380 results on '"Ilardi, Gennaro"'
Search Results
102. Confocal laser endomicroscopy in breast surgery: a pilot study
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De Palma, Giovanni D, primary, Esposito, Dario, additional, Luglio, Gaetano, additional, Limite, Gennaro, additional, Accurso, Antonello, additional, Sollazzo, Viviana, additional, Maione, Francesco, additional, Cassese, Gianluca, additional, Siciliano, Saverio, additional, Gennarelli, Nicola, additional, Ilardi, Gennaro, additional, Paternoster, Mariano, additional, Giglio, Mariano C, additional, and Forestieri, Pietro, additional
- Published
- 2015
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103. FTIR microspectroscopic characterization of Spitz nevi
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Giorgini, Elisabetta, primary, Tosi, Giorgio, additional, Conti, Carla, additional, Staibano, Stefania, additional, Ilardi, Gennaro, additional, and Sabbatini, Simona, additional
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- 2015
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104. FBXW7 and USP7 regulate CCDC6 turnover during the cell cycle and affect cancer drugs susceptibility in NSCLC
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Morra, Francesco, primary, Luise, Chiara, additional, Merolla, Francesco, additional, Poser, Ina, additional, Visconti, Roberta, additional, Ilardi, Gennaro, additional, Paladino, Simona, additional, Inuzuka, Hiroyuki, additional, Guggino, Gianluca, additional, Monaco, Roberto, additional, Colecchia, David, additional, Monaco, Guglielmo, additional, Cerrato, Aniello, additional, Chiariello, Mario, additional, Denning, Krista, additional, Claudio, Pier Paolo, additional, Staibano, Stefania, additional, and Celetti, Angela, additional
- Published
- 2015
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105. High expression of a spliced variant of FKBP51 in peripheral blood mononuclear cells of melanoma patients may be related to PDL-1 on tumour and predictive of response to Ipilimumab
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Simeone, Ester, primary, Romano, Maria fiammetta, additional, Grimaldi, Antonio Maria, additional, Esposito, Assunta, additional, Curvietto, Marcello, additional, Paone, Miriam, additional, Rinaldi, Giovanni, additional, Di monta, Gianluca, additional, Di marzo, Massimiliano, additional, Hauber, Federica, additional, Festino, Lucia, additional, D'Angelillo, Anna, additional, Romano, Simona, additional, Staibano, Stefania, additional, Ilardi, Gennaro, additional, Bisogni, Rita, additional, Mozzillo, Nicola, additional, and Ascierto, Paolo Antonio, additional
- Published
- 2014
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106. Confocal microscopy and imaging profilometry: A new tool aimed to evaluate aesthetic procedures.
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Fabbrocini, Gabriella, Mazzella, Caterina, Montagnaro, Fabio, De Padova, Maria Pia, Lorenzi, Sandra, Tedeschi, Aurora, Forgione, Patrizia, Capasso, Claudia, Sivero, Luigi, Velotti, Carla, Russo, Daniela, Vitiello, Rosa, and Ilardi, Gennaro
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CONFOCAL microscopy ,THERAPEUTIC use of hyaluronic acid ,PROFILOMETER ,PLASTIC surgery ,DERMATOLOGY - Abstract
According to the American Academy of Aesthetic Plastic Surgeons, more than 11 million cosmetic surgical and nonsurgical procedures were performed by board-certified plastic surgeons, dermatologists and otolaryngologists in the United States, totaling more than 12 billion dollars. We performed a retrospective observational multi-centric study on patients treated with a non-animal origin cross-linked hyaluronic acid with different molecular weights for nasolabial folds, evaluating through a new imaging system, profilometric techniques with the confocal microscopy, the durability, the efficacy and the safety of this product. From 25 patients, 150 silicone casts were obtained: 75 casts of the right nasolabial fold and 75 casts of the left nasolabial fold. Roughness arithmetical average of the right fold at T2 decreased by 50%versusT0 and by 40% compared to T1; at T2, it decreased by the 45%versusT0 and by 35% compared to T1. No side effects were reported. Results proved that the analysis of the skin microreliefs through confocal microscopy is a new imaging system that allows to evaluate with precision and safety the results of aesthetic treatments such as fillers objectively. [ABSTRACT FROM AUTHOR]
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- 2017
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107. New therapeutic perspectives in CCDC6 deficient lung cancer cells
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Morra, Francesco, primary, Luise, Chiara, additional, Visconti, Roberta, additional, Staibano, Stefania, additional, Merolla, Francesco, additional, Ilardi, Gennaro, additional, Guggino, Gianluca, additional, Paladino, Simona, additional, Sarnataro, Daniela, additional, Franco, Renato, additional, Monaco, Roberto, additional, Zitomarino, Federica, additional, Pacelli, Roberto, additional, Monaco, Guglielmo, additional, Rocco, Gaetano, additional, Cerrato, Aniello, additional, Linardopoulos, Spiros, additional, Muller, Mark T., additional, and Celetti, Angela, additional
- Published
- 2014
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108. Abstract 2912: The isoform 2 of FKBP51 is induced by PDL-1/PD1 interaction and marks peripheral blood mononuclear cells of melanoma patients
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Romano, Maria Fiammetta, primary, D'Angelillo, Anna, additional, Romano, Simona, additional, Simeone, Ester, additional, Ascierto, Paolo, additional, Staibano, Stefania, additional, D'Arrigo, Paolo, additional, Scalvenzi, Massimiliano, additional, Ilardi, Gennaro, additional, and Bisogni, Rita, additional
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- 2014
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109. Chromatin Assembly Factor-1/p60 overexpression: a potential index of psoriasis severity
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Mascolo, Massimo, additional, Ayala, Fabio, additional, Ilardi, Gennaro, additional, Balato, Anna, additional, and Lembo, Serena, additional
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- 2014
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110. Genetic, Epigenetic and Molecular Changes in Melanoma: A New Paradigm for Biological Classification
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Staibano, Stefania, Mascolo, Massimo, Siano, Maria, Ilardi, Gennaro, De Rosa, Gaetano, Staibano, Stefania, Mascolo, Massimo, Siano, Maria, Ilardi, Gennaro, and De Rosa, Gaetano
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- 2011
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111. Clinical, dermoscopic and histological features of a Merkel cell carcinoma of the hand
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Scalvenzi, Massimiliano, primary, Palmisano, Franco, additional, Ilardi, Gennaro, additional, Varricchio, Silvia, additional, and Costa, Claudia, additional
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- 2013
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112. Glottic-SubGlottic adenoid cystic carcinoma. A case report and review of the literature
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Testa, Domenico, primary, Guerra, Germano, additional, Conzo, Giovanni, additional, Nunziata, Michele, additional, D'Errico, Gioacchino, additional, Siano, Maria, additional, Ilardi, Gennaro, additional, Vitale, Mario, additional, Riccitiello, Francesco, additional, and Motta, Gaetano, additional
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- 2013
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113. Tissue Microarray-Based Evaluation of Chromatin Assembly Factor-1 (CAF-1)/p60 as Tumour Prognostic Marker
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Mascolo, Massimo, primary, Ilardi, Gennaro, additional, Merolla, Francesco, additional, Russo, Daniela, additional, Vecchione, Maria Luisa, additional, de Rosa, Gaetano, additional, and Staibano, Stefania, additional
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- 2012
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114. Abstract 5626: FKBP51 is a crucial modulator of melanoma plasticity and promising molecular target for preventing melanoma metastasis
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Romano, Maria Fiammetta, primary, Romano, Simona, additional, Staibano, Stefania, additional, Greco, Adelaide, additional, Brunetti, Arturo, additional, Ilardi, Gennaro, additional, Mascolo, Massimo, additional, Bisogni, Rita, additional, and Alfano, Bruno, additional
- Published
- 2012
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115. Animal type melanoma: An unusual case with aggressive histological features?
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Russo, Daniela, primary, Vita, Giulia, additional, Ilardi, Gennaro, additional, Siano, Maria, additional, and Mascolo, Massimo, additional
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- 2012
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116. Epigenetic Disregulation in Oral Cancer
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Mascolo, Massimo, primary, Siano, Maria, additional, Ilardi, Gennaro, additional, Russo, Daniela, additional, Merolla, Francesco, additional, Rosa, Gaetano De, additional, and Staibano, Stefania, additional
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- 2012
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117. Probe-Based Confocal Laser Endomicroscopy Evaluation of Colon Preneoplastic Lesions, with Particular Attention to the Aberrant Crypt Foci, and Comparative Assessment with Histological Features Obtained by Conventional Endoscopy
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Mascolo, Massimo, primary, Staibano, Stefania, additional, Ilardi, Gennaro, additional, Siano, Maria, additional, Vecchione, Maria Luisa, additional, Esposito, Dario, additional, De Rosa, Gaetano, additional, and De Palma, Giovanni Domenico, additional
- Published
- 2012
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118. Abstract 4999: FK506 binding protein 51 (FKBP51) sustains stemness and the metastatic potential of malignant melanoma
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Romano, Simona, primary, Sorrentino, Antonio, additional, Pace, AnnaLaura Di, additional, Staibano, Stefania, additional, Mascolo, Massimo, additional, Bisogni, Rita, additional, Ilardi, Gennaro, additional, and Romano, Maria Fiammetta, additional
- Published
- 2011
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119. Overexpression of Chromatin Assembly Factor-1/p60 helps to predict the prognosis of melanoma patients
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Mascolo, Massimo, primary, Vecchione, Maria Luisa, additional, Ilardi, Gennaro, additional, Scalvenzi, Massimiliano, additional, Molea, Guido, additional, Di Benedetto, Maria, additional, Nugnes, Loredana, additional, Siano, Maria, additional, De Rosa, Gaetano, additional, and Staibano, Stefania, additional
- Published
- 2010
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120. Non-Hodgkin’s lymphoma in systemic sclerosis: case and literature review
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Vettori, Serena, primary, Staibano, Stefania, additional, Mascolo, Massimo, additional, Ilardi, Gennaro, additional, and Valentini, Gabriele, additional
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- 2009
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121. ˵Synthetic Lethality″: Molecular Co-targeting to Restore the DNA Repair Mechanisms in Prostate Cancer Cells.
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Ilardi, Gennaro and Staibano, Stefania
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- 2013
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122. Perioperative characterization of anastomotic doughnuts with high-resolution probe-based confocal laser endomicroscopy in colorectal cancer surgery: a feasibility study.
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Palma, Giovanni, Luglio, Gaetano, Staibano, Stefania, Bucci, Luigi, Esposito, Dario, Maione, Francesco, Mascolo, Massimo, Ilardi, Gennaro, and Forestieri, Pietro
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COLON cancer treatment ,MEDICAL microscopy ,ENDOSCOPY ,MEDICAL lasers ,HISTOPATHOLOGY - Abstract
Background: Confocal laser enables in vivo real-time histopathology of the mucosa layer of gastrointestinal tract. The aim of this study was to assess the feasibility and the role of probe-based confocal laser endomicroscopy in extemporary examination of staple rings of patients with colorectal cancer. Methods: This was a prospective, single-center pilot study. Patients who underwent end-to-end stapled surgical resection for colorectal cancer were included. Confocal imaging was analyzed with great attention to image quality evaluation of cellular morphology and cellular structures of the serosal, muscular, and mucosal layers of the doughnuts than comparing results with definitive histopathology. Results: Twenty-six doughnuts were analyzed. Real-time video sequences were obtained in all patients, with a total of 204 mosaic images. For each doughnut, most of the images were adequate for evaluation of cellular morphology and cellular structure of the serosal, muscular, and mucosal layers. Conclusions: Perioperative assessment of doughnut tissues in patients with colorectal cancer by confocal laser endomicroscopy is feasible and safe. Prospective studies are warranted for further evaluation of the clinical impact of this technology during surgery. [ABSTRACT FROM AUTHOR]
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- 2014
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123. Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors.
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Staibano, Stefania, Ilardi, Gennaro, Leone, Vincenza, Luise, Chiara, Merolla, Francesco, Esposito, Francesco, Morra, Francesco, Siano, Maria, Franco, Renato, Fusco, Alfredo, Chieffi, Paolo, and Celetti, Angela
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DNA damage , *NEOPLASTIC cell transformation , *PHOSPHOPROTEINS , *IMMUNOHISTOCHEMISTRY , *BIOCHEMICAL genetics , *REACTIVE oxygen species , *ANIMAL experimentation , *APOPTOSIS , *CELL lines , *COMPARATIVE studies , *CYTOSKELETAL proteins , *GENE expression , *GENES , *GERM cell tumors , *HEMOPROTEINS , *RESEARCH methodology , *MEDICAL cooperation , *MICE , *PEROXIDES , *RESEARCH , *TESTIS , *TESTIS tumors , *EVALUATION research , *GERMINOMA - Abstract
Background: DNA damage response has been clearly described as an anti-cancer barrier in early human tumorigenesis. Moreover, interestingly, testicular germ cell tumors (TGCTs) have been reported to lack the DNA Damage Response (DDR) pathway activation. CCDC6 is a pro-apoptotic phosphoprotein substrate of the kinase ataxia telangectasia mutated (ATM) able to sustain DNA damage checkpoint in response to genotoxic stress and is commonly rearranged in malignancies upon fusion with different partners. In our study we sought to determine whether CCDC6 could have a role in the patho-genesis of testicular germ cell tumors.Methods: To achieve this aim, analysis for CCDC6 expression has been evaluated on serial sections of the mouse testis by immunohistochemistry and on separate populations of murine testicular cells by western blot. Next, the resistance to DNA damage-induced apoptosis and the production of reactive oxygen species has been investigated in GC1 cells, derived from immortalized type B murine germ cells, following CCDC6 silencing. Finally, the CCDC6 expression in normal human testicular cells, in Intratubular Germ Cell Neoplasia Unclassified (IGCNU), in a large series of male germ cell tumours and in the unique human seminoma TCam2 cell line has been evaluated by immunohistochemistry and by Western Blot analyses.Results: The analysis of the CCDC6 expression revealed its presence in Sertoli cells and in spermatogonial cells. CCDC6 loss was the most consistent feature among the primary tumours and TCam2 cells. Interestingly, following treatment with low doses of H₂O₂, the silencing of CCDC6 in GC1 cells caused a decrease in the oxidized form of cytochrome c and low detection of Bad, PARP-1 and Caspase 3 proteins. Moreover, in the silenced cells, upon oxidative damage, the cell viability was protected, the γH2AX activation was impaired and the Reactive Oxygen Species (ROS) release was decreased.Conclusions: Therefore, our results suggest that the loss of CCDC6 could aid the spermatogonial cells to be part of a pro-survival pathway that helps to evade the toxic effects of endogenous oxidants and contributes to testicular neoplastic growth. [ABSTRACT FROM AUTHOR]- Published
- 2013
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124. Overexpression of Chromatin AssemblyFactor-1/p60 helps to predict the prognosisof melanoma patients.
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Mascolo, Massimo, Vecchione, Maria Luisa, Ilardi, Gennaro, Scalvenzi, Massimiliano, Molea, Guido, Di Benedetto, Maria, Nugnes, Loredana, Siano, Maria, De Rosa, Gaetano, and Staibano, Stefania
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MELANOMA ,NEUROENDOCRINE tumors ,DNA synthesis ,PROGNOSIS ,CHROMATIN - Abstract
Background: Cutaneous melanoma (CM) is the most lethal form of skin malignancy, which registers a constant increase in incidence worldwide. The identification of molecular alteration(s) involved in its biological aggressiveness represents a major challenge for researchers, considering that existing therapies are ineffective to treat metastasizing cases. The epigenetic control of chromatin dynamics during DNA synthesis, replication, and repair is fundamental for the orderly progression of cell proliferation. The Chromatin Assembly Factor 1 (CAF-1) complex acts as a major regulator of this process; its intermediate (p60) subunit has been recently proposed as a novel proliferation and prognostic marker for several tumors. We aimed to establish if the evaluation of the expression of CAF-1/p60 in primary CM may help define the prevision of outcome of patients. Methods: Immunohistochemistry with anti-CAF-1/p60 was performed on paraffin-embedded tissue sections of 130 cases of primary CM retrieved from the archive files of the Department of Biomorphological and Functional Sciences, Section of Pathology, University "Federico II" of Naples, Italy. Results were compared with histopathological and follow-up data of patients. Results: CAF-1/p60 was expressed in all CM. A significant statistical association between the overexpression of the protein and the occurrence of skin, node and/or distant metastases (P < 0.05) emerged, independently from histopathological prognostic factors. Conclusions: CAF-1/p60 looks promising as a new prognostic marker for CM and sheds new light on the molecular events associated with photocancerogenesis and melanoma biology. The screening for CAF-1/p60 might contribute to the molecular sub-classification of CM, with improved translational outcomes. [ABSTRACT FROM AUTHOR]
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- 2010
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125. Epigenetics of oral and oropharyngeal cancers (Review).
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Russo, Daniela, Merolla, Francesco, Varricchio, Silvia, Salzano, Giovanni, Zarrilli, Giovanni, Mascolo, Massimo, Strazzullo, Viviana, Crescenzo, Rosa Maria Di, Celetti, Angela, and Ilardi, Gennaro
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OROPHARYNGEAL cancer ,ORAL cancer ,EPIGENETICS - Abstract
Biomed Rep 9:275-283, 2018; DOI: 10.3892/br.2018.1136 Following the publication of the above review, the authors have noted that acronym "SS" should not have been featured in the Authors' contributions section of the Declarations; this was an error made during the transcription of the article, and there is no such author with these initials on the Review. The authors apologize to the readership for any confusion this may have caused. [Extracted from the article]
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- 2020
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126. The disruption of the CCDC6 – PP4 axis induces a BRCAness like phenotype and sensitivity to PARP inhibitors in high-grade serous ovarian carcinoma.
- Author
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Morra, Francesco, Merolla, Francesco, Damia, Giovanna, Ricci, Francesca, Varricchio, Silvia, Ilardi, Gennaro, Arenare, Laura, Califano, Daniela, Napolitano, Virginia, Fruscio, Robert, Melillo, Rosa Marina, Palazzo, Luca, and Celetti, Angela
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POLY(ADP-ribose) polymerase , *OVARIAN cancer , *PHENOTYPES , *TUMOR budding , *CARCINOMA , *PROTEIN expression , *DNA mismatch repair - Abstract
Background: Treatment with PARP inhibitors (PARPi) is primarily effective against high-grade serous ovarian cancers (HGSOC) with BRCA1/2 mutations or other deficiencies in homologous recombination (HR) repair mechanisms. However, resistance to PARPi frequently develops, mostly as a result of BRCA1/2 reversion mutations. The tumour suppressor CCDC6 is involved in HR repair by regulating the PP4c phosphatase activity on γH2AX. In this work, we reported that in ovarian cancer cells, a physical or functional loss of CCDC6 results synthetic lethal with the PARP-inhibitors drugs, by affecting the HR repair. We also unravelled a role for CCDC6 as predictive marker of PARPi sensitivity in ovarian cancer, and the impact of CCDC6 downregulation in overcoming PARPi resistance in these tumours. Methods: A panel of HGSOC cell lines (either BRCA-wild type or mutant) were treated with PARPi after CCDC6 was attenuated by silencing or by inhibiting USP7, a CCDC6-deubiquitinating enzyme, and the effects on cell survival were assessed. At the cellular and molecular levels, the processes underlying the CCDC6-dependent modification of drugs' sensitivity were examined. Patient-derived xenografts (PDXs) were immunostained for CCDC6, and the expression of the protein was analysed statistically after digital or visual means. Results: HGSOC cells acquired PARPi sensitivity after CCDC6 depletion. Notably, CCDC6 downregulation restored the PARPi sensitivity in newly generated or spontaneously resistant cells containing either wild type- or mutant-BRCA2. When in an un-phosphorylated state, the CCDC6 residue threonine 427 is crucial for effective CCDC6-PP4 complex formation and PP4 sequestration, which maintains high γH2AX levels and effective HR. Remarkably, the PP4-dependent control of HR repair is influenced by the CCDC6 constitutively phosphorylated mutant T427D or by the CCDC6 loss, favouring PARPi sensitivity. As a result, the PP4 regulatory component PP4R3α showed to be essential for both the activity of the PP4 complex and the CCDC6 dependent PARPi sensitivity. It's interesting to note that immunohistochemistry revealed an intense CCDC6 protein staining in olaparib-resistant HGSOC cells and PDXs. Conclusions: Our findings suggest that the physical loss or the functional impairment of CCDC6 enhances the PP4c complex activity, which causes BRCAness and PARPi sensitivity in HGSOC cells. Moreover, CCDC6 downregulation might overcome PARPi resistance in HGSOCs, thus supporting the potential of targeting CCDC6 by USP7 inhibitors to tackle PARPi resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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127. Immunohistochemical analysis of FKBP51 in human cancers
- Author
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Staibano, Stefania, Mascolo, Massimo, Ilardi, Gennaro, Siano, Maria, and De Rosa, Gaetano
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IMMUNOHISTOCHEMISTRY , *CANCER cell growth , *TUMOR proteins , *GENETIC regulation , *CANCER chemotherapy , *CANCER radiotherapy - Abstract
FKBP51 is a FK506-binding immunophilin involved in the regulation of several fundamental biological processes. A growing body of data indicates that this protein has also a role in the abnormal cell growth of cancers, and could be considered as a promising new marker of tumor progression and response to radio/chemotherapy. However, the data concerning the expression of FKBP51 in cancer are not conclusive, and partially contradictory. They delineate a very complex scenario, in which many molecular FKBP51-related pathways are variously intersected among different tumors. This review reports the available data concerning FKBP51 expression in normal tissues and human malignancies, outlining the role of the immunohistochemical analysis as a fundamental tool for better understanding the role of this immunophilin in cancer biology. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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128. Coexistent Squamous Cell Carcinoma and Granular Cell Tumor of Head and Neck Region: Report of Two Very Rare Cases and Review of the Literature.
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Caroppo, Danila, Salerno, Grazia, Merolla, Francesco, Mesolella, Massimo, Ilardi, Gennaro, Pagliuca, Francesca, De Dominicis, Gianfranco, Califano, Luigi, Ciancia, Giuseppe, Russo, Daniela, and Mascolo, Massimo
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CANCER treatment , *SQUAMOUS cell carcinoma , *HEAD & neck cancer treatment , *SURGICAL excision , *NEUROECTODERMAL tumors , *EPITHELIUM , *LARYNX - Abstract
Granular cell tumor (GCT), a relatively rare neuroectodermal tumor occurring most often in the head and neck region, is not uncommonly associated with pseudoepitheliomatous hyperplasia of the overlying surface epithelium, which may be at times nonreadily distinguishable from well-differentiated squamous cell carcinoma (SCC). To the best of our knowledge, only a handful of coexisting SCC and GCT, mostly described in the esophagus, have been reported in (the current) literature so far. We herein report 2 new cases of coexisting GCT and SCC of the head and neck region, located, respectively, in larynx and tongue; comment on their clinical, imaging, and pathologic features; and discuss their management. In the present work, we also review the literature concerning this association to contribute to the head and neck pathologists' and surgeons' awareness regarding the possibility of this association for an adequate surgical excision and a better management of these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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129. Immunohistochemical expression of PRAME is a marker of poor prognosis in uveal melanoma: A clinico-pathologic and immunohistochemical study on a series of 85 cases.
- Author
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Broggi, Giuseppe, Failla, Maria, Russo, Andrea, Longo, Antonio, Palicelli, Andrea, Zanelli, Magda, Lombardo, Claudia, Loreto, Carla, Merolla, Francesco, Di Crescenzo, Rosa Maria, Ilardi, Gennaro, Varricchio, Silvia, Staibano, Stefania, and Caltabiano, Rosario
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TESTICULAR cancer , *BREAST , *RENAL cancer , *MELANOMA , *PROGNOSIS , *OVARIAN cancer - Abstract
PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen, first isolated in tumor-reactive T-cell clones from a metastatic melanoma patient. It has been widely studied in skin pathology as an immunohistochemical marker capable of distinguishing between benign nevi and malignant melanomas. PRAME has been found to be also expressed in non-melanocytic tumors, including lung, breast, kidney and ovarian cancer. However, less is known about the diagnostic and/or prognostic role of this protein in uveal melanoma (UM); few studies have reported that PRAME expression seems to give to UM patients an additional metastatic risk beyond the other already-known prognostic parameters. In the present retrospective study, we aimed to correlate PRAME immunoreactivity to other clinico-pathologic features and follow-up data on a large series of 85 cases (45 non-metastasizing and 40 metastasizing tumors) of primary UM. A statistically significant correlation was found between PRAME expression and higher metastatic risk and lower metastasis-free survival. We propose to include PRAME in the immunohistochemical panel of UM as an easily usable marker capable of predicting higher metastatic risk and stratifying patients' outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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130. Our experience in the treatment of Malignant Fibrous Hystiocytoma of the larynx: clinical diagnosis, therapeutic approach and review of literature.
- Author
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Testa, Domenico, Motta, Sergio, Marcuccio, Giuseppina, Paccone, Marianna, Rocca, Aldo, Ilardi, Gennaro, Tafuri, Domenico, Mesolella, Massimo, and Motta, Gaetano
- Abstract
Hereditary spherocytosis (HS) and Chronic myelocytic leukemia (CML) are both life threatening hemotologic diseases. They are rarely seen to occur simultaneously in one individual patient. Here we demonstrate a case of HS associated with CML in this study. The patient is a young female, diagnosed with HS in 2005, and was given partial embolization of the splenic artery. She got significant remission after the procedure. In 2008, she was found abnormal in blood routine test, after bone marrow routine, chromosome and fusion gene tests, she was diagnosed with CML (chronic phase). She did not receive regular treatment until 3 months prior, and is currently being treated with Dasatimib. She achieved hematological remission, but had no significant improvement in chromosome and fusion gene figures. Due to her severe condition of hemolysis, a splenectomy or an allogeneic hematopoietic stem cell transplantation is considered. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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131. Tissue Expression of Carbonic Anhydrase IX Correlates to More Aggressive Phenotype of Basal Cell Carcinoma
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Silvia Varricchio, Sara Pignatiello, Gennaro Ilardi, Francesco Martino, Massimo Mascolo, Daniela Russo, Massimiliano Scalvenzi, Francesco Merolla, Rosa Maria Di Crescenzo, Claudia Costa, Stefania Staibano, Russo, Daniela, Varricchio, Silvia, Ilardi, Gennaro, Martino, Francesco, Di Crescenzo, Rosa Maria, Pignatiello, Sara, Scalvenzi, Massimiliano, Costa, Claudia, Mascolo, Massimo, Merolla, Francesco, and Staibano, Stefania
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Cancer Research ,Stromal cell ,Population ,risk stratification ,lcsh:RC254-282 ,carbonic anhydrase IX ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,basal cell carcinoma ,medicine ,Basal cell carcinoma ,education ,Hedgehog ,Original Research ,education.field_of_study ,skin cancer ,business.industry ,Cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Phenotype ,IHC ,prognosis ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Immunohistochemistry ,Skin cancer ,business ,prognosi - Abstract
Basal cell carcinoma (BCC) is the most common cancer in the white-skinned population accounting for about 15% of all neoplasms. Its incidence is increasing worldwide, at a rate of about 10% per year. BCC, although infrequently metastasizing, very often causes extensive tissue losses, due to the high propensity toward stromal infiltration, particularly in its dedifferentiated forms, with disfiguring and debilitating results. To date, there still is limited availability of therapeutic treatments alternative to surgery. We evaluated the immunohistochemical expression of the carbonic anhydrase IX (CAIX), one of the main markers of tissue hypoxia, in a set of 85 archived FFPE BCC tissues, including the main subtypes, with different clinical outcomes, to demonstrate a possible relationship between hypoxic phenotype and biological aggressiveness of these neoplasms. Our results showed that the expression level of the CAIX protein contributes to the stratification of BCC in the different risk classes for recurrence. We hypothesize for CAIX a potential therapeutic role as a target therapy in the treatment of more aggressive BCCs, thus providing an alternative to surgical and pharmacological therapy with Hedgehog inhibitors, a promising example of target therapy in BCCs.
- Published
- 2021
132. BRIT‐1 expression and its relationship with PARP‐1 and CAF‐1/p60 in cutaneous melanoma
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Antonio Travaglino, Massimiliano Scalvenzi, Massimo Mascolo, Antonio Raffone, Silvia Varricchio, Claudia Costa, Stefania Staibano, Gabriella Fabbrocini, Daniela Russo, Gennaro Ilardi, Francesco Merolla, Russo, Daniela, Travaglino, Antonio, Varricchio, Silvia, Merolla, Francesco, Ilardi, Gennaro, Raffone, Antonio, Scalvenzi, Massimiliano, Costa, Claudia, Fabbrocini, Gabriella, Staibano, Stefania, and Mascolo, Massimo
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Skin Neoplasms ,Poly ADP ribose polymerase ,Poly (ADP-Ribose) Polymerase-1 ,Cell Cycle Proteins ,Dermatology ,Poly(ADP-ribose) Polymerase Inhibitors ,Poly (ADP-Ribose) Polymerase Inhibitor ,Text mining ,Chromatin Assembly Factor-1 ,Humans ,Prognosis ,Melanoma ,melanoma ,Medicine ,prognostic factor ,CAF-1 ,business.industry ,medicine.disease ,Cytoskeletal Proteins ,Infectious Diseases ,Cutaneous melanoma ,MVD ,Cancer research ,metastasi ,business ,Transcription Factors - Abstract
Uveal melanoma (UM) is the most frequent primary ocular malignancy of adults; it exhibits an almost invariably poor prognosis with onset of liver metastases within 10–15 years after the diagnosis. Serine and arginine-rich splicing factor 1 (SRSF1) is an RNA-binding protein with proto-oncogene functions, including stimulation of angiogenesis, cell migration and cell growth; regarding the complex regulation of tumor angiogenesis, it has been suggested that SRSF1 regulates the alternative splicing of vascular endothelial growth factor-α, promoting the formation of its pro-angiogenic isoform. The immunohistochemical expression of SRSF1 on a series of 85 primary UMs, including 39 metastasizing and 46 non-metastasizing cases, was investigated; to clarify the potential pathogenetic role of SRSF1 in this tumor and its effect on angiogenesis, we correlated our immunohistochemical findings with the clinico-pathological features, the prognostic data and blood vascular microvessel density (MVD) findings of the cases from our series. Cases with higher immunohistochemical expression of SRSF1 also had higher MVD, higher metastatic potential and shorter metastasis-free survival; conversely, cases with lower SRSF1 immunoexpression showed lower MVD, lower metastatic risk and longer metastasis-free survival times. Our results suggested that SRSF1 has a negative prognostic role and a pro-angiogenic function in UM.
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- 2021
133. A 45-Year Old Man With An Intraventricular Mass
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Sara Pignatiello, Roberta Sgariglia, Marialaura Del Basso De Caro, Domenico Solari, Elia Guadagno, Gennaro Ilardi, Paolo Cappabianca, Teresa Somma, Guadagno, Elia, Solari, Domenico, Pignatiello, Sara, Somma, Teresa, Sgariglia, Roberta, Ilardi, Gennaro, Cappabianca, Paolo, and De Caro, Marialaura Del Basso
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Male ,Pediatrics ,medicine.medical_specialty ,business.industry ,General Neuroscience ,MEDLINE ,Middle Aged ,Pathology and Forensic Medicine ,Craniopharyngioma ,Text mining ,Fatal Outcome ,Medicine ,Humans ,Pituitary Neoplasms ,Neurology (clinical) ,business ,Cases of the Month - Published
- 2020
134. TBX1 and Basal Cell Carcinoma: Expression and Interactions with Gli2 and Dvl2 Signaling
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Marchesa Bilio, Cinzia Caprio, Gennaro Ilardi, Daniela Alfano, Stefania Staibano, Antonio Baldini, Federica Feo, Rosa Ferrentino, Daniela Russo, Silvia Varricchio, Caterina Missero, Caprio, Cinzia, Varricchio, Silvia, Bilio, Marchesa, Feo, Federica, Ferrentino, Rosa, Russo, Daniela, Staibano, Stefania, Alfano, Daniela, Missero, Caterina, Ilardi, Gennaro, and Baldini, Antonio
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animal structures ,T-box transcription factor TBX1 ,basal cell carcinoma ,genetic marker ,Biology ,Fibroblast growth factor ,Catalysis ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,GLI2 ,Physical and Theoretical Chemistry ,Progenitor cell ,Molecular Biology ,Transcription factor ,lcsh:QH301-705.5 ,Spectroscopy ,030304 developmental biology ,0303 health sciences ,integumentary system ,Cell growth ,Organic Chemistry ,Wnt signaling pathway ,Signal transducing adaptor protein ,t-box transcription factor tbx1 ,General Medicine ,Computer Science Applications ,Cell biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,embryonic structures ,Smoothened - Abstract
Early events of basal cell carcinoma (BCC) tumorigenesis are triggered by inappropriate activation of SHH signaling, via the loss of Patched1 (Ptch1) or by activating mutations of Smoothened (Smo). TBX1 is a key regulator of pharyngeal development, mainly through expression in multipotent progenitor cells of the cardiopharyngeal lineage. This transcription factor is connected to several major signaling systems, such as FGF, WNT, and SHH, and it has been linked to cell proliferation and to the regulation of cell shape and cell dynamics. Here, we show that TBX1 was expressed in all of the 51 BCC samples that we have tested, while in healthy human skin it was only expressed in the hair follicle. Signal intensity and distribution was heterogeneous among tumor samples. Experiments performed on a cellular model of mouse BCC showed that Tbx1 is downstream to GLI2, a factor in the SHH signaling, and that, in turn, it regulates the expression of Dvl2, which encodes an adaptor protein that is necessary for the transduction of WNT signaling. Consistently, Tbx1 depletion in the cellular model significantly reduced cell migration. These results suggest that TBX1 is part of a core transcription network that promotes BCC tumorigenesis.
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- 2020
135. Macular peeling-induced retinal damage: clinical and histopathological evaluation after using different dyes
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Cesare Mariotti, Mario R. Romano, Mariantonia Ferrara, Giovanni Cennamo, Gilda Cennamo, Stefania Staibano, Gennaro Ilardi, Barbara Parolini, Romano, Mario R., Ilardi, Gennaro, Ferrara, Mariantonia, Cennamo, Gilda, Parolini, Barbara, Mariotti, Cesare, Staibano, Stefania, and Cennamo, Giovanni
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Male ,Retinal Ganglion Cells ,Time Factors ,Visual acuity ,genetic structures ,Basement Membrane ,chemistry.chemical_compound ,0302 clinical medicine ,Vitrectomy ,Prospective Studies ,Fluorescein Angiography ,Coloring Agents ,Intraoperative Complications ,Aged, 80 and over ,Glial fibrillary acidic protein ,biology ,Inner limiting membrane ,Middle Aged ,Immunohistochemistry ,Sensory Systems ,medicine.anatomical_structure ,Female ,Trypan blue ,Epiretinal membrane ,medicine.symptom ,Pars plana ,medicine.medical_specialty ,Neurofilament ,Dye ,Fundus Oculi ,Ependymoglial Cells ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Ophthalmology ,medicine ,Humans ,Neurofilament protein ,Aged ,business.industry ,Müller cell ,Pars plana vitrectomy ,Macular peeling ,medicine.disease ,eye diseases ,chemistry ,030221 ophthalmology & optometry ,biology.protein ,sense organs ,Sensory System ,business ,Indocyanine green ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Purpose: To describe functional and histopathological findings after macular peeling using different dyes. Methods: Prospective, randomized, comparative, interventional, and immunohistochemical study. Forty-five eyes from 45 patients with idiopathic epiretinal membrane (ERM) underwent pars plana chromovitrectomy with ERM and inner limiting membrane (ILM) using trypan blue 0.15% + brilliant blue 0.05% + lutein 2% in group 1 (15 eyes), trypan blue 0.15% + brilliant blue 0.025% + polyethylene glycol 3350 4% in group 2 (15 eyes), and indocyanine green 0.05% in group 3 (15 eyes). We evaluated visual acuity (VA) and macular sensitivity (MS) preoperatively, 1, 3, and 6 months after surgery. The expression of glial fibrillary acidic protein (GFAP) and neurofilament protein (NF) was assessed immunohistochemically on the ILMs peeled as markers of glial and neuronal cells. Results: In group 1, both mean VA and MS were significantly better at 1 and 3 months after surgery (P < 0.05), whereas no significant difference was found after 6 months. GFAP and NF expression was significantly lower in group 1 (P < 0.05). Conclusions: The ERM/ILM peeling is thought to rip off the intraretinal tissue, based on the amounts of GFAP and NF in the specimens. The use of lutein dyes reduces iatrogenic stress to the retinal tissue and allows a faster functional recovery in the first 3 months after surgery, suggesting a less iatrogenic adhesion to the retinal tissue
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- 2018
136. CCDC6 and USP7 expression levels suggest novel treatment options in high-grade urothelial bladder cancer
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Francesco Morra, Aniello Cerrato, Roberta Visconti, Angela Celetti, Luigi Insabato, Stefania Staibano, Daniela Criscuolo, Francesco Merolla, Riccardo Giannella, Gennaro Ilardi, Morra, Francesco, Merolla, Francesco, Criscuolo, Daniela, Insabato, Luigi, Giannella, Riccardo, Ilardi, Gennaro, Cerrato, Aniello, Visconti, Roberta, Staibano, Stefania, and Celetti, Angela
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0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,Ubiquitin-Specific Peptidase 7 ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,Genes, Tumor Suppressor ,Tumor ,Precision medicine ,Epigenetic ,Nitro Compounds ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Oncology ,P5091 ,030220 oncology & carcinogenesis ,PARP inhibitor ,Immunotherapy ,Tumor Suppressor ,PARP-inhibitor ,DNA damage ,DNA repair ,Antineoplastic Agents ,Thiophenes ,Poly(ADP-ribose) Polymerase Inhibitors ,Cycloheximide ,lcsh:RC254-282 ,Cell Line ,03 medical and health sciences ,Biomarkers ,RRx-001 ,Viral mimicry ,Azetidines ,Biomarkers, Tumor ,Cell Line, Tumor ,Cytoskeletal Proteins ,DNA Damage ,Humans ,Urinary Bladder Neoplasms ,Viability assay ,Bladder cancer ,business.industry ,Research ,Biomarker ,medicine.disease ,030104 developmental biology ,Genes ,chemistry ,Apoptosis ,Cancer research ,business - Abstract
Background The muscle invasive form of urothelial bladder cancer (UBC) is a deadly disease. Currently, the therapeutic approach of UBC is mostly based on surgery and standard chemotherapy. Biomarkers to establish appropriate drugs usage are missing. Deficiency of the tumor suppressor CCDC6 determines PARP-inhibitor sensitivity. The CCDC6 levels are modulated by the deubiquitinase USP7. In this work we scored CCDC6 and USP7 expression levels in primary UBC and we evaluated the expression levels of CCDC6 in correlation with the effects of the PARP-inhibitors combined with the USP7 inhibitor, P5091, in vitro. Since PARP-inhibitors could be enhanced by conventional chemotherapy or DNA damage inducers, we tested the new agent RRx-001, able to induce DNA damage, to prove the benefit of combined treatments in bladder cancer cells. Methods The J82, T24, 5637 and KU-19-19 bladder cancer cells were exposed to USP7 inhibitor P5091 in presence of cycloheximide to analyse the CCDC6 stability. Upon the CCDC6 degradation induced by P5091, the cells sensitivity to PARP-inhibitor was evaluated by cell viability assays. The ability of the DNA damage inducer RRx-001 to modulate CCDC6 protein levels and H2AX phosphorylation was detected at immunoblot. The combination of USP7 inhibitor plus RRx-001 enhanced the PARP-inhibitor sensitivity, as evaluated by cell viability assays. The results of the scores and correlation of CCDC6 and USP7 expression levels obtained by UBC primary biopsies staining were used to cluster patients by a K-mean cluster analysis. Results P5091 determining CCDC6 degradation promoted bladder cancer cells sensitivity to PARP-inhibitor drugs. RRx-001, by inducing DNA damage, enhanced the effects of the combined treatment. The immunohistochemical staining of both CCDC6 and USP7 proteins allowed to cluster the high grade (G3) UBC patients, on the basis of CCDC6 expression levels. Conclusions In high grade UBC the identification of two clusters of patients based on CCDC6 and USP7 expession can possibly indicate the use of PARP-inhibitor drugs, in combination with USP7 inhibitor in addition to the DNA damage inducer RRx-001, that also acts as an immunomodulatory agent, offering novel therapeutic strategy for personalized medicine in bladder cancer patients. Electronic supplementary material The online version of this article (10.1186/s13046-019-1087-1) contains supplementary material, which is available to authorized users.
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- 2019
137. TRAF2 and FKBP51 as possible markers for identification of suitable melanoma tumors for tumor necrosis factor-α inhibition
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Stefania Staibano, Maria Fiammetta Romano, Martina Tufano, Gennaro Ilardi, Anna Rea, Paolo D'Arrigo, Francesco Merolla, Simona Romano, Antonello Petrella, Romano, Simona, D'Arrigo, Paolo, Tufano, Martina, Staibano, Stefania, Rea, Anna, Merolla, Francesco, Ilardi, Gennaro, Petrella, Antonello, and Romano, Maria F
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0301 basic medicine ,Cancer Research ,TRAF2 ,Skin Neoplasms ,medicine.medical_treatment ,nuclear factor-κB ,Dermatology ,IκB kinase ,Cell Line ,Tacrolimus Binding Proteins ,03 medical and health sciences ,0302 clinical medicine ,tumor necrosis factor receptor-Associated factor 2 ,Cell Line, Tumor ,medicine ,Humans ,Melanoma ,Tumor ,Chemistry ,FK506-binding protein 51 ,tumor necrosis factor-α ,Biomarkers ,TNF Receptor-Associated Factor 2 ,medicine.disease ,030104 developmental biology ,Cytokine ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Immunohistochemistry ,Tumor necrosis factor alpha - Abstract
Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine, whose role in melanoma is controversial. Although high-dose TNF-α is approved for the treatment of patients with in transit-metastatic melanoma confined to the limb, diverse preclinical models of melanoma have shown that TNF-α can induce cell invasion. Biomarkers that can differentiate between the dual role of TNF-α are needed. TRAF2 is critical to TNF receptor-induced activation of nuclear factor-κB (NF-κB), allowing shifting from death to survival-signaling cascades. The large immunophilin FKBP51 acts as a scaffold and catalyst in the IκB kinase complex assembly and activation. Here, using microscopy and an electrophoretic mobility-shift assay, we provide further evidence in support of the essential role of FKBP51 in sustaining the TNF-α NF-κB signaling in melanoma. Through the cross-linking reaction with the chemical linker disuccinimidyl glutarate, we show that a direct interaction occurs between FKBP51 and TRAF2 in melanoma cells. Immunohistochemistry of tumor samples from 24 patients with cutaneous melanomas showed a correlation between the expressions of the two proteins. Given the association of FKBP51 and TRAF2 with TNF-α-induced NF-κB signaling and their correlation in tumor samples, we propose that the two proteins can be exploited as useful markers for the identification of those melanoma tumors that can benefit from TNF-α inhibition. Future studies will address this hypothesis.
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- 2019
138. MAPK15 upregulation promotes cell proliferation and prevents DNA damage in male germ cell tumors
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Angela Strambi, Mario Chiariello, Mario Acunzo, Matteo Rossi, Federica Sasdelli, Gennaro Ilardi, Giovanni Nigita, Stefania Staibano, Angela Celetti, David Colecchia, Carlo M. Croce, Rossi, Matteo, Colecchia, David, Ilardi, Gennaro, Acunzo, Mario, Nigita, Giovanni, Sasdelli, Federica, Celetti, Angela, Strambi, Angela, Staibano, Stefania, Croce, Carlo Maria, and Chiariello, Mario
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embryonal carcinoma ,0301 basic medicine ,p53 ,Male ,Transcriptional Activation ,autophagy ,DNA damage ,Mice, Nude ,Endogeny ,Apoptosis ,Biology ,Malignant transformation ,03 medical and health sciences ,Mice ,Downregulation and upregulation ,Testicular Neoplasms ,medicine ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Animals ,Humans ,Extracellular Signal-Regulated MAP Kinases ,Cell Proliferation ,embryonal carcinomas ,Cell growth ,Cell Cycle ,Cell cycle ,Neoplasms, Germ Cell and Embryonal ,medicine.disease ,Xenograft Model Antitumor Assays ,Up-Regulation ,030104 developmental biology ,MAP kinases ,Oncology ,Immunology ,Cancer research ,MAP kinase ,Female ,Germ cell tumors ,Tumor Suppressor Protein p53 ,Research Paper - Abstract
Germ cell tumors (GCT) are the most common malignancies in males between 15 and 35 years of age. Despite the high cure rate, achieved through chemotherapy and/or surgery, the molecular basis of GCT etiology is still largely obscure. Here, we show a positive correlation between MAPK15 (ERK8; ERK7) expression and specific GCT subtypes, with the highest levels found in the aggressive embryonal carcinomas (EC). Indeed, in corresponding cellular models for EC, MAPK15 enhanced tumorigenicity in vivo and promoted cell proliferation in vitro, supporting a role for this kinase in human GCT. At molecular level, we demonstrated that endogenous MAPK15 is necessary to sustain cell cycle progression of EC cells, by limiting p53 activation and preventing the triggering of p53-dependent mechanisms resulting in cell cycle arrest. To understand MAPK15-dependent mechanisms impinging on p53 activation, we demonstrate that this kinase efficiently protects cells from DNA damage. Moreover, we show that the ability of MAPK15 to control the autophagic process is necessary for basal management of DNA damage and for tumor formation controlled by the kinase. In conclusion, our findings suggest that MAPK15 overexpression may contribute to the malignant transformation of germ cells by controlling a "stress support" autophagic pathway, able to prevent DNA damage and the consequent activation of the p53 tumor suppressor. Moreover, in light of these results, MAPK15-specific inhibitors might represent new tools to enhance the therapeutic index of cytotoxic therapy in GCT treatment, and to increase the sensitivity to DNA-damaging drugs in other chemotherapy-resistant human tumors.
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- 2016
139. N-Formyl Peptide Receptors Induce Radical Oxygen Production in Fibroblasts Derived From Systemic Sclerosis by Interacting With a Cleaved Form of Urokinase Receptor
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Filomena Napolitano, Francesca Wanda Rossi, Ada Pesapane, Silvia Varricchio, Gennaro Ilardi, Massimo Mascolo, Stefania Staibano, Antonio Lavecchia, Pia Ragno, Carmine Selleri, Gianni Marone, Marco Matucci-Cerinic, Amato de Paulis, Nunzia Montuori, Napolitano, Filomena, Rossi, Francesca Wanda, Pesapane, Ada, Varricchio, Silvia, Ilardi, Gennaro, Mascolo, Massimo, Staibano, Stefania, Lavecchia, Antonio, Ragno, Pia, Selleri, Carmine, Marone, Gianni, Matucci-Cerinic, Marco, de Paulis, Amato, and Montuori, Nunzia
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lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,MAPK/ERK pathway ,Fibrosi ,systemic sclerosis ,integrin ,Integrin ,Immunology ,FPRs ,RAC1 ,03 medical and health sciences ,Systemic sclerosi ,0302 clinical medicine ,fibroblasts ,medicine ,Immunology and Allergy ,Receptor ,Fibroblast ,skin and connective tissue diseases ,Original Research ,NADPH oxidase ,biology ,Chemistry ,fibrosis ,Chemotaxis ,ROS ,Cell biology ,Urokinase receptor ,Fibroblasts ,Fibrosis ,Inflammation ,Systemic sclerosis ,UPAR ,030104 developmental biology ,medicine.anatomical_structure ,inflammation ,030220 oncology & carcinogenesis ,biology.protein ,FPR ,lcsh:RC581-607 ,uPAR - Abstract
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis, alteration in the microvasculature and immunologic abnormalities. It has been hypothesized that an abnormal redox state could regulate the persistent fibrotic phenotype in SSc patients. N-Formyl peptide receptors (FPRs) are chemotactic receptors overexpressed in fibroblasts derived from SSc patients. In this study, we demonstrated that stimulation of FPRs promotes the generation of reactive oxygen species (ROS) in skin fibroblasts. In fibroblast cells, ROS production was due to FPRs interaction with the urokinase receptor (uPAR) and to β1 integrin engagement. FPRs cross-talk with uPAR and integrins led to Rac1 and ERKs activation. FPRs stimulation increased gp91phox and p67phox expression as well as the direct interaction between GTP-Rac1 and p67phox, thus promoting assembly and activation of the NADPH oxidase complex. FPRs functions occur through interaction with a specific domain of uPAR (residues 88SRSRY92) that can be exposed on the cell membrane by protease-mediated receptor cleavage. Immunohistochemistry analysis with a specific anti-SRSRY antibody showed increased expression of uPAR in a cleaved form, which exposes the SRSRY sequence at its N-terminus (DIIDIII-uPAR88–92) in skin biopsies from SSc patients. As expected by the increased expression of both FPRs and DII-DIII-uPAR88-92, fibroblasts derived from SSc patients showed a significantly increase in ROS generation both at a basal level than after FPRs stimulation, as compared to fibroblasts from normal subjects. C37, a small molecule blocking the interaction between FPRs and uPAR, and selumetinib, a clinically approved MAPKK/ERK inhibitor, significantly inhibited FPRs-mediated ROS production in fibroblasts derived from SSc patients. Thus, FPRs, through the interaction with the uPA/uPAR system, can induce ROS generation in fibroblasts by activating the NADPH oxidase, playing a role in the alteration of the redox state observed in SSc.
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- 2018
140. Ingenol Mebutate: When the Patient Refuses Surgery
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Claudia Costa, Silvia Varricchio, Sara Pignatiello, Francesco Martino, Gennaro Ilardi, Daniela Russo, Francesco Merolla, Massimiliano Scalvenzi, Milena Cappello, Costa, Claudia, Scalvenzi, Massimiliano, Cappello, Milena, Martino, Francesco, Pignatiello, Sara, Varricchio, Silvia, and Ilardi, Gennaro
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Laser skin resurfacing ,medicine.medical_specialty ,chemistry.chemical_compound ,chemistry ,Eyelid surgery ,business.industry ,medicine ,Ingenol mebutate ,Acne treatment ,Pediatric dermatology ,business ,Cosmetic dermatology ,Surgery - Abstract
Basal-cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSC) in white individuals. The main risk factor of BCC is intense exposure to ultraviolet radiation. The gold standard of diagnosis of BCC is histopathology. Treatment options for BCC consist of surgery, vismodegib, radiotherapy and topical or ablative treatments. Surgical excision is usually the preferred treatment for nodular and aggressive BCC subtypes. Here in, we report the case of a 51 year-old Caucasian woman successfully treated with ingenol mebutate (IM) 0.05% gel on a large-sized (ø3 cm) superficial BCC (sBCC) localized on the right shoulder. IM appears to be an effective, simple, safe and comfortable treatment even for large-sized sBCC with good cosmetic results.
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- 2018
141. HPV virus transcriptional status assessment in a case of sinonasal carcinoma
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Virginia Napolitano, Francesco Merolla, Francesco Martino, Massimo Mascolo, Giovanni Salzano, Silvia Varricchio, Daniela Russo, Giovanni Dell'Aversana Orabona, Stefania Staibano, Rosa Maria Di Crescenzo, Gennaro Ilardi, Alessandra Borzillo, Ilardi, Gennaro, Russo, Daniela, Varricchio, Silvia, Salzano, Giovanni, Dell'Aversana Orabona, Giovanni, Napolitano, Virginia, DI CRESCENZO, ROSA MARIA, Borzillo, Alessandra, Martino, Francesco, Merolla, Francesco, Mascolo, Massimo, and Staibano, Stefania
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0301 basic medicine ,HPV ,INNO-Lipa ,p16INK4a ,RNAscope® ,Sinonasal carcinoma ,Catalysis ,Molecular Biology ,Spectroscopy ,Computer Science Applications1707 Computer Vision and Pattern Recognition ,Physical and Theoretical Chemistry ,Organic Chemistry ,Inorganic Chemistry ,Case Report ,In situ hybridization ,medicine.disease_cause ,Virus ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Genotyping ,lcsh:QH301-705.5 ,RNAscope® ,Sinonasal Carcinoma ,business.industry ,HPV infection ,virus diseases ,General Medicine ,Sinonasal Tract ,medicine.disease ,female genital diseases and pregnancy complications ,Computer Science Applications ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,Cancer research ,Immunohistochemistry ,business ,Carcinogenesis - Abstract
Human Papilloma Virus (HPV) can play a causative role in the development of sinonasal tract malignancies. In fact, HPV may be the most significant causative agent implicated in sinonasal tumorigenesis and is implicated in as many as 21% of sinonasal carcinomas. To date, there are no definitive, reliable and cost-effective, diagnostic tests approved by the FDA for the unequivocal determination of HPV status in head and neck cancers. We followed an exhaustive algorithm to correctly test HPV infection, including a sequential approach with p16INK4a IHC, viral DNA genotyping and in situ hybridization for E6/E7 mRNA. Here, we report a case of sinonasal carcinoma with discordant results using HPV test assays. The tumor we describe showed an irregular immunoreactivity for p16INK4a, and it tested positive for HPV DNA; nevertheless, it was negative for HR-HPV mRNA. We discuss the possible meaning of this discrepancy. It would be advisable to test HPV transcriptional status of sinonasal carcinoma on a diagnostic routine basis, not only by p16INK4a IHC assay, but also by HPV DNA genotyping and HR-HPV mRNA assessment.
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- 2018
142. Intraretinal changes in idiopathic versus diabetic epiretinal membranes after macular peeling
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Gilda Cennamo, Ciro Costagliola, Davide Allegrini, Giovanni Cennamo, Pia Clara Pafundi, Mario R. Romano, Stefania Staibano, Gennaro Ilardi, Mariantonia Ferrara, Romano, Mario R., Ilardi, Gennaro, Ferrara, Mariantonia, Cennamo, Gilda, Allegrini, Davide, Pafundi, Pia, Costagliola, Ciro, Staibano, Stefania, and Cennamo, Giovanni
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0301 basic medicine ,Male ,Visual acuity ,genetic structures ,Cardiovascular Procedures ,Vision ,medicine.medical_treatment ,Visual Acuity ,Social Sciences ,lcsh:Medicine ,Vascular Surgery ,Vitrectomy ,Ophthalmologic Surgical Procedures ,Eye ,Basement Membrane ,Endocrinology ,0302 clinical medicine ,Medicine and Health Sciences ,Psychology ,Medicine ,Macula Lutea ,Postoperative Period ,lcsh:Science ,Staining ,Multidisciplinary ,Glial fibrillary acidic protein ,biology ,Cell Staining ,Epiretinal Membrane ,Diabetic retinopathy ,medicine.anatomical_structure ,Retinal Disorders ,Sensory Perception ,Female ,Anatomy ,medicine.symptom ,Epiretinal membrane ,Tomography, Optical Coherence ,Research Article ,medicine.medical_specialty ,Endocrine Disorders ,Ocular Anatomy ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,Retina ,03 medical and health sciences ,Ocular System ,Ophthalmology ,Diabetes Mellitus ,Humans ,Retinopathy ,Aged ,Diabetic Retinopathy ,Biochemistry, Genetics and Molecular Biology (all) ,business.industry ,lcsh:R ,Biology and Life Sciences ,Free zone ,Correction ,medicine.disease ,eye diseases ,Cell staining ,030104 developmental biology ,Agricultural and Biological Sciences (all) ,Specimen Preparation and Treatment ,Metabolic Disorders ,030221 ophthalmology & optometry ,biology.protein ,Eyes ,lcsh:Q ,sense organs ,business ,Head ,Neuroscience - Abstract
Introduction Epiretinal traction is not responsible only for epiretinal but also intraretinal changes. This study aims to describe structural and vascular intraretinal changes after macular peeling in idiopathic (iERM) vs diabetic ERM (dERM). Methods We conducted a prospective interventional study on forty-two eyes, 23 with iERMs and 19 with dERMs, undergoing ERM-ILM peeling. We performed SD-OCT preoperatively, 1 and 6 months postoperatively to assess central macular thickness (CMT), intraretinal cysts (IC) and/or continuous ectopic inner foveal layers (CEIFL), superficial and deep capillary free zone (CFZ) area on OCT-A. Glial fibrillary acidic protein (GFAP), as a Muller cells marker, was detected immunohistochemically on ILM specimens, to assess Muller cells iatrogenic damage. Results The CEIFLs were significantly more common in iERMs (12 (52.2%) in iERMs vs 2 (10.5%) in dERMs, p = 0.004), whereas ICs in dERMs (6 (26.1%) in iERMs vs 17 (89.5%) in dERMs, p
- Published
- 2018
143. Coexistent Squamous Cell Carcinoma and Granular Cell Tumor of Head and Neck Region: Report of Two Very Rare Cases and Review of the Literature
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Gennaro Ilardi, Luigi Califano, Gianfranco De Dominicis, Francesca Pagliuca, Massimo Mascolo, Giuseppe Ciancia, Grazia Salerno, Danila Caroppo, Francesco Merolla, Daniela Russo, Massimo Mesolella, Caroppo, Danila, Salerno, Grazia, Merolla, Francesco, Mesolella, Massimo, Ilardi, Gennaro, Pagliuca, Francesca, De Dominicis, Gianfranco, Califano, Luigi, Ciancia, Giuseppe, Russo, Daniela, and Mascolo, Massimo
- Subjects
Oncology ,Larynx ,squamous cell carcinoma ,Adult ,Male ,medicine.medical_specialty ,Pathology ,Pseudoepitheliomatous Hyperplasia ,Pathology and Forensic Medicine ,Neoplasms, Multiple Primary ,03 medical and health sciences ,0302 clinical medicine ,Tongue ,Internal medicine ,medicine ,Humans ,Basal cell ,granular cell tumor ,head and neck region ,Esophagus ,030223 otorhinolaryngology ,Neuroectodermal tumor ,Head and neck ,Granular cell tumor ,business.industry ,Middle Aged ,medicine.disease ,stomatognathic diseases ,medicine.anatomical_structure ,Granular Cell Tumor ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Surgery ,Female ,Anatomy ,business - Abstract
Granular cell tumor (GCT), a relatively rare neuroectodermal tumor occurring most often in the head and neck region, is not uncommonly associated with pseudoepitheliomatous hyperplasia of the overlying surface epithelium, which may be at times nonreadily distinguishable from well-differentiated squamous cell carcinoma (SCC). To the best of our knowledge, only a handful of coexisting SCC and GCT, mostly described in the esophagus, have been reported in (the current) literature so far. We herein report 2 new cases of coexisting GCT and SCC of the head and neck region, located, respectively, in larynx and tongue; comment on their clinical, imaging, and pathologic features; and discuss their management. In the present work, we also review the literature concerning this association to contribute to the head and neck pathologists’ and surgeons’ awareness regarding the possibility of this association for an adequate surgical excision and a better management of these patients.
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- 2017
144. USP7 inhibitors, downregulating CCDC6, sensitize lung neuroendocrine cancer cells to PARP-inhibitor drugs
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Francesco Morra, Gianluca Guggino, Francesco Merolla, Roberta Visconti, Giancarlo Troncone, Guglielmo Monaco, Stefania Staibano, Aniello Cerrato, Virginia Napolitano, Gennaro Ilardi, Umberto Malapelle, Roberto Monaco, Angela Celetti, Malapelle, Umberto, Morra, Francesco, Ilardi, Gennaro, Visconti, Roberta, Merolla, Francesco, Cerrato, Aniello, Napolitano, Virginia, Monaco, Roberto, Guggino, Gianluca, Monaco, Guglielmo, Staibano, Stefania, Troncone, Giancarlo, and Celetti, Angela
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Male ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,PARP-Inhibitors ,Neuroendocrine tumors ,Poly (ADP-Ribose) Polymerase Inhibitor ,Ubiquitin-Specific Peptidase 7 ,0302 clinical medicine ,AMP-Activated Protein Kinase Kinases ,Genes, Tumor Suppressor ,Aged, 80 and over ,L-NET ,Tissue microarray ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Neuroendocrine Tumors ,Oncology ,P5091 ,030220 oncology & carcinogenesis ,NGS ,PARP inhibitor ,Female ,Ubiquitin Thiolesterase ,DAB2IP Gene ,medicine.drug ,Pulmonary and Respiratory Medicine ,DNA damage ,Down-Regulation ,Antineoplastic Agents ,Thiophenes ,Poly(ADP-ribose) Polymerase Inhibitors ,Protein Serine-Threonine Kinases ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Predictive Value of Tests ,medicine ,Humans ,Aged ,Cisplatin ,Tumor Suppressor Proteins ,PARP-Inhibitor ,CCDC6 ,USP7 ,Genes, p53 ,medicine.disease ,Molecular biology ,Carcinoma, Neuroendocrine ,Cytoskeletal Proteins ,030104 developmental biology ,Mutation ,Cancer research ,Tumor Suppressor Protein p53 ,Protein Processing, Post-Translational ,Immunostaining - Abstract
Objectives CCDC6 gene product is a tumor-suppressor pro-apoptotic protein, substrate of ATM, involved in DNA damage response and repair. Altered levels of CCDC6 expression are dependent on post-translational modifications, being the de-ubiquitinating enzyme USP7 responsible of the fine tuning of the CCDC6 stability. Thus, our aim was to investigate CCDC6 and USP7 expression levels in Lung-Neuroendocrine Tumors (L-NETs) to verify if they correlate and may be exploited as novel predictive therapeutic markers. Materials and methods Tumor tissues from 29 L-NET patients were investigated on tissue microarrays. CCDC6 levels were scored and correlated with immunoreactivity for USP7. Next generation sequencing (NGS) of a homogenous group of Large Cell Neuroendocrine Carcinoma (LCNEC) (N=8) was performed by Ion AmpliSeq NGS platform and the Ion AmpliSeq Cancer Hotspot Panel v2. The inhibition of USP7, using P5091, was assayed in vitro to accelerate CCDC6 turnover in order to sensitize the neuroendocrine cancer cells to PARP-inhibitors, alone or in association with cisplatinum. Results The immunostaining of 29 primary L-NETs showed that the intensity of CCDC6 staining correlated with the levels of USP7 expression (p≤0.05). The NGS analysis of 8 LCNEC revealed mutations in the hot spot regions of the p53 gene (in 6 out of 8). Moreover, gene polymorphisms were identified in the druggable STK11, MET and ALK genes. High intensity of p53 immunostaining was reported in the 6 tissues carrying the TP53 mutations. The inhibition of USP7 by P5091 accelerated the degradation of CCDC6 versus control in cycloheximide treated L-NET cells in vitro and sensitized the cells to PARP-inhibitors alone and in combination with cisplatinum. Conclusion Our data suggest that CCDC6 and USP7 have a predictive value for the clinical usage of USP7 inhibitors in combination with the PARP-inhibitors in L-NET in addition to standard therapy.
- Published
- 2017
145. The combined effect of USP7 inhibitors and PARP inhibitors in hormone-sensitive and castration-resistant prostate cancer cells
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Gennaro Ilardi, Simona Paladino, Caterina Miro, Francesco Morra, Virginia Napolitano, Angela Celetti, Francesco Merolla, Stefania Staibano, Aniello Cerrato, Morra, Francesco, Merolla, Francesco, Napolitano, Virginia, Ilardi, Gennaro, Miro, Caterina, Paladino, Simona, Staibano, Stefania, Cerrato, Aniello, and Celetti, Angela
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0301 basic medicine ,Male ,Antineoplastic Agents, Hormonal ,DNA Repair ,Antineoplastic Agents ,Apoptosis ,Poly(ADP-ribose) Polymerase Inhibitors ,ARFL and V7 ,olaparib ,Olaparib ,Ubiquitin-Specific Peptidase 7 ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,Prostate ,Cell Line, Tumor ,Medicine ,Humans ,DNA Breaks, Double-Stranded ,CCDC6 ,P5091 ,USP7 ,Cell Proliferation ,Tissue microarray ,business.industry ,Protein Stability ,Drug Synergism ,medicine.disease ,Molecular medicine ,Androgen receptor ,Prostatic Neoplasms, Castration-Resistant ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer cell ,Immunology ,Cancer research ,business ,Research Paper - Abstract
// Francesco Morra 1 , Francesco Merolla 2, 3 , Virginia Napolitano 1, 2 , Gennaro Ilardi 2 , Caterina Miro 1 , Simona Paladino 4 , Stefania Staibano 2 , Aniello Cerrato 1 , Angela Celetti 1 1 Institute for Experimental Endocrinology and Oncology, Research National Council, Naples, Italy 2 Department of Advanced Biomedical Sciences, University “Federico II”, Naples, Italy 3 Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy 4 Department of Molecular Medicine and Medical Biotechnology, University “Federico II”, Naples, Italy Correspondence to: Angela Celetti, email: celetti@unina.it Keywords: CCDC6, USP7, ARFL and V7, P5091, olaparib Received: December 08, 2016 Accepted: March 15, 2017 Published: March 22, 2017 ABSTRACT Purpose of the study: Reduced levels of the tumor suppressor protein CCDC6 sensitize cancer cells to the treatment with PARP-inhibitors. The turnover of CCDC6 protein is regulated by the de-ubiquitinase USP7, which also controls the androgen receptor (AR) stability. Here, we correlated the expression levels of CCDC6 and USP7 proteins in primary prostate cancers (PC). Moreover, we tested the efficacy of the USP7 inhibitors, in combination with PARP-inhibitors as a novel therapeutic option in advanced prostate cancer. Experimental techniques: PC cells were exposed to USP7 inhibitor, P5091, together with cycloheximide, to investigate the turnover of the USP7 substrates, AR and CCDC6. As outcome of the AR downregulation, transcription targets of AR and its variant V7 were examined by qPCR. As a result of CCDC6 degradation, the induction of PARP inhibitors sensitivity was evaluated by analyzing PC cells viability and foci formation. We scored and correlated CCDC6 and USP7 expression levels in a prostate cancer tissue microarray (TMA). Results: P5091 accelerated the degradation of AR and V7 isoform affecting PSA, UBE2C, CDC20 transcription and PC cells proliferation. Moreover, P5091 accelerated the degradation of CCDC6 sensitizing the cells to PARP-inhibitors, that acted sinergistically with genotoxic agents. The immunohistochemical analysis of both CCDC6 and USP7 proteins exhibited significant correlation for the intensity of staining ( p ≤ 0.05). Data interpretation: Thus, CCDC6 and USP7 represent predictive markers for the combined treatment of the USP7-inhibitors and PARP-inhibitors in advanced prostate cancer.
- Published
- 2017
146. FKBP51 immunohistochemical expression: A new prognostic biomarker for OSCC?
- Author
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Maria Fiammetta Romano, Massimo Mascolo, Gennaro Ilardi, Luigi Califano, Virginia Napolitano, Simona Romano, Loredana Postiglione, Daniela Russo, Giovanni Orabona Dell’Aversana, Stefania Staibano, Angela Celetti, Pierpaolo Di Lorenzo, Silvia Varricchio, Francesco Merolla, F Astarita, Russo, Daniela, Merolla, Francesco, Mascolo, Massimo, Ilardi, Gennaro, Romano, Simona, Varricchio, Silvia, Napolitano, Virginia, Celetti, Angela, Postiglione, Loredana, DI LORENZO, Pierpaolo, Califano, Luigi, DELL'AVERSANA ORABONA, Giovanni, Astarita, Fabio, Romano, MARIA FIAMMETTA, and Staibano, Stefania
- Subjects
0301 basic medicine ,Oncology ,Male ,Pathology ,Bayes theorem ,medicine.medical_treatment ,Gene Expression ,Kaplan-Meier Estimate ,Pathogenesis ,lcsh:Chemistry ,0302 clinical medicine ,Squamous cell carcinoma ,lcsh:QH301-705.5 ,Spectroscopy ,Aged, 80 and over ,Human papillomavirus 16 ,Oral cancer ,Computer Science Applications1707 Computer Vision and Pattern Recognition ,General Medicine ,Middle Aged ,FKBP51 ,Immunotherapy ,Prognosis ,Catalysis ,Molecular Biology ,Physical and Theoretical Chemistry ,Organic Chemistry ,Inorganic Chemistry ,Immunohistochemistry ,Computer Science Applications ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Carcinoma, Squamous Cell ,Female ,Mouth Neoplasms ,prognosi ,Adult ,medicine.medical_specialty ,In situ hybridization ,Article ,Tacrolimus Binding Proteins ,03 medical and health sciences ,Immune system ,Tongue ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Neoplasm Staging ,Chemotherapy ,business.industry ,Radiation therapy ,stomatognathic diseases ,oral cancer ,prognosis ,immunotherapy ,squamous cell carcinoma ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cutaneous melanoma ,Neoplasm Grading ,business - Abstract
Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients’ risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors. We already investigated the role of the immune modulator FK506-binding protein 51 (FKBP51), a FK506-binding immunophilin, in cutaneous melanoma biology, and its expression in several human solid tumors. In the present study, we aimed to assess the value of FKBP51 expression in OSCC tumor cells as a marker of outcome. We collected clinical data from 72 patients who underwent surgery for Squamous Cell Carcinoma (SCC) of the tongue, floor, lips and palate. FKBP51 expression was assessed by immunohistochemistry on paraffin-embedded tumor tissues. In addition, we evaluated the human papillomavirus (HPV) status of primary tumors by immunohistochemistry, viral subtyping and In Situ Hybridization (ISH) assay. We found that high FKBP51-expressing tumors characterized the OSCCs with the worst prognosis: the high immunohistochemical expression of FKBP51 associated with death occurring within five years from the diagnosis with a sensitivity of 88.46% and a specificity of 91.67%. The estimated positive predictive value of the test was 88.45% and negative predictive value 91.67%. We tested FKBP51 mRNA presence, by RT-PCR assay, in a selected series of OSCC tumors, and we found that mRNA correlated well to the protein expression and to the clinical outcome. Applying the Bayes formula, we estimated an 88% probability of dying within five years from the diagnosis of OSCC patients with a high FKBP51 immunohistochemical (IHC) test result (>51% of FKBP51 positive tumor cells). On the basis of our analysis, we propose tumor tissue expression of FKBP51 protein as a reliable prognostic marker for OSCC tumors.
- Published
- 2017
147. Confocal microscopy and imaging profilometry: A new tool aimed to evaluate aesthetic procedures
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Claudia Capasso, Sandra Lorenzi, Gennaro Ilardi, Gabriella Fabbrocini, Luigi Sivero, Caterina Mazzella, Maria Pia De Padova, Daniela Russo, Carla Velotti, Patrizia Forgione, Aurora Tedeschi, Rosa Vitiello, Fabio Montagnaro, Fabbrocini, Gabriella, Mazzella, Caterina, Montagnaro, Fabio, De Padova, Maria Pia, Lorenzi, Sandra, Tedeschi, Aurora, Forgione, Patrizia, Capasso, Claudia, Sivero, Luigi, Velotti, Carla, Russo, Daniela, Vitiello, Rosa, and Ilardi, Gennaro
- Subjects
Adult ,medicine.medical_specialty ,Nasolabial Fold ,Time Factors ,Treatment outcome ,Dentistry ,Dermatology ,Left nasolabial fold ,Cosmetic Techniques ,profilometry ,law.invention ,hyaluronic acid filler ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Confocal microscopy ,law ,Dermal Fillers ,medicine ,Humans ,Hyaluronic Acid ,Retrospective Studies ,Microscopy, Confocal ,Right nasolabial fold ,business.industry ,Middle Aged ,Nasolabial fold ,Surgery ,Molecular Weight ,medicine.anatomical_structure ,Treatment Outcome ,030221 ophthalmology & optometry ,Female ,business - Abstract
According to the American Academy of Aesthetic Plastic Surgeons, more than 11 million cosmetic surgical and nonsurgical procedures were performed by board-certified plastic surgeons, dermatologists and otolaryngologists in the United States, totaling more than 12 billion dollars. We performed a retrospective observational multi-centric study on patients treated with a non-animal origin cross-linked hyaluronic acid with different molecular weights for nasolabial folds, evaluating through a new imaging system, profilometric techniques with the confocal microscopy, the durability, the efficacy and the safety of this product. From 25 patients, 150 silicone casts were obtained: 75 casts of the right nasolabial fold and 75 casts of the left nasolabial fold. Roughness arithmetical average of the right fold at T2 decreased by 50% versus T0 and by 40% compared to T1; at T2, it decreased by the 45% versus T0 and by 35% compared to T1. No side effects were reported. Results proved that the analysis of the skin microreliefs through confocal microscopy is a new imaging system that allows to evaluate with precision and safety the results of aesthetic treatments such as fillers objectively.
- Published
- 2016
148. CAF-1 Subunits Levels Suggest Combined Treatments with PARP-Inhibitors and Ionizing Radiation in Advanced HNSCC
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Roberto Pacelli, Francesco Merolla, Ida Picardi, Gennaro Ilardi, Daniela Russo, Massimo Mascolo, Angela Celetti, Stefania Staibano, Silvia Varricchio, Federica Liotti, Francesco Morra, Luca Palazzo, Morra, Francesco, Merolla, Francesco, Picardi, Ida, Russo, Daniela, Ilardi, Gennaro, Varricchio, Silvia, Liotti, Federica, Pacelli, Roberto, Palazzo, Luca, Mascolo, Massimo, Celetti, Angela, and Staibano, Stefania
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0301 basic medicine ,Cancer Research ,DNA repair ,Poly ADP ribose polymerase ,Cell ,homologous recombination ,head and neck squamous cell carcinoma ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Viability assay ,p60/p150 CAF-1 subunit ,Tissue microarray ,business.industry ,biomarkers ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,personalized treatment ,Head and neck squamous-cell carcinoma ,3. Good health ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,CAL27 ,p60/p150 CAF-1 subunits ,Cancer research ,biomarker ,Immunohistochemistry ,business ,SCC90 - Abstract
Oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas show high morbidity and mortality rates. We aimed to investigate the role of the &ldquo, Chromatin Assembly Factor-1&rdquo, (CAF-1) p60 and p150 subunits, involved in DNA repair and replication, in OSCC and OPSCC progression and in response to Poly(ADP-ribose) polymerase (PARP)-inhibitors and exposure to ionizing radiation (IR). We immunostained tissue microarrays (TMAs), including 112 OSCC and 42 OPSCC, with anti-CAF-1/p60 and anti-CAF-1/p150 specific antibodies, correlating their expression with prognosis. Moreover, we assessed the sensitivity to PARP inhibitors and the double-strand breaks repair proficiency by cell viability and HR reporter assays, respectively, in HPV-positive and HPV-negative cell lines upon CAF-1/p60 and CAF-1/p150 depletion. The immunohistochemical analysis revealed a significant prognostic value of both tissue biomarkers combined expression in OSCC but not in OPSCC. In in vitro studies, the p60/150 CAF-1 subunits&rsquo, depletion impaired the proficiency of Homologous Recombination DNA damage repair, inducing sensitivity to the PARP-inhibitors, able to sensitize both the cell lines to IR. These results indicate that regardless of the prognostic meaning of p60/p150 tissue expression, the pharmacological depletion of CAF-1 complex&rsquo, s function, combined to PARP-inhibitors and/or IR treatment, could represent a valid therapeutic strategy for squamous cell carcinomas of head and neck region.
- Published
- 2019
149. An 'ex vivo model' contributing to the diagnosis and evaluation of new drugs in cystic fibrosis
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G. Ilardi, Elena Cantone, A. M. Di Lullo, Giuseppe Castaldo, Manuela Scorza, Maurizio Iengo, Marika Comegna, Valeria Raia, Luigi Maiuri, Felice Amato, DI LULLO, ANTONELLA MIRIAM, Scorza, M, Amato, Felice, Comegna, Marika, Raia, Valeria, Maiuri, L, Ilardi, Gennaro, Cantone, E, Castaldo, Giuseppe, and Iengo, Maurizio
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Pathology ,medicine.medical_specialty ,Cystic Fibrosis ,Cystic Fibrosis Transmembrane Conductance Regulator ,Butyrate ,medicine.disease_cause ,Cystic fibrosis ,03 medical and health sciences ,0302 clinical medicine ,Genotype ,Medicine ,Humans ,CFTR ,030223 otorhinolaryngology ,Cystic Fibrosi ,Gene ,Cells, Cultured ,Mutation ,business.industry ,Nasal brushing ,CF ,Rhinology ,medicine.disease ,Transmembrane protein ,Nasal Mucosa ,General Energy ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,RNA splicing ,Cancer research ,business ,Ex vivo ,Mutations - Abstract
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. About 2000 mutations have been described so far. We setup an ex vivo model of human nasal epithelial cells (HNECs) to study CF patients testing the effect of novel mutations and molecular therapies. We performed sampling (by brushing), followed by culture and analysis of HNECs using a series of molecular techniques. We performed 50 brushings from CF patients and controls. Using cultured cells, we: i) demonstrated the widely heterogeneous CFTR expression in patients and in controls; ii) defined the splicing effect of a CFTR mutation; iii) assessed the CFTR gating activity in patients bearing different mutations; iv) demonstrated that butyrate significantly enhances CFTR expression. Based on our data, we can conclude: 1) HNEC brushing is performed without anaesthesia and is well tolerated in all CF patients (children and adults); 2) HNECs can be preserved for up to 48 hours before culture allowings multicentre studies; 3) HNECs culture can be considered a suitable model to study the molecular effects of new CFTR gene mutations and/or uncertain meaning specific mutations of carriers; 4) an ex vivo model of HNECs may be used to evaluate, before human use, the effect of new drugs on patients' cells bearing specific CFTR mutations; 5) the methodology is adequate for a quantitative measurement, by fluorescence, of the CFTR gating activity of the HNECs from patients with different genotypes identifying: a) CF patients bearing two severe mutations with an activity10% (compared to controls - 100%); b) CF patients bearing at least a mild mutation with an activity of 10-20%; c) CF carriers (heterozygous subjects) with an activity between 40-70%.La fibrosi cistica (FC) è una malattia autosomica recessiva causata da mutazioni nel gene CFTR (Cystic Fibrosis Transmembrane conductance Regulator). Finora sono state descritte circa 2000 mutazioni, ma per la maggior parte di esse è difficile definirne l’effetto senza complesse procedure in vitro. Abbiamo effettuato il campionamento (mediante brushing), la cultura e l’analisi di cellule epiteliali nasali umane (HNEC) utilizzando una serie di tecniche che possono aiutare a testare l’effetto delle mutazioni CFTR. Abbiamo eseguito 50 brushing da pazienti FC e controlli, e in 45 casi si è ottenuta una coltura positiva. Utilizzando cellule in coltura: i) abbiamo dimostrato l’espressione ampiamente eterogenea del CFTR nei pazienti e nei controlli; ii) abbiamo definito l’effetto di splicing di una mutazione sul gene CFTR; iii) abbiamo valutato l’attività di gating di CFTR in pazienti portatori di differenti mutazioni; iv) abbiamo dimostrato che il butirrato migliora in modo significativo l’espressione di CFTR. I dati provenienti dal nostro studio sperimentale dimostrano che l’uso del modello ex-vivo di cellule epiteliali nasali è un importante e valido strumento di ricerca e di diagnosi nella studio della FC e può anche essere mirato alla sperimentazione ed alla verifica di nuovi farmaci. In definitiva, in base ai nostri dati è possibile esprimere le seguenti conclusioni: 1) il prelievo delle cellule epiteliali nasali mediante brushing è applicabile senza alcuna anestesia ed è ben tollerato da tutti i pazienti affetti da FC (bambini e adulti), è scarsamente invasivo e facilmente ripetibile, è anche in grado di ottenere una sufficiente quantità di HNECs rappresentative, ben conservate, idonee allo studio della funzionalità di CFTR; 2) la conservazione delle cellule prelevate è possibile fino a 48 ore prima che si provveda all’allestimento della coltura e ciò permette di avviare studi multicentrici con prelievi in ogni sede e quindi di ottenere una ampia numerosità campionaria; 3) la coltura di cellule epiteliali nasali può essere considerata un modello adatto a studiare l’effetto molecolare di nuove mutazioni del gene CFTR e/o mutazioni specifiche di pazienti “carriers” dal significato incerto; 4) il modello ex-vivo delle HNECs consente inoltre di valutare, prima dell’impiego nell’uomo, l’effetto di farmaci (potenziatori e/o correttori) sulle cellule di pazienti portatori di mutazioni specifiche di CFTR; tali farmaci possono modulare l’espressione genica del canale CFTR aprendo così nuove frontiere terapeutiche e migliori prospettive di vita per pazienti affetti da una patologia cronica come la Fibrosi Cistica; 5) la metodologia da noi istituita risulta essere idonea alla misura quantitativa, mediante fluorescenza, dell’attività di gating del canale CFTR presente nelle membrane delle cellule epiteliali nasali prelevate da pazienti portatori di differenti genotipi; in tal modo è possibile individuare: a) pazienti FC portatori di 2 mutazioni gravi con un’attività10% (in rapporto ai controlli -100%), b) soggetti FC portatori contemporaneamente di una mutazione grave e di una lieve con un’attività tra 10-30%, c) i cosiddetti portatori “carriers”- eterozigoti - con un’attività tra 40-70%. In conclusione la possibilità di misurare l’attività del canale CFTR in HNECs fornisce un importante contributo alla diagnosi di FC, mediante individuazione di un “cut-off diagnostico”, ed anche alla previsione della gravità fenotipica della malattia; quindi quanto rilevabile dalla misura del suddetto canale permette di prospettare per il futuro la possibilità di valutare meglio i pazienti per i quali il test del sudore ha dato risultati ambigui (borderline o negativi). La metodica da noi sperimentata consente anche di monitorare i pazienti durante il trattamento farmacologico, valutando in tal modo i reali effetti delle nuove terapie.
- Published
- 2016
150. Nucleotide excision repair and head and neck cancers
- Author
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Massimo Mascolo, Francesco Merolla, Angela Celetti, Gennaro Ilardi, Stefania Staibano, Maria Siano, Vincenzo Graziano, Daniela Russo, Merolla, Francesco, Mascolo, Massimo, Ilardi, Gennaro, Siano, Maria, Russo, Daniela, Graziano, Vincenzo, Celetti, Angela, and Staibano, Stefania
- Subjects
0301 basic medicine ,Genome instability ,DNA Replication ,HPV ,DNA Repair ,DNA damage ,DNA repair ,Context (language use) ,Review ,Genomic Instability ,03 medical and health sciences ,EBV ,Tobacco ,Humans ,Cisplatinum ,CAF-1 ,biology ,DNA replication ,Chromatin ,HNSCC: Dna Damage response ,HNC ,030104 developmental biology ,Histone ,Head and Neck Neoplasms ,NER ,biology.protein ,Cancer research ,Carcinogens ,ERCC1 ,Alcohol ,Nucleotide excision repair ,DNA Damage - Abstract
Genome integrity maintenance is crucial for cell survival and for counteracting cancer onset and progression. Mammary cells invest great amount of energy in DNA repair, in order to avoid errors accumulation in DNA sequence. Nucleotide Excision Repair (NER) removes a broad spectrum of DNA damages, mainly bulky DNA lesions. Tissues of Head and Neck region are heavily exposed to bulky lesions inducing carcinogens, this making NER process of great interest in the field. Here we review the recent literature about NER in HNC and we also discuss the role played by NER in HNSCC in the chromatin context; to this aim we particularly focus on the role played by histones chaperon CAF-1, essential in restoring the chromatin structure following DNA replication and DNA damage repair, including NER. A better understanding of basic mechanisms underlying the DNA damage response, particularly involving NER, especially in the chromatin context, will provide us with new promising way to bypass the repair block, possibly becoming an unexpected mode of "transversal" control also of the proliferative deregulation, classically observed in HNSCC.
- Published
- 2016
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