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1,366 results on '"Croce, Cm"'

1. Allele-specific loss and transcription of the miR-15a/16-1 cluster in chronic lymphocytic leukemia

Author

Veronese, A, Pepe, F, Chiacchia, J, Pagotto, S, Lanuti, P, Veschi, S, Di Marco, M, D'Argenio, A, Innocenti, I, Vannata, B, Autore, F, Marchisio, M, Wernicke, D, Verginelli, F, Leone, G, Rassenti, LZ, Kipps, TJ, Mariani-Costantini, R, Laurenti, L, Croce, CM, and Visone, R

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Rare Diseases, Lymphoma, Hematology, Genetics, Cancer, Alleles, Base Sequence, Biomarkers, Tumor, Cell Line, Tumor, Chromatin Immunoprecipitation, DNA, DNA Copy Number Variations, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, MicroRNAs, Molecular Sequence Data, Polymorphism, Single Nucleotide, Real-Time Polymerase Chain Reaction, Transcription, Genetic, Immunology, Cardiovascular medicine and haematology, Clinical sciences, Oncology and carcinogenesis
Abstract

Deregulation of the miR-15a/16-1 cluster has a key role in the pathogenesis of chronic lymphocytic leukemia (CLL), a clinically heterogeneous disease with indolent and aggressive forms. The miR-15a/16-1 locus is located at 13q14, the most frequently deleted region in CLL. Starting from functional investigations of a rare SNP upstream the miR cluster, we identified a novel allele-specific mechanism that exploits a cryptic activator region to recruit the RNA polymerase III for miR-15a/16-1 transcription. This regulation of the miR-15a/16- locus is independent of the DLEU2 host gene, which is often transcribed monoallellically by RPII. We found that normally one allele of miR-15a/16-1 is transcribed by RNAPII, the other one by RNAPIII. In our subset of CLL patients harboring 13q14 deletions, exclusive RNA polymerase III (RPIII)-driven transcription of the miR-15a/16-1 was the consequence of loss of the RPII-regulated allele and correlated with high expression of the poor prognostic marker ZAP70 (P=0.019). Thus, our findings point to a novel biological process, characterized by double allele-specific transcriptional regulation of the miR-15a/16-1 locus by alternative mechanisms. Differential usage of these mechanisms may distinguish at onset aggressive from indolent forms of CLL. This provides a basis for the clinical heterogeneity of the CLL patients carrying 13q14 deletions.

Published
2015

2. Circulating Micrornas Predict Survival of Patients with Tumors of Glial Origin

Author

Drusco A, P. Fadda, Nigita G, Fassan M, Bottoni A, Gardiman MP, D. Sacchi, Calore F, Carosi M, Antenucci A, B. Casini, Kelani H, Pescarmona E, Di Leva G, Zanesi N, Berger MS, and Croce CM

Subjects
Medicine, Medicine (General), R5-920
Abstract

The World Health Organization has recently introduced molecular prognostic-diagnostic biomarkers in the classification of Central Nervous System (CNS) tumors. In order to characterize subclasses of tumors that cannot find a precise location in the current classification, and, or cannot be tested because of scant material, it is important to find new molecular biomarkers in tissue and, or biological fluid samples. In this study, we identified serum microRNAs that could serve as biomarkers for the diagnosis and prognosis of patients with tumors of glial origin. We retrospectively analyzed microRNA expression in the serum extracellular vesicles of patients with tumors of glial origin. Extracellular vesicles RNA was analyzed by Nanostring. qRT-PCR confirmed 6 overexpressed microRNAs: hsa-miR-4443, hsa-miR-422a, hsa-miR-494-3p, hsa-miR-502-5p, hsa-miR-520f-3p, and hsa-miR-549a. Hsa-miR-4443 was the only microRNA that showed significant differences in most comparisons. In situ hybridization (ISH), confirmed that our signature was mostly expressed in cancer cells.Importantly, hsa-miR-549a and hsa-miR-502-5p expression predicted prognosis in patients with tumors of glial origin. Although more studies are needed, we demonstrated that serum vesicles microRNA profiles are promising diagnostic and prognostic molecular biomarkers that will find an actual application in the clinical practice of CNS tumors. Keywords: microRNA, CNS tumors, Serum, Biomarkers, Diagnosis, Prognosis

Published
2018
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10. Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

Author

Nanda, VGY, Peng, W, Hwu, P, Davies, MA, Ciliberto, G, Fattore, L, Malpicci, D, Aurisicchio, L, Ascierto, PA, Croce, CM, Mancini, R, Spranger, S, Gajewski, TF, Wang, Y, Ferrone, S, Vanpouille-Box, C, Wennerberg, E, Pilones, KA, Formenti, SC, Demaria, S, Tang, H, Fu, Y-X, Dummer, R, Puzanov, I, Tarhini, A, Chauvin, J-M, Pagliano, O, Fourcade, J, Sun, Z, Wang, H, Sanders, C, Kirkwood, JM, Chen, T-HT, Maurer, M, Korman, AJ, Zarour, HM, Stroncek, DF, Huber, V, Rivoltini, L, Thurin, M, Rau, T, Lugli, A, Pagès, F, Camarero, J, Sancho, A, Jommi, C, de Coaña, YP, Wolodarski, M, Yoshimoto, Y, Gentilcore, G, Poschke, I, Masucci, GV, Hansson, J, Kiessling, R, Scognamiglio, G, Sabbatino, F, Marino, FZ, Anniciello, AM, Cantile, M, Cerrone, M, Scala, S, D’alterio, C, Ianaro, A, Cirin, G, Liguori, G, Bott, G, Chapman, PB, Robert, C, Larkin, J, Haanen, JB, Ribas, A, Hogg, D, Hamid, O, Testori, A, Lorigan, P, Sosman, JA, Flaherty, KT, Yue, H, Coleman, S, Caro, I, Hauschild, A, McArthur, GA, Sznol, M, Callahan, MK, Kluger, H, Postow, MA, Gordan, R, Segal, NH, Rizvi, NA, Lesokhin, A, Atkins, MB, Burke, MM, Ralabate, A, Rivera, A, Kronenberg, SA, Agunwamba, B, Ruisi, M, Horak, C, Jiang, J, Wolchok, J, Liszkay, G, Maio, M, Mandalà, M, Demidov, L, Stoyakovskiy, D, Thomas, L, de la Cruz-Merino, L, Atkinson, V, Dutriaux, C, Garbe, C, Wongchenko, M, Chang, I, Koralek, DO, Rooney, I, Yan, Y, Dréno, B, Sullivan, R, Patel, M, Hodi, S, Amaria, R, Boasberg, P, Wallin, J, He, X, Cha, E, Richie, N, Ballinger, M, Smith, DC, Bauer, TM, Wasser, JS, Luke, JJ, Balmanoukian, AS, Kaufman, DR, Zhao, Y, Maleski, J, Leopold, L, Gangadhar, TC, Long, GV, Michielin, O, VanderWalde, A, Andtbacka, RHI, Cebon, J, Fernandez, E, Malvehy, J, Olszanski, AJ, Gause, C, Chen, L, Chou, J, Stephen Hodi, F, Brady, B, Mortier, L, Hassel, JC, Rutkowski, P, McNeil, C, Kalinka-Warzocha, E, Lebbé, C, Ny, L, Chacon, M, Queirolo, P, Loquai, C, Cheema, P, Berrocal, A, Eizmendi, KM, Bar-Sela, G, Hardy, H, Weber, JS, Grob, J-J, Marquez-Rodas, I, Schmidt, H, Briscoe, K, Baurain, J-F, Wolchok, JD, Pinto, R, De Summa, S, Garrisi, VM, Strippoli, S, Azzariti, A, Guida, G, Guida, M, Tommasi, S, Jacquelot, N, Enot, D, Flament, C, Pitt, JM, Vimond, N, Blattner, C, Yamazaki, T, Roberti, M-P, Vetizou, M, Daillere, R, Poirier-Colame, V, la Semeraro, M, Caignard, A, Slingluff, CL, Sallusto, F, Rusakiewicz, S, Weide, B, Marabelle, A, Kohrt, H, Dalle, S, Cavalcanti, A, Kroemer, G, Di Giacomo, AM, Wong, P, Yuan, J, Umansky, V, Eggermont, A, Zitvogel, L, Anna, P, Marco, T, Stefania, S, Francesco, M, Mariaelena, C, Gabriele, M, Antonio, AP, Franco, S, Roberti, MP, Enot, DP, Semeraro, M, Jégou, S, Flores, C, Kwon, BS, Anderson, AC, Borg, C, Aubin, F, Ayyoub, M, De Presbiteris, AL, Cordaro, FG, Camerlingo, R, Fratangelo, F, Mozzillo, N, Pirozzi, G, Patriarca, EJ, Caputo, E, Motti, ML, Falcon, R, Miceli, R, Capone, M, Madonna, G, Mallardo, D, Carrier, MV, Panza, E, De Cicco, P, Armogida, C, Ercolano, G, Botti, G, Cirino, G, Sandru, A, Blank, M, Balatoni, T, Olasz, J, Farkas, E, Szollar, A, Savolt, A, Godeny, M, Csuka, O, Horvath, S, Eles, K, Shoenfeld, Y, Kasler, M, Costantini, S, Capone, F, Moradi, F, Berglund, P, Leandersson, K, Linnskog, R, Andersson, T, Prasad, CP, Nigro, CL, Lattanzio, L, Proby, C, Syed, N, Occelli, M, Cauchi, C, Merlano, M, Harwood, C, Thompson, A, Crook, T, Bifulco, K, Ingangi, V, Minopoli, M, Ragone, C, Pessi, A, Mannavola, F, D’Oronzo, S, Felici, C, Tucci, M, Doronzo, A, Silvestris, F, Ferretta, A, Guida, S, Maida, I, Cocco, T, Passarelli, A, Quaresmini, D, Franzese, O, Palermo, B, Di Donna, C, Sperduti, I, Foddai, M, Stabile, H, Gismondi, A, Santoni, A, Nisticò, P, Sponghini, AP, Platini, F, Marra, E, Rondonotti, D, Alabiso, O, Fierro, MT, Savoia, P, Stratica, F, Quaglino, P, Di Monta, G, Corrado, C, Di Marzo, M, Ugo, M, Di Cecilia, ML, Nicola, M, Fusciello, C, Marra, A, Guarrasi, R, Baldi, C, Russo, R, Di Giulio, G, Faiola, V, Zeppa, P, Pepe, S, Gambale, E, Carella, C, Di Paolo, A, De Tursi, M, Marra, L, De Murtas, F, Sorrentino, V, Voinea, S, Panaitescu, E, Bolovan, M, Stanciu, A, Cinca, S, Botti, C, Aquino, G, Anniciello, A, Fortes, C, Mastroeni, S, Caggiati, A, Passarelli, F, Zappalà, A, Capuano, M, Bono, R, Nudo, M, Marino, C, Michelozzi, P, De Biasio, V, Battarra, VC, Formenti, S, Ascierto, ML, McMiller, TL, Berger, AE, Danilova, L, Anders, RA, Netto, GJ, Xu, H, Pritchard, TS, Fan, J, Cheadle, C, Cope, L, Drake, CG, Pardoll, DM, Taube, JM, Topalian, SL, Gnjatic, S, Nataraj, S, Imai, N, Rahman, A, Jungbluth, AA, Pan, L, Venhaus, R, Park, A, Lehmann, FF, Lendvai, N, Cohen, AD, Cho, HJ, Daniel, S, Hirsh, V, Nanda, VGY, Peng, W, Hwu, P, Davies, MA, Ciliberto, G, Fattore, L, Malpicci, D, Aurisicchio, L, Ascierto, PA, Croce, CM, Mancini, R, Spranger, S, Gajewski, TF, Wang, Y, Ferrone, S, Vanpouille-Box, C, Wennerberg, E, Pilones, KA, Formenti, SC, Demaria, S, Tang, H, Fu, Y-X, Dummer, R, Puzanov, I, Tarhini, A, Chauvin, J-M, Pagliano, O, Fourcade, J, Sun, Z, Wang, H, Sanders, C, Kirkwood, JM, Chen, T-HT, Maurer, M, Korman, AJ, Zarour, HM, Stroncek, DF, Huber, V, Rivoltini, L, Thurin, M, Rau, T, Lugli, A, Pagès, F, Camarero, J, Sancho, A, Jommi, C, de Coaña, YP, Wolodarski, M, Yoshimoto, Y, Gentilcore, G, Poschke, I, Masucci, GV, Hansson, J, Kiessling, R, Scognamiglio, G, Sabbatino, F, Marino, FZ, Anniciello, AM, Cantile, M, Cerrone, M, Scala, S, D’alterio, C, Ianaro, A, Cirin, G, Liguori, G, Bott, G, Chapman, PB, Robert, C, Larkin, J, Haanen, JB, Ribas, A, Hogg, D, Hamid, O, Testori, A, Lorigan, P, Sosman, JA, Flaherty, KT, Yue, H, Coleman, S, Caro, I, Hauschild, A, McArthur, GA, Sznol, M, Callahan, MK, Kluger, H, Postow, MA, Gordan, R, Segal, NH, Rizvi, NA, Lesokhin, A, Atkins, MB, Burke, MM, Ralabate, A, Rivera, A, Kronenberg, SA, Agunwamba, B, Ruisi, M, Horak, C, Jiang, J, Wolchok, J, Liszkay, G, Maio, M, Mandalà, M, Demidov, L, Stoyakovskiy, D, Thomas, L, de la Cruz-Merino, L, Atkinson, V, Dutriaux, C, Garbe, C, Wongchenko, M, Chang, I, Koralek, DO, Rooney, I, Yan, Y, Dréno, B, Sullivan, R, Patel, M, Hodi, S, Amaria, R, Boasberg, P, Wallin, J, He, X, Cha, E, Richie, N, Ballinger, M, Smith, DC, Bauer, TM, Wasser, JS, Luke, JJ, Balmanoukian, AS, Kaufman, DR, Zhao, Y, Maleski, J, Leopold, L, Gangadhar, TC, Long, GV, Michielin, O, VanderWalde, A, Andtbacka, RHI, Cebon, J, Fernandez, E, Malvehy, J, Olszanski, AJ, Gause, C, Chen, L, Chou, J, Stephen Hodi, F, Brady, B, Mortier, L, Hassel, JC, Rutkowski, P, McNeil, C, Kalinka-Warzocha, E, Lebbé, C, Ny, L, Chacon, M, Queirolo, P, Loquai, C, Cheema, P, Berrocal, A, Eizmendi, KM, Bar-Sela, G, Hardy, H, Weber, JS, Grob, J-J, Marquez-Rodas, I, Schmidt, H, Briscoe, K, Baurain, J-F, Wolchok, JD, Pinto, R, De Summa, S, Garrisi, VM, Strippoli, S, Azzariti, A, Guida, G, Guida, M, Tommasi, S, Jacquelot, N, Enot, D, Flament, C, Pitt, JM, Vimond, N, Blattner, C, Yamazaki, T, Roberti, M-P, Vetizou, M, Daillere, R, Poirier-Colame, V, la Semeraro, M, Caignard, A, Slingluff, CL, Sallusto, F, Rusakiewicz, S, Weide, B, Marabelle, A, Kohrt, H, Dalle, S, Cavalcanti, A, Kroemer, G, Di Giacomo, AM, Wong, P, Yuan, J, Umansky, V, Eggermont, A, Zitvogel, L, Anna, P, Marco, T, Stefania, S, Francesco, M, Mariaelena, C, Gabriele, M, Antonio, AP, Franco, S, Roberti, MP, Enot, DP, Semeraro, M, Jégou, S, Flores, C, Kwon, BS, Anderson, AC, Borg, C, Aubin, F, Ayyoub, M, De Presbiteris, AL, Cordaro, FG, Camerlingo, R, Fratangelo, F, Mozzillo, N, Pirozzi, G, Patriarca, EJ, Caputo, E, Motti, ML, Falcon, R, Miceli, R, Capone, M, Madonna, G, Mallardo, D, Carrier, MV, Panza, E, De Cicco, P, Armogida, C, Ercolano, G, Botti, G, Cirino, G, Sandru, A, Blank, M, Balatoni, T, Olasz, J, Farkas, E, Szollar, A, Savolt, A, Godeny, M, Csuka, O, Horvath, S, Eles, K, Shoenfeld, Y, Kasler, M, Costantini, S, Capone, F, Moradi, F, Berglund, P, Leandersson, K, Linnskog, R, Andersson, T, Prasad, CP, Nigro, CL, Lattanzio, L, Proby, C, Syed, N, Occelli, M, Cauchi, C, Merlano, M, Harwood, C, Thompson, A, Crook, T, Bifulco, K, Ingangi, V, Minopoli, M, Ragone, C, Pessi, A, Mannavola, F, D’Oronzo, S, Felici, C, Tucci, M, Doronzo, A, Silvestris, F, Ferretta, A, Guida, S, Maida, I, Cocco, T, Passarelli, A, Quaresmini, D, Franzese, O, Palermo, B, Di Donna, C, Sperduti, I, Foddai, M, Stabile, H, Gismondi, A, Santoni, A, Nisticò, P, Sponghini, AP, Platini, F, Marra, E, Rondonotti, D, Alabiso, O, Fierro, MT, Savoia, P, Stratica, F, Quaglino, P, Di Monta, G, Corrado, C, Di Marzo, M, Ugo, M, Di Cecilia, ML, Nicola, M, Fusciello, C, Marra, A, Guarrasi, R, Baldi, C, Russo, R, Di Giulio, G, Faiola, V, Zeppa, P, Pepe, S, Gambale, E, Carella, C, Di Paolo, A, De Tursi, M, Marra, L, De Murtas, F, Sorrentino, V, Voinea, S, Panaitescu, E, Bolovan, M, Stanciu, A, Cinca, S, Botti, C, Aquino, G, Anniciello, A, Fortes, C, Mastroeni, S, Caggiati, A, Passarelli, F, Zappalà, A, Capuano, M, Bono, R, Nudo, M, Marino, C, Michelozzi, P, De Biasio, V, Battarra, VC, Formenti, S, Ascierto, ML, McMiller, TL, Berger, AE, Danilova, L, Anders, RA, Netto, GJ, Xu, H, Pritchard, TS, Fan, J, Cheadle, C, Cope, L, Drake, CG, Pardoll, DM, Taube, JM, Topalian, SL, Gnjatic, S, Nataraj, S, Imai, N, Rahman, A, Jungbluth, AA, Pan, L, Venhaus, R, Park, A, Lehmann, FF, Lendvai, N, Cohen, AD, Cho, HJ, Daniel, S, and Hirsh, V

Abstract

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancini K3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidance Stefani Spranger, Thomas F. Gajewski K4 Intracellular tumor antigens as a source of targets of antibody-based immunotherapy of melanoma Yangyang Wang, Soldano Ferrone Combination therapies K5 Harnessing radiotherapy to improve responses to immunotherapy in cancer Claire Vanpouille-Box, Erik Wennerberg, Karsten A. Pilones, Silvia C. Formenti, Sandra Demaria K6 Creating a T cell-inflamed tumor microenvironment overcomes resistance to checkpoint blockade Haidong Tang, Yang Wang, Yang-Xin Fu K7 Biomarkers for treatment decisions? Reinhard Dummer K8 Combining oncolytic therapies in the era of checkpoint inhibitors Igor Puzanov K9 Immune checkpoint blockade for melanoma: should we combine or sequence ipilimumab and PD-1 antibody therapy? Michael A. Postow News in immunotherapy K10 An update on adjuvant and neoadjuvant therapy for melanom Ahmad Tarhini K11 Targeting multiple inhibitory receptors in melanoma Joe-Marc Chauvin, Ornella Pagliano, Julien Fourcade, Zhaojun Sun, Hong Wang, Cindy Sanders, John M. Kirkwood, Tseng-hui Timothy Chen, Mark Maurer, Alan J. Korman, Hassane M. Zarour K12 Improving adoptive immune therapy using genetically engineered T cells David F. Stroncek Tumor microenvironment and biomarkers K13 Myeloid cells and tumor exosomes: a crosstalk for assessing immunosuppression? Veronica Huber, Licia Rivoltini K14 Update on the SITC biomarker taskforce: progress and challenges Magdalena Thurin World-wide immunosc

Published
2016

11. The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells

Author

Saulep-Easton, D, Vincent, FB, Quah, PS, Wei, A, Ting, SB, Croce, CM, Tam, C, Mackay, F, Saulep-Easton, D, Vincent, FB, Quah, PS, Wei, A, Ting, SB, Croce, CM, Tam, C, and Mackay, F

Abstract

Interleukin (IL)-10-producing B cells (B10 cells) have emerged as important regulatory elements with immunosuppressive roles. Chronic lymphocytic leukemia (CLL) B cells also secrete IL-10 and share features of B10 cells, suggesting a possible contribution of CLL B cells to immunosuppression in CLL patients. Factors controlling the emergence of B10 cells are not known. B-cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) is critical for B-cell maturation and survival, and is implicated in the development and progression of CLL. We sought to investigate the role of BAFF in the emergence of IL-10-producing regulatory B cells in healthy donors and CLL patients. Here, we report that BAFF signaling promotes IL-10 production by CLL B cells in a mouse model of CLL and in CLL patients. Moreover, BAFF-mediated IL-10 production by normal and CLL B cells is mediated via its receptor transmembrane activator and cyclophilin ligand interactor. Our work uncovered a major targetable pathway important for the generation of regulatory B cells that is detrimental to immunity in CLL.

Published
2016

12. Akt regulates drugs induced cell death through the anti-apoptotic protein Bcl-w

Author

Garofalo M, Quintavalle C, Zanca C, de Rienzo A., Romano G, Acunzo M, Puca L, Incoronato M, Croce CM, CONDORELLI, GEROLAMA, Garofalo, M, Quintavalle, C, Zanca, C, de Rienzo, A., Romano, G, Acunzo, M, Puca, L, Incoronato, M, Croce, Cm, and Condorelli, Gerolama

Subjects
apoptosis cancer bcl-w
Abstract

Akt is a serine threonine kinase with a major role in transducing survival signals and regulating proteins involved in apoptosis. To find new interactors of Akt involved in cell survival, we performed a two-hybrid screening in yeast using human full-length Akt c-DNA as bait and a murine c-DNA library as prey. Among the 80 clones obtained, two were identified as Bcl-w. Bcl-w is a member of the Bcl-2 family that is essential for the regulation of cellular survival, and that is up-regulated in different human tumors, such as gastric and colorectal carcinomas. Direct interaction of Bcl-w with Akt was confirmed by immunoprecipitation assays. Subsequently, we addressed the function of this interaction: by interfering with the activity or amount of Akt, we have demonstrated that Akt modulates the amount of Bcl-w protein. We have found that inhibition of Akt activity may promote apoptosis through the downregulation of Bcl-w protein and the consequential reduction in interaction of Bcl-w with proapoptotic members of the Bcl-2 family. Our data provide evidence that Bcl-w is a new member of the Akt pathway and that Akt may induce anti-apoptotic signals at least in part through the regulation of the amount and activity of Bcl-w.

Published
2008

15. A TSH-CREB1-microRNA Loop Is Required for Thyroid Cell Growth

Author

Leone V, D'Angelo D, Ferraro A, Pallante P, Rubio I, Santoro M, Croce CM, and Fusco A.

Subjects
endocrine system, endocrine system diseases
Abstract

MicroRNA (miRNA or miR) are an important class of regulators that participate in such biological functions as development, cell proliferation, differentiation, and apoptosis. The aim of this study was to elucidate the role of miRNA in cell proliferation using a unique cell system, namely thyroid cells that require thyrotropin for their growth. Here, we report the identification of a set of five specific miRNA (miR-1, miR-28-A, miR-290-5p, miR-296-3p, and miR-297a), whose down-regulation by thyrotropin is required for thyroid cell growth. In fact, overexpression of these miRNA negatively affects cell growth. We show that three of these miRNA target cAMP-responsive element binding protein (CREB)1, a thyrotropin-activated transcription factor, and that CREB1 binds the regulatory regions of the down-regulated miRNA. Hence, these data indicate that a synergistic loop involving thyrotropin, CREB1, and miRNA is required for thyroid cell proliferation.

Published
2011

16. EGFR and MET induce tumorigenesis and gefitinib resistance in lung cancers by controlling microRNA expression

Author

Garofalo M1, Romano G, Di Leva G, Nuovo G, Jeon YJ, Ngankeu A, Sun J, Lovat F, Alder H, Condorelli G, Engelman JA, Ono M, Rho JK, Cascione L, Volinia S, Nephew KP, and Croce CM.

Subjects
EGFR, MET, tumorigenesis, cancers, microRNA, respiratory tract diseases
Abstract

The involvement of the MET oncogene in de novo and acquired resistance of non-small cell lung cancers (NSCLCs) to tyrosine kinase inhibitors (TKIs) has previously been reported, but the precise mechanism by which MET overexpression contributes to TKI-resistant NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand their role in TKI-resistant NSCLCs, we examined changes in miRNA that are mediated by tyrosine kinase receptors. Here we report that miR-30b, miR-30c, miR-221 and miR-222 are modulated by both epidermal growth factor (EGF) and MET receptors, whereas miR-103 and miR-203 are controlled only by MET. We showed that these miRNAs have important roles in gefitinib-induced apoptosis and epithelial-mesenchymal transition of NSCLC cells in vitro and in vivo by inhibiting the expression of the genes encoding BCL2-like 11 (BIM), apoptotic peptidase activating factor 1 (APAF-1), protein kinase C ? (PKC-?) and sarcoma viral oncogene homolog (SRC). These findings suggest that modulation of specific miRNAs may provide a therapeutic approach for the treatment of NSCLCs.

Published
2011

17. Deregulation of microRNA expression in follicular cell-derived human thyroid carcinomas

Author

Pallante P, Visone R, Croce CM, and Fusco A.

Subjects
endocrine system, endocrine system diseases
Abstract

Carcinoma of the thyroid gland is an uncommon cancer, but one of the most frequent malignancies of the endocrine system. Most thyroid cancers are derived from the follicular cells. Follicular carcinoma is considered more malignant than papillary thyroid carcinoma (PTC), and anaplastic thyroid cancer (ATC) is one of the most lethal human cancers. Even though several genetic lesions have been already described in human thyroid cancer, particularly in the papillary histotype, the mechanisms underlying the development of these neoplasias are still far from being completely elucidated. Some years ago, several studies were undertaken to analyze the expression of microRNAs (miRNAs or miRs) in thyroid carcinoma to evaluate a possible role of their deregulation in the process of carcinogenesis. These studies showed an aberrant microRNA expression profile that distinguishes unequivocally among PTC, ATC, and normal thyroid tissue. Here, other than summarizing the current findings on microRNA expression in human thyroid carcinomas, we discuss the mechanisms by which microRNA deregulation may play a role in thyroid carcinogenesis, and the possible use of microRNA knowledge in the diagnosis and therapy of thyroid neoplasms.

Published
2010

18. Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition

Author

Sapienza, Mr, Fuligni, F, Agostinelli, C, Tripodo, C, Righi, S, Laginestra, Ma, Pileri, A, Mancini, M, Rossi, M, Ricci, F, Gazzola, A, Melle, F, Mannu, C, Ulbar, F, Arpinati, M, Paulli, M, Maeda, T, Gibellini, D, Pagano, Livio, Pimpinelli, N, Santucci, M, Cerroni, L, Croce, Cm, Facchetti, F, Piccaluga, Pp, Pileri, Sa, Pagano, Livio (ORCID:0000-0001-8287-928X), Sapienza, Mr, Fuligni, F, Agostinelli, C, Tripodo, C, Righi, S, Laginestra, Ma, Pileri, A, Mancini, M, Rossi, M, Ricci, F, Gazzola, A, Melle, F, Mannu, C, Ulbar, F, Arpinati, M, Paulli, M, Maeda, T, Gibellini, D, Pagano, Livio, Pimpinelli, N, Santucci, M, Cerroni, L, Croce, Cm, Facchetti, F, Piccaluga, Pp, Pileri, Sa, and Pagano, Livio (ORCID:0000-0001-8287-928X)

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease of controversial origin recently recognized as a neoplasm deriving from plasmacytoid dendritic cells (pDCs). Nevertheless, it remains an orphan tumor with obscure biology and dismal prognosis. To better understand the pathobiology of BPDCN and discover new targets for effective therapies, the gene expression profile (GEP) of 25 BPDCN samples was analyzed and compared with that of pDCs, their postulated normal counterpart. Validation was performed by immunohistochemistry (IHC), whereas functional experiments were carried out ex vivo. For the first time at the molecular level, we definitely recognized the cellular derivation of BPDCN that proved to originate from the myeloid lineage and in particular, from resting pDCs. Furthermore, thanks to an integrated bioinformatic approach we discovered aberrant activation of the NF-kB pathway and suggested it as a novel therapeutic target. We tested the efficacy of anti-NF-kB-treatment on the BPDCN cell line CAL-1, and successfully demonstrated by GEP and IHC the molecular shutoff of the NF-kB pathway. In conclusion, we identified a molecular signature representative of the transcriptional abnormalities of BPDCN and developed a cellular model proposing a novel therapeutic approach in the setting of this otherwise incurable disease.

Published
2014

19. Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice

Author

Costinean, S, Sandhu, SK, Pedersen, IM, Tili, E, Trotta, R, Perrotti, D, Ciarlariello, D, Neviani, P, Harb, J, Kauffman, LR, Shidham, A, and Croce, CM

Subjects
Lymphoma, B-Cell, Interleukin-6, Gene Expression Regulation, Leukemic, CCAAT-Enhancer-Binding Protein-beta, Precursor Cells, B-Lymphoid, Inositol Polyphosphate 5-Phosphatases, Down-Regulation, Mice, Transgenic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Phosphoric Monoester Hydrolases, Mice, MicroRNAs, Cell Transformation, Neoplastic, hemic and lymphatic diseases, Animals, Signal Transduction
Abstract

We showed that Emicro-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre-B-cell proliferation, have variable clinical presentation, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain-containing inositol-5-phosphatase (SHIP) and CCAAT enhancer-binding protein beta (C/EBPbeta), 2 important regulators of the interleukin-6 signaling pathway, are direct targets of MiR-155 and become gradually more down-regulated in the leukemic than in the preleukemic mice. We hypothesize that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.

Published
2009
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21. Altered expression of selected microRNAs in melanoma: antiproliferative and proapoptotic activity of miRNA-155

Author

(1) Levati L, (2) Alvino E, (1) Pagani E, (1) ArcelliD, (1) Caporaso P, (3) Bondanza S, (4, 5) Di Leva G, (6, 7) Ferracin M, 5, 8) Volinia S, (2, 9) Bonmassar E, 5) Croce CM, and (1) D'Atri S.

Subjects
microRNA, proliferation, microRNA-155, melanoma, apoptosis
Abstract

Altered expression of microRNAs (miRNAs) has been detected in cancer, suggesting that these small non-coding RNAs can act as oncogenes or tumor suppressor genes. In the present study, we investigated the expression of miRNA-17-5p, miRNA-18a, miRNA-20a, miRNA-92a, miRNA-146a, miRNA-146b and miRNA-155 by real-time quantitative RT-PCR in a panel of melanocyte cultures and melanoma cell lines and explored the possible role of miRNA-155 in melanoma cell proliferation and survival. The analyzed miRNAs were selected on the basis of previous studies strongly supporting their involvement in cancer development and/or progression. We found that miRNA-17-5p, miRNA-18a, miRNA-20a, and miRNA-92a were overexpressed, whereas miRNA-146a, miRNA-146b and miRNA-155 were down-regulated in the majority of melanoma cell lines with respect to melanocytes. Ectopic expression of miRNA-155 significantly inhibited proliferation in 12 of 13 melanoma cell lines with reduced levels of this miRNA and induced apoptosis in 4 out of 4 cell lines analyzed. In conclusion, our data further support the finding of altered miRNA expression in melanoma cells and establish for the first time that miRNA-155 is a negative regulator of melanoma cell proliferation and survival.

Published
2009

25. MicroRNA-133 controls cardiac myocyte hypertrophy

Author

Carè, A, Catalucci, D, Felicetti, F, Bonci, D., Addario, A, Gallo, P, Bang, Ml, Segnalini, P, Gu, Y, Dalton, Nd, Elia, L, Latronico, Mv, Høydal, M, Autore, Camillo, Russo, Matteo Antonio, DORN GW ND, Ellingsen, O, RUIZ LOZANO, P, Peterson, Kl, Croce, Cm, Peschle, C, and Condorelli, G.

Published
2007

28. High-mobility-group A1 (HMGA1) proteins down-regulate the expression of the recombination activating gene 2 (RAG2)

Author

Battista S, Fedele M, Martinez Hoyos J, Pentimalli F, Pierantoni GM, Visone R, De Martino I, Croce CM, and Fusco A.

Subjects
embryonic structures, chemical and pharmacologic phenomena, hemic and immune systems
Abstract

HMGA1 (high-mobility-group A1) proteins are architectural transcription factors that are found overexpressed in embryogenesis and malignant tumours. We have shown previously that they have a role in lymphopoiesis, since the loss of HMGA1 expression leads to an impairment of T-cell development and to an increase in B-cell population. Since RAGs (recombination activating genes) are key regulators of lymphoid differentiation, in the present study we investigate whether RAG2 expression is dependent on HMGA1 activity. We show that RAG2 gene expression is up-regulated in Hmga1-/- ES (embryonic stem) cells and EBs (embryoid bodies) as well as in yolk sacs and fibroblasts from Hmga1-/- mice, suggesting that HMGA1 proteins control RAG2 gene expression both in vitro and in vivo. We show that the effect of HMGA1 on RAG2 expression is direct, identify the responsible region in the RAG2 promoter and demonstrate binding to the promoter in vivo using chromatin immunoprecipitation. Since RAG2 is necessary for lymphoid cell development, our results suggest a novel mechanism by which HMGA1 might regulate lymphoid differentiation.

Published
2005

32. Evolutionary conservation of the Eps8 gene and its mapping to human-chromosome 12q23-q24

Author

WONG WT, DRUCK T, BARLETTA C, CROCE CM, HEUBNER K, KRAUS MH, DI FIORE PP, CARLOMAGNO, Francesca, Wong, Wt, Carlomagno, Francesca, Druck, T, Barletta, C, Croce, Cm, Heubner, K, Kraus, Mh, and DI FIORE, Pp

Abstract

We have previously isolated the coding sequence for a novel substrate for tyrosine kinases, eps8, from NIH3T3 fibroblasts. Eps8 was phosphorylated in vivo by several receptor tyrosine kinases (RTKs) and, upon overexpression, was able to enhance EGFR-mediated mitogenic signaling in NIH3T3 cells. To gain understanding of eps8 function as well as its role in normal and neoplastic proliferation, we cloned the human eps8 coding sequence and studied expression of the human RNA and protein, evolutionary conservation, and chromosomal location. In addition to a previously identified SH3 domain, the predicted amino acid sequence of human eps8 revealed a non-random distribution of prolines, clustered in a way to suggest SH3-binding sites and a putative PH domain. Eps8 was expressed in all epithelial and fibroblastic lines examined and in some, but not all, hematopoietic cells. An essential function of eps8 in cell growth regulation was underscored by its conservation during evolution, where eps8-related sequences were detected as early as in Saccharomyces cerevisiae. Finally, the human EPS8 locus was mapped to chromosome 12q23-q24.

Published
1994

33. The Human Eps15 gene encoding a tyrosine kinase substrate is conserved in evolution and map to 1p31-1p32

Author

WONG WT, KRAUS MH, ZELANO A, DRUCK T, CROCE CM, HEUBENER K, DI FIORE PP, CARLOMAGNO, Francesca, Wong, Wt, Kraus, Mh, Carlomagno, Francesca, Zelano, A, Druck, T, Croce, Cm, Heubener, K, and DI FIORE, Pp

Abstract

Employing an expression cloning approach for tyrosine kinase substrates, we have previously isolated the coding sequence for a novel putative EGFR substrate, eps15, from NIH3T3 fibroblasts. Eps15 displayed a receptor-specific pattern of tyrosine phosphorylation in vivo and was able to transform NIH3T3 cells upon overexpression. To gain understanding of eps15 function as well as its role in normal and neoplastic proliferation, we cloned the human eps15 coding sequence and studied expression of the human RNA and protein, evolutionary conservation, and chromosomal location. The close structural similarity of human eps15 with the murine homologue is indicated by 89% and 90% identity of nucleotide and predicted amino acid sequences, respectively. Using the human eps15 coding sequence as probe, we demonstrate that eps15 is member of a gene family that is highly conserved during evolution. An essential function of eps15 in cell growth regulation is underscored by our observation of ubiquitous expression at the transcript and the protein level in normal and malignant human cells. The human EPS15 locus maps to chromosome 1p31-p32, a region involved in deletion in neuroblastoma, translocations in acute lymphoblastic leukemia, and exhibiting a fragile site.

Published
1994

38. Loss of FHIT expression in gastric carcinoma

Author

Baffa, Raffaele, Veronese, Ml, Santoro, R, Mandes, B, Palazzo, Jp, Rugge, Massimo, Santoro, E, Croce, Cm, and Huebner, K.

Subjects
Blotting, Southern, Stomach Neoplasms, Tumor Cells, Cultured, Humans, Loss of Heterozygosity, Proteins, Genes, Tumor Suppressor, Chromosomes, Human, Pair 3, Polymerase Chain Reaction, Acid Anhydride Hydrolases, Neoplasm Proteins
Abstract

Loss of heterozygosity involving the short arm of chromosome 3 has been reported in gastric and other human tumors. We have cloned and mapped a candidate tumor suppressor gene, FHIT (fragile histidine triad), to this chromosomal region (3p14.2). To investigate the role of FHIT gene alterations in the development of gastric carcinoma, we examined 8 gastric carcinoma-derived cell lines and 32 primary adenocarcinoma samples by Southern blot analysis. We also analyzed the integrity of FHIT transcripts by reverse transcription-PCR. The occurrence of alterations in the FHIT gene and its transcript correlated with the absence of Fhit protein expression by immunoblot analysis in the cancer cell lines. Four of eight cell lines showed deletion or rearrangement within the FHIT gene, together with the absence of the wild-type transcript and the Fhit protein. Among the primary gastric carcinomas, rearrangement of the FHIT gene and/or aberrant reverse transcription-PCR products were detected in 17 of 32 (53%) tumors, and 20 of 30 (67%) samples exhibited an absence of Fhit protein expression. Gastric cancer is thought to develop from carcinogenic exposure, possibly explaining the high frequency of abnormalities in the FHIT gene, a fragile locus exhibiting susceptibility to carcinogen-induced alterations. The consequent absence or reduction of Fhit protein expression is consistent with the proposal that the FHIT gene is a preferential target of environmental carcinogens and that FHIT inactivation plays a role in the development of gastric cancer.

Published
1998

47. Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations

Author

Cimino, Giuseppe, Moir, Dt, Canaani, O, Williams, K, Crist, Wm, Katzav, S, Cannizzaro, L, Lange, B, Nowell, Pc, and Croce, Cm

Subjects
Antigens, Differentiation, T-Lymphocyte, CD3 Complex, Chromosomes, Human, Pair 11, Restriction Mapping, Receptors, Antigen, T-Cell, Chromosome Mapping, DNA, Neoplasm, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Blotting, Northern, Translocation, Genetic, Blotting, Southern, Humans, RNA, Messenger, RNA, Neoplasm, Chromosomes, Human, Pair 4, Cloning, Molecular, Chromosomes, Human, Pair 9, Chromosomes, Human, Pair 19
Abstract

Chromosomal region 11q23 participates in a number of reciprocal translocations with specific regions of chromosomes 4, 9, 19, and others. These translocations are associated with acute lymphocytic leukemia and acute myelomonocytic, monocytic, and myelogenous leukemia. From a yeast artificial chromosome containing human DNA derived from 11q23 we cloned a DNA fragment which can be used as a probe to detect rearrangements in leukemic cells from the majority of patients with the t(4;11), t(9;11), and t(11;19) translocations. The breakpoints cluster in a small DNA region of less than 5.8 kilobases.

Published
1991

48. Chromosome locations of the MYB related genes, AMYB and BMYB

Author

Barletta, C, Druck, T, Laforgia, S, Calabretta, Bruno, Drabkin, H, Patterson, D, Croce, Cm, and Huebner, K.

Subjects
Chromosome Aberrations, Proto-Oncogene Proteins/genetics, Proto-Oncogene Proteins c-myb, X Chromosome, Neoplasms, Proto-Oncogene Proteins, Proto-Oncogenes, Chromosome Mapping, Humans, Chromosomes, Human, Pair 8
Abstract

The MYB related loci, AMYB and BMYB, were localized to specific human chromosome regions by Southern blot analysis of their segregation patterns in a panel of rodent-human hybrid DNAs using radiolabeled AMYB and BMYB probes. The AMYB locus was present in hybrids retaining the chromosome region 8cen----8q22 and was absent in hybrids which had lost this chromosome region. The presence of the BMYB locus in rodent-human hybrids correlated with, and only with, chromosome region Xq13. Chromosomal in situ hybridization refined the localization of AMYB to region 8q22-23 and confirmed the localization of BMYB to region Xq13. Chromosome region 8q22 is involved in recurrent translocations in malignant lymphoma and in acute myeloid leukemia (AML-M2); therefore AMYB is a candidate for involvement in such translocations. A region on Xq13 is also involved in chromosomal abnormalities in acute myeloid leukemia and myelodysplasias.

Published
1991

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