137 results on '"Monica Cantile"'
Search Results
2. Bispecific aptamer-decorated and light-triggered nanoparticles targeting tumor and stromal cells in breast cancer derived organoids: implications for precision phototherapies
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Simona Camorani, Alessandra Caliendo, Elena Morrone, Lisa Agnello, Matteo Martini, Monica Cantile, Margherita Cerrone, Antonella Zannetti, Massimo La Deda, Monica Fedele, Loredana Ricciardi, and Laura Cerchia
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Aptamer ,EGFR ,PDGFRβ ,Dual targeting ,Nanomedicine ,Patient-derived cancer organoids ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Based on the established role of cancer-stroma cross-talk in tumor growth, progression and chemoresistance, targeting interactions between tumor cells and their stroma provides new therapeutic approaches. Dual-targeted nanotherapeutics selectively acting on both tumor and stromal cells may overcome the limits of tumor cell-targeting single-ligand nanomedicine due to the complexity of the tumor microenvironment. Methods Gold-core/silica-shell nanoparticles embedding a water-soluble iridium(III) complex as photosensitizer and luminescent probe (Iren-AuSiO2_COOH) were efficiently decorated with amino-terminated EGFR (CL4) and PDGFRβ (Gint4.T) aptamers (Iren-AuSiO2_Aptamer). The targeting specificity, and the synergistic photodynamic and photothermal effects of either single- and dual-aptamer-decorated nanoparticles have been assessed by confocal microscopy and cell viability assays, respectively, on different human cell types including mesenchymal subtype triple-negative breast cancer (MES-TNBC) MDA-MB-231 and BT-549 cell lines (both EGFR and PDGFRβ positive), luminal/HER2-positive breast cancer BT-474 and epidermoid carcinoma A431 cells (only EGFR positive) and adipose-derived mesenchymal stromal/stem cells (MSCs) (only PDGFRβ positive). Cells lacking expression of both receptors were used as negative controls. To take into account the tumor-stroma interplay, fluorescence imaging and cytotoxicity were evaluated in preclinical three-dimensional (3D) stroma-rich breast cancer models. Results We show efficient capability of Iren-AuSiO2_Aptamer nanoplatforms to selectively enter into target cells, and kill them, through EGFR and/or PDGFRβ recognition. Importantly, by targeting EGFR+ tumor/PDGFRβ+ stromal cells in the entire tumor bulk, the dual-aptamer-engineered nanoparticles resulted more effective than unconjugated or single-aptamer-conjugated nanoparticles in either 3D spheroids cocultures of tumor cells and MSCs, and in breast cancer organoids derived from pathologically and molecularly well-characterized tumors. Conclusions Our study proposes smart, novel and safe multifunctional nanoplatforms simultaneously addressing cancer-stroma within the tumor microenvironment, which are: (i) actively delivered to the targeted cells through highly specific aptamers; (ii) localized by means of their luminescence, and (iii) activated via minimally invasive light, launching efficient tumor death, thus providing innovative precision therapeutics. Given the unique features, the proposed dual targeted nanoformulations may open a new door to precision cancer treatment.
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- 2024
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3. The role of HOTAIR in the modulation of resistance to anticancer therapy
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Monica Cantile, Valentina Belli, Giosuè Scognamiglio, Anna Martorana, Giovanna De Pietro, Maura Tracey, and Alfredo Budillon
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long non-coding RNAs ,resistance to anti-cancer therapies ,HOTAIR in drugresistance ,HOTAIR as circulating biomarker ,HOTAIR as therapeutic target ,Biology (General) ,QH301-705.5 - Abstract
Leading anti-tumour therapeutic strategies typically involve surgery and radiotherapy for locally advanced (non-metastatic) cancers, while hormone therapy, chemotherapy, and molecular targeted therapy are the current treatment options for metastatic cancer. Despite the initially high sensitivity rate to anticancer therapies, a large number of patients develop resistance, leading to a poor prognosis. The mechanisms related to drug resistance are highly complex, and long non-coding RNAs appear to play a crucial role in these processes. Among these, the lncRNA homeobox transcript antisense intergenic RNA (HOTAIR), widely implicated in cancer initiation and progression, likewise plays a significant role in anticancer drug resistance. It can modulate cell activities such as proliferation, apoptosis, hypoxia, autophagy, as well as epithelial-mesenchymal transition, thereby contributing to the development of resistant tumour cells. In this manuscript, we describe different mechanisms of antitumor drug resistance in which HOTAIR is involved and suggest its potential as a therapeutic predictive biomarker for the management of cancer patients.
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- 2024
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4. Identification of functional pathways and molecular signatures in neuroendocrine neoplasms by multi-omics analysis
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Viola Melone, Annamaria Salvati, Domenico Palumbo, Giorgio Giurato, Giovanni Nassa, Francesca Rizzo, Luigi Palo, Alessandro Giordano, Mariarosaria Incoronato, Mario Vitale, Caterina Mian, Immacolata Di Biase, Stefano Cristiano, Viviana Narciso, Monica Cantile, Annabella Di Mauro, Fabiana Tatangelo, Salvatore Tafuto, Roberta Modica, Claudia Pivonello, Marco Salvatore, Annamaria Colao, Alessandro Weisz, and Roberta Tarallo
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Neuroendocrine neoplasms ,Molecular signatures ,ATM signaling ,Circulating biomarkers ,Medicine - Abstract
Abstract Background Neuroendocrine neoplasms (NENs) represent a heterogeneous class of rare tumors with increasing incidence. They are characterized by the ability to secrete peptide hormones and biogenic amines but other reliable biomarkers are lacking, making diagnosis and identification of the primary site very challenging. While in some NENs, such as the pancreatic ones, next generation sequencing technologies allowed the identification of new molecular hallmarks, our knowledge of the molecular profile of NENs from other anatomical sites is still poor. Methods Starting from the concept that NENs from different organs may be clinically and genetically correlated, we applied a multi-omics approach by combining multigene panel testing, CGH-array, transcriptome and miRNome profiling and computational analyses, with the aim to highlight common molecular and functional signatures of gastroenteropancreatic (GEP)-NENs and medullary thyroid carcinomas (MTCs) that could aid diagnosis, prognosis and therapy. Results By comparing genomic and transcriptional profiles, ATM-dependent signaling emerged among the most significant pathways at multiple levels, involving gene variations and miRNA-mediated regulation, thus representing a novel putative druggable pathway in these cancer types. Moreover, a set of circulating miRNAs was also selected as possible diagnostic/prognostic biomarkers useful for clinical management of NENs. Conclusions These findings depict a complex molecular and functional landscape of NENs, shedding light on novel therapeutic targets and disease biomarkers to be exploited.
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- 2022
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5. Epicardial Adipose Tissue-Derived IL-1β Triggers Postoperative Atrial Fibrillation
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Serena Cabaro, Maddalena Conte, Donato Moschetta, Laura Petraglia, Vincenza Valerio, Serena Romano, Michele Francesco Di Tolla, Pasquale Campana, Giuseppe Comentale, Emanuele Pilato, Vittoria D’Esposito, Annabella Di Mauro, Monica Cantile, Paolo Poggio, Valentina Parisi, Dario Leosco, and Pietro Formisano
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epicardial adipose tissue ,cytokines ,inflammation ,atrial fibrillation ,fibrosis ,cardiac remodeling ,Biology (General) ,QH301-705.5 - Abstract
Background and aims: Post-operative atrial fibrillation (POAF), defined as new-onset AF in the immediate period after surgery, is associated with poor adverse cardiovascular events and a higher risk of permanent AF. Mechanisms leading to POAF are not completely understood and epicardial adipose tissue (EAT) inflammation could be a potent trigger. Here, we aim at exploring the link between EAT-secreted interleukin (IL)-1β, atrial remodeling, and POAF in a population of coronary artery disease (CAD) patients.Methods: We collected EAT and atrial biopsies from 40 CAD patients undergoing cardiac surgery. Serum samples and EAT-conditioned media were screened for IL-1β and IL-1ra. Atrial fibrosis was evaluated at histology. The potential role of NLRP3 inflammasome activation in promoting fibrosis was explored in vitro by exposing human atrial fibroblasts to IL-1β and IL-18.Results: 40% of patients developed POAF. Patients with and without POAF were homogeneous for clinical and echocardiographic parameters, including left atrial volume and EAT thickness. POAF was not associated with atrial fibrosis at histology. No significant difference was observed in serum IL-1β and IL-1ra levels between POAF and no-POAF patients. EAT-mediated IL-1β secretion and expression were significantly higher in the POAF group compared to the no-POAF group. The in vitro study showed that both IL-1β and IL-18 increase fibroblasts’ proliferation and collagen production. Moreover, the stimulated cells perpetuated inflammation and fibrosis by producing IL-1β and transforming growth factor (TGF)-β.Conclusion: EAT could exert a relevant role both in POAF occurrence and in atrial fibrotic remodeling.
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- 2022
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6. Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer
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Simona Camorani, Margherita Passariello, Lisa Agnello, Silvia Esposito, Francesca Collina, Monica Cantile, Maurizio Di Bonito, Ilya V. Ulasov, Monica Fedele, Antonella Zannetti, Claudia De Lorenzo, and Laura Cerchia
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Aptamer ,Antitumor immunity ,PDGFRβ ,PD-L1 monoclonal antibody ,TNBC ,Tumor microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers allowing for combination therapies with immune-checkpoint blockade. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in invasive TNBC, both on tumor cells and tumor microenvironment. We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC. Methods The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4 T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4 T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAb combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. Results We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAb-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in mice. It acts on both tumor cells, inhibiting Akt and ERK1/2 signaling pathways, and immune populations, increasing intratumoral CD8 + T cells and reducing FOXP3 + Treg cells. Conclusion Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first time an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.
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- 2020
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7. Posterior HOX genes and HOTAIR expression in the proximal and distal colon cancer pathogenesis
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Fabiana Tatangelo, Annabella Di Mauro, Giosuè Scognamiglio, Gabriella Aquino, Antonio Lettiero, Paolo Delrio, Antonio Avallone, Monica Cantile, and Gerardo Botti
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Proximal and distal CRC pathogenesis ,HOX genes ,Prognosis ,Medicine - Abstract
Abstract Background Increasing evidences showed that the location of the primary tumor on the right (proximal) or left (distal) side of the colon have a prognostic/predictive value for colon cancer patients. However, the understanding of the molecular mechanisms that contribute to the pathogenesis in different location of colon is still unclear. Probably an important role could be played by genes that control the spatial–temporal development of bodily structures, such as HOX genes. Methods The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes and of the HOX regulating lncRNA HOTAIR in distal and proximal CRC cases. We have carried out a Tissue Micro Array with left and right CRC samples associated with all clinical-pathological parameters of patients. The expression of HOX genes was evaluated by immunohistochemistry and the staining of HOTAIR was performed by in situ hybridization using a specifically designed LNA probe. Results All paralogous 13 HOX genes and HOTAIR are silent in normal tissue and expressed in CRC samples. HOXB13, HOXC13 and HOTAIR showed a statistical association with lymph nodes metastasis (p value = 0.003, p value = 0.05, p value = 0.04). HOXB13, HOXC13 and lncRNA HOTAIR are overexpressed in right CRCs samples (p value
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- 2018
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8. Prune-1 drives polarization of tumor-associated macrophages (TAMs) within the lung metastatic niche in triple-negative breast cancer
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Veronica Ferrucci, Fatemeh Asadzadeh, Francesca Collina, Roberto Siciliano, Angelo Boccia, Laura Marrone, Daniela Spano, Marianeve Carotenuto, Cristina Maria Chiarolla, Daniela De Martino, Gennaro De Vita, Alessandra Macrì, Luisa Dassi, Jonathan Vandenbussche, Natascia Marino, Monica Cantile, Giovanni Paolella, Francesco D'Andrea, Maurizio di Bonito, Kris Gevaert, and Massimo Zollo
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Molecular Biology ,Immunology ,Cancer ,Science - Abstract
Summary: M2-tumor-associated macrophages (M2-TAMs) in the tumor microenvironment represent a prognostic indicator for poor outcome in triple-negative breast cancer (TNBC).Here we show that Prune-1 overexpression in human TNBC patients has positive correlation to lung metastasis and infiltrating M2-TAMs. Thus, we demonstrate that Prune-1 promotes lung metastasis in a genetically engineered mouse model of metastatic TNBC augmenting M2-polarization of TAMs within the tumor microenvironment. Thus, this occurs through TGF-β enhancement, IL-17F secretion, and extracellular vesicle protein content modulation.We also find murine inactivating gene variants in human TNBC patient cohorts that are involved in activation of the innate immune response, cell adhesion, apoptotic pathways, and DNA repair. Altogether, we indicate that the overexpression of Prune-1, IL-10, COL4A1, ILR1, and PDGFB, together with inactivating mutations of PDE9A, CD244, Sirpb1b, SV140, Iqca1, and PIP5K1B genes, might represent a route of metastatic lung dissemination that need future prognostic validations.
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- 2021
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9. Novel Aptamers Selected on Living Cells for Specific Recognition of Triple-Negative Breast Cancer
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Simona Camorani, Ilaria Granata, Francesca Collina, Francesco Leonetti, Monica Cantile, Gerardo Botti, Monica Fedele, Mario Rosario Guarracino, and Laura Cerchia
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Science - Abstract
Summary: Triple-negative breast cancer (TNBC) is a high heterogeneous group of tumors with a distinctly aggressive nature and high rates of relapse. So far, the lack of any known targetable proteins has not allowed a specific anti-tumor treatment. Therefore, the identification of novel agents for specific TNBC targeting and treatment is desperately needed. Here, by integrating cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) for the specific recognition of TNBC cells with high-throughput sequencing technology, we identified a panel of 2′-fluoropyrimidine-RNA aptamers binding to TNBC cells and their cisplatin- and doxorubicin-resistant derivatives at low nanomolar affinity. These aptamers distinguish TNBC cells from both non-malignant and non-TNBC breast cancer cells and are able to differentiate TNBC histological specimens. Importantly, they inhibit TNBC cell capacity of growing in vitro as mammospheres, indicating they could also act as anti-tumor agents. Therefore, our newly identified aptamers are a valuable tool for selectively dealing with TNBC. : Biochemistry; Cell Biology; Cancer Subject Areas: Biochemistry, Cell Biology, Cancer
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- 2020
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10. TLR4 Expression in Ex-Lichenoid Lesions—Oral Squamous Cell Carcinomas and Its Surrounding Epithelium: The Role of Tumor Inflammatory Microenvironment
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Fernanda Visioli, Julia Silveira Nunes, Maria Carmela Pedicillo, Rosalia Leonardi, Angela Santoro, Gian Franco Zannoni, Gabriella Aquino, Margherita Cerrone, Monica Cantile, Nunzia Simona Losito, Vito Rodolico, Giuseppina Campisi, Giuseppe Colella, Ilenia Sara De Stefano, Maria Antonietta Ramunno, Cristina Pizzulli, Marco Visconti, Lorenzo Lo Muzio, and Giuseppe Pannone
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head and neck cancer ,tumor microenvironment ,inflammation ,toll-like receptors ,TLR4 ,Microbiology ,QR1-502 - Abstract
Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its inflammatory microenvironment. This study included 150 human samples: 30 normal oral control (NOC), 38 non-lichenoid epithelium surrounding OSCC (NLE-OSCC), 28 lichenoid epithelium surrounding OSCC (LE-OSCC), 30 OSCC ex-non oral lichenoid lesion (OSCC Ex-NOLL), and 24 OSCC ex-oral lichenoid lesion (OSCC Ex-OLL). TLR4 expression was investigated by immunohistochemistry and the percentage of positive cells was quantified. In addition, a semiquantitative analysis of staining intensity was performed. Immunohistochemical analysis revealed that TLR4 is strongly upregulated in LE-OSCC as compared to normal control epithelium and NLE-OSCC. TLR4 expression was associated with the inflammatory environment, since the percentage of positive cells increases from NOC and NLE-OSCC to LE-OSCC, reaching the highest value in OSCC Ex–OLL. TLR4 was detected in the basal third of the epithelium in NLE-OSCC, while in LE-OSCC, TLR4 expression reached the intermediate layer. These results demonstrated that an inflammatory microenvironment can upregulate TLR4, which may boost tumor development.
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- 2022
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11. Immunotherapy Bridge 2017 and Melanoma Bridge 2017: meeting abstracts
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David Carbone, Michael Sharpnack, Kai He, Lisa H. Butterfield, Alexander M. M. Eggermont, Maria Gonzalez-Cao, Niki Karachaliou, Guillermo Crespo, Erika Aldeguer, Ana Drozdowskyj, Ana Giménez-Capitán, Cristina Teixidó, Miguel Angel Molina-Vila, Santiago Viteri Ramírez, Salvador Martin Algarra, Elisabeth Pérez-Ruiz, Iván Márquez-Rodas, Delvys Rodriguez-Abreu, Remei Blanco, Teresa Puértolas, Maria Angeles Royo, Rafael Rosell, Maria Libera Ascierto, Svetlana Hamm, Tanja Wulff, Kerstin Kronthaler, Sabine Schrepfer, Ulrike Parnitzke, Anne Catherine Bretz, Roland Baumgartner, Veronica Ferrucci, Francesco Paolo Pennino, Luisa Dassi, Fatemeh Asadzadeh, Roberto Siciliano, Marianeve Carotenuto, Daniela Spano, Cristina Maria Chiarolla, Adelaide Greco, Monica Cantile, Maurizio Di Bonito, Gerardo Botti, Vandenbussche Jonathan, Gevaert Kris, Massimo Zollo, Teresa Amaral, Ioanna Tampouri, Ulrike Keim, Thomas Eigentler, Claus Garbe, Andrea Forschner, Alessandra Cesano, Sarah Warren, Duane Moogk, Kaitao Li, Zhou Yuan, Shi Zhong, Zhiya Yu, Ivan Liadi, William Rittase, Victoria Fang, Janna Dougherty, Arianne Perez-Garcia, Iman Osman, Navin Varadarajan, Nicholas P. Restifo, Alan Frey, Cheng Zhu, Michelle Krogsgaard, Claire Vanpouille-Box, Silvia C. Formenti, Sandra Demaria, Cristiana Lo Nigro, Alexander Renziehausen, Andreas G. Tzakos, Hexiao Wang, Bhavya Rao, Rubeta Matin, Catherine Harwood, Daniela Vivenza, Federica Tonissi, Marcella Occelli, Lynda Weir, Su Li, Van Ren Sim, Kevin O’Neill, Alan Evans, Alastair Thompson, Peter Szlosarek, Colin Fleming, Charlotte Proby, Nelofer Syed, Marco Merlano, Tim Crook, Robert Ferguson, Danny Simpson, Carlos Martinez, Matjaz Vogelsang, Esther Kazlow, Melissa Wilson, Anna Pavlick, Jeffrey Weber, Ryan Sullivan, Keith Flaherty, Antoni Ribas, Tomas Kirchhoff, Antonio D’Avino, Licia Guida, Augusto Cosacco, Roberta D’Aniello, Piera Maiolino, Teresa Tramontano, Maria R. Sarno, Ida Palazzo, Angela Di Napoli, Gianclaudio Acunzo, Mariarosanna De Fina, Antonia Silvestri, Monica Specchia, Michela Musacchio, Gianfranco Giglio, Francesco Carrozza, Liberato Di Lullo, Gian Marco De Maddi, Adele Venturelli, Elisabetta Gambale, Alessia Gatta, Davide Brocco, Consiglia Carella, Michele De Tursi, Thomas F. Gajewski, Costanza M. Cristiani, Rossana Tallerico, Valeria Ventura, Mariaelena Capone, Gabriele Madonna, Domenico Mallardo, Eliska Selinger, Cinzia Garofalo, Elina Staaf, Ester Simeone, Antonio M. Grimaldi, Genny del Zotto, Elio Gulletta, Gennaro Ciliberto, Alessandro Moretta, Paolo A. Ascierto, Ennio Carbone, Susan Costantini, Angela Sorice, Francesca Capone, Alfredo Budillon, Carolina Cauchi, Grazia Sciancalepore, Michela Rovera, Chiara Varamo, Zelda Seia, Stefania Palazzini, Fabiana Errico, Davide Basso, Laura Quaranta, Giuseppe Forte, Fulvio Lavagna, Silvia Violante, Paolo Bosio, Laura Lattanzio, Marco C Merlano, Mike Gowen, Jeremy Tchack, Hua Zhou, Keith Giles, Scott Paschke, Una Moran, David Fenyo, Aris Tsirigos, Michael Pacold, Silvana Morello, Claudia Sorrentino, Diana Giannarelli, Aldo Pinto, Federica Fratangelo, Rosaria Falcone, Vito Vanella, Dirk Schadendorf, Karl Lewis, Michele Maio, Lev Demidov, Mario Mandalà, Igor Bondarenko, Christopher Herbert, Andrzej Mackiewicz, Piotr Rutkowski, Alexander Guminski, Grant Goodman, Brian Simmons, Chenglin Ye, Gregory Hooper, Matthew J. Wongchenko, Yibing Yan, Frank Hermann, Astrid Ammendola, René Bartz, Bulotta Alessandra, Colombo Letizia, Mirabile Aurora, Lazzari Chiara, Mercuri Santo Raffaele, Parolini Danilo, Rizzo Nathalie, Martella Stefano, Modorati Giulio, Brianti Pina, Cestone Enza, Bellinzona Federica, Miserocchi Elisabetta, Gianni Luca, Gregorc Vanesa, Sanjiv Agarwala, B. Mark Smithers, Axel Haushild, Eric Watcher, Luigi Fattore, Ciro Francesco Ruggiero, Domenico Liguoro, Andrea Cerri, Maria Elena Pisanu, and Rita Mancini
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Medicine - Published
- 2018
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12. Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
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Elena Alexandrova, Jessica Lamberti, Pasquale Saggese, Giovanni Pecoraro, Domenico Memoli, Valeria Mirici Cappa, Maria Ravo, Roberta Iorio, Roberta Tarallo, Francesca Rizzo, Francesca Collina, Monica Cantile, Maurizio Di Bonito, Gerardo Botti, Giovanni Nassa, Alessandro Weisz, and Giorgio Giurato
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triple-negative breast cancer ,estrogen receptor beta ,small non-coding RNAs ,microRNA ,cholesterol biosynthesis ,Cytology ,QH573-671 - Abstract
Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ERα), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression. Estrogen receptor beta (ERβ) is present in a fraction of TNBC patients, where its expression correlates with improved patient outcomes, supported by the fact that it exerts oncosuppressive effects in TNBC cell models in vitro. ERβ is involved in microRNA-mediated regulation of gene expression in hormone-responsive BC cells and could mediate its actions through small noncoding RNAs (sncRNAs) in TNBCs also. To verify this possibility, smallRNA sequencing was performed on three ERβ-expressing cell lines from different TNBC molecular subtypes. Several sncRNAs resulted modulated by ERβ, with a subset being regulated in a tumor subtype-independent manner. Interestingly, sncRNA profiling of 12 ERβ+and 32 ERβ− primary TNBC biopsies identified 7 microRNAs, 1 PIWI-interacting RNA (piRNA), and 1 transfer RNA (tRNA) differentially expressed in ERβ+ compared to ERβ− tumors and cell lines. Among them, miR-181a-5p was found to be overexpressed in ERβ+ tumors and predicted target key components of the cholesterol biosynthesis pathway previously found to be inhibited by ERβ in TNBC cells.
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- 2020
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13. Correlation of Serum Cystatin C with Glomerular Filtration Rate in Patients Receiving Platinum-Based Chemotherapy
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Ernesta Cavalcanti, Vittoria Barchiesi, Dionigio Cerasuolo, Flaviano Di Paola, Monica Cantile, Sabrina Chiara Cecere, Sandro Pignata, Alessandro Morabito, Raffaele Costanzo, Massimo Di Maio, and Francesco Perrone
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Objectives. Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR) compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy. Design and Methods. Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations. Results. In the overall series, for the prediction of a fall of GFR < 80 mL/min/1.73 m2, the AUC of the ROC curve for cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%). For a GFR fall < 60 mL/min/1.73 m2, the AUC of ROC curve for cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%). Conclusions. Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy.
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- 2016
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14. Circulating progastrin-releasing peptide in the diagnosis of Small Cell Lung Cancer (SCLC) and in therapeutic monitoring
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Alessandro Morabito, Vittorio Simeon, Paolo Chiodini, Claudia Sandomenico, Ernesta Cavalcanti, Vittoria Barchiesi, Monica Cantile, Dionigio Cerasuolo, Barchiesi, Vittoria, Simeon, Vittorio, Sandomenico, Claudia, Cantile, Monica, Cerasuolo, Dionigio, Chiodini, Paolo, Morabito, Alessandro, and Cavalcanti, Ernesta
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medicine.medical_specialty ,medicine.medical_treatment ,Clinical Biochemistry ,Enolase ,Peptide ,Serum biomarker ,Immunofluorescence ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Carcinoembryonic antigen ,Internal medicine ,medicine ,Original Research Article ,030212 general & internal medicine ,Lung cancer ,neoplasms ,chemistry.chemical_classification ,Chemotherapy ,medicine.diagnostic_test ,biology ,business.industry ,Biochemistry (medical) ,medicine.disease ,respiratory tract diseases ,proGRP ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Non small cell ,Differential diagnosis ,business - Abstract
Introduction: Progastrin-releasing peptide (proGRP), a precursor of GRP, has been recently reported as a putative circulating biomarker for differential diagnosis between non–small cell lung cancer (NSCLC) and SCLC. We evaluated the diagnostic effectiveness of proGRP to differentiate patients with NSCLC and SCLC and the usefulness of combined measurement of proGRP and neuron-specific enolase (NSE) for diagnosing SCLC. Methods: Serum proGRP, NSE, cytokeratin 19 fragment 21-1 (CYFRA 21.1), squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA) were prospectively collected and measured in patients with a new diagnosis of lung cancer. Serum proGRP was also measured in healthy subjects. The serum proGRP, NSE, CYFRA 21.1 and CEA concentrations were determined by an electrochemiluminescence immunoassay and the serum SCC Ag concentration was determined by an automated immunofluorescence assay. Differences between proGRP and NSE in patients with SCLC and NSCLC were evaluated and compared using Mann-Whitney test. Results: A total of 77 patients affected by SCLC (n = 17) and NSCLC (n = 60) were enrolled in the present study. Moreover, 50 cases of healthy subjects were analyzed for proGRP. SCLC patients showed a significantly higher proGRP (1,484 pg/mL; range 168-3,777) levels compared to NSCLC patients (45 pg/mL; range 31.7-60.6), p
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- 2021
15. Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer
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Maurizio Di Bonito, Monica Fedele, Simona Camorani, Silvia Esposito, Margherita Passariello, Claudia De Lorenzo, Lisa Agnello, Laura Cerchia, Monica Cantile, Ilya V. Ulasov, Antonella Zannetti, Francesca Collina, Camorani, Simona, Passariello, Margherita, Agnello, Lisa, Esposito, Silvia, Collina, Francesca, Cantile, Monica, Di Bonito, Maurizio, Ulasov, Ilya V, Fedele, Monica, Zannetti, Antonella, De Lorenzo, Claudia, and Cerchia, Laura
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0301 basic medicine ,Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,PDGFRβ ,Metastase ,Apoptosis ,Triple Negative Breast Neoplasms ,Metastases ,Metastasis ,Targeted therapy ,Mice ,0302 clinical medicine ,Tumor Cells, Cultured ,Molecular Targeted Therapy ,Immune Checkpoint Inhibitors ,Triple-negative breast cancer ,Mice, Inbred BALB C ,Chemistry ,Aptamers, Nucleotide ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Oncology ,Tumor microenvironment ,030220 oncology & carcinogenesis ,Drug Therapy, Combination ,Female ,TNBC ,PD-L1 monoclonal antibody ,Aptamer ,medicine.drug_class ,Mice, Nude ,Monoclonal antibody ,lcsh:RC254-282 ,Receptor, Platelet-Derived Growth Factor beta ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,Growth factor receptor ,medicine ,Animals ,Humans ,Cell Proliferation ,Research ,Immunotherapy ,medicine.disease ,Xenograft Model Antitumor Assays ,Immune checkpoint ,030104 developmental biology ,Antitumor immunity ,PDGFR? ,Cancer research - Abstract
Abstract Background Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers allowing for combination therapies with immune-checkpoint blockade. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in invasive TNBC, both on tumor cells and tumor microenvironment. We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC. Methods The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4 T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4 T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAb combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. Results We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAb-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in mice. It acts on both tumor cells, inhibiting Akt and ERK1/2 signaling pathways, and immune populations, increasing intratumoral CD8 + T cells and reducing FOXP3 + Treg cells. Conclusion Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first time an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.
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- 2020
16. The Role of lncRNAs in Rare Tumors with a Focus on HOX Transcript Antisense RNA (HOTAIR)
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Monica Cantile, Margherita Cerrone, Maura Tracey de Bellis, Gerardo Botti, Giuseppina Liguori, Salvatore Tafuto, Maurizio Di Bonito, and Annarosaria De Chiara
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Poor prognosis ,Stromal cell ,QH301-705.5 ,rare cancers ,lncRNAs ,Review ,Biology ,Catalysis ,Inorganic Chemistry ,Molecular classification ,HOTAIR ,Neoplasms ,Animals ,Humans ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,Predictive biomarker ,Organic Chemistry ,General Medicine ,Computer Science Applications ,Biomarker (cell) ,Gene Expression Regulation, Neoplastic ,Chemistry ,Tumor progression ,Cancer research ,RNA, Long Noncoding ,HOX Transcript Antisense RNA - Abstract
Rare cancers are identified as those with an annual incidence of fewer than 6 per 100,000 persons and includes both epithelial and stromal tumors from different anatomical areas. The advancement of analytical methods has produced an accurate molecular characterization of most human cancers, suggesting a “molecular classification” that has allowed the establishment of increasingly personalized therapeutic strategies. However, the limited availability of rare cancer samples has resulted in very few therapeutic options for these tumors, often leading to poor prognosis. Long non coding RNAs (lncRNAs) are a class of non-coding RNAs mostly involved in tumor progression and drug response. In particular, the lncRNA HOX transcript antisense RNA (HOTAIR) represents an emergent diagnostic, prognostic and predictive biomarker in many human cancers. The aim of this review is to highlight the role of HOTAIR in rare cancers, proposing it as a new biomarker usable in the management of these tumors.
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- 2021
17. Aberrant Expression of Long Non Coding RNA HOTAIR and De-Regulation of the Paralogous 13 HOX Genes Are Strongly Associated with Aggressive Behavior of Gastro-Entero-Pancreatic Neuroendocrine Tumors
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Giuseppina Liguori, Salvatore Tafuto, Giosuè Scognamiglio, Maurizio Di Bonito, Fabiana Tatangelo, Gabriella Aquino, Margherita Cerrone, Gerardo Botti, Ottavia Clemente, Monica Cantile, and Annabella Di Mauro
- Subjects
Adult ,Male ,QH301-705.5 ,Gastro entero pancreatic ,Biology ,Neuroendocrine tumors ,Catalysis ,Article ,Inorganic Chemistry ,Stomach Neoplasms ,Intestinal Neoplasms ,medicine ,Humans ,Physical and Theoretical Chemistry ,Biology (General) ,Hox gene ,Molecular Biology ,QD1-999 ,Spectroscopy ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Gastrointestinal tract ,Transition (genetics) ,Organic Chemistry ,Genes, Homeobox ,HOTAIR ,General Medicine ,Middle Aged ,medicine.disease ,lncRNA HOTAIR ,HOX genes ,Long non-coding RNA ,digestive system diseases ,Computer Science Applications ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,Chemistry ,medicine.anatomical_structure ,GEP-NENs ,Cancer research ,Disease Progression ,Female ,RNA, Long Noncoding ,Neoplasm Grading ,Pancreas - Abstract
Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA HOTAIR in GEP-NENs. The expression of HOX genes is gradually lost in the transition from GEP NET G1 to NET/NEC G3 tumors, while HOTAIR expression, inversely correlated with HOX genes expression and weakly expressed in low-grade GEP NENs, becomes aberrant in NET G3 and NEC G3 categories. Our data highlights their potential role in the molecular stratification of GEP-NENs by suggesting new prognostic markers and potential therapeutic targets.
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- 2021
18. Pathological and molecular characteristics of inflammatory breast cancer
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Monica Cantile, Maurizio Di Bonito, and Gerardo Botti
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tumor biology ,Cancer Research ,Tumor microenvironment ,Axillary lymph nodes ,biology ,Inflammatory breast cancer (IBC) ,business.industry ,Review Article ,medicine.disease ,medicine.disease_cause ,Inflammatory breast cancer ,Phenotype ,Pathogenesis ,Breast cancer ,medicine.anatomical_structure ,Oncology ,medicine ,Cancer research ,biology.protein ,PTEN ,Radiology, Nuclear Medicine and imaging ,KRAS ,skin and connective tissue diseases ,business ,inflammatory pathways - Abstract
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by the presence of many dermal tumor emboli in the papillary and reticular dermis of the skin overlying the breast. IBC patients, compared to other breast cancer patients, have more frequently metastatic axillary lymph nodes. IBC is often high grade, negative for hormone receptors and presents with amplification of the HER2 gene. Invasive IBC is frequently of ductal phenotype, even if a specific histological distinction for these lesions has not been described. The pathogenesis and evolution of IBC are strongly dependent upon tumor microenvironment, characterized by several macrophages/monocytes and lymphocytes. The tumor and microenvironment cells are well molecularly characterized, showing the main contributor of inflammatory pathways in tumor biology of IBC. In addition, several molecular alterations are described in this tumor, such as mutations of ERBB2, KRAS, BRAF, EGFR, PIK3CA, PTEN, AKT1 , and AKT3 genes that could suggest a therapeutic stratification of IBC patients with the combination of different biological target therapies.
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- 2019
19. Noncoding RNAs as circulating biomarkers in osteosarcoma patients
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Anna De Chiara, Monica Cantile, Antonio Giordano, Florinda Feroce, and Gerardo Botti
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0301 basic medicine ,circulating ncRNAs ,Disease status ,RNA, Untranslated ,Physiology ,Clinical Biochemistry ,Biology ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,Biomarkers, Tumor ,medicine ,circulating miRNAs ,Humans ,In patient ,Osteosarcoma ,Cancer ,Cell Biology ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Circulating biomarkers ,osteosarcoma ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,RNA, Long Noncoding ,Sarcoma - Abstract
Noncoding RNAs (ncRNAs) identify a large family of RNAs that do not encode proteins and represent an important group of tumor biomarkers, directly involved in the process of tumor pathogenesis and progression. Many of them have also been identified in biological fluids of patients with cancer, especially blood, suggesting their role as an emerging class of circulating biomarkers. Many ncRNAs, both miRNAs and lncRNAs, are deregulated in sarcoma tissues, with the most consistent data in osteosarcomas. In patients with osteosarcoma, the role of ncRNAs as circulating biomarkers is taking enormous value, above all for their ability to vary expression levels during disease progression and in response to therapy. In this mini-review, we summarize the main studies supporting the role of circulating ncRNAs in monitoring disease status in patients with osteosarcoma.
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- 2019
20. Morphological and pathological features of basal-like breast cancer
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Sabrina Sarno, Francesca Collina, Monica Cantile, Annamaria Anniciello, Gerardo Botti, Margherita Cerrone, and Maurizio Di Bonito
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Cancer Research ,molecular markers ,Review Article ,Biology ,medicine.disease ,Basal-Like Breast Cancer ,Lymphocytic Infiltrate ,Cytokeratin ,Breast cancer ,Oncology ,Basal-like breast cancer (BLBC) ,histological features ,medicine ,Cancer research ,biology.protein ,Immunohistochemistry ,PTEN ,Radiology, Nuclear Medicine and imaging ,Pathological ,Mitosis - Abstract
Basal-like breast cancer (BLBC) is characterized by high grade, high mitotic indices, presence of central necrotic or fibrotic zones, and lymphocytic infiltrate. Patients presenting with BLBC have a poor prognosis and a short-term disease-free and overall survival. BLBCs may include different histological types of breast cancers but the most common histological type is represented by invasive ductal carcinomas of no special type (IDC-NST). Typical immunohistochemical markers for these tumors are basal-type cytokeratin markers such as CK5/6, CK14, CK17, but several BLBCs also express luminal-type CKs, such as CK8/18, CK19. Different molecular alterations, including BRCA1 dysfunction, p53 mutations, up-regulation of EGFR, inactivation of PTEN and the aberrant expression of many non-coding RNAs molecules are detected in BLBC cells suggesting the possibility of defining new targeted therapeutic strategies for this tumor type.
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- 2019
21. Posterior HOX genes and HOTAIR expression in the proximal and distal colon cancer pathogenesis
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Annabella Di Mauro, Antonio Lettiero, Fabiana Tatangelo, Paolo Delrio, Gabriella Aquino, Monica Cantile, Antonio Avallone, Giosuè Scognamiglio, and Gerardo Botti
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Male ,0301 basic medicine ,Colorectal cancer ,Proximal and distal CRC pathogenesis ,lcsh:Medicine ,In situ hybridization ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Hox gene ,Aged ,Aged, 80 and over ,Research ,lcsh:R ,Genes, Homeobox ,HOTAIR ,General Medicine ,Middle Aged ,medicine.disease ,HOX genes ,Prognosis ,Primary tumor ,Carcinoembryonic Antigen ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Cancer research ,Immunohistochemistry ,Female ,RNA, Long Noncoding ,Carcinogenesis - Abstract
Background Increasing evidences showed that the location of the primary tumor on the right (proximal) or left (distal) side of the colon have a prognostic/predictive value for colon cancer patients. However, the understanding of the molecular mechanisms that contribute to the pathogenesis in different location of colon is still unclear. Probably an important role could be played by genes that control the spatial–temporal development of bodily structures, such as HOX genes. Methods The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes and of the HOX regulating lncRNA HOTAIR in distal and proximal CRC cases. We have carried out a Tissue Micro Array with left and right CRC samples associated with all clinical-pathological parameters of patients. The expression of HOX genes was evaluated by immunohistochemistry and the staining of HOTAIR was performed by in situ hybridization using a specifically designed LNA probe. Results All paralogous 13 HOX genes and HOTAIR are silent in normal tissue and expressed in CRC samples. HOXB13, HOXC13 and HOTAIR showed a statistical association with lymph nodes metastasis (p value = 0.003, p value = 0.05, p value = 0.04). HOXB13, HOXC13 and lncRNA HOTAIR are overexpressed in right CRCs samples (p value
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- 2018
22. Functional Interaction among lncRNA HOTAIR and MicroRNAs in Cancer and Other Human Diseases
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Maura Tracey de Bellis, Monica Cantile, Maurizio Di Bonito, and Gerardo Botti
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0301 basic medicine ,Cancer Research ,Cancer ,HOTAIR ,Computational biology ,Review ,Biology ,medicine.disease ,lncRNA HOTAIR ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,cancer progression ,lcsh:RC254-282 ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,microRNA ,miRNAs ,medicine ,Cancer development ,Gene ,HOX Transcript Antisense RNA ,Predictive biomarker - Abstract
Simple Summary This review aimed to describe the contribution of functional interaction between the lncRNA HOTAIR and microRNAs in human diseases, including cancer. HOTAIR/miRNAs complexes interfere with different cellular processes during carcinogenesis, mainly deregulating a series of oncogenic signaling pathways. A great number of ncRNAs-related databases have been established, supported by bioinformatics technologies, to identify the ncRNA-mediated sponge regulatory network. These approaches need experimental validation through cells and animal models studies. The optimization of systems to interfere with HOTAIR/miRNAs interplay could represent a new tool for the definition of diagnostic therapeutics in cancer patients. Abstract LncRNAs are a class of non-coding RNAs mostly involved in regulation of cancer initiation, metastatic progression, and drug resistance, through participation in post-transcription regulatory processes by interacting with different miRNAs. LncRNAs are able to compete with endogenous RNAs by binding and sequestering miRNAs and thereby regulating the expression of their target genes, often represented by oncogenes. The lncRNA HOX transcript antisense RNA (HOTAIR) represents a diagnostic, prognostic, and predictive biomarker in many human cancers, and its functional interaction with miRNAs has been described as crucial in the modulation of different cellular processes during cancer development. The aim of this review is to highlight the relation between lncRNA HOTAIR and different microRNAs in human diseases, discussing the contribution of these functional interactions, especially in cancer development and progression.
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- 2021
23. Detection of SARS-CoV-2 infection in a pediatric population from south Italy without symptoms of Coronavirus Disease 2019
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Chiara, Botti, Antonio, Maglione, Adolfo, Russo, Alberto, Micillo, Giosu, Scognamiglio, and Monica, Cantile
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Original Article - Abstract
Background: SARS-CoV-2 has had dramatic consequences on the world population in morbidity and mortality and socially. Clinical manifestations range from common cold-like to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. The pediatric population may be infected with SARS-CoV-2, but is less likely to be symptomatic or develop severe symptoms. Methods: We analyzed a cohort of pediatric subjects from Campania Region, south Italy, without symptoms of SARS-CoV2, to evaluate the distribution of infection in relation to gender and age. Detection on nasopharyngeal swabs was performed with two different RT-PCR methods, a qualitative rapid test (VitaPCR(TM) SARS-CoV-2 assay) and a quantitative test (SARS-CoV-2 ELITe MGB(®) assay). Results: Positive subjects were 52.63% male and 47.36% female. Regarding age distribution, we described a consistent increase of detection rate (82.45%) in 0-2 year-old patients. Conclusion: The importance of children in transmitting the virus remains uncertain; however our analysis of the distribution of the infection in these subjects may help monitor SARS-CoV2 spread in the general population.
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- 2021
24. Organoid biobanks as a new tool for pre-clinical validation of candidate drug efficacy and safety
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Gerardo, Botti, Maurizio, Di Bonito, and Monica, Cantile
- Subjects
Original Article - Abstract
The growing need for personalized medicine for cancer patients has enhanced and optimized the production of living tumor organoids that have become optimal preclinical models for the discovery and screening of anticancer drugs. The systematic collection and storage of tumor organoids through the establishment of dedicated biobanks will represent a fundamental tool for cancer research and clinical trials.
- Published
- 2021
25. The ratio of grzb+ − foxp3+ over cd3+ t cells as a potential predictor of response to nivolumab in patients with metastatic melanoma
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Margherita Cerrone, Sabrina Sarno, Annabella Di Mauro, Mariaelena Capone, Giosuè Scognamiglio, Anna Maria Anniciello, Paolo A. Ascierto, Francesco Sabbatino, Monica Cantile, Marco Palla, Antonio M. Grimaldi, Gabriele Madonna, Domenico Mallardo, Gerardo Botti, and Maurizio Di Bonito
- Subjects
0301 basic medicine ,Cancer Research ,Immunoscore ,Immunotherapy ,Melanoma ,Multiplex immunostaining ,Tumor microenvironment ,medicine.medical_treatment ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cancer immunotherapy ,Medicine ,RC254-282 ,business.industry ,FOXP3 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Immune checkpoint ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Nivolumab ,business - Abstract
Simple Summary Despite the recent success of immunotherapy in the treatment of malignant melanoma, many patients still do not benefit from these treatments, due to their failure to activate an antitumor immune response them. There is therefore a need to select patients who can truly benefit from these treatments. We have focused our study on immune cells present in the tumor microenvironment, and we have developed a formula (ratio) that correlates with the response to anti-PD1 therapy and progression-free and overall survival, based on the numerical difference between GRZB+ and FOXP3+ cells over the total CD3+ lymphocytes. This developed ratio could be useful to better select patients that may or may not benefit from anti-PD-1 treatment. Abstract The understanding of the molecular pathways involved in the dynamic modulation of the tumor microenvironment (TME) has led to the development of innovative treatments for advanced melanoma, including immune checkpoint blockade therapies. These approaches have revolutionized the treatment of melanoma, but are not effective in all patients, resulting in responder and non-responder populations. Physical interactions among immune cells, tumor cells and all the other components of the TME (i.e., cancer-associated fibroblasts, keratinocytes, adipocytes, extracellular matrix, etc.) are essential for effective antitumor immunotherapy, suggesting the need to define an immune score model which can help to predict an efficient immunotherapeutic response. In this study, we performed a multiplex immunostaining of CD3, FOXP3 and GRZB on both primary and unmatched in-transit metastatic melanoma lesions and defined a novel ratio between different lymphocyte subpopulations, demonstrating its potential prognostic role for cancer immunotherapy. The application of the suggested ratio can be useful for the stratification of melanoma patients that may or may not benefit from anti-PD-1 treatment.
- Published
- 2021
26. Relation between Anti-Transglutaminase IgA e Anti-Thyroperoxidase in a Pediatric Patient Cohort
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Bernardino Pennucci, Alberto Micillo, Martina D’Antonio, Giuseppe Ricci, Giosuè Scognamiglio, Chiara Botti, and Monica Cantile
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Pathology ,medicine.medical_specialty ,biology ,business.industry ,Tissue transglutaminase ,digestive, oral, and skin physiology ,Thyroid ,nutritional and metabolic diseases ,Inflammation ,General Medicine ,Disease ,digestive system ,digestive system diseases ,medicine.anatomical_structure ,Thyroid peroxidase ,Cohort ,medicine ,biology.protein ,medicine.symptom ,Antibody ,Villous atrophy ,business - Abstract
Celiac Disease (CD) is an autoimmune disorder characterized by inflammation, villous atrophy, and crypt hyperplasia of small...
- Published
- 2020
27. Long Non-Coding RNA
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Monica, Cantile, Maurizio, Di Bonito, Margherita, Cerrone, Francesca, Collina, Michelino, De Laurentiis, and Gerardo, Botti
- Subjects
breast cancer ,drug resistance ,breast cancer therapy ,Review ,lncRNA HOTAIR - Abstract
Breast cancer (BC) is the most common cancer type among women, and morbidity and mortality rates are still very high. Despite new innovative therapeutic approaches for all BC molecular subtypes, the discovery of new molecular biomarkers involved in tumor progression has been fundamental for the implementation of personalized treatment strategies and improvement of patient management. Many experimental studies indicate that long non-coding RNAs (lncRNAs) are strongly involved in BC initiation, metastatic progression, and drug resistance. In particular, aberrant expression of HOX transcript antisense intergenic RNA (HOTAIR) lncRNA plays an important role in BC contributing to its progression and represents a predictor of BC metastasis. For its proven prognostic value, HOTAIR could represent a potential therapeutic target in BC. In the present review, we summarize the role of HOTAIR in cancer progression and drug resistance, in particular in BC, and we illustrate the main approaches for silencing it.
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- 2020
28. Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
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Jessica Lamberti, Giorgio Giurato, Valeria Mirici Cappa, Maurizio Di Bonito, Giovanni Nassa, Alessandro Weisz, Elena Alexandrova, Maria Ravo, Gerardo Botti, Domenico Memoli, Monica Cantile, Francesca Rizzo, Francesca Collina, Roberta Tarallo, Roberta Iorio, Giovanni Pecoraro, and Pasquale Saggese
- Subjects
Adult ,Triple Negative Breast Neoplasms ,cholesterol biosynthesis ,estrogen receptor beta ,microRNA ,small non-coding RNAs ,triple-negative breast cancer ,Receptor tyrosine kinase ,Article ,Cell Line, Tumor ,Progesterone receptor ,Humans ,RNA, Messenger ,skin and connective tissue diseases ,lcsh:QH301-705.5 ,Estrogen receptor beta ,Triple-negative breast cancer ,Aged ,Regulation of gene expression ,Aged, 80 and over ,biology ,General Medicine ,Middle Aged ,Non-coding RNA ,Survival Analysis ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cholesterol ,lcsh:Biology (General) ,biology.protein ,Cancer research ,RNA, Small Untranslated ,Estrogen receptor alpha - Abstract
Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ER&alpha, ), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression. Estrogen receptor beta (ER&beta, ) is present in a fraction of TNBC patients, where its expression correlates with improved patient outcomes, supported by the fact that it exerts oncosuppressive effects in TNBC cell models in vitro. ER&beta, is involved in microRNA-mediated regulation of gene expression in hormone-responsive BC cells and could mediate its actions through small noncoding RNAs (sncRNAs) in TNBCs also. To verify this possibility, smallRNA sequencing was performed on three ER&beta, expressing cell lines from different TNBC molecular subtypes. Several sncRNAs resulted modulated by ER&beta, with a subset being regulated in a tumor subtype-independent manner. Interestingly, sncRNA profiling of 12 ER&beta, +and 32 ER&beta, &minus, primary TNBC biopsies identified 7 microRNAs, 1 PIWI-interacting RNA (piRNA), and 1 transfer RNA (tRNA) differentially expressed in ER&beta, + compared to ER&beta, tumors and cell lines. Among them, miR-181a-5p was found to be overexpressed in ER&beta, + tumors and predicted target key components of the cholesterol biosynthesis pathway previously found to be inhibited by ER&beta, in TNBC cells.
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- 2020
29. Novel Aptamers Selected on Living Cells for Specific Recognition of Triple-Negative Breast Cancer
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Gerardo Botti, Laura Cerchia, Monica Cantile, Francesca Collina, Francesco Leonetti, Monica Fedele, Simona Camorani, Mario Rosario Guarracino, and Ilaria Granata
- Subjects
0301 basic medicine ,Aptamer ,02 engineering and technology ,Biology ,Biochemistry ,Article ,03 medical and health sciences ,Breast cancer ,0502 economics and business ,medicine ,050207 economics ,lcsh:Science ,Triple-negative breast cancer ,Cancer ,Cell Biology ,High rate ,Cisplatin ,Multidisciplinary ,050208 finance ,05 social sciences ,021001 nanoscience & nanotechnology ,Tnbc cell ,medicine.disease ,In vitro ,3. Good health ,030104 developmental biology ,Cancer research ,lcsh:Q ,0210 nano-technology ,Systematic evolution of ligands by exponential enrichment ,medicine.drug - Abstract
Summary Triple-negative breast cancer (TNBC) is a high heterogeneous group of tumors with a distinctly aggressive nature and high rates of relapse. So far, the lack of any known targetable proteins has not allowed a specific anti-tumor treatment. Therefore, the identification of novel agents for specific TNBC targeting and treatment is desperately needed. Here, by integrating cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) for the specific recognition of TNBC cells with high-throughput sequencing technology, we identified a panel of 2′-fluoropyrimidine-RNA aptamers binding to TNBC cells and their cisplatin- and doxorubicin-resistant derivatives at low nanomolar affinity. These aptamers distinguish TNBC cells from both non-malignant and non-TNBC breast cancer cells and are able to differentiate TNBC histological specimens. Importantly, they inhibit TNBC cell capacity of growing in vitro as mammospheres, indicating they could also act as anti-tumor agents. Therefore, our newly identified aptamers are a valuable tool for selectively dealing with TNBC., Graphical Abstract, Highlights • Six 2′FPy-RNA aptamers were obtained by TNBC Cell-SELEX/NGS • They distinguish TNBC cells from non-malignant and non-TNBC breast cancer cells • They differentiate TNBC histological specimens by aptamer-based staining • They inhibit TNBC cell lines capacity of growing in vitro as mammospheres, Biochemistry; Cell Biology; Cancer
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- 2020
30. Long non-coding rna hotair in breast cancer therapy
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Monica Cantile, Michelino De Laurentiis, Margherita Cerrone, Gerardo Botti, Francesca Collina, Maurizio Di Bonito, Cantile, M., Di Bonito, M., Cerrone, M., Collina, F., De Laurentiis, M., and Botti, G.
- Subjects
Breast cancer therapy ,Cancer Research ,business.industry ,Cancer ,HOTAIR ,LncRNA HOTAIR ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Long non-coding RNA ,Metastasis ,Breast cancer ,lncRNA HOTAIR ,Oncology ,Tumor progression ,Drug resistance ,medicine ,Cancer research ,Gene silencing ,business ,Hox gene - Abstract
Breast cancer (BC) is the most common cancer type among women, and morbidity and mortality rates are still very high. Despite new innovative therapeutic approaches for all BC molecular subtypes, the discovery of new molecular biomarkers involved in tumor progression has been fundamental for the implementation of personalized treatment strategies and improvement of patient management. Many experimental studies indicate that long non-coding RNAs (lncRNAs) are strongly involved in BC initiation, metastatic progression, and drug resistance. In particular, aberrant expression of HOX transcript antisense intergenic RNA (HOTAIR) lncRNA plays an important role in BC contributing to its progression and represents a predictor of BC metastasis. For its proven prognostic value, HOTAIR could represent a potential therapeutic target in BC. In the present review, we summarize the role of HOTAIR in cancer progression and drug resistance, in particular in BC, and we illustrate the main approaches for silencing it.
- Published
- 2020
31. Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer
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Jessica Lamberti, Giovanni Pecoraro, Tuula A. Nyman, Roberta Tarallo, Elena Alexandrova, Domenico Rocco, Francesca Rizzo, Pasquale Saggese, Alessandro Weisz, Gerardo Botti, Giorgio Giurato, Francesca Collina, Maurizio Di Bonito, Maria Ravo, Monica Cantile, and Giovanni Nassa
- Subjects
Proteomics ,Interaction proteomics ,Triple Negative Breast Neoplasms ,Biology ,Breast cancer ,Cancer Biology ,Cell biology ,Cholesterol biosynthesis ,Estrogen Receptor beta ,Label-free quantification ,Polycomb Repressor Complexes ,Transcriptional Regulation ,Triple-negative breast cancer ,Tumor suppressors ,Biochemistry ,Chromatin remodeling ,Analytical Chemistry ,03 medical and health sciences ,Cell Line, Tumor ,Transcriptional regulation ,Humans ,Molecular Biology ,Transcription factor ,Estrogen receptor beta ,Cell Proliferation ,030304 developmental biology ,Regulation of gene expression ,0303 health sciences ,Gene Expression Profiling ,Research ,Cell Cycle ,030302 biochemistry & molecular biology ,Chromatin ,Cholesterol ,Nuclear receptor ,Cancer research ,Female - Abstract
Triple-negative breast cancer (TNBC) is characterized by poor response to therapy and low overall patient survival. Recently, Estrogen Receptor beta (ERβ) has been found to be expressed in a fraction of TNBCs where, because of its oncosuppressive actions on the genome, it represents a potential therapeutic target, provided a better understanding of its actions in these tumors becomes available. To this end, the cell lines Hs 578T, MDA-MB-468 and HCC1806, representing the claudin-low, basal-like 1 and 2 TNBC molecular subtypes respectively, were engineered to express ERβ under the control of a Tetracycline-inducible promoter and used to investigate the effects of this transcription factor on gene activity. The antiproliferative effects of ERβ in these cells were confirmed by multiple functional approaches, including transcriptome profiling and global mapping of receptor binding sites in the genome, that revealed direct negative regulation by ERβ of genes, encoding for key components of cellular pathways associated to TNBC aggressiveness representing novel therapeutic targets such as angiogenesis, invasion, metastasis and cholesterol biosynthesis. Supporting these results, interaction proteomics by immunoprecipitation coupled to nano LC-MS/MS mass spectrometry revealed ERβ association with several potential nuclear protein partners, including key components of regulatory complexes known to control chromatin remodeling, transcriptional and post-transcriptional gene regulation and RNA splicing. Among these, ERβ association with the Polycomb Repressor Complexes 1 and 2 (PRC1/2), known for their central role in gene regulation in cancer cells, was confirmed in all three TNBC subtypes investigated, suggesting its occurrence independently from the cellular context. These results demonstrate a significant impact of ERβ in TNBC genome activity mediated by its cooperation with regulatory multiprotein chromatin remodeling complexes, providing novel ground to devise new strategies for the treatment of these diseases based on ligands affecting the activity of this nuclear receptor or some of its protein partners.
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- 2020
32. Targeted imaging and inhibition of triple-negative breast cancer metastases by a PDGFRβ aptamer
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Simona Camorani, Antonella Zannetti, Maria Napolitano, Sara Gargiulo, Laura Cerchia, Monica Fedele, Maurizio Di Bonito, Monica Cantile, Francesca Collina, Billy Samuel Hill, and Gerardo Botti
- Subjects
0301 basic medicine ,invasiveness ,PDGFRβ ,Medicine (miscellaneous) ,aptamer ,PDGFR beta ,mesenchymal TNBC subtype ,metastases ,Triple Negative Breast Neoplasms ,Theranostic Nanomedicine ,Flow cytometry ,Receptor, Platelet-Derived Growth Factor beta ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Breast cancer ,Growth factor receptor ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Neoplasm Metastasis ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Triple-negative breast cancer ,Cell Proliferation ,Tube formation ,Tissue microarray ,medicine.diagnostic_test ,business.industry ,Mesenchymal stem cell ,Optical Imaging ,Cancer ,Mesenchymal Stem Cells ,Aptamers, Nucleotide ,medicine.disease ,Immunohistochemistry ,Molecular Imaging ,Disease Models, Animal ,030104 developmental biology ,Treatment Outcome ,Tissue Array Analysis ,030220 oncology & carcinogenesis ,Cancer research ,business ,Research Paper ,Protein Binding - Abstract
While the overall mortality for breast cancer has recently declined, management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and the lack of targeted therapies. Genomic profiling studies highlighted the high level of heterogeneity of this cancer, which comprises different subtypes with unique phenotypes and response to treatment. Platelet-derived growth factor receptor ? (PDGFR?) is an established mesenchymal/stem cell-specific marker in human glioblastoma and, as recently suggested, it may uniquely mark breast cancer cells with stem-like characteristics and/or that have undergone epithelial-mesenchymal transition. Methods: Immunohistochemical analysis for PDGFR? expression was performed on a human TNBC tissue microarray. Functional assays were conducted on mesenchymal-like TNBC cells to investigate the effect of a previously validated PDGFR? aptamer on invasive cell growth in three-dimensional culture conditions, migration, invasion and tube formation. The aptamer was labeled with a near-infrared (NIR) dye and its binding specificity to PDGFR? was assessed both in vitro (confocal microscopy and flow cytometry analyses) and in vivo (fluorescence molecular tomography in mice bearing TNBC xenografts). A mouse model of TNBC lung metastases formation was established and NIR-labeled PDGFR? aptamer was used to detect lung metastases in mice untreated or intravenously injected with unlabeled aptamer. Results: Here, we present novel data showing that tumor cell expression of PDGFR? identifies a subgroup of mesenchymal tumors with invasive and stem-like phenotype, and propose a previously unappreciated role for PDGFR? in driving TNBC cell invasiveness and metastases formation. We show that the PDGFR? aptamer blocked invasive growth and migration/invasion of mesenchymal TNBC cell lines and prevented TNBC lung metastases formation. Further, upon NIR-labeling, the aptamer specifically bound to TNBC xenografts and detected lung metastases. Conclusions: We propose PDGFR? as a reliable biomarker of a subgroup of mesenchymal TNBCs with invasive and stem-like phenotype as well as the use of the PDGFR? aptamer as a high efficacious tool for imaging and suppression of TNBC lung metastases. This study will allow for the significant expansion of the current repertoire of strategies for managing patients with more aggressive TNBC.
- Published
- 2018
33. Noncoding RNAs within the HOX gene network in tumor pathogenesis and progression
- Author
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Anna De Chiara, Maria Gabriella Malzone, Gerardo Botti, Maurizio Di Bonito, Margherita Cerrone, Francesca Collina, and Monica Cantile
- Subjects
0301 basic medicine ,animal structures ,Physiology ,Cellular differentiation ,Clinical Biochemistry ,Computational biology ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Intergenic region ,Neoplasms ,microRNA ,Humans ,Gene Regulatory Networks ,Hox gene ,Gene ,Genes, Homeobox ,Cell Differentiation ,Cell Biology ,Non-coding RNA ,Long non-coding RNA ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Cell metabolism ,030220 oncology & carcinogenesis ,embryonic structures ,Disease Progression ,RNA, Long Noncoding - Abstract
HOX genes are involved with normal development, cell identity, cell differentiation, cell metabolism, apoptosis, autophagy as well as with diseases such as tumor pathogenesis and progression. In particular, the genes belonging to HOX paralogous 13 seem to carry out a relevant role in both tumor development and disease progression. In recent years, several noncoding RNAs (ncRNA) sequences have been identified in HOX loci, including long noncoding RNA (lncRNA) and microRNA (miRNA), highly conserved during evolution. Many studies have shown that specific intergenic ncRNAs in HOX loci could directly modulate HOX genes expression in normal and pathological conditions. In the present review we attempt to describe the role of these ncRNAs, through the regulation of the HOX gene network, in normal cell biology, and, with particular emphasis, in diseases such as in cancer pathogenesis and progression.
- Published
- 2018
34. LncRNA HOTAIR Polymorphisms Association with Cancer Susceptibility in Different Tumor Types
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Giuseppina Liguori, Gerardo Botti, Vincenzo Gigantino, Giosuè Scognamiglio, Francesca Collina, Maria Gabriella Malzone, Monica Cantile, Gabriella Aquino, and Margherita Cerrone
- Subjects
Male ,0301 basic medicine ,Clinical Biochemistry ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Neoplasms ,Drug Discovery ,Gene expression ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Genetic variability ,Gene ,Pharmacology ,Genetics ,HOTAIR ,Non-coding RNA ,Phenotype ,Long non-coding RNA ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,Disease Progression ,Molecular Medicine ,Female ,RNA, Long Noncoding - Abstract
Single nucleotide polymorphisms (SNPs) in non-coding RNAs (ncRNA) molecules affect gene and protein expression and generate genetic variability influencing the risk of tumor diseases. HOTAIR locates at the heart of the cell memory gene program and represents a prototype of long non coding RNA (LncRNA) due to its capacity to regulate in-trans a distant chromosome landscape. Aberrant expression of HOTAIR is frequently associated with pathogenesis and mostly with metastatic progression of several human cancers. Different polymorphisms, particularly present in intronic sequences, as well as in promoter regions of HOTAIR, are often associated with its aberrant expression, patient prognosis, and cancer susceptibility in different tumor phenotypes. In this minireview, we have summarized the main SNPs in HOTAIR sequence and their relation with cancer risk in several types of solid tumors.
- Published
- 2018
35. HOTAIR role in melanoma progression and its identification in the blood of patients with advanced disease
- Author
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Giosuè Scognamiglio, Giuseppina Liguori, Maria Gabriella Malzone, Laura Marra, Renato Franco, Gerardo Botti, Gabriella Aquino, Monica Cantile, Paolo A. Ascierto, Maurizio Di Bonito, Maria Rosaria Falcone, Chiara Botti, Cantile, Monica, Scognamiglio, Giosuã¨, Marra, Laura, Aquino, Gabriella, Botti, Chiara, Falcone, Maria Rosaria, Malzone, Maria Gabriella, Liguori, Giuseppina, Di Bonito, Maurizio, Franco, Renato, Ascierto, Paolo Antonio, and Botti, Gerardo
- Subjects
Male ,0301 basic medicine ,Skin Neoplasms ,Metastatic melanoma ,Physiology ,Lymphocyte ,Clinical Biochemistry ,circulating marker ,Disease ,Biology ,Real-Time Polymerase Chain Reaction ,03 medical and health sciences ,HOTAIR ,lncRNA ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Biomarkers, Tumor ,Tumor Microenvironment ,Advanced disease ,medicine ,Humans ,Hox gene ,Melanoma ,In Situ Hybridization ,Neoplasm Staging ,Tumor microenvironment ,Cell Biology ,Middle Aged ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,medicine.anatomical_structure ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,melanoma progression ,Cancer research ,Female ,RNA, Long Noncoding - Abstract
The molecular mechanisms responsible for the metastatic progression of melanoma have not been fully defined yet. We have recently shown that an important role in this process is certainly played by HOX genes, whose regulation is under control of particular non-coding RNAs, some of which are present within the HOX locus. HOTAIR is the most studied among them, whose aberrant expression is associated with the metastatic progression of many malignancies. The aim of this study was to verify the role played by HOTAIR in metastatic progression of melanoma and to evaluate the circulating levels of HOTAIR in the blood of patients with metastatic melanoma. A series of melanocytic lesions were selected to evaluate the potential changes in the expression of HOTAIR during the evolution of the disease through in situ and molecular approaches. None of the benign melanocytic lesions showed the presence of HOTAIR. The staining of HOTAIR resulted very weak in the primary pT1 lesions, while it was very strong in all pairs of primary tissues and corresponding metastases. Surprisingly, we found the presence of HOTAIR in some intratumoral lymphocytes, while this positivity decreased in lymphocyte component further away from the tumor. HOTAIR was also detected in the serum of selected metastatic patients. These data allowed us to speculate on the fundamental role played by HOTAIR in tumor evolution of melanoma. Its presence in intratumoral lymphocytes might suggest that its involvement in the modulation of tumor microenvironment and the detection in the serum could be used in the management of melanoma patients.
- Published
- 2017
36. Programmed Death Ligand 1 (PD-L1) Expression in Primary Angiosarcoma
- Author
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Maurizio Di Bonito, Rossella De Cecio, Monica Cantile, Laura Marra, Giosuè Scognamiglio, Antonio Pizzolorusso, Gerardo Botti, and Annarosaria De Chiara
- Subjects
PD-L1 ,0301 basic medicine ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Angiosarcoma ,IHC evaluation ,angiosarcoma ,biology ,business.industry ,Cancer ,Immunotherapy ,Primary Angiosarcoma ,medicine.disease ,030104 developmental biology ,Lymphatic system ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Immunohistochemistry ,Antibody ,business ,Research Paper - Abstract
Angiosarcomas are rare malignant endothelial-cell tumors of vascular or lymphatic origin, and are among the most aggressive subtypes of soft-tissue sarcomas. The prognosis is poor and treatment is challenging in many cases. PD-1/PD-L1 pathway plays a critical role in immune escape of tumor cells. Recent studies described that PD-L1 is widely expressed in various types of cancer, providing the basis for the development of PD1/PD-L1 antibodies as anti-cancer immunotherapy. Despite the well-known potential of PD-L1 as prognostic and predictive biomarker, only few studies described its IHC expression in cancer subtypes for the extreme difficulty in developing standard protocol with the different antibody clones available. We analyzed the IHC expression of PD-L1 on a series of angiosarcomas at different body location, showing its aberrant expression in about 66% of samples with no relation with prognosis. Our study allowed us to correctly define PD-L1 staining in angiosarcoma tumor tissues with final purpose to stratify patients for immune checkpoint inhibitors therapies.
- Published
- 2017
37. Immunohistochemical detection of paralogous 13 HOX genes in phyllodes tumor of the breast as a useful diagnostic tool
- Author
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Sabrina, Sarno, Margherita, Cerrone, Vincenzo, Gigantino, Giosuè, Scognamiglio, Monica, Cantile, Gerardo, Botti, and Maurizio, Di Bonito
- Subjects
animal structures ,Original Article - Abstract
Phyllodes tumor of the breast is a rare fibroepithelial lesion characterized by a propensity for local recurrence and distant metastasis. Its histologic classification, based on morphology, mitotic index and tumor margin, includes malignant, borderline, and benign. These tumors show similar cellular morphology, which may contribute to difficulty in classifying them histologically and in prediction of their clinical behavior. Thus, the identification of new biomarkers detectable also by in situ methods has become indispensable. Paralogous HOX13 genes (HOX A13, HOX B13, HOX C13 and HOX D13) play a relevant role in tumor development and progression in particular in breast cancer. In this study we analyzed the immunohistochemical expression of paralogous HOX13 homeoproteins on a phyllodes tumor case series to validate their usefulness in histologic classification.
- Published
- 2019
38. LncRNA HOTAIR in Tumor Microenvironment: What Role?
- Author
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Giosuè Scognamiglio, Giuseppina Liguori, Monica Cantile, Gabriella Aquino, and Gerardo Botti
- Subjects
tumor progression ,Biology ,medicine.disease_cause ,Catalysis ,HOTAIR ,Inorganic Chemistry ,lcsh:Chemistry ,medicine ,Tumor growth ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Regulation of gene expression ,Tumor microenvironment ,Organic Chemistry ,TME ,Cancer ,General Medicine ,medicine.disease ,Computer Science Applications ,lcsh:Biology (General) ,lcsh:QD1-999 ,Tumor progression ,Cancer research ,sense organs ,Carcinogenesis ,Function (biology) - Abstract
lncRNAs participate in many cellular processes, including regulation of gene expression at the transcriptional and post-transcriptional levels. In addition, many lncRNAs can contribute to the development of different human diseases including cancer. The tumor microenvironment (TME) plays an important role during tumor growth and metastatic progression, and most of these lncRNAs have a key function in TME intracellular signaling. Among the numerous identified lncRNAs, several experimental evidences have shown the fundamental role of the lncRNA HOTAIR in carcinogenesis, also highlighting its use as a circulating biomarker. In this review we described the contribution of HOTAIR in the TME modulation, highlighting its relation with cellular and non-cellular components during tumor evolution and progression.
- Published
- 2019
39. Paralogous HOX13 Genes in Human Cancers
- Author
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Maria Gabriella Malzone, Gerardo Botti, Clemente Cillo, Monica Cantile, and Rossella De Cecio
- Subjects
0301 basic medicine ,Cancer Research ,animal structures ,HOX gene network ,paralogous HOX 13 genes ,Review ,Biology ,medicine.disease_cause ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Gene family ,Hox gene ,Gene ,Genetics ,Embryogenesis ,Wnt signaling pathway ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,tumor diseases ,030104 developmental biology ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,embryonic structures ,Body region ,Carcinogenesis - Abstract
Hox genes (HOX in humans), an evolutionary preserved gene family, are key determinants of embryonic development and cell memory gene program. Hox genes are organized in four clusters on four chromosomal loci aligned in 13 paralogous groups based on sequence homology (Hox gene network). During development Hox genes are transcribed, according to the rule of “spatio-temporal collinearity”, with early regulators of anterior body regions located at the 3’ end of each Hox cluster and the later regulators of posterior body regions placed at the distal 5’ end. The onset of 3’ Hox gene activation is determined by Wingless-type MMTV integration site family (Wnt) signaling, whereas 5’ Hox activation is due to paralogous group 13 genes, which act as posterior-inhibitors of more anterior Hox proteins (posterior prevalence). Deregulation of HOX genes is associated with developmental abnormalities and different human diseases. Paralogous HOX13 genes (HOX A13, HOX B13, HOX C13 and HOX D13) also play a relevant role in tumor development and progression. In this review, we will discuss the role of paralogous HOX13 genes regarding their regulatory mechanisms during carcinogenesis and tumor progression and their use as biomarkers for cancer diagnosis and treatment.
- Published
- 2019
40. LncRNA
- Author
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Gerardo, Botti, Giosuè, Scognamiglio, Gabriella, Aquino, Giuseppina, Liguori, and Monica, Cantile
- Subjects
Gene Expression Regulation, Neoplastic ,HOTAIR ,Carcinogenesis ,Neoplasms ,Tumor Microenvironment ,TME ,Humans ,RNA, Long Noncoding ,tumor progression ,sense organs ,Review ,Cell Proliferation - Abstract
lncRNAs participate in many cellular processes, including regulation of gene expression at the transcriptional and post-transcriptional levels. In addition, many lncRNAs can contribute to the development of different human diseases including cancer. The tumor microenvironment (TME) plays an important role during tumor growth and metastatic progression, and most of these lncRNAs have a key function in TME intracellular signaling. Among the numerous identified lncRNAs, several experimental evidences have shown the fundamental role of the lncRNA HOTAIR in carcinogenesis, also highlighting its use as a circulating biomarker. In this review we described the contribution of HOTAIR in the TME modulation, highlighting its relation with cellular and non-cellular components during tumor evolution and progression.
- Published
- 2019
41. LncRNA HOTAIR up-regulation is strongly related with lymph nodes metastasis and LAR subtype of triple negative breast cancer
- Author
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Marianna Brogna, Francesca Collina, Sabrina Cipolletta, Maurizio Di Bonito, Gabriella Aquino, Michelino De Laurentiis, Monica Cantile, Gerardo Botti, G. Buonfanti, Collina, F., Aquino, G., Brogna, M., Cipolletta, S., Buonfanti, G., De Laurentiis, M., Bonito, M. D., Cantile, M., and Botti, G.
- Subjects
0301 basic medicine ,Regulation of gene expression ,business.industry ,HOTAIR ,medicine.disease ,Metastasis ,Androgen receptor ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Androgen Receptor ,medicine ,Cancer research ,Cancer biomarkers ,business ,TNBC ,Triple-negative breast cancer - Abstract
Triple-negative breast cancers (TNBCs) represent a heterogeneous disease characterized by several molecular subtypes with different prognoses and responses to therapy. For a correct clinical management of TNBC patients the knowledge of the gene regulation mechanisms related to tumor progression and drug response has become fundamental. LncRNAs regulate gene expression through various processes, including chromatin modification, transcription and post-transcription and they are emerging as important cancer biomarkers being involved in tumor pathogenesis, metastatic progression and drug resistance. In this study we aimed to analyze the expression of the lncRNA HOTAIR, mainly involved in breast cancer disease, in a large case series of TNBC patients. We used ISH methods by a RNA probe to better define its staining in tumor tissues and its relation with clinical-pathological parameters and outcomes of patients. Our results show that high HOTAIR expression in tumor tissues is strongly correlated with lymph nodes metastasis (LNM) (p=0.039), as reported also for other tumor types, and has a direct strong association with Androgen Receptor (AR) expression (p= 0.019). These data confirm the prognostic role of HOTAIR in TNBC, and, its involvement in the regulation of AR pathway, suggests the possibility to establish new therapeutic strategies for AR+TNBC patients.
- Published
- 2019
42. AXL Is a Novel Predictive Factor and Therapeutic Target for Radioactive Iodine Refractory Thyroid Cancer
- Author
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Luciano Pezzullo, Nella Prevete, Maria Grazia Chiofalo, Nunzia Simona Losito, Giuseppina Liguori, Francesca Collina, Laura Arenare, Elvira La Mantia, Francesca Di Gennaro, Monica Cantile, Rosa Marina Melillo, Giancarlo Vecchio, Renato Franco, Gerardo Botti, Lucia La Sala, Gabriella Aquino, Federica Liotti, Collina, F, La Sala, L, Liotti, F, Prevete, N, La Mantia, E, Chiofalo, Mg, Aquino, G, Arenare, L, Cantile, M, Liguori, G, Di Gennaro, F, Pezzullo, L, Losito, N, Vecchio, G, Botti, G, Melillo, Rm, Franco, R., Collina, Francesca, La Sala, Lucia, Liotti, Federica, Prevete, Nella, La Mantia, Elvira, Chiofalo, Maria Grazia, Aquino, Gabriella, Arenare, Laura, Cantile, Monica, Liguori, Giuseppina, Di Gennaro, Francesca, Pezzullo, Luciano, Losito, Nunzia Simona, Vecchio, Giancarlo, Botti, Gerardo, Melillo, Rosa Marina, and Franco, Renato
- Subjects
0301 basic medicine ,Cancer Research ,Thymoma ,endocrine system diseases ,AKT1 ,P65 NF-kB activation ,Radioactive iodine (RAI)-refractorine ,lcsh:RC254-282 ,Article ,Receptor tyrosine kinase ,Thyroid cancer ,Thyroid carcinoma ,03 medical and health sciences ,0302 clinical medicine ,radioactive iodine (RAI)-refractoriness ,hemic and lymphatic diseases ,medicine ,biology ,GAS6 ,business.industry ,AXL ,disease persistence/recurrence ,p65 NF-kB activation ,thyroid cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Immunohistochemistry ,business ,Disease persistence/recurrence ,V600E - Abstract
Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness. Immunohistochemistry was used to assess AXL positivity in a cohort of human PTC samples. Normal and cancerous thyroid cell lines were used in vitro for signaling, survival and RAI uptake evaluations. 38.2% of human PTCs displayed high expression of AXL that positively correlated with RAI-refractoriness and disease persistence or recurrence, especially when combined with v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation. In human PTC samples, AXL expression correlated with V-akt murine thymoma viral oncogene homolog 1 (AKT1) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation levels. Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture. Enforced expression or activation of AXL in normal rat thyroid cells significantly reduced the expression of the sodium/iodide symporter (NIS) and the radioiodine uptake. These data indicate that AXL expression levels could be used as predictor of RAI refractoriness and as a possible novel therapeutic target of RAI resistant PTCs. Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness. Immunohistochemistry was used to assess AXL positivity in a cohort of human PTC samples. Normal and cancerous thyroid cell lines were used in vitro for signaling, survival and RAI uptake evaluations. 38.2% of human PTCs displayed high expression of AXL that positively correlated with RAI-refractoriness and disease persistence or recurrence, especially when combined with v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation. In human PTC samples, AXL expression correlated with V-akt murine thymoma viral oncogene homolog 1 (AKT1) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation levels. Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture. Enforced expression or activation of AXL in normal rat thyroid cells significantly reduced the expression of the sodium/iodide symporter (NIS) and the radioiodine uptake. These data indicate that AXL expression levels could be used as predictor of RAI refractoriness and as a possible novel therapeutic target of RAI resistant PTCs.
- Published
- 2019
43. Gastric schwannoma misdiagnosed as GIST: A case report with immunohistochemical and molecular study
- Author
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Andrea Belli, F. Bianco, Fabiana Tatangelo, Monica Cantile, Silvia De Franciscis, Francesca Collina, and Gerardo Botti
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,PDGFRA ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,otorhinolaryngologic diseases ,medicine ,Gastric Schwannoma ,Stromal tumor ,neoplasms ,GiST ,business.industry ,Stomach ,Cancer ,Articles ,medicine.disease ,digestive system diseases ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Immunohistochemistry ,030211 gastroenterology & hepatology ,medicine.symptom ,business - Abstract
Schwannomas are tumors derived from Schwann cells. Generally, they are benign and their typical site of origin is the subcutaneous tissue of the distal extremities or of the head and neck region. Gastrointestinal localization of schwannomas is extremely rare, and the stomach is the prevalent site. The present study describes the case of a gastric schwannoma in a 61-year-old male who underwent subtotal gastrectomy following a clinical diagnosis of a gastrointestinal stromal tumor (GIST). A histological, immunohistochemical and molecular study was performed to exclude the misdiagnosis of GIST. The histomorphological features of the lesion and absence of c-Kit and PDGFRA mutations indicated the diagnosis of gastric schwannoma.
- Published
- 2016
44. Primary breast angiosarcoma in young women from the same geographic region in a short period of time: Only a coincidence or an increased risk?
- Author
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Monica Cantile, Margherita Cerrone, Maurizio Di Bonito, Antonio Pizzolorusso, Gerardo Botti, Gaetano Apice, and Annarosaria De Chiara
- Subjects
Gynecology ,medicine.medical_specialty ,Obstetrics ,business.industry ,Period (gene) ,Breast angiosarcoma ,03 medical and health sciences ,0302 clinical medicine ,Increased risk ,Oncology ,030220 oncology & carcinogenesis ,Internal Medicine ,medicine ,Geographic regions ,Surgery ,030212 general & internal medicine ,business - Published
- 2017
45. Abstract 5256: Toward biomarkers discovery: Profiling triple-negative breast cancer cells by cell-SELEX
- Author
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Laura Cerchia, Francesca Collina, Antonella Zannetti, Monica Cantile, Francesco Leonetti, Gerardo Botti, Monica Fedele, and Simona Camorani
- Subjects
Cancer Research ,Tissue microarray ,Antibody microarray ,Aptamer ,Biology ,medicine.disease ,Breast cancer ,Oncology ,medicine ,biology.protein ,Cancer research ,Cancer biomarkers ,Antibody ,Receptor ,Triple-negative breast cancer - Abstract
Triple-negative breast cancer (TNBC) is a high heterogeneous group of tumors with a distinctly aggressive nature and high rates of relapse. So far, the lack of any known targetable proteins has not allowed a specific anti-tumor treatment, thus the identification of novel agents for specific TNBC recognition and treatment is desperately needed. Nucleic acids aptamers are emerging as the most promising candidates for targeting tumor cells. They are also termed "chemical antibodies" because their form unique tertiary structures, which allow specific binding to their target molecules. Recently, by cell-SELEX integrated to advanced Next Generation Sequencing and bioinformatics, we isolated a panel of six nuclease-resistant RNA aptamers able to bind at high affinity to TNBC cells, discriminating them from both normal cells and non-TNBC breast cancer cells, and interfere with their growth as mammospheres. Also, they diversify TNBC histological specimens in a tissue microarray without recognizing samples from both ER+, PR+, HER2+ breast cancers and normal adjacent tissues. Here, short versions of the aptamers have been generated, by truncating their length from 84 nt up to nearly 30 nt, which preserve efficacious targeting and anti-tumor properties as the parental moieties. In order to identify the targets of the above aptamers, which might be important surface cancer biomarkers crucial for the malignant phenotype, different biochemical approaches are harnessed that include aptamer-mediated affinity purification coupled to Mass Spectrometry and/or antibody array for human soluble receptors. Binding analyses on recombinant proteins, cells or tissues are used to verify the putative targets. Results obtained so far indicate that the target of one of the six aptamers is a secreted protein tightly and specifically associated to TNBC cell surface and with a poor prognosis. This protein identification and the functional role of its targeting by the aptamer will be shown here in detail. The proposed cell-targeting aptamer strategy could provide an important new avenue for selective TNBC therapy. Citation Format: Simona Camorani, Francesco Leonetti, Francesca Collina, Monica Cantile, Gerardo Botti, Antonella Zannetti, Monica Fedele, Laura Cerchia. Toward biomarkers discovery: Profiling triple-negative breast cancer cells by cell-SELEX [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5256.
- Published
- 2020
46. Molecular characterization of a bladder pleomorphic rhabdomyosarcoma in an adult patient
- Author
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Gerardo Botti, Sisto Perdonà, Monica Cantile, Francesca Collina, Annarosaria De Chiara, Florinda Feroce, Giosuè Scognamiglio, Luigi Castaldo, and Gabriella Aquino
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Necrosis ,business.industry ,Poorly differentiated ,Soft tissue ,Cell Biology ,Pathology and Forensic Medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Medicine ,Pleomorphic rhabdomyosarcoma ,Desmin ,medicine.symptom ,Adult Pleomorphic Rhabdomyosarcoma ,business ,Myogenin - Abstract
Pleomorphic rhabdomyosarcoma (PRMS) is a rare but highly aggressive soft tissue tumor, accounting for 3% of soft tissue sarcomas. PRMS is the most frequent subtype of RMS in adulthood and it is mainly located in the large muscles of the extremities, particularly the lower limbs and the trunk, more rarely in other locations especially in the bladder. At our knowledge, only six cases of adult pleomorphic rhabdomyosarcoma of the bladder have been reported in the literature. In this study, we report a case of PRMS of bladder with a very poor prognosis. In fact, the patient died a month after surgery. The tumor was characterized by poorly differentiated, medium-sized sometimes rhabdoid cells, mixed with large-sized and pleomorphic elements with evident anisonucleosis, and with large areas of necrosis. We used an extensive immunohistochemical panel to exclude other tumors much more frequently reported at this site. The positivity for myogenic markers such as actin, desmin, myogenin and MyoD1 allowed the correct diagnosis. Furthermore, since preliminary studies highlighted a series of specific molecular alterations in PMRS cell lines, we analyzed a panel of specific mutations and gene rearrangements by RT-PCR and FISH methods. We showed a copy gains of CCND1 and MALT genes in our samples, suggesting an accurate molecular characterization of PRMS to establish a better management of patients and new therapeutic opportunities.
- Published
- 2020
47. Geo-location of Oncological Diseases in the Extra-urban Areas of Naples and Creation of Territorial Biobanks: An Important Tool to Study Potential Connections Between Environmental Factors and Cancer
- Author
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Gerardo Botti, Monica Cantile, Margherita Cerrone, and Ornella Sacco
- Subjects
Cancer Research ,medicine.medical_specialty ,Individual susceptibility ,Bladder cancer ,business.industry ,Cancer ,General Medicine ,medicine.disease ,Biobank ,Suburban Health ,Suburban Population ,Geolocation ,Oncology ,Italy ,Environmental health ,Neoplasms ,Epidemiology ,Medicine ,Humans ,Molecular Profile ,business ,Grading (tumors) ,Medical Informatics ,Biological Specimen Banks ,Environmental Monitoring - Abstract
Many areas of the Campania region of Italy are more frequently at risk of neoplastic diseases due to environmental factors. However, the results of epidemiological studies, although numerous and detailed, do not explain tumor pathogenesis mechanisms in relation to the contribution of exposure to environmental pollutants. The Oncological Biobank of the G. Pascale Foundation (BBI) centralizes the collection and storage of biomaterials, both healthy and pathological human tissues, from urban and extra-urban areas of Naples, associating them with clinicopathological characteristics (type of tumor, histological type, grading, immunohistochemical and molecular profile, etc.). Geo-location of tumor samples is made by an IT platform in which demographic and clinical data are systematically uploaded. For the extra-urban areas of Naples, our experience of tumor sample geolocation highlighted cancer types with high impact of environmental pollutants as being lung, gastric and bladder cancer. In this mini-review, we underline that the possibility of specifically selecting tumor samples in circumscribed territories may allow targeted studies to verify potential connections between environmental factors and cancer. Moreover, the collection of biological fluids (serum, saliva, urine) from healthy individuals from specific areas may be a useful tool for the research of specific genetic polymorphisms linked to individual susceptibility.
- Published
- 2018
48. Integrative Histologic and Bioinformatics Analysis of BIRC5/Survivin Expression in Oral Squamous Cell Carcinoma
- Author
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Giovanni Di Gioia, Franco Ionna, Giuseppe Troiano, Giuseppe Pannone, Monica Cantile, Francesco Longo, Maria Carmela Pedicillo, Nunzia Simona Losito, Maria Addolorata Mariggiò, Gabriella Aquino, Antonio Pennella, Lucio Lo Russo, Gerardo Botti, Agostino Guida, Lorenzo Lo Muzio, and Silvana Papagerakis
- Subjects
0301 basic medicine ,Male ,Survivin ,Gene mutation ,Biology ,Catalysis ,Article ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,Carcinoma ,medicine ,Humans ,Gene Regulatory Networks ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Aged ,Mouth neoplasm ,bioinformatic ,Cell growth ,Organic Chemistry ,BIRC5 ,Computational Biology ,General Medicine ,Methylation ,Middle Aged ,oral cancer ,TCGA ,medicine.disease ,Prognosis ,Computer Science Applications ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,immunohistochemistry ,Cancer research ,Carcinoma, Squamous Cell ,Immunohistochemistry ,Female ,Mouth Neoplasms - Abstract
Survivin is a well-known protein involved in the inhibition of apoptosis in many different cancer types. The aim of this study was to perform an integrated bioinformatic and histologic analysis in order to study the expression and prognostic role of Survivin and its related gene BIRC5 in oral cancer. Publicly available databases were accessed via Gene Expression Omnibus and Oncomine, in addition raw data from The Cancer Genome Atlas (TCGA) were also obtained in order to analyze the rate of gene mutation, expression and methylation in patients with oral squamous cells carcinoma (OSCC). Immunohistochemistry (IHC) was also performed in order to evaluate the nuclear and cytoplasmic expression of Survivin and their correlation with cell proliferation in samples from OSCC patients. Results of this study revealed that Survivin is rarely mutated in OSCC samples and upregulated when compared to non-cancerous tissue. A negative correlation between the methylation of the island cg25986496 and BIRC5 mRNA expression was detected from TCGA data. IHC staining revealed that cytoplasmic (and not nuclear) expression of Survivin is associated with poor overall survival in OSCC patients, while the nuclear expression correlates with higher proliferation rate. In addition, data from TCGA database revealed that BIRC5 gene expression is an independent prognostic factor for OSCC patients.
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- 2018
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49. LncRNA
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Francesca, Collina, Gabriella, Aquino, Marianna, Brogna, Sabrina, Cipolletta, Gaetano, Buonfanti, Michelino, De Laurentiis, Maurizio, Di Bonito, Monica, Cantile, and Gerardo, Botti
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HOTAIR ,Androgen Receptor ,TNBC ,Research Paper - Abstract
Triple-negative breast cancers (TNBCs) represent a heterogeneous disease characterized by several molecular subtypes with different prognoses and responses to therapy. For a correct clinical management of TNBC patients the knowledge of the gene regulation mechanisms related to tumor progression and drug response has become fundamental. LncRNAs regulate gene expression through various processes, including chromatin modification, transcription and post-transcription and they are emerging as important cancer biomarkers being involved in tumor pathogenesis, metastatic progression and drug resistance. In this study we aimed to analyze the expression of the lncRNA HOTAIR, mainly involved in breast cancer disease, in a large case series of TNBC patients. We used ISH methods by a RNA probe to better define its staining in tumor tissues and its relation with clinical-pathological parameters and outcomes of patients. Our results show that high HOTAIR expression in tumor tissues is strongly correlated with lymph nodes metastasis (LNM) (p=0.039), as reported also for other tumor types, and has a direct strong association with Androgen Receptor (AR) expression (p= 0.019). These data confirm the prognostic role of HOTAIR in TNBC, and, its involvement in the regulation of AR pathway, suggests the possibility to establish new therapeutic strategies for AR+TNBC patients.
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- 2018
50. Atypical amplification of chromosome region 22q12 in melanoma: A case report
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Mirella D'Andrea, Francesca Collina, Michele Caraglia, Laura Marra, Monica Cantile, Giuseppina Liguori, Gerardo Botti, Giovanni Francesco Nicoletti, Anna De Chiara, Renato Franco, Liguori, Giuseppina, Cantile, Monica, Collina, Francesca, Marra, Laura, de Chiara, Anna, Franco, Renato, Caraglia, Michele, Botti, Gerardo, D'Andrea, Mirella, and Nicoletti, Giovanni Francesco
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Cancer Research ,Pathology ,medicine.medical_specialty ,ATF1 ,medicine.diagnostic_test ,EWSR1 gene ,Fluorescence in situ hybridization ,Melanoma ,Differential diagnosi ,Chromosome ,Chromosomal translocation ,Articles ,Biology ,medicine.disease ,Oncology ,Chromosome regions ,medicine ,Clear-cell sarcoma ,Differential diagnosis ,Clear cell sarcoma - Abstract
Morphological, ultrastructural and immunohistochemical characteristics of clear cell sarcoma (CCS) of the soft tissue frequently overlap with those of malignant melanoma. Thus, the differential diagnosis between the two lesions represents an important diagnostic dilemma. However, a number of genetic factors can be used to differentiate the two tumors; in particular, the t(12;22)(q13;q12) chromosomal translocation is typical of CCS, resulting in fusion of the EWSR1 gene on chromosome 22q12 and the ATF1 gene on chromosome 12q13. The detection of this molecular alteration has proved useful in the differential diagnosis of the two lesions. The present study reports the case of a 71-year-old male patient with a suspicious lymph node mass. Immunohistochemical analysis of the lesion indicated a diagnosis of metastatic melanoma, however, cytogenetic analysis using fluorescence in situ hybridization was additionally performed to investigate the chromosomal rearrangements of the 22q12 region and completely exclude the possibility of CCS. The current case did not demonstrate the presence of the translocation, supporting the diagnosis of melanoma. However, a clear orange amplification signal was observed relative to an ~500-kb region adjacent to the EWSR1 gene in the centromeric direction of chromosome 22q12. To the best of our knowledge, this is the first description of a 22q12 chromosomal alteration in melanoma. Furthermore, despite the presence of numerous genes in this region, their amplification has not previously been associated with the pathogenesis of melanoma.
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- 2015
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