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7. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

Author

Mantovani, Giovanna, Bastepe, Murat, Monk, David, de Sanctis, Luisa, Thiele, Susanne, Usardi, Alessia, Ahmed, S. Faisal, Bufo, Roberto, Choplin, Timothée, De Filippo, Gianpaolo, Devernois, Guillemette, Eggermann, Thomas, Elli, Francesca M., Freson, Kathleen, García Ramirez, Aurora, Germain-Lee, Emily L., Groussin, Lionel, Hamdy, Neveen, Hanna, Patrick, Hiort, Olaf, Jüppner, Harald, Kamenický, Peter, Knight, Nina, Kottler, Marie-Laure, Le Norcy, Elvire, Lecumberri, Beatriz, Levine, Michael A., Mäkitie, Outi, Martin, Regina, Martos-Moreno, Gabriel Ángel, Minagawa, Masanori, Murray, Philip, Pereda, Arrate, Pignolo, Robert, Rejnmark, Lars, Rodado, Rebecca, Rothenbuhler, Anya, Saraff, Vrinda, Shoemaker, Ashley H., Shore, Eileen M., Silve, Caroline, Turan, Serap, Woods, Philip, Zillikens, M. Carola, Perez de Nanclares, Guiomar, and Linglart, Agnès

Published
2018
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9. Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial

Author

Normanno, N., Rachiglio, A.M., Lambiase, M., Martinelli, E., Fenizia, F., Esposito, C., Roma, C., Troiani, T., Rizzi, D., Tatangelo, F., Botti, G., Maiello, E., Colucci, G., Ciardiello, F., Giuliani, F., Simone, G., Febbraro, A., Tommaselli, E., Cinieri, S., Criscuolo, M., Perrino, A., Rinaldi, A., Bordonaro, R., Manusia, M., Romito, S., Bufo, P., Cartenì, G., Biglietto, M., Nappi, O., Cardarelli, A., Montesarchio, E., Micheli, P., Nasti, G., Chicchinelli, N., Iannaccone, A., Russo, A., Cabibi, D., Giaccone, P., Barone, C., Rindi, G., Tonini, G., Onetti Muda, A., Perrone, G., Latiano, T., Graziano, P., Pisconti, S., and Sebastio, A.

Published
2015
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23. 93rd annual convention podium and poster abstracts

Author

Davis, C. M., Strong, S. A., Hellinger, M. D., Williamson, P. R., Larach, S. W., Ferrara, A., Blake, T. B., Medich, D. S., Ziv, Y., Oakley, J. R., Reissman, P., Piccirillo, M., Ulrich, A., Nogueras, J. J., Wexner, S. D., Rubin, M. S., Bodenstein, L. E., Kent, K. C., Williamson, M. E. R., Lewis, W. G., Sagar, P. M., Holdsworth, P. J., Johnston, D., Fazio, V. W., Goldblum, J. R., Sirimarco, M. T., Lavery, I. C., Petras, R. E., Treem, W. R., Cohen, J., Davis, P. M., Hyams, J. S., Eu, K. W., Bartolo, D. C. C., Green, J. D., Riether, R. D., Rosen, L., Stasik, J. J., Sheets, J. A., Reed, J., Khubchandani, I. T., Armitage, N. C., Chapman, M., Hardcastle, J. D., Viamonte, M., Plasencia, G., Wiltz, O., Jacobs, M., Finan, P. J., Passaro, M., Church, J. M., McGannon, E., Wilson, M., Hull-Boiner, S., Kollmorgen, C. F., Meagher, A. P., Wolff, B. G., Pemberton, J. H., Martenson, J. A., Ilstrup, D. M., Moran, M. R., Ramos, A., Rothenberger, D. A., Goldberg, S. M., Johnson, D., Madoff, R. D., Wong, W. D., Finne, III, C. O., Konishi, F., Furuta, K., Kanazawa, K., Lockhart, D., Schmitt, S., Caushaj, P. P., Garcia-Aguilar, J., Belmonte, C., Schiesel, E. C., Mazier, W. P., Senagore, A. J., Piccirillo, M. F., Teoh, T. -A., Yoon, K. -S., Paul, R. A. Patino, Lucas, J., Nelson, R., Norton, N., Cautley, E., Schouten, W. R., Briel, J. W., Auwerda, J. J. A., de Graaf, E. J. R., Lowry, A. C., Sentovich, S. M., Blatchford, G. J., Rivela, L. J., Thorson, A. G., Christensen, M. A., Jorge, J. M. N., Yang, Y. K., Shafik, A., Allendorf, J. D. F., Kayton, M. L., Libutti, S. K., Trokel, M. J., Whelan, R. L., Treat, M. R., Nowygrod, R., Bessler, M., Frank, R. E., Saclarides, T. J., Leurgans, S., Speziale, N. J., Drab, E., Rubin, D., Hull, T. L., Schroeder, T. K., Scholefield, J. H., Ogunbiyi, O. A., Smith, J. H. F., Rogers, K., Sharp, F., Longo, W. E., Vernava, III, A. M., Wade, T. P., Coplin, M. A., Virgo, K. S., Johnson, F. E., Brady, M., Kavolius, J., Quan, S. H. Q., Goldstein, E. T., Feldman, S., Shub, H. A., Bennett, D. R., Kumar, R., McMillen, M. A., Thornton, S., Khoury, D. A., Opelka, F. G., Teoh, T -A., Cohen, S. M., Weiss, E. G., Ortiz, H., De Miguel, M., Armendáriz, P., Rodriguez, J., Chocarro, C., Farouk, R., Dorrance, H. R., Duthie, G. S., Rainey, J. B., Morgado, Jr., P. J., Corman, M. L., Kawamura, Y. J., Sawada, T., Muto, T., Nagai, H., Hill, J., MacLennan, I., Binderow, S. R., Daniel, N., Ehrenpreis, E. D., Jensen, J. E., Bonner, G. F., Ruderman, W. B., Milsom, J. W., Gibbs, D. H., Beck, D. E., Hicks, T. C., Timmcke, A. E., Gathright, Jr, J. B., Cheong, D., Lucas, F. V., McGinity, M., Taylor, B. A., Godwin, P., Holdsworth, P., Lewis, W., Quirke, P., Williamson, M., Kokoszka, J., Pavel, D., Abcarian, H., Stephenson, B. M., Morgan, A. R., Salaman, J. R., Wheeler, M. H., Tran, T. C. K., Willemsen, W., Kuijpers, H. C., Lehman, J. F., Wiseman, J. S., MacFie, J., Sedman, P., May, J., Mancey-Jones, B., Johnstone, D., Nwariaku, F. E., Rochon, R. B., Huber, P. J., Carrico, C. J., Ortega, A., Beart, R., Winchester, D., Steele, G., Green, R., Caushaj, P. F., Devereaux, D., Griffey, S., Reiver, D., Kmiot, W. A., Baker, R., Luchtefeld, M. A., Anthone, G., Schlinkert, R., Roig, J. V., Villoslada, C., Solana, A., Alos, R., Hinojosa, J., Lledo, S., Johnson, D. R. E., Buie, W. D., Jensen, L. L., Heine, J., Hoffmann, B., Timmcke, A., Hicks, T., Opelka, F., Beck, D., Sousa, Jr., A., AraÚjo, S. A., Damico, F. M., Cordeiro, A. C., Pinotti, H. W., Gama, A. H., Fengler, S., Pearl, R., Orsay, C., Seow-Choen, F., Ho, J. M. S., Wiltz, O. H., Torregrosa, M., Brasch, R. C., Bufo, A. J., Krienberg, P., Johnson, G. P., Gowen, G. F., Mullen, P. D., Behrens, D., Hughes, T. G., Wynn, M., Pollack, J. S., Rajagopal, A. S., Huynh, T., Schanbacher, C., Hickson, W. G. E., Yang, Y. -K., Heymen, S., Choi, S. -K., Teoh, T. -A., Wexner, S. D., Vaccaro, C. A., Teoh, T. A., Nogueras, J. J., Choi, S. K., Cheong, D. M. O., Salanga, V. D., MacDonald, A., Baxter, J. N., Finlay, I. G., Mellgren, A., Bremmer, S., Dolk, A., Gillgren, P., Johansson, C., Ahlbäck, S. O., Udén, R., Holmström, B., Ferrara, A., O'Donovan, S., Larach, S. W., Williamson, P. R., Neto, J. A. Reis, Ciquini, S., Quilici, F. A., Reis, Jr., J. A., Torrabadella, L., Salgado, G., Whelan, R. L., Horvath, K. D., Golub, R., Ahsan, H., Cirocco, W., Ziv, Y., Fazio, V. W., Oakley, J. R., Church, J. M., Milsom, J. W., Lavery, L. C., Cohen, S. M., Kmiot, W. A., Reiver, D., Reissman, P., Weiss, E. G., Alós, R., García-Granero, E., Roig, J. V., Uribe, N., Sala, C., Lledo, S., Ozuner, G., Strong, S. A., Bufo, A. J., Daniels, G., Lieberman, R. C., Feldman, S., Lucas, F. V., Longo, W. E., Polites, G., Deshpande, Y., Vernava, A. M., Niehoff, M., Chandel, B., Berglund, D. D., Madoff, R. D., Gemlo, B. T., Spencer, M. P., Goldberg, S. M., Lowry, A. C., Marcello, P. W., Roberts, P. L., Schoetz, D. J., Murray, J. J., Coller, J. A., Veidenheimer, M. C., Koltun, W. A., Bloomer, M. M., Colony, P., Ruggeiro, F., Fleshner, P. R., Michelassi, F., Lewis, W., Williamson, M., Holdsworth, P., Finan, P., Ash, D., Johnston, D., Moran, M. R., Ramos, A., Rothenberger, D. A., Antonenko, D. R., Khanduja, K. S., Fitzgerald, S. D., Meagher, A. P., Moniz-Pereira, P., Wolff, B. G., Outwater, E. K., Marks, G. J., Mohiuddin, M., Sagar, P. M., Hartley, M. N., Mancey-Jones, B., Sedman, P., May, J., MacFie, J., Holbrook, R. F., Rodriguez-Bigas, M. A., Ramakrishnan, K., Palmer, M. L., Petrelli, N. J., Takahashi, T., Nivatvongs, S., Batts, K. P., Lucas, S. W., Klein, S. N., Keidan, R. D., Bannon, J. P., Zhou, J., Armitage, N. C., Hunt, L. M., Robinson, M. H., Hugkulstone, C. E., Clarke, B., Vernon, S. A., Gregson, R. H., Hardcastle, J. D., Ryan, M., Dutta, S., Levine, A., Ortega, A., Anthone, G., Beart, R., Dominguez, J. M., Saclarides, T. J., Bolan, P., Bines, S. D., Adachi, M., Watanabe, T., Sawada, T., Okinaga, K., Muto, T., Hase, K., Shatney, C., Mochizuki, H., Johnson, D., Ure, T., Dehghan, K., Andrus, C. A., Daniel, G. L., D'Emilia, J. C., Rodriguez-Bigas, M., Suh, O. K., Brewer, D. A., Fung, C., Chapuis, P., Bokey, E. L., Garcia, J. C., Banerjee, S., Remzi, F. H., Lavery, I. C., Jorge, J. M. N., Ger, G. C., Gonzalez, L., Gee, A. S., Roe, A. M., Durdey, P., Kaye, M. D., Kyzer, S., Gordon, P. H., Hasegawa, M., Bun, P. Tae, Ikeuchi, D., Onodera, H., Imamura, M., Maetani, S., Blake, T., Hellinger, M., Grewal, H., Klimstra, D. S., Cohen, A. M., Guillem, J. G., Rooney, P. S., Gifford, K. -A., Clarke, P. A., Kuhn, J. A., Bryce, K., Frank, N., Dignan, R. D., Lichliter, W. E., Franko, E., Jacobson, R. M., Preskitt, J. T., Lieberman, Z., Tulanon, P., Steinbach, H., McCarty, T., Simons, T., Plasencia, G., Viamonte, M., Wiltz, O., Jacobs, M., Chen, W. S., Leu, S. Y., Hsu, H., Bessler, M., Halverson, A., Kayton, M. L., Treat, M. R., Nowygrod, R., Congilosi, S., Madoff, R., Wong, W. D., Rothenberger, D., Buie, W. D., Paterson, R., Cartmill, J. A., Trokel, M. J., Gingold, B. S., Cooper, M., Gorfine, S. R., Bauer, J. J., Gelernt, I. M., Kreel, I., Harris, M. T., Vallejo, J. F., Kestenberg, A., Miyajima, N., Kano, N., Ishikawa, Y., Sakai, S., Yamakawa, T., Otchy, D. P., Van Heerden, J. A., Ilstrup, D. M., Weaver, A. L., Winter, L. D., Mav, J., Lee, P. Y., Vetto, J. T., Sullivan, E. S., Rabkin, J., Mayoral, J. L., Matas, A. J., Bove, P., Visser, T., Barkel, D., Villalba, M., Bendick, P., Glover, J., Golub, R. W., Cirocco, W. C., Daniel, N., Altringer, W., Domingues, J. M., Brubaker, L. T., Smith, C. S., Kumar, S., and Gilbert, P.

Published
1994
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26. Epigenetic Profiling of Oral Cancer

Author

Santoro, A., primary, Pannone, G., additional, Papagerakis, S., additional, Serpico, R., additional, Guida, A., additional, Lo, L., additional, and Bufo, P., additional

Published
2012
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35. Expression and clinical implication of cyclooxygenase-2 and E-cadherin in oral squamous cell carcinomas

Author

Santoro, Angela, Bufo, P, Russo, G, Cagiano, S, Papagerakis, S, Bucci, P, Aquino, G, Longo, F, Feola, A, Giordano, A, Di Carlo, A, Di Domenico, M, Pannone, G, Santoro A (ORCID:0000-0002-6964-5152), Santoro, Angela, Bufo, P, Russo, G, Cagiano, S, Papagerakis, S, Bucci, P, Aquino, G, Longo, F, Feola, A, Giordano, A, Di Carlo, A, Di Domenico, M, Pannone, G, and Santoro A (ORCID:0000-0002-6964-5152)

Abstract

Epithelial-Mesenchymal Transition (EMT) and angiogenesis are crucial events for development of aggressive and often fatal Oral Squamous Cell Carcinomas (OSCCs). Both promote cancer progression and metastasis development, but while the former induces the loss of E-cadherin expression and, hence cadherin switching; the latter produces hematic blood vessel neo-formation and contribute to OSCC cell growth, tumor mass development, and dissemination. Cyclooxygenase-2 (COX-2) has an important role, not only in angiogenic mechanisms, but also in favoring cancer invasion. Indeed it decreases the expression of E-cadherin and leads to phenotypic changes in epithelial cells (EMT) enhancing their carcinogenic potential. Our aim is to evaluate the interplay between E-cadherin cytoplasmic delocalization, COX-2 up-regulation and COX-2 induced neo-angiogenesis in 120 cases of OSCC. We have analyzed the distribution and the number of neo-formed endothelial buds surrounding infiltrating cells that express COX-2, as well as the neo-formed vessels in chronic inflammatory infiltrate, which surround the tumor. A double immunostaining method was employed in order to verify co-localization of endothelial cell marker (CD34) and COX-2. IHC has also been used to assess E-cadherin expression. Our data demonstrate that the OSCC cells, which lose membranous E-cadherin staining, acquiring a cytoplasmic delocalization, overexpress COX-2. Moreover, we find a new CD34+ vessel formation (sprouting angiogenesis). Only basaloid type of OSCC showes low level of COX-2 expression together with very low level of neo-angiogenesis and consequent tumor necrosis. The well-known anti-metastatic effect of certain COX-2 inhibitors suggests that these molecules might have clinical utility in the management of advanced cancers.

Published
2020

36. Podium presentations

Author

Foley, E. F., Marcello, P. W., Roberts, P. L., Murray, J. J., Coller, J. A., Veidenheimer, M. C., Schoetz, D. J., McIntyre, P. B., Pemberton, J. H., Wolff, B. G., Beart, Jr., R. W., Kelly, K. A., Dozois, R. R., Sugita, A., Fukushima, T., Harada, H., Yamamoto, M., Shimada, H., Tjandra, J. J., Fazio, V. W., Milson, J. W., Lavery, I. C., Oakley, J. R., Fabre, J. M., Karch, L. A., Bauer, J. J., Gorfine, S. R., Gelernt, I. M., Metcalf, A. M., Varilek, G., Keck, J. O., Hoffmann, D. C., Sgambati, S. A., Sardella, W. V., Marts, B. C., Longo, W. E., Vernava, III, A. M., Kennedy, D. J., Daniel, G. L., Jones, I., Venkatesh, K. S., Diamond, L. W., Larson, D. M., Ramanujam, P. J., Hicks, J. R., Ellis, C. N., Blakemore, W. S., Nathanson, S. D., Linden, M. D., Tender, P., Zarbo, R. J., Nelson, L., Bannon, J., Marks, G., Zhou, J., Mohiuddin, M., Marks, J., Pollard, C. W., Nivatvongs, S., Rojanasakul, A., Ilstrup, D. M., Speziale, N. J., Saclarides, T. J., Rubin, D. B., Szeluga, D. J., Morgado, P. J., Gomez, L. G., Morgado, Jr., P. J., Neto, J. A. Reis, Quilici, F. A., Cordeiro, F., Reis, Jr., J. A., Nitecki, S., Benn, P., Sarr, M. G., Weiland, L. H., Elhadad, A., Rouffet, F., Baillet, P., Akasu, T., Moriya, Y., Hojo, K., Sugihara, K., Oshima, H., Liu, S. K., Church, J. M., Kirkpatrick, J. R., Danielson, C. L., Dominguez, J. M., Jakate, S. M., Savin, M. H., Altringer, W. J., Lee, C. S., Spencer, M. P., Madoff, R. D., Barrett, R. C., Oster, M. A., Durdey, P., Stein, B. L., Staniunas, R. J., Grewal, H., Guillem, J. G., Quan, S., Enker, W. E., Cohen, A. M., van Tets, W. F., Kuijpers, H. C., Kerner, B. A., Wise, Jr., W. E., Golub, R. W., Arnold, M. W., Aguilar, P. S., Pernikoff, B. J., Eisenstat, T. E., Rubin, R. J., Oliver, G. C., Salvati, E. P., Lunniss, P. J., Sultan, A. H., Barker, P. G., Armstrong, P., Bartram, C. I., Phillips, R. K. S., Schouten, W. R., Briel, J. W., Auwerda, J. J. A., Harnsberger, J. R., Robbins, P. L., Brabbee, G. W., Ryhammer, A. M., Bek, K. M., Hanberg-Sørensen, F., Laurberg, S., Hoff, S. D., Bailey, H. R., Butts, D. R., Max, E., Smith, K. W., Zamora, L. F., Skakun, G. B., Khanduja, K. S., Lee, H., Beart, R. W., Spencer, R., Wiseman, J. S., Senagore, A. J., Bain, I. M., Oliff, J., Min, L., Neoptolomos, J., Keighley, M. R. B., O'Kelly, T. J., Davies, J., Brading, A. F., Mortensen, N. J. McC, Park, J. -G., Han, H. J., Kang, M. S., Nakamura, Y., Goldberg, G. S., Orkin, B. A., Smith, L. E., Fleshner, P. R., Freilich, M. I., Meagher, A. P., Adams, W. J., Lubowski, D. Z., King, D. W., Moran, M., Opelka, F., Timmcke, A., Hicks, T., Gathright, Jr., J. B., Leu, S. Y., Hsu, H., Dean, P. A., Ramsey, P. S., Nelson, H., Philpott, G., Siegel, B., Schwarz, S., Fleshman, J., Welch, M., Connett, J., Buie, W. D., Johnson, D. R., Heine, J. A., Wong, W. D., Rothenberger, D. A., Goldberg, S. M., Shafik, A., MacDonald, A., Craig, J. W., Finlay, I. G., Baxter, J. N., Muir, T. C., Parikh, S., Gold, R. P., Gottesman, L., Annibali, R., Öresland, T., Hallgren, T., Fasth, S., Hultén, L., Farouk, R., Duthie, G. S., MacGregor, A. B., Bartolo, D. C. C., Williamson, M. E. R., Lewis, W. G., Holdsworth, P. J., Hall, N., Finan, P. J., Johnston, D., Seow-Choen, F., Goh, H. S., Motson, R. W., Walsh, C. J., Mooney, E., Yamashita, H. J., Wise, W. E., Hartmann, R. F., Seccia, M., Menconi, C., Ghiselli, G., Cavina, E., Salomon, M. C., Ferrara, A., Larach, S. W., Williamson, P. R., Bass, E. M., Orsay, C. P., Firfer, B., Ramakrishnan, V., Abcarian, H., Bufo, A. J., Feldman, S., Daniels, G. A., Lieberman, R. C., Loder, P. B., Kamm, M. A., Nicholls, R. J., Kum, C. K., Ngoi, S. S., Goh, P. M. Y., Tekant, Y., Isaac, J. R., Gerstle, J. T., Kauffman, G. L., and Koltun, W. A.

Published
1993
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38. Removal of imidacloprid from polluted water using adsorption and membrane separation technologies

Author

Qurie, Mohannad, Alkhatib, Mahmoud, Bufo, Sabino Aurelio, Scrano, Laura, Khamis, Mustafa, Ayyad, Ibrahim, and Karaman, Rafik

Abstract

In this work, the stability of imidacloprid in fresh water and sludge was studied. The results revealed that the pesticide is unstable in both media. In fresh water, it underwent hydrolysis whereas a degradation to several metabolites has been observed in sludge. The rate constants for the hydrolysis and degradation at 25°C were 0.0.0067 and 0.0.0099 d–1, respectively. Monitoring the degradation of imidacloprid in sludge by high-pressure liquid chromatography-mass spec trometry (HPLC-MS) revealed that five metabolites have emerged during the study. These metab-olites include imidacloprid urea, imidacloprid-guanidine, 6-hydroxynicotinic acid, an olefin, and 5-hydroxy, 1-(6-chloro-3-pyridylmethyl)-2-(nitroimino)-imidazolidin-5-ol. The efficiency of Al-Quds University Wastewater Treatment Plant towards the removal of imidacloprid indicates that the ultrafiltration-hollow fiber unit was insufficient, whereas the ultrafiltration-spiral wound, activated carbon, and reverse osmosis units were efficient for complete removal of the pesticide. Adsorption experiments of imidacloprid using either activated charcoal or micelle-clay complex were found to fit Langmuir isotherms better than Freundlich isotherm. The data demonstrate a higher Langmuir Qmax value for the activated charcoal (126.6 mg g–1) when compared to the micelle-clay complex (11.76 mg g–1). Filtration column experiments conducted with mixed micelle-clay complex and sand (using a ratio of 1/50 by mass) at a flow rate of 2 mL min–1 and influent concentration of 50 mg L–1 revealed that a sufficient removal of imidacloprid was achieved in the first fraction of 100 Ml elution. These findings indicate that the adsorption technology using the micelle-clay comple provides efficient removal of imidacloprid in continuous flow mode.

Published
2021
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39. Efficient photooxidation processes for the removal of sildenafil from aqueous environments: A comparative study

Author

Zizzamia, Angelica R., Tesoro, Carmen, Bianco, Giuliana, Bufo, Sabino A., Ciriello, Rosanna, Brienza, Monica, Scrano, Laura, and Lelario, Filomena

Abstract

The erectile dysfunction drug sildenafil has attracted a great deal of attention in recent years due to its widespread legal and illegal use around the world and its increasing use by young people for recreational rather than medical purposes. Due to sildenafil's high stability in various environmental conditions and its accumulation or phototransformation in receiving waters, this dangerous trend poses a significant risk to both human health and the environment. Therefore, in-depth studies are needed to find innovative methods for completely removing sildenafil from the aquatic environment while limiting the formation of more toxic derivatives. This study investigated the efficacy of photooxidation processes for removing sildenafil and its potentially toxic derivatives from water. Distilled water and synthetic wastewater were treated with three different oxidants: peroxymonosulfate (PMS), persulfate (PS) hydrogen peroxide (H2O2), and a heterogeneous catalyst, TiO2. The investigation also considered the formation of potentially toxic phototransformation products, performing a tentative structural identification by LC-ESI-MS and MSn. The results proved that the Sunlight/PMS system is the most effective for entirely and environmentally friendly removal of this drug and its transformation products from aqueous environments, achieving complete degradation in distilled water and synthetic wastewater after 80 and 130 minutes of irradiation, respectively. Toxicity testing with Vibrio fishericonfirmed the non-toxic nature of the phototransformed products. This study highlights the potential of Sunlight/PMS photooxidation as a promising strategy for mitigating the environmental risks associated with sildenafil contamination.

Published
2024
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40. The role of the innate immune response in HPV-related oral and oropharyngeal cancer

Author

Pannone, G, Santoro, A, Lo Muzio, L, Leonardi, R, Bufo, P., CAMPISI, Giuseppina, Pannone, G, Santoro, A, Campisi, G, Lo Muzio, L, Leonardi, R, and Bufo, P

Subjects
HPV, oral and oropharyngeal cancer
Abstract

Introduction. During the last 20 years, the incidence of HPV-associated oropharyngeal cancer is increased. Principal actors of the innate immune response against HPV are represented by the TLRs (Toll like receptors). On the other hand different studies have reported that HPV can directly inhibit the functions of the TLRs pathway through interferons (IFNs). There are very few preliminary studies on the role of TLRs mediated HPV clearance in human oncology. Our study aim has been to evaluate whether TLR4 identifies HR-HPV integration state in OSCC. Methods. Protein levels of TLR4 in OSCC were assessed using Immunohistochemistry (IHC). In situ hybridization (ISH) for HPV-DNA detection in morphological context and Pyro-sequencing method have been performed in order to detect viral integration or episomic status. The relationship between TLR expression with or without HPV infection has been elucidated. Results. ISH HPV positive samples have reported lower TLR4 intensity than negative samples and it has confirmed by statistically significant difference (p = .002). There is no statistical correlation between TLR4 intensity and PCR HPV results (p > 0.05). Point-biserial correlation coefficient revealed statistically significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). Conclusions. We retain that TLR4 down-regulation is not associated to the histological tumoral grade but rather to HPV-16 infection and to its integration state into the host DNA.

Published
2014

41. Autophagy analysis in oral carcinogenesis

Author

de Lima, T.B., primary, Paz, A.H.R., additional, Rados, P.V., additional, Leonardi, R., additional, Bufo, P., additional, Pedicillo, M.C., additional, Santoro, A., additional, Cagiano, S., additional, Aquino, G., additional, Botti, G., additional, Pannone, G., additional, and Visioli, F., additional

Published
2017
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42. Toll-Like Receptor 4 Expression in the Epithelium of Inflammatory Periapical Lesions

Author

Leonardi, R., Perrotta, R.E., Loreto, C., Musumeci, G., Crimi, S., dos Santos, J.N., Rusu, M.C., Bufo, P., Barbato, E., and Pannone, G.

Subjects
Adult, Inflammation, Male, Radicular Cyst, Cell Survival, Brief Report, Epithelial Cells, Middle Aged, Immunohistochemistry, radicular cysts, Toll-Like Receptor 4, periapical inflammatory granulomas, Gene Expression Regulation, Humans, Female, TLR4
Abstract

Toll-like receptors (TLR) are essential for the innate immune response against invading pathogens and have been described in immunocompetent cells of areas affected by periapical disease. Besides initiating the inflammatory response, they also directly regulate epithelial cell proliferation and survival in a variety of settings. This study evaluates the in situ expression of TLR4 in periapical granulomas (PG) and radicular cysts, focusing on the epithelial compartment. Twenty-one periapical cysts (PC) and 10 PG were analyzed; 7 dentigerous non-inflamed follicular cyst (DC) served as control. TLR4 expression was assessed by immunohistochemistry. TLR4 immunoreaction products were detected in the epithelium of all specimens, with a higher percentage of immunostained cells in PG. Although TLR4 overexpression was detected in both PG and PC, there were differences that seemed to be related to the nature of the lesion, since in PG all epithelial cells of strands, islands and trabeculae were strongly immunoreactive for TLR4, whereas in PC only some areas of the basal and suprabasal epithelial layers were immunostained. This staining pattern is consistent with the action of TLR4: in PG it could promote formation of epithelial cell rests of Malassez and in epithelial strands and islands the enhancement of cell survival, proliferation and migration, whereas in PC TLR4 could protect the lining epithelium from extensive apoptosis. These findings go some way towards answering the intriguing question of why many epithelial strands or islands in PG and the lining epithelium of apical cysts regress after non-surgical endodontic therapy, and suggest that TLR4 plays a key role in the pathobiology of the inflammatory process related to periapical disease.

Published
2015

43. Beta-catenin and surviving expression in keratocystic odontogenic tumor (KCOT). A comparative immunohistochemical study in primary, recurrent and nevoid basal cell carcinoma syndrome (NBCCS)-associated lesions

Author

Leonardi, R., Matthews, J. B., Loreto, C., Musumeci, G., giuseppina campisi, Lo Muzio, L., Dos Santos, J. N., Pastorino, L., Bufo, P., Pannone, G., Leonardi, R, Matthews, JB, Loreto, C, Musumeci, G, Campisi, G, Lo Muzio, L, dos Santos, JN, Pastorino, L, Bufo, P, and Pannone, G

Subjects
Adult, Male, Histology, Adolescent, Survivin, 6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología [CDU], Settore MED/50 - Scienze Tecniche Mediche Applicate, Apoptosis, Odontogenic Tumors, ß-catenin, NBCCS, Inhibitor of Apoptosis Proteins, Settore MED/29 - Chirurgia Maxillofacciale, Young Adult, Recurrence, Settore MED/28 - Malattie Odontostomatologiche, Humans, beta Catenin, Cell Cycle, NBCCS, ß-catenin, Survivin, KCOT, Basal Cell Nevus Syndrome, Middle Aged, Immunohistochemistry, Gene Expression Regulation, Neoplastic, stomatognathic diseases, KCOT, 2734, Keratins, Female
Abstract

Aim: To determine the epithelial expression of ß-catenin and survivin in sporadic (primary, and recurrent) and nevoid basal cell carcinoma syndrome (NBCCS) keratocystic odontogenic tumour (KCOT) in order to assess activation of the ß-catenin pathway and evidence of apoptotic inhibition, processes that may contribute to the known differences in their biological behaviour. Materials and Methods: Sections from 40 cases of KCOT (19 sporadic/primary; 9 sporadic/recurrent and 12 NBCCS-associated) were immunohistochemically stained for ß-catenin and survivin. The extent and intensity of immunoreactivity within the lining epithelium was assessed, using semi-quantitative scales, independently by two pathologists who were blinded to the clinical-pathological data. Data were analysed using Kruskal-Wallis test and, for pair-wise comparisons, Mann-Whitney test with Bonferroni correction. Results: All cystic epithelial linings stained for ß- catenin and survivin but there were differences in the pattern and intensity of staining among KCOT types. Sporadic primary KCOT showed weaker staining for ß- catenin (P=0.0003) and survivin (P

Published
2013

45. Histopathological pattern of lymph-node metastases from Oral Squamous Cell Carcinoma. An unicentric retrospective study on 146 neck dissections

Author

Contaldo M, FRANCO, Renato, Franco Ionna F, Santoro A, Sbordone C, Longo F, PASQUALI, Daniela, Loreto C, SERPICO, Rosario, Bufo P, Pannone G., Contaldo, M, Franco, Renato, Franco Ionna, F, Santoro, A, Sbordone, C, Longo, F, Pasquali, Daniela, Loreto, C, Serpico, Rosario, Bufo, P, and Pannone, G.

Abstract

Lymph node metastases are responsible for shorter survival in oral squamous cell carcinoma (OSCC). The aim of the present study was to assess the node metastasis frequency and survival according to the node metastasis features in 121 neck dissections (NDs) performed for OSCC, identifying evidence-based correlations and contrasts with previous literature. The retrospective study involved 121 patients affected by OSCC who had undergone modified radical ND (MRND) for therapeutic, elective reasons or after intraoperative positivity to metastasis of sentinel lymph nodes (SLN+). Node metastasis frequency and behaviour (typical vs. atypical) and their number and distribution according to pre-surgical cTNM cancer staging were considered and overall survival Kaplan-Meier curves were calculated for each group in order to compare mortality according to ND type (elective, therapeutic, after SLN+), lymph node metastatic pattern (typical or atypical), size (micrometastasis vs. macrometastasis) and number. Results showed statistically significant different overall survival according to pre-surgical staging, number of lymph nodes harvested and intent to surgery. Sentinel lymph node resulted in the sole positive node affected by metastasis in small cT1- cT2/cN0 OSCC and an ND subsequent to its positivity during intraoperative assessment may be considered an overtreatment.

Published
2013

46. Urinary RKIP/p-RKIP is a potential diagnostic and prognostic marker of clear cell renal cell carcinoma

Author

Papale, M., Vocino, G., Lucarelli, G., Rutigliano, M., Gigante, M., Rocchetti, M. T., Pesce, F., Sanguedolce, F., Bufo, P., Battaglia, M., Stallone, G., Grandaliano, Giuseppe, Carrieri, G., Gesualdo, L., Ranieri, E., Grandaliano G. (ORCID:0000-0003-1213-2177), Papale, M., Vocino, G., Lucarelli, G., Rutigliano, M., Gigante, M., Rocchetti, M. T., Pesce, F., Sanguedolce, F., Bufo, P., Battaglia, M., Stallone, G., Grandaliano, Giuseppe, Carrieri, G., Gesualdo, L., Ranieri, E., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Clear cell Renal Cell Carcinoma (ccRCC) causes over 13,000 deaths each year, and about 20,000 new cases/year in Europe. In most cases, the causes are unknown and, most importantly, there are no reliable biomarkers for the diagnosis and prognosis of this disease. The search for sensitive biomarkers for early diagnosis and prognosis of clear cell Renal Cell Carcinoma (ccRCC) is currently a fast growing field. We carried out proteomics analysis of 93 urinary samples of healthy subjects (HS) and patients affected by ccRCC, prostate cancer (PCa) and chronic kidney disease (CKD), that was able to successfully distinguish each group. The most significant candidate biomarker was identified by mass spectrometry as Raf Kinase Inhibitor Protein (RKIP), a key regulator of cell signaling, already described in several cancer types as a metastasis suppressor. By combining ELISA, immunoblotting and tissue microarray, we demonstrated that, in ccRCC, urinary excretion of RKIP and its phosphorylated form (p-RKIP) reflected the tissue expression of these putative biomarkers. Baseline urinary RKIP, evaluated in an independent cohort of 56 ccRCC patients and 28 HS, successfully distinguished both groups and, most importantly, a cut-offvalue of 10 ng/mg/g Pr/uCr enabled a highly accurate prediction of Cancer-specific survival and Progression-free survival. Furthermore, p-RKIP was totally undetectable in both tissue and urine samples of ccRCC, showing a great potential for diagnostics purposes. Our data indicate that urinary RKIP encompasses both the unphosphorylated and the phosphorylated form and that their combined evaluation can help in the diagnosis and prognosis of ccRCC.

Published
2017

47. Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 Immunohistochemistry, Consensus PCR HPV-DNA, and In Situ Hybridization.[Identificatico Scopus: 2-s2.0-84857478688]

Author

Pannone G, Rodolico V, Santoro A, Lo Muzio L, Franco R, Botti G, Aquino G, Pedicillo MC, Cagiano S, Campisi G, Rubini C, Papagerakis S, Tornesello ML, Buonaguro FM, Bufo P., DE ROSA, GAETANO, STAIBANO, STEFANIA, Pannone, G, Rodolico, V, Santoro, A, Lo Muzio, L, Franco, R, Botti, G, Aquino, G, Pedicillo, Mc, Cagiano, S, Campisi, G, Rubini, C, Papagerakis, S, DE ROSA, Gaetano, Tornesello, Ml, Buonaguro, Fm, Staibano, Stefania, and Bufo, P.

Subjects
HN-SCC, HPV, Human papillomaviru, Methylation-Specific PCR, OPSCC, DNA consensus PCR, Epigenetic, Head and neck squamous cell carcinoma, OSCC, p16-IHC, Immunohistochemistry, IHC
Abstract

Recent emerging evidences identify Human Papillomavirus (HPV) related Head and Neck squamous cell carcinomas (HN-SCCs) as a separate subgroup among Head and Neck Cancers with different epidemiology, histopathological characteristics, therapeutic response to chemo-radiation treatment and clinical outcome. However, there is not a worldwide consensus on the methods to be used in clinical practice. The endpoint of this study was to demonstrate the reliability of a triple method which combines evaluation of: 1. p16 protein expression by immunohistochemistry (p16-IHC); 2. HPV-DNA genotyping by consensus HPV-DNA PCR methods (Consensus PCR); and 3 viral integration into the host by in situ hybridization method (ISH). This triple method has been applied to HN-SCC originated from oral cavity (OSCC) and oropharynx (OPSCC), the two anatomical sites in which high risk (HR) HPVs have been clearly implicated as etiologic factors. Methylation-Specific PCR (MSP) was performed to study inactivation of p16-CDKN2a locus by epigenetic events. Reliability of multiple methods was measured by Kappa statistics.All the HN-SCCs confirmed HPV positive by PCR and/or ISH were also p16 positive by IHC, with the latter showing a very high level of sensitivity as single test (100\% in both OSCC and OPSCC) but lower specificity level (74\% in OSCC and 93\% in OPSCC).Concordance analysis between ISH and Consensus PCR showed a faint agreement in OPSCC (κ = 0.38) and a moderate agreement in OSCC (κ = 0.44). Furthermore, the addition of double positive score (ISHpositive and Consensus PCR positive) increased significantly the specificity of HR-HPV detection on formalin-fixed paraffin embedded (FFPE) samples (100\% in OSCC and 78.5\% in OPSCC), but reduced the sensitivity (33\% in OSCC and 60\% in OPSCC). The significant reduction of sensitivity by the double method was compensated by a very high sensitivity of p16-IHC detection in the triple approach.Although HR-HPVs detection is of utmost importance in clinical settings for the Head and Neck Cancer patients, there is no consensus on which to consider the 'golden standard' among the numerous detection methods available either as single test or combinations. Until recently, quantitative E6 RNA PCR has been considered the 'golden standard' since it was demonstrated to have very high accuracy level and very high statistical significance associated with prognostic parameters. In contrast, quantitative E6 DNA PCR has proven to have very high level of accuracy but lesser prognostic association with clinical outcome than the HPV E6 oncoprotein RNA PCR. However, although it is theoretically possible to perform quantitative PCR detection methods also on FFPE samples, they reach the maximum of accuracy on fresh frozen tissue. Furthermore, worldwide diagnostic laboratories have not all the same ability to analyze simultaneously both FFPE and fresh tissues with these quantitative molecular detection methods. Therefore, in the current clinical practice a p16-IHC test is considered as sufficient for HPV diagnostic in accordance with the recently published Head and Neck Cancer international guidelines. Although p16-IHC may serve as a good prognostic indicator, our study clearly demonstrated that it is not satisfactory when used exclusively as the only HPV detecting method. Adding ISH, although known as less sensitive than PCR-based detection methods, has the advantage to preserve the morphological context of HPV-DNA signals in FFPE samples and, thus increase the overall specificity of p16/Consensus PCR combination tests.

Published
2012

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