable), fatty acid binding protein 1 (FABP1), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), mucin 13 cell surface associated (MUC13), guanylate cyclase activator 2A (GUCA2A), amiloride binding protein 1 (ABP1), galactoside-binding, solute carrier family 26, member 3 (SLC26A3). The mRNA expression of these genes was evaluated in 8 samples from subjects diagnosed with CRC and 9 from healthy controls. We observed the expression of 2 of the 6 investigated genes in the blood samples of the vast majority of patients considered, but also in a subset of the controls. Our data confirm the extreme sensitivity of RT-PCR, making this technique able to detect minimal amounts of mRNA expressed in a non-tissue-specific manner. Moreover, DGED remains a powerful tool to identify candidate epithelial markers in blood, such as colon related mRNAs. However, to date, none of these qualified as tumour markers.
- Published
- 2010
40. Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines
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Giampaolo Ugolini, Domenico Coppola, Rossella Solmi, Desiree Martini, Mirko Francesconi, Mario Taffurelli, Mattia Lauriola, Giancarlo Rosati, Furio Pezzetti, Alessandro Ruggeri, Manuela Voltattorni, Donatella Santini, Simone Zanotti, Isacco Montroni, Pierluigi Strippoli, Lia Guidotti, Gastone Castellani, Gabriella Mattei, Claudio Ceccarelli, Solmi R, Lauriola M, Francesconi M, Martini D, Voltattorni M, Ceccarelli C, Ugolini G, Rosati G, Zanotti S, Montroni I, Mattei G, Taffurelli M, Santini D, Pezzetti F, Ruggeri A, Castellani G, Guidotti L, Coppola D, and Strippoli P.
- Subjects
Cancer Research ,Cell Survival ,Biology ,Antibodies, Monoclonal, Humanized ,lcsh:RC254-282 ,GEFITINIB ,Gefitinib ,MICROARRAY ,Epidermal growth factor ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Genetics ,Cluster Analysis ,Humans ,Oligonucleotide Array Sequence Analysis ,EGFR inhibitors ,EGF ,Epidermal Growth Factor ,Microvilli ,Cetuximab ,Cell growth ,Gene Expression Profiling ,Cell Cycle ,Antibodies, Monoclonal ,Cell cycle ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Molecular biology ,CETUXIMAB ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,Oncology ,Apoptosis ,Colonic Neoplasms ,SEM ,Microscopy, Electron, Scanning ,Quinazolines ,Research Article ,medicine.drug - Abstract
Background EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. Methods Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. Results Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. Conclusion This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an expression pattern that inversely correlates with EGF treatment. We found interesting cyto-morphological features closely relating to gene expression profile. Both drugs have an effect on differentiation towards cellular death.
- Published
- 2008
41. Submicroscopic alterations and gene expression profiles of human colon cancer cell lines in response to cetuximab, gefitinib and EGF
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LAURIOLA, MATTIA, FRANCESCONI, MIRKO, MARTINI, DESIREE, VOLTATTORNI, MANUELA, CECCARELLI, CLAUDIO, UGOLINI, GIAMPAOLO, ROSATI, GIANCARLO, ZANOTTI, SIMONE, MONTRONI, ISACCO, MATTEI, GABRIELLA, TAFFURELLI, MARIO, SANTINI, DONATELLA, PEZZETTI, FURIO, RUGGERI, ALESSANDRO, CASTELLANI, GASTONE, GUIDOTTI, LIA, STRIPPOLI, PIERLUIGI, SOLMI, ROSSELLA, Nanì S, Coppola D, MOZZON GIUNTINA S.P.A IL SEDICESIMO - FIRENZE, Lauriola M, Francesconi M, Martini D, Voltattorni M, Ceccarelli C, Ugolini G, Rosati G, Zanotti S, Montroni I, Mattei G, Taffurelli M, Santini D, Pezzetti F, Nanì S, Ruggeri A, Castellani G, Guidotti L, Coppola D, Strippoli P, and Solmi R.
- Subjects
MICROARRAY ,SEM ,CETUXIMAB ,EGF ,GEFITINIB - Abstract
Epidermal growth factor receptor (EGFR), one of the most important cell membrane receptors expressed in normal cells, is frequently overexpressed in colon cancer. EGFR is a pleiotropic signaler and the integrated biological response to EGFR activation varies from mitogenesis to apoptosis, to differentiation and to dedifferentiation even in the same cell, depending on the context. We have investigated the effect of cetuximab or gefitinib (EGFR target therapy molecules) alone and in combination with EGF, the natural ligand binding to EGFR, on human colon cancer cell lines (Caco-2 and HT-29). The aim of the study is to detect changes in gene expression profiles induced with these drug treatments, and to correlate them with the associated cell behaviors. Both drugs affect differentiation and apoptosis. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; on the other hand, when treated with gefitinib, they acquired cytoplasmic vesicles, and displayed reshape of the cellular membrane. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines, and directly correlated with EGF treatment. We found interesting cyto-morphological features closely related to gene expression profile. The EGFR inhibitors had a weaker effect in the presence of EGF. Our data show interesting cyto-morphological features possibly correlated to the clinical effects of cetuximab and gefitinib, and these could have implications for cancer therapy, especially as concerns the cellular microenvironment.
- Published
- 2008
42. Lung regions differently modulate bronchial branching development and extracellular matrix plays a role in regulating the development of chick embryo whole lung
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Stabellini, G., Calvitti, M., Becchetti, E., Carinci, P., Calastrini, C., Lilli, C., ROSSELLA SOLMI, Vizzotto, L., Baroni, T., Stabellini G., Calvitti M., Becchetti E., Carinci P., Calastrini C., Lilli C., Solmi R., Vizzotto L., and Baroni T.
- Subjects
Settore BIO/17 - Istologia ,Settore BIO/16 - Anatomia Umana ,Hyaluronoglucosaminidase ,Bronchi ,Chick Embryo ,respiratory system ,Chondroitin ABC Lyase ,CHICK EMBRIO ,respiratory tract diseases ,Extracellular Matrix ,DEVELOPMENT ,Organ Culture Techniques ,lcsh:Biology (General) ,Acetylglucosaminidase ,Animals ,lcsh:QH301-705.5 ,Lung - Abstract
Normal branching development is dependent on the correlation between cells and extracellular matrix. In this interaction glycosaminoglycans, cytokines and growth factors play a fundamental role. In order to verify the distribution and influence of extracellular matrix and related enzymes on chick embryo lung development, 6 day-old whole lungs were maintained in vitro with testicular hyaluronidase, beta-N-acetyl-D-glucosaminidase and chondrotinase ABC or in linkage with apical, medial and caudal lung regions of 6-day development before and after enzyme treatment. In a separate lung region beta-N-acetyl-D-glucosaminidase and hyaluronidase were determined. Our data show that the whole lung cultures increase bronchial branching development when the medial region is admixed separately, while the separate apical or caudal regions or apical combined with caudal region do not affect bronchial branching development. The enzyme treatment of medial region prevents the branching development in associated whole lung. The bronchial branching development of whole lung cultured in medium containing the enzymes related to glycosaminoglycans turnover is significantly altered. In conclusion, these data show that the different influence of separate apical, medial, caudal lung regions on bronchial branching development is related to the extracellular matrix composition.
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- 2007
43. RDF and TopicMaps interoperability: a model-driven approach
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DI IORIO, ANGELO, DUCA, SILVIA, PRESUTTI, VALENTINA, SOLMI, RICCARDO, VITALI, FABIO, Di Iorio A., Duca S., Presutti V., Solmi R., and Vitali F.
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InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,InformationSystems_DATABASEMANAGEMENT - Abstract
We present a model-driven approach for interoperability between RDF and TopicMaps
- Published
- 2007
44. Identification of candidate genes involved in the reversal of malignant phenotype of osteosarcoma cells transfected with the liver/bone/kidney alkaline phosphatase gene
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Michele Bianchini, Maria Cristina Manara, Luisa Valvassori, Stefania Benini, Cinzia Zucchini, Paolo Carinci, Katia Scotlandi, Pierluigi Strippoli, Rossella Solmi, Piero Picci, Stefania Perdichizzi, ZUCCHINI C., BIANCHINI M., VALVASSORI L., PERDICHIZZI S., BENINI S., MANARA MC., SOLMI R., STRIPPOLI P., PICCI P., CARINCI P., and SCOTLANDI K.
- Subjects
musculoskeletal diseases ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Phosphatase ,Biology ,Kidney ,Transfection ,Bone and Bones ,Cell Line, Tumor ,Gene expression ,medicine ,Cluster Analysis ,Humans ,RNA, Messenger ,Neoplasm Metastasis ,Cell adhesion ,Oligonucleotide Array Sequence Analysis ,Osteosarcoma ,Cadherin ,Cell growth ,medicine.disease ,Alkaline Phosphatase ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Cell Transformation, Neoplastic ,Phenotype ,Liver ,Immunology ,Gene chip analysis ,Alkaline phosphatase - Abstract
Alkaline phosphatases (ALPs) are a family of cell surface glycoproteins that catalyze the hydrolysis of phosphomonoesters with release of inorganic phosphate. Liver/bone/kidney (L/B/K) ALP participates in bone mineralization, but its other physiological and pathological functions remain obscure. In human osteosarcoma, an inverse relationship has been found between cellular L/B/K ALP expression and aggressiveness. To explore this relationship, we employed cDNA microarray technology to characterize and compare the gene expression profile of two U-2 OS osteosarcoma clones with high L/B/K ALP activity (U-2/ALP28 and U-2/ALP40) and one with contrasting characteristics (U-2/ALP23). We identified 79 differentially expressed genes (58 upregulated in U-2/ALP28 and U-2/ALP40 compared to U-2/ALP23). Using GenMAPP/MAPPFinder, we highlighted nine functional groups strictly related to high L/B/K ALP activity, including microtubule-based movement and cell adhesion groups, two functions well related to tumor invasiveness. Notably, cadherin 13 ( CDH13 ) and caveolin 1 ( CAV1 ) genes were upregulated in our cells. Since these two genes are involved in cell–cell adhesion and cell growth, their co-expression with L/B/K ALP could help explain the lower levels of malignancy found in osteosarcoma cells with high L/B/K ALP activity. Although functional studies are needed to better define the role of CDH13 and CAV1 in the malignant behavior of osteosarcoma cells, the data presented here provide an aid to understanding the biological functions of L/B/K ALP in bone tumors.
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- 2003
45. Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer
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Giampaolo Ugolini, Giancarlo Rosati, Domenico Coppola, Isacco Montroni, Lia Guidotti, Marco Del Governatore, Mario Taffurelli, Pierluigi Strippoli, Simone Zanotti, Mattia Lauriola, Rossella Solmi, Donatella Santini, Antonello Caira, Paolo Carinci, Solmi R., Ugolini G., Rosati G., Zanotti S., Lauriola M., Montroni I., Del Governatore M., Caira A., Taffurelli M., Santini D., Coppola D., Guidotti L., Carinci P., and Strippoli P.
- Subjects
Adult ,Male ,Nucleocytoplasmic Transport Proteins ,Cancer Research ,Microarray ,Colorectal cancer ,RT-PCR ,Keratin-20 ,Biology ,lcsh:RC254-282 ,law.invention ,Automation ,MICROARRAY ,law ,Complementary DNA ,medicine ,Genetics ,Humans ,RNA, Messenger ,RNA, Neoplasm ,Polymerase chain reaction ,Aged ,Oligonucleotide Array Sequence Analysis ,COLORECTAL CANCER ,Reverse Transcriptase Polymerase Chain Reaction ,Keratin 20 ,Gene Expression Profiling ,Serine Endopeptidases ,Membrane Proteins ,Nuclear Proteins ,Epithelial Cells ,Middle Aged ,medicine.disease ,Neoplastic Cells, Circulating ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Molecular biology ,Reverse transcriptase ,Gene expression profiling ,PERIFERAL BLOOD CELLS ,Real-time polymerase chain reaction ,Oncology ,Colonic Neoplasms ,Keratins ,Female ,Research Article - Abstract
Background The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. Methods In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22) that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription – polymerase chain reaction (RT-PCR). Results Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. Conclusion The design of new approaches to identify such markers is warranted.
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46. The Roadmap of Colorectal Cancer Screening.
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Ferlizza E, Solmi R, Sgarzi M, Ricciardiello L, and Lauriola M
- Abstract
Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. National screening programs based on fecal occult blood tests and subsequent colonoscopy have reduced the incidence and mortality, however improvements are needed since the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of the CRC screening globally and the state of the art in approaches aimed at improving accuracy and participation in CRC screening, also considering the need for gender and age differentiation. New fecal tests and biomarkers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel biomarkers and panels, such as circulating mRNA, micro- and long-non-coding RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods that could be easily applied to routine screening, or arrays and sequencing assays that should be better exploited to describe and identify candidate biomarkers in blood samples.
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- 2021
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47. Colorectal cancer screening: Assessment of CEACAM6 , LGALS4 , TSPAN8 and COL1A2 as blood markers in faecal immunochemical test negative subjects.
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Ferlizza E, Solmi R, Miglio R, Nardi E, Mattei G, Sgarzi M, and Lauriola M
- Abstract
Prevention is essential to reduce Colorectal Cancer (CRC) mortality. We previously reported a panel of four genes: CEACAM6, LGALS4, TSPAN8, COL1A2 (CELTiC) able to discriminate patients with CRC. Here, we assessed the CELTiC panel by quantitative polymerase chain reaction, in the blood of 174 healthy subjects, who resulted negative to the faecal immunochemical test (FITN). Using non-parametric statistic and multinomial logistic models, the FITN were compared to previously analysed subjects: 36 false positive FIT (NFIT), who were negative at colonoscopy, 36 patients with low risk lesions (LR) and 92 patients with high risk lesions or CRC (HR/CRC). FITN showed a significantly lower expression of the four genes when compared to HR/CRC. Moreover, FITN showed a significantly lower expression of TSPAN8 and COL1A2 compared to NFIT and LR patients. The multinomial logistic model confirmed that TSPAN8 alone specifically discriminated FITN from NFIT, LR and HR/CRC, while LGALS4 was able to differentiate FITN from false positive FIT. Finally, ROC curves analysis of the comparisons between FITN and HR/CRC, LR or NFIT reported AUC greater than 0.87, with a sensitivity and specificity of 83% and 76%, respectively. The CELTiC panel was confirmed a useful tool to identify CRC patients and to discriminate false FIT positive subjects., (© 2020 THE AUTHORS. Published by Elsevier BV on behalf of Cairo University.)
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- 2020
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48. Glucocorticoid Receptor Modulates EGFR Feedback upon Acquisition of Resistance to Monoclonal Antibodies.
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Gelfo V, Pontis F, Mazzeschi M, Sgarzi M, Mazzarini M, Solmi R, D'Uva G, and Lauriola M
- Abstract
Evidences of a crosstalk between Epidermal Growth Factor Receptor (EGFR) and Glucocorticoid Receptor (GR) has been reported, ranging from the modulation of receptor levels or GR mediated transcriptional repression of EGFR target genes, with modifications of epigenetic markers. The present study focuses on the involvement of EGFR positive and negative feedback genes in the establishment of cetuximab (CTX) resistance in metastatic Colorectal Cancer (CRC) patients. We evaluated the expression profile of the EGFR ligands TGFA and HBEGF, along with the pro-inflammatory cytokines IL-1B and IL-8, which were previously reported to be negatively associated with monoclonal antibody response, both in mice and patient specimens. Among EGFR negative feedback loops, we focused on ERRFI1, DUSP1, LRIG3, and LRIG1. We observed that EGFR positive feedback genes are increased in CTX-resistant cells, whereas negative feedback genes are reduced. Next, we tested the expression of these genes in CTX-resistant cells upon GR modulation. We unveiled that GR activation leads to an increase in ERRFI1, DUSP1, and LRIG1, which were shown to restrict EGFR activity, along with a decrease in the EGFR activators (TGFA and IL-8). Finally, in a cohort of xenopatients, stratified for response to cetuximab, we observed an inverse association between the expression level of LRIG1 and CRC progression upon CTX treatment. Our model implies that combining GR modulation to EGFR inhibition may yield an effective treatment strategy in halting cancer progression.
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- 2019
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49. LGALS4, CEACAM6, TSPAN8, and COL1A2: Blood Markers for Colorectal Cancer-Validation in a Cohort of Subjects With Positive Fecal Immunochemical Test Result.
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Rodia MT, Solmi R, Pasini F, Nardi E, Mattei G, Ugolini G, Ricciardiello L, Strippoli P, Miglio R, and Lauriola M
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- Aged, Antigens, CD blood, Area Under Curve, Cell Adhesion Molecules blood, Collagen Type I blood, Feces chemistry, Female, GPI-Linked Proteins blood, Galectin 4 blood, Humans, Immunohistochemistry, Male, Mass Screening methods, Middle Aged, RNA, Messenger blood, ROC Curve, Real-Time Polymerase Chain Reaction methods, Sensitivity and Specificity, Tetraspanins blood, Biomarkers, Tumor blood, Colorectal Neoplasms blood, Colorectal Neoplasms diagnosis, Early Detection of Cancer methods
- Abstract
Background: A noninvasive blood test for the early detection of colorectal cancer (CRC) is highly required. We evaluated a panel of 4 mRNAs as putative markers of CRC., Materials and Methods: We tested LGALS4, CEACAM6, TSPAN8, and COL1A2, referred to as the CELTiC panel, using quantitative reverse transcription polymerase chain reaction, on subjects with positive fecal immunochemical test (FIT) results and undergoing colonoscopy. Using a nonparametric test and multinomial logistic model, FIT-positive subjects were compared with CRC patients and healthy individuals., Results: All the genes of the CELTiC panel displayed statistically significant differences between the healthy subjects (n = 67), both low-risk (n = 36) and high-risk/CRC (n = 92) subjects, and those in the negative-colonoscopy, FIT-positive group (n = 36). The multinomial logistic model revealed LGALS4 was the most powerful marker discriminating the 4 groups. When assessing the diagnostic values by analysis of the areas under the receiver operating characteristic curves (AUCs), the CELTiC panel reached an AUC of 0.91 (sensitivity, 79%; specificity, 94%) comparing normal subjects to low-risk subjects, and 0.88 (sensitivity, 75%; specificity, 87%) comparing normal and high-risk/CRC subjects. The comparison between the normal subjects and the negative-colonoscopy, FIT-positive group revealed an AUC of 0.93 (sensitivity, 82%; specificity, 97%)., Conclusion: The CELTiC panel could represent a useful tool for discriminating subjects with positive FIT findings and for the early detection of precancerous adenomatous lesions and CRC., (Copyright © 2017 Elsevier Inc. All rights reserved.)
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- 2018
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50. A module of inflammatory cytokines defines resistance of colorectal cancer to EGFR inhibitors.
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Gelfo V, Rodia MT, Pucci M, Dall'Ora M, Santi S, Solmi R, Roth L, Lindzen M, Bonafè M, Bertotti A, Caramelli E, Lollini PL, Trusolino L, Yarden Y, D'Uva G, and Lauriola M
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- Animals, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological therapeutic use, Caco-2 Cells, Cell Culture Techniques, Cell Proliferation drug effects, Cetuximab therapeutic use, Colorectal Neoplasms pathology, ErbB Receptors antagonists & inhibitors, Humans, Interleukin-1alpha metabolism, Interleukin-1beta metabolism, Interleukin-8 metabolism, Microscopy, Confocal, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Signal Transduction drug effects, Spheroids, Cellular metabolism, Up-Regulation, Xenograft Model Antitumor Assays, Antineoplastic Agents, Immunological pharmacology, Cetuximab pharmacology, Colorectal Neoplasms drug therapy, Drug Resistance, Neoplasm, ErbB Receptors metabolism
- Abstract
Epidermal Growth Factor Receptor (EGFR) activates a robust signalling network to which colon cancer tumours often become addicted. Cetuximab, one of the monoclonal antibodies targeting this pathway, is employed to treat patients with colorectal cancer. However, many patients are intrinsically refractory to this treatment, and those who respond develop secondary resistance along time. Mechanisms of cancer cell resistance include either acquisition of new mutations or non genomic activation of alternative signalling routes. In this study, we employed a colon cancer model to assess potential mechanisms driving resistance to cetuximab. Resistant cells displayed increased ability to grow in suspension as colonspheres and this phenotype was associated with poorly organized structures. Factors secreted from resistant cells were causally involved in sustaining resistance, indeed administration to parental cells of conditioned medium collected from resistant cells was sufficient to reduce cetuximab efficacy. Among secreted factors, we report herein that a signature of inflammatory cytokines, including IL1A, IL1B and IL8, which are produced following EGFR pathway activation, was associated with the acquisition of an unresponsive phenotype to cetuximab in vitro. This signature correlated with lack of response to EGFR targeting also in patient-derived tumour xenografts. Collectively, these results highlight the contribution of inflammatory cytokines to reduced sensitivity to EGFR blockade and suggest that inhibition of this panel of cytokines in combination with cetuximab might yield an effective treatment strategy for CRC patients refractory to anti-EGFR targeting.
- Published
- 2016
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