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2. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

Author

Wang, Anqi, Shen, Jiayi, Rodriguez, Alex A., Saunders, Edward J., Chen, Fei, Janivara, Rohini, Darst, Burcu F., Sheng, Xin, Xu, Yili, Chou, Alisha J., Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Plym, Anna, Sahimi, Ali, Hoffman, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Laisk, Triin, Figuerêdo, Jéssica, Muir, Kenneth, Ito, Shuji, Liu, Xiaoxi, Uchio, Yuji, Kubo, Michiaki, Kamatani, Yoichiro, Lophatananon, Artitaya, Wan, Peggy, Andrews, Caroline, Lori, Adriana, Choudhury, Parichoy P., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher T., Cho, Kelly, Mcmahon, Benjamin H., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Røder, Andreas, Stroomberg, Hein V., Batra, Jyotsna, Chambers, Suzanne, Horvath, Lisa, Clements, Judith A., Tilly, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordstrom, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie, Cook, Michael B., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Jr., Ian M., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L., Ostrander, Elaine A., Koutros, Stella, Beane Freeman, Laura E., Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Geraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Butler, Ebonee N., Mohler, James L., Taylor, Jack A., Kogevinas, Manolis, Dierssen-Sotos, Trinidad, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Pilie, Patrick, Yu, Yao, Bohlender, Ryan J., Gu, Jian, Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Brenner, Hermann, Chen, Xuechen, Holleczek, Bernd, Schöttker, Ben, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine M., Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Abraham, Aswin, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer, Petrovics, Gyorgy, Casey, Graham, Wang, Ying, Tettey, Yao, Lachance, Joseph, Tang, Wei, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Yamoah, Kosj, Govindasami, Koveela, Chokkalingam, Anand P., Keaton, Jacob M., Hellwege, Jacklyn N., Clark, Peter E., Jalloh, Mohamed, Gueye, Serigne M., Niang, Lamine, Ogunbiyi, Olufemi, Shittu, Olayiwola, Amodu, Olukemi, Adebiyi, Akindele O., Aisuodionoe-Shadrach, Oseremen I., Ajibola, Hafees O., Jamda, Mustapha A., Oluwole, Olabode P., Nwegbu, Maxwell, Adusei, Ben, Mante, Sunny, Darkwa-Abrahams, Afua, Diop, Halimatou, Gundell, Susan M., Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Kachuri, Linda, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Preuss, Michael H., Loos, Ruth J. F., Zawistowski, Matthew, Zöllner, Sebastian, Lu, Zeyun, Van Den Eeden, Stephen K., Easton, Douglas F., Ambs, Stefan, Edwards, Todd L., Mägi, Reedik, Rebbeck, Timothy R., Fritsche, Lars, Chanock, Stephen J., Berndt, Sonja I., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Gaziano, J. Michael, Justice, Amy C., Mancuso, Nick, Terao, Chikashi, Eeles, Rosalind A., Kote-Jarai, Zsofia, Madduri, Ravi K., Conti, David V., and Haiman, Christopher A.

Published
2023
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4. An Approach to an Online EdD in Community College Leadership Program

Author

Harrington, Christine, Hooper, Kimberlee, Hughes, AnnMarie, Klein, Eric, Melendez, John, Siddique, Faraz, and Wasserman, Ellen

Abstract

The purpose of this article is to provide an example of how an EdD in Community College Leadership program is offered in an online format. First, the benefits of online programs, including increased access and flexibility for working professionals and higher levels of diversity among the student body are discussed. Then, several strategies to promote connection among students and to facilitate a supportive, engaging learning environment virtually are shared. For example, the value of using a cohort model, a carefully designed curriculum with assignments that have practical value, and a balance of synchronous and asynchronous learning activities are described. Finally, the important role of and strategies for incorporating models and mentors into an online doctoral program are discussed.

Published
2021

5. Analysis of separate training and validation radical prostatectomy cohorts identifies 0.25 mm diameter as an optimal definition for "large" cribriform prostatic adenocarcinoma.

Author

Chan, Emily, McKenney, Jesse K, Hawley, Sarah, Corrigan, Dillon, Auman, Heidi, Newcomb, Lisa F, Boyer, Hilary D, Carroll, Peter R, Cooperberg, Matthew R, Klein, Eric, Fazli, Ladan, Gleave, Martin E, Hurtado-Coll, Antonio, Simko, Jeffry P, Nelson, Peter S, Thompson, Ian M, Tretiakova, Maria S, Troyer, Dean, True, Lawrence D, Vakar-Lopez, Funda, Lin, Daniel W, Brooks, James D, Feng, Ziding, and Nguyen, Jane K

Subjects
Humans, Adenocarcinoma, Prostatic Neoplasms, Prostatectomy, Retrospective Studies, Male, Neoplasm Grading, Clinical Research, Cancer, Medical and Health Sciences, Pathology
Abstract

Cribriform growth pattern is well-established as an adverse pathologic feature in prostate cancer. The literature suggests "large" cribriform glands associate with aggressive behavior; however, published studies use varying definitions for "large". We aimed to identify an outcome-based quantitative cut-off for "large" vs "small" cribriform glands. We conducted an initial training phase using the tissue microarray based Canary retrospective radical prostatectomy cohort. Of 1287 patients analyzed, cribriform growth was observed in 307 (24%). Using Kaplan-Meier estimates of recurrence-free survival curves (RFS) that were stratified by cribriform gland size, we identified 0.25 mm as the optimal cutoff to identify more aggressive disease. In univariable and multivariable Cox proportional hazard analyses, size >0.25 mm was a significant predictor of worse RFS compared to patients with cribriform glands ≤0.25 mm, independent of pre-operative PSA, grade, stage and margin status (p 0.25 mm had a significantly lower RFS relative to patients with cribriform glands ≤0.25 mm (each subset p = 0.004). Furthermore, there was no significant difference in outcomes between patients with cribriform glands ≤ 0.25 mm and patients without cribriform glands. The >0.25 mm cut-off was validated as statistically significant in a separate 419 patient, completely embedded whole-section radical prostatectomy cohort by biochemical recurrence, metastasis-free survival, and disease specific death, even when cases with admixed Gleason pattern 5 carcinoma were excluded. In summary, our findings support reporting cribriform gland size and identify 0.25 mm as an optimal outcome-based quantitative measure for defining "large" cribriform glands. Moreover, cribriform glands >0.25 mm are associated with potential for metastatic disease independent of Gleason pattern 5 adenocarcinoma.

Published
2022

7. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Author

Abe, Mitsunori, Abhaichand, Rajpal K, Abhayaratna, Walter P, Abhyankar, Atul, Abidin, Imran B Zainal, Abou Assi, Hiba, Accini Mendoza, Jose L, Adas, Mine, Agaiby, John M, Agarwal, Devendra K, Agha, Maher, Ahmed, Azazuddin, Ahtiainen, Petteri, Aigner, Elmar, Ajay, Naik, Ali, Norsiah, Al-Karadsheh, Amer, Allison, Roy, Allison, Dale C, Alpenidze, Diana, Altuntas, Yuksel, Al-Zoebi, Ayham, Ambuj, Roy, Amerena, John, Anderson, Robert J, Ando, Toshiaki, Andrews, Robert, Antonova, Elizaveta, Appel, Karl-Friedrich, Arantes, Flávia B, Araz, Mustafa, Arbel, Yaron, Arenas León, José L, Argyrakopoulou, Georgia, Ariani, Mehrdad, Arias Mendoza, Maria A, Arif, Ahmed A, Arneja, Jaspal, Aroda, Vanita R, Aronne, Louis J, Arstall, Margaret, Asamoah, Njaimeh, Asanin, Milika, Audish, Hanid, Avram, Rodica, Badat, Aysha, Badiu, Corin V, Bakdash, Wa'el, Bakiner, Okan S, Bandezi, Vuyokazi N, Bang, Liew H, Bansal, Sandeep, Baranyai, Marietta, Barbarash, Olga, Barber, Mark, Barnum, Otis, Barone Rochette, Gilles, Bashkin, Amir, Baum, Seth, Bays, Harold E, Bazzoni Ruiz, Alberto E, Beckowski, Maciej, Beerachee, Yaswin, Bellary, Srikanth, Belousova, Lidia, Berk, Martin, Bernstein, Marc, Berra, Cesare, Beshay, Isaac, Bhagwat, Ajit, Bhan, Arti, Biggs, William C, Billings, Liana, Bitar, Fahed, Block, Bradley, Bo, Simona, Bogdanski, Pawel, Bolshakova, Olga O, Boshchenko, Alla A, Bosworth, Hayden, Botero Lopez, Rodrigo, Bôttcher, Morten, Bourgeois, Ronald, Brautigam, Donald, Breton, Cristian F, Broadley, Andrew, Brockmyre, Andrew P, Brodie, Steven K, Bucci, Marco, Budincevic, Hrvoje, Budoff, Matthew J, Buffman, Barry, Buljubasic, Nediljka, Buranapin, Supawan, Burgess, Lesley, Burguera, Bartolomé, Buriakovska, Olena, Buscemi, Silvio, Busch, Robert, Buse, John B, Buynak, Robert, Byrne, Maria, Caceaune, Elena, Cadena Bonfanti, Alberto J, Calinescu, Cornell V, Call, Robert S, Canecki Varzic, Silvija, Cannon, Kevin, Capehorn, Matt, Cariou, Bertrand, Carr, Jeffrey, Carrillo-Jimenez, Rodolfo, Casas, Marcelo, Castro, Almudena, Celik, Ahmet, Cercato, Cintia, Cermak, Ondrej, Cha, James Y, Chacon, Carolina, Chaicha-Brom, Tira, Chandra, Sandeep, Chettibi, Mohamed, Chevts, Julia, Christopher, Johann, Chrustowski, Witold, Cif, Adriana, Clark, Rebecca, Clark, Wayne, Clifford, Piers, Coetzee, Kathleen, Cogni, Giulia, Colao, Anna Maria, Colquhoun, David M, Concha, Mauricio, Condit, Jonathan, Constance, Christian, Constantin, Ciprian, Constantinescu, Silviana, Corbett, Clive, Cornett, George M, Correia, Marcelo, Cortinovis, Fiorenzo, Cosma, Dana, Creely, Steven, Cross, David, Curtis, Brian, Czochra, Wojciech, Daboul, Nizar Y, Dagdelen, Selcuk, D'agostino, Ronald, Dang, Cuong, Datta, Sudip, Davuluri, Ashwini K, Dawood, Saleem Y, De Jong, Douwe M, De La Cuesta, Carmen, De Los Rios Ibarra, Manuel O, De Pablo, Carmen, De Pauw, Michel, Dela Llana, Alexander, Delibasic, Maja, Delic-Brkljacic, Diana, Demicheli, Thibaud, Denger, Ralf J, Desai, Devang, Desai, Piyush, Desouza, Cyrus V, Dicker, Dror, Djenic, Nemanja, Dobson, Simon, Doi, Masayuki, Doran, Jesse A, Dorman, Reinhart, Dotta, Francesco, Dukes, Carl E, Duronto, Ernesto, Durst, Ronen, Dvoryashina, Irina V, Ebrahim, Iftikhar O, Eggebrecht, Holger, Egstrup, Kenneth, Ekinci, Elif I, Eliasson, Björn, Eliasson, Ken, Enache, Georgiana, Enculescu, Dan, English, Patrick, Ermakova, Polina, Ershova, Olga, Ezaki, Hirotaka, Ezhov, Marat, Farias, Eduardo, Farias, Javier M, Farsky, Pedro S, Ferreira, Daniel, Filteau, Pierre, Finneran, Matthew P, Folkens, Eric M, Fonseca, Alberto G, Fonseca, Luisa, Fordan, Steven, Fourie, Nyda, França, Sara, Franco, Denise R, Franek, Edward, Friedman, Keith, Frittitta, Lucia, Froer, Michael, Fuckar, Krunoslav, Fujii, Kenshi, Fujita, Ryoko, Fukushima, Yasushi, Fulat, Mohamed, Fulwani, Mahesh, Gajos, Grzegorz, Galyavich, Albert, Gambill, Michael L, Gandotra, Dheeraj, Winston, Gandy, Jr., Garcia Hernandez, Pedro A, García Reza, Raymundo, Garg, Naveen, Garg, Sandeep, Garvey, William T, Garza, Juan C, Gatta-Cherifi, Blandine, Gelev, Valeri, Geller, Steven A, Geohas, Jeffrey G, Georgiev, Borislav, Ghazi, Adline, Gilbert, Matthew P, Gilinskaya, Olga, Gislason, Gunnar, Gogas Yavuz, Dilek, González Albarrán, Olga, Gordeev, Ivan G, Gorton, Sidney C, Goudev, Assen, Gretland Valderhaug, Tone, Groenemeijer, Bjorn, Gul, Ibrahim, Gullestad, Lars, Gurieva, Irina, Guseva, Galina N, Hagenow, Andreas, Haluzik, Martin, Halvorsen, Sigrun, Hammoudi, Naima, Hanaoka, Keiichi, Hancu, Nicolae, Hanusch, Ursula, Harris, Kathleen, Harris, Barry, Hartleib, Michael, Hartman, Aaron N, Hata, Yoshiki, Heimer, Brian, Herman, Lee, Herzog, William, Hewitt, Eric, Heymer, Peter, Hiremath, Shirish, Hjelmesaeth, Joeran, Høgalmen, Rasmus Geir, Høivik, Hans Olav, Holmer, Helene, Horoshko, Olha, Houser, Patricia M, Hove, Jens D, Hsieh, I-Chang, Hulot, Jean-Sébastien, Hussein, Zanariah, Ilashchuk, Tetiana, Ilveskoski, Erkki, Ipatko, Irina, Iranmanesh, Ali, Isawa, Tsuyoshi, Issa, Moises, Iteld, Bruce, Iwasawa, Takamasa, Jabbar, Danish, Jackson, Richard A, Jackson-Voyzey, Ewart, Jacob, Stephan, Jaffrani, Naseem A, Jardula, Michael F, Jastreboff, Ania, Jensen, Svend E, Jerkins, Terri, Jimenez-Ramos, Silvia A, Jitendra Pal Singh, Sawhney, Johnson, Wallace, Joyce, John M, Jozefowska, Malgorzata, Jugnundan, Prakash, Jungmair, Wolfgang, Jurowiecki, Jaroslaw, Kadokami, Toshiaki, Kahali, Dhiman, Kahrmann, Gerd, Kaiser, Sergio E, Kalmucki, Piotr, Kanadasi, Mehmet, Kandath, David, Kania, Grzegorz, Kannan, J, Kapp, Cornelia, Karczmarczyk, Agnieszka, Kartalis, Athanasios, Kaser, Susanne, Kasim, Sazzli Shahlan, Kastelic, Richard, Kato, Toshiaki, Katova, Tzvetana, Kaul, Upendra, Kautzky-Willer, Alexandra, Kawanishi, Masahiro, Kayikcioglu, Meral, Kazakova, Elena E, Keeling, Philip, Kempe, Hans-Peter, Kereiakes, Dean J, Kerneis, Mathieu, Keski-Opas, Tiina, Khadra, Suhail, Khaisheva, Larisa, Kharakhulakh, Marina, Khlevchuk, Tatiana, Khoo, Jeffrey, Kiatchoosakun, Songsak, Kinoshita, Noriyuki, Kinoshita, Masaharu, Kitamura, Ryoji, Kiyosue, Arihiro, Klavina, Irina, Klein, Eric J, Klimsa, Zdenek, Klonoff, David, Klug, Eric, Kobalava, Zhanna, Kodera, Satoshi, Koga, Tokushi, Kokkinos, Alexander, Koleckar, Pavel, Könyves, László, Koren, Michael J, Kormann, Adrian P, Kostner, Karam, Kreutzmann, Kristin, Krishinan, Saravanan, Krishnasamy, Sathya S, Krivosheeva, Inga, Kruljac, Ivan, Kubicki, Ted, Kuchar, Ladislav, Kujawiak, Monika, Kunishige, Hideyuki, Kurtinecz, Melinda, Kurtz Lisboa, Hugo R, Kushnir, Mykola, Kyyak, Yulian, Lace, Arija, Lakka, Timo, Lalic, Nebojsa, Lalic, Katarina, Lambadiari, Vaia, Lanaras, Leonidas, Lang, Chim, Langlois, Marie-France, Lash, Joseph, Latkovskis, Gustavs, Lau, David, Lazcano Soto, José Roberto, Le Roux, Carel, Ledesma, Gilbert N, Lee, Li Yuan, Lee, Thung-Lip, Lee, Kelvin, Lehrke, Michael, Leite, Silmara O, Leksycka, Agata, Lenzmeier, Thomas, Leonetti, Frida, Leonidova, Viktoriia, Lepor, Norman, Leung, Melissa, Levchenko, Olena, Levins, Peter, Levy, Louis J, Lewis, Matthew, Liberopoulos, Evangelos, Liberty, Idit, Lindholm, Carl-Johan, Lingvay, Ildiko, Linhart, Ales, Liu, Ming-En, Liu, Jenny, Lofton, Holly, Logemann, Timothy, Lombaard, Johannes J, Lombard, Landman, Lorraine, Richard, Lovell, Charles F, Ludvik, Bernhard, Lukaszewicz, Monika, Lupkovics, Géza, Lupovitch, Steven, Lupu, Sirona, Lynch, Mary, Lysak, Zoreslava, Lysenko, Tatyana A, Maeda, Hajime, Maeda, Itaru, Mæng, Michael, Mahajan, Ajay U, Maher, Vincent, Maia, Lilia N, Makotoko, Ellen M, Malavazos, Alexis, Malecha, Jan, Malicherova, Emilia, Manita, Mamoru, Mannucci, Edoardo, Mareev, Viacheslav, Marin, Liliana, Markova, Tatiana, Marso, Steven P, Martens, F.M.A.C., Martinez, Cuper, Martinez Cano, Carlos A, Martins, Cristina, Masmiquel Comas, Luis, Matsumoto, Takashi, Mcdonald, Kenneth, Mcgowan, Barbara, Mcgrew, Frank, Mclean, Barry K, Mcpherson, David D, Merino Torres, Juan Francisco, Meyers, Peter, Meyhöfer, Sebastian, Mezquita Raya, Pedro, Milanova, Maria, Milicic, Davor, Miller, Gary, Mills, Richard E, Mîndrescu, Nicoleta M, Mingrone, Geltrude, Minkova, Dotska A, Mirani, Marco, Miras, Alexander, Mistodie, Cristina V, Mitomo, Satoru, Mittal, Sanjay, Miyake, Taiji, Miyamoto, Naomasa, Molony, David, Monteiro, Pedro, Mooe, Thomas, Moosa, Naeem, Morales Portillo, Cristobal, Morales Villegas, Enrique C, Morawski, Emily J, Morbey, Claire, Morin, Robert P, Morisaki, Kuniaki, Morosanu, Magdalena, Mosenzon, Ofri, Mostovoy, Yuriy, Munir, Iqbal, Muratori, Fabrizio, Murray, Ryan, Murthy, Avinash, Myint, Min, Myshanych, Galyna, Nafornita, Valerica, Nagano, Takuya, Nair, Sunil, Nakhle, Samer N, Natsuaki, Masahiro, Nayak, Bindu M, Nibouche, Djamel Eddine, Nicholls, Stephen, Nicolau, José C, Nicolescu, Georgiana, Nierop, Peter, Niskanen, Leo, Ntaios, George, Nygård, Ottar Kjell, Oaks, Joshua B, Obrezan, Andrey, O'donnell, Philip, Oguri, Mitsutoshi, Oguzhan, Abdurrahman, Oh, Fumiki, Ohsugi, Mitsuru, Okada, Yoshio, Okayama, Hideki, Onaca, Adriana, Onaka, Haruhiko, Oneil, Patrick, Ong, Tiong Kiam, Ong, Stephen, Ono, Yasuhiro, Opsahl, Paul J, Ostrowska, Lucyna, Oviedo, Alejandra, Ozdogan, Oner, Ozpelit, Ebru, Pagkalos, Emmanouil, Pagotto, Uberto, Páll, Dénes, Pandey, Amritanshu- Shekhar, Parkhomenko, Oleksandr, Parvathareddy, Krishna Malakondareddy, Patel, Minesh B, Patsilinakos, Sotirios, Paul, Neil, Pedersen, Sue, Pereira, Isabel, Pereira, Edward Scott, Perez Terns, Paula, Perez-Vargas, Elba A, Pergaeva, Yulia, Perkelvald, Alexander, Peskov, Andrey B, Peter, Jonathan, Peters, Karina, Petit, Catherine, Petrov, Ivo, Philis-Tsimikas, Athena, Pietilä, Mikko, Pinto, Fausto, Piros, Annamária, Piyayotai, Dilok, Platonov, Dmitriy, Poirier, Paul, Pop, Lavinia, Popa, Bogdan, Pop-Busui, Rodica, Poremba, John, Porto, Alejandro, Postadzhiyan, Arman, Pothineni, Ramesh B, Potu, Ranganatha P, Powell, Talessa, Prafulla, Kerkar G, Prager, Rudolf, Prakova-Teneva, Zhulieta R, Pratley, Richard E, Price, Hermione, Pulka, Grazyna, Pullman, John, Punt, Zelda E, Purighalla, Raman S, Purnell, Peter, Qureshi, Mansoor, Rabasa-Lhoret, Remi, Raikhel, Marina A, Rancane, Gita, Randeva, Harpal, Rasouli, Neda, Reurean Pintilei, Delia V, Reyes, Ciro R, Rezgale, Inga, Rice, Eva, Riley, Thaddeus H, Risser, Joseph A, Ristic, Arsen, Rivas Fernández, Margarita, Robbins, David, Robitaille, Yves, Rodbard, Helena W, Rodriguez Plazas, Jaime A, Römer, T.J., Rosen, Glenn, Rosman, Dr Azhari, Rossi, Paulo, Rudenko, Leonid, Ruffin, Omari, Ruhani, Anwar Irawan, Runev, Nikolay, Ruyatkin, Dmitriy, Ruzic, Alen, Ryabov, Vyacheslav V, Rydén, Lars, Saggar, Suraj, Sakamoto, Tomohiro, Salter, Tim, Samal, Aditya K, Samoilova, Yulia, Sanabria, Hugo D, Sancak, Seda, Sangrigoli, Renee, Sansanayudh, Nakarin, Santini, Ferruccio, Saraiva, José F, Sardinov, Ruslan, Sargeant, William, Sari, Ramazan, Sathananthan, Airani, Sathyapalan, Thozhukat, Sato, Atsushi, Sauter, Joachim, Sbraccia, Paolo, Schaap, J., Schaum, Thomas, Schiele, François, Scott, John, Segal Lieberman, Gabriella, Segner, Alexander, Senior, Roxy, Sergeeva-Kondrachenko, Marina Y, Serota, Harvey, Serusclat, Pierre, Sethi, Rishi, Shah, Manoj K, Shah, Neerav, Shalaev, Sergey, Sharma, Raj, Sharma, Sumeet, Shaydyuk, Oksana, Shea, Heidi C, Shechter, Michael, Shehadeh, Naim, Shirazi, Mitra, Shlesinger, Yshay, Shneker, Ayham, Shutemova, Elena, Siasos, Gerasimos, Siddiqui, Imran A, Sidey, Jennifer, Sigal, Felix, Sime, Iveta, Singh, Narendra, Siraj, Elias, Sivalingam, Kanagaratnam, Skoczylas, Grzegorz, Smith, Stephen K, Smolenskaya, Olga, Snyder, Brian, Sofer, Yael, Sofley, C.W., Solano, Royce, Sonmez, Yusuf A, Sorokin, Maxim, Soto González, Alfonso, Sotolongo, Carlos, Soufer, Joseph, Soyluk Selcukbiricik, Ozlem, Spaic, Tamara, Spriggs, Douglas, Sreenan, Seamus, Stahl, Hans-Detlev, Stamatelopoulos, Kimon, Stanislavchuk, Mykola, Stankovic, Goran, Stasek, Josef, Steg, Gabriel, Steindorf, Joerg, Stephan, Dominique, Stewart, John, Still, Christopher, St-Maurice, Francois, Stogowska-Nikiciuk, Barbara, Stoker, Jeff, Stokic, Edita, Strzelecka, Anna, Sturm, Kerstin, Sueyoshi, Atsushi, Sugiura, Toshiyuki, Sultan, Senan, Suplotova, Lyudmila A, Suwanagool, Arisara, Suwanwalaikorn, Sompongse, Sveklina, Tatiana, Swanson, Neil, Swart, Henk, Swenson, Bradley P, Szyprowska, Ewa, Tait, Graeme, Takács, Róbert, Takeuchi, Yuzo, Tamirisa, Aparna, Tanaka, Hideki, Tatovic, Danijela, Tellier, Guy, Teragawa, Hiroki, Teterovska, Dace, Thomas, Nihal, Thuan, Jean-Francois, Tinahones, Francisco, Tisheva-Gospodinova, Snezhanka, Toarba, Cristina, Todoriuk, Liudmyla, Tokmakova, Mariya, Tonstad, Serena, Toplak, Hermann, Tran, Henry, Tripathy, Devjit, Trusau, Aliaksandr, Tsabedze, Nqoba, Tsougos, Elias, Tsoukas, George M, Tuccinardi, Dario, Tuna, Mazhar M, Turatti, Luiz A, Tziomalos, Konstantinos, Udommongkol, Chesda, Ueda, Osamu, Ukkola, Olavi, Unubol, Mustafa, Urbach, Dorothea, Urina Triana, Miguel A, Usdan, Lisa, Vaidya, Bijay, Vale, Noah, Vallieres, Gerald, Van Beek, Andre P, Van De Borne, Philippe, Van Der Walt, Eugene, Van Der Zwaan, C., Van Nieuwenhuizen, Elane, Van Zyl, Louis, Vanduynhoven, Philippe, Varghese, Kiron, Vasileva, Svetla P, Vassilev, Dobrin, Vathesatogkit, Prin, Velychko, Valentyna, Vercammen, Chris, Verges, Bruno, Verma, Subodh, Verwerft, Jan, Vesela, Alica, Veselovskaya, Nadezhda G, Vettor, Roberto, Veze, Irina, Vijan, Vinod, Vijayaraghavan, Ram, Villarino, Adriana, Vincent, Royce, Vinogradova, Oksana, Vishlitzky, Victor, Vlad, Adrian, Vladu, Ionela Mihaela, Vo, Anthony, Von Engelhardt, Charlotte, Von Münchhausen, Candy, Vorobyeva, Olga, Vossenberg, T., Vrolix, Mathias, Vukicevic, Marjana, Vyshnyvetskyy, Ivan, Wadvalla, Shahid, Wagner, Jan, Wakeling, John, Wallace, James, Wan Mohamed, Wan Mohd Izani, Wander, Gurpreet S, Ward, Kathleen, Warren, Mark L, Watanabe, Atsuyuki, Weber, Bruce, Weintraub, Howard, Weisnagel, John, Welker, James, Wendisch, Ulrich, Wenocur, Howard S, Wierum, Craig, Wilding, John, William, Maged, Wilson, Pete, Wilson, Jonathan P, Wong, Yuk-Ki, Wongcharoen, Wanwarang, Wozniak, Iwona, Wu, Chau-Chung, Wyatt, Nell, Wynne, Alan, Yamaguchi, Hiroshi, Yamasaki, Masahiro, Yazici, Dilek, Yeh, Hung-I, Yotov, Yoto, Yuan, Qingyang, Zacher, Jeffrey, Zagrebelnaya, Olga, Zaidman, Cesar J, Zalevskaya, Alsu, Zarich, Stuart, Zatelli, Maria Chiara, Zeller, Helga, Zhdanova, Elena A, Zornitzki, Taiba, Zrazhevskiy, Konstantin, Zykov, Mikhail, Lincoff, A Michael, Ryan, Donna H, Colhoun, Helen M, Deanfield, John E, Emerson, Scott S, Kahn, Steven E, Kushner, Robert F, Plutzky, Jorge, Brown-Frandsen, Kirstine, Hovingh, G Kees, Hardt-Lindberg, Soren, Tornøe, Christoffer W, Deanfield, John, Scirica, Benjamin M, Ryan, Donna, Kosiborod, Mikhail N, Hardt-Lindberg, Søren, Frenkel, Ofir, Weeke, Peter E, Rasmussen, Søren, Lang, Chim C, and Urina-Triana, Miguel

Published
2024
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8. Caulobacter lipid A is conditionally dispensable in the absence of fur and in the presence of anionic sphingolipids

Author

Zik, Justin J, Yoon, Sung Hwan, Guan, Ziqiang, Skidmore, Gabriele Stankeviciute, Gudoor, Ridhi R, Davies, Karen M, Deutschbauer, Adam M, Goodlett, David R, Klein, Eric A, and Ryan, Kathleen R

Subjects
Biochemistry and Cell Biology, Biological Sciences, Infectious Diseases, Caulobacter, Caulobacter crescentus, Lipid A, Lipopolysaccharides, Sphingolipids, CP: Microbiology, Fur, ceramide, iron, lipid A, lipopolysaccharide, outer membrane, sphingolipid, Medical Physiology, Biological sciences
Abstract

Lipid A, the membrane-anchored portion of lipopolysaccharide (LPS), is an essential component of the outer membrane (OM) of nearly all Gram-negative bacteria. Here we identify regulatory and structural factors that together render lipid A nonessential in Caulobacter crescentus. Mutations in the ferric uptake regulator fur allow Caulobacter to survive in the absence of either LpxC, which catalyzes an early step of lipid A synthesis, or CtpA, a tyrosine phosphatase homolog we find is needed for wild-type lipid A structure and abundance. Alterations in Fur-regulated processes, rather than iron status per se, underlie the ability to survive when lipid A synthesis is blocked. Fitness of lipid A-deficient Caulobacter requires an anionic sphingolipid, ceramide phosphoglycerate (CPG), which also mediates sensitivity to the antibiotic colistin. Our results demonstrate that, in an altered regulatory landscape, anionic sphingolipids can support the integrity of a lipid A-deficient OM.

Published
2022

11. Prospective Multicenter Comparison of Open and Robotic Radical Prostatectomy: The PROST-QA/RP2 Consortium

Author

Chang, Peter, Wagner, Andrew A, Regan, Meredith M, Smith, Joseph A, Saigal, Christopher S, Litwin, Mark S, Hu, Jim C, Cooperberg, Matthew R, Carroll, Peter R, Klein, Eric A, Kibel, Adam S, Andriole, Gerald L, Han, Misop, Partin, Alan W, Wood, David P, Crociani, Catrina M, Greenfield, Thomas K, Patil, Dattatraya, Hembroff, Larry A, Davis, Kyle, Stork, Linda, Spratt, Daniel E, Wei, John T, Sanda, Martin G, and Consortium, and the PROST-QA RP2

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Pain Research, Chronic Pain, Urologic Diseases, Cancer, 6.4 Surgery, Evaluation of treatments and therapeutic interventions, Aged, Humans, Laparoscopy, Male, Middle Aged, Prospective Studies, Prostatectomy, Prostatic Neoplasms, Quality of Life, Robotic Surgical Procedures, Treatment Outcome, prostatectomy, robotic surgical procedures, quality of life, PROST-QA/RP2 Consortium
Abstract

PurposeOur goal was to evaluate the comparative effectiveness of robot-assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) in a multicenter study.Materials and methodsWe evaluated men with localized prostate cancer at 11 high-volume academic medical centers in the United States from the PROST-QA (2003-2006) and the PROST-QA/RP2 cohorts (2010-2013) with a pre-specified goal of comparing RALP (549) and ORP (545). We measured longitudinal patient-reported health-related quality of life (HRQOL) at pre-treatment and at 2, 6, 12, and 24 months, and pathological and perioperative outcomes/complications.ResultsDemographics, cancer characteristics, and margin status were similar between surgical approaches. ORP subjects were more likely to undergo lymphadenectomy (89% vs 47%; p

Published
2022

12. Genetic factors associated with prostate cancer conversion from active surveillance to treatment

Author

Jiang, Yu, Meyers, Travis J, Emeka, Adaeze A, Cooley, Lauren Folgosa, Cooper, Phillip R, Lancki, Nicola, Helenowski, Irene, Kachuri, Linda, Lin, Daniel W, Stanford, Janet L, Newcomb, Lisa F, Kolb, Suzanne, Finelli, Antonio, Fleshner, Neil E, Komisarenko, Maria, Eastham, James A, Ehdaie, Behfar, Benfante, Nicole, Logothetis, Christopher J, Gregg, Justin R, Perez, Cherie A, Garza, Sergio, Kim, Jeri, Marks, Leonard S, Delfin, Merdie, Barsa, Danielle, Vesprini, Danny, Klotz, Laurence H, Loblaw, Andrew, Mamedov, Alexandre, Goldenberg, S Larry, Higano, Celestia S, Spillane, Maria, Wu, Eugenia, Carter, H Ballentine, Pavlovich, Christian P, Mamawala, Mufaddal, Landis, Tricia, Carroll, Peter R, Chan, June M, Cooperberg, Matthew R, Cowan, Janet E, Morgan, Todd M, Siddiqui, Javed, Martin, Rabia, Klein, Eric A, Brittain, Karen, Gotwald, Paige, Barocas, Daniel A, Dallmer, Jeremiah R, Gordetsky, Jennifer B, Steele, Pam, Kundu, Shilajit D, Stockdale, Jazmine, Roobol, Monique J, Venderbos, Lionne DF, Sanda, Martin G, Arnold, Rebecca, Patil, Dattatraya, Evans, Christopher P, Dall’Era, Marc A, Vij, Anjali, Costello, Anthony J, Chow, Ken, Corcoran, Niall M, Rais-Bahrami, Soroush, Phares, Courtney, Scherr, Douglas S, Flynn, Thomas, Karnes, R Jeffrey, Koch, Michael, Dhondt, Courtney Rose, Nelson, Joel B, McBride, Dawn, Cookson, Michael S, Stratton, Kelly L, Farriester, Stephen, Hemken, Erin, Stadler, Walter M, Pera, Tuula, Banionyte, Deimante, Bianco, Fernando J, Lopez, Isabel H, Loeb, Stacy, Taneja, Samir S, Byrne, Nataliya, Amling, Christopher L, Martinez, Ann, Boileau, Luc, Gaylis, Franklin D, Petkewicz, Jacqueline, Kirwen, Nicholas, Helfand, Brian T, Xu, Jianfeng, Scholtens, Denise M, Catalona, William J, and Witte, John S

Subjects
Biological Sciences, Genetics, Clinical Research, Prevention, Human Genome, Clinical Trials and Supportive Activities, Urologic Diseases, Aging, Cancer, Prostate Cancer, genetics, genome-wide association study, prostate, prostatic neoplasms
Abstract

Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9×10-7 and GAB2, p = 2.0×10-6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS-versus treatment for the initial management of patients with low-risk PC.

Published
2022

13. Performance of a Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography–Derived Risk-Stratification Tool for High-risk and Very High-risk Prostate Cancer

Author

Xiang, Michael, Martin, Ting, Savjani, Ricky, Pollom, Erqi L, Karnes, R Jeffrey, Grogan, Tristan, Wong, Jessica K, Motterle, Giovanni, Tosoian, Jeffrey J, Trock, Bruce J, Klein, Eric A, Stish, Bradley J, Dess, Robert T, Spratt, Daniel E, Pilar, Avinash, Reddy, Chandana, Levin-Epstein, Rebecca, Wedde, Trude B, Lilleby, Wolfgang A, Fiano, Ryan, Merrick, Gregory S, Stock, Richard G, Demanes, D Jeffrey, Moran, Brian J, Huland, Hartwig, Tran, Phuoc T, Martin, Santiago, Martinez-Monge, Rafael, Krauss, Daniel J, Abu-Isa, Eyad I, Alam, Ridwan, Schwen, Zeyad, Pisansky, Thomas M, Choo, C Richard, Song, Daniel Y, Greco, Stephen, Deville, Curtiland, McNutt, Todd, DeWeese, Theodore L, Ross, Ashley E, Ciezki, Jay P, Boutros, Paul C, Nickols, Nicholas G, Bhat, Prashant, Shabsovich, David, Juarez, Jesus E, Chong, Natalie, Kupelian, Patrick A, Rettig, Matthew B, Zaorsky, Nicholas G, Berlin, Alejandro, Tward, Jonathan D, Davis, Brian J, Reiter, Robert E, Steinberg, Michael L, Elashoff, David, Horwitz, Eric M, Tendulkar, Rahul D, Tilki, Derya, Czernin, Johannes, Gafita, Andrei, Romero, Tahmineh, Calais, Jeremie, and Kishan, Amar U

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Biomedical Imaging, Prostate Cancer, Cancer, Clinical Research, Urologic Diseases, Aging, Prevention, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Adult, Aged, Aged, 80 and over, Antigens, Surface, Biomarkers, Tumor, Clinical Decision Rules, Follow-Up Studies, Glutamate Carboxypeptidase II, Humans, Male, Middle Aged, Neoplasm Staging, Nomograms, Positron Emission Tomography Computed Tomography, Prognosis, Prostatic Neoplasms, Retrospective Studies, Risk Assessment, SEER Program, Survival Analysis, Biomedical and clinical sciences, Health sciences
Abstract

ImportanceProstate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear.ObjectivesTo evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools.Design, setting, and participantsThis cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021.ExposuresCurative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy.Main outcomes and measuresPSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index.ResultsOf 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P

Published
2021

14. Factors Associated with Time to Conversion from Active Surveillance to Treatment for Prostate Cancer in a Multi-Institutional Cohort

Author

Cooley, Lauren Folgosa, Emeka, Adaeze A, Meyers, Travis J, Cooper, Phillip R, Lin, Daniel W, Finelli, Antonio, Eastham, James A, Logothetis, Christopher J, Marks, Leonard S, Vesprini, Danny, Goldenberg, S Larry, Higano, Celestia S, Pavlovich, Christian P, Chan, June M, Morgan, Todd M, Klein, Eric A, Barocas, Daniel A, Loeb, Stacy, Helfand, Brian T, Scholtens, Denise M, Witte, John S, and Catalona, William J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Cancer, Aging, Urologic Diseases, Prostate Cancer, Aged, Biopsy, Large-Core Needle, Disease Progression, Follow-Up Studies, Humans, Kallikreins, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Prostate, Prostate-Specific Antigen, Prostatectomy, Prostatic Neoplasms, Risk Assessment, Risk Factors, Time Factors, Tumor Burden, Watchful Waiting, Collaborators, human genetics, prostatic neoplasms, race factors, watchful waiting
Abstract

PurposeWe examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer.Materials and methodsA multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses.ResultsOf 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36-1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29-2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11-1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41-1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19-5.96) and number of cancerous biopsy cores (3 vs 1-2 cores aHR 1.59, 95% CI 1.37-1.84; ≥4 vs 1-2 cores aHR 3.29, 95% CI 2.94-3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93-0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry.ConclusionsA shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.

Published
2021

15. Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer

Author

Philipson, Rebecca G, Romero, Tahmineh, Wong, Jessica K, Stish, Bradley J, Dess, Robert T, Spratt, Daniel E, Pilar, Avinash, Reddy, Chandana, Wedde, Trude B, Lilleby, Wolfgang A, Fiano, Ryan, Merrick, Gregory S, Stock, Richard G, Demanes, D Jeffrey, Moran, Brian J, Braccioforte, Michelle, Tran, Phuoc T, Martin, Santiago, Martinez-Monge, Rafael, Krauss, Daniel J, Abu-Isa, Eyad I, Valle, Luca, Chong, Natalie, Pisansky, Thomas M, Choo, C Richard, Song, Daniel Y, Greco, Stephen, Deville, Curtiland, McNutt, Todd, DeWeese, Theodore L, Ross, Ashley E, Ciezki, Jay P, Tilki, Derya, Karnes, R Jeffrey, Klein, Eric A, Tosoian, Jeffrey J, Boutros, Paul C, Nickols, Nicholas G, Bhat, Prashant, Shabsovich, David, Juarez, Jesus E, Kupelian, Patrick A, Rettig, Matthew B, Berlin, Alejandro, Tward, Jonathan D, Davis, Brian J, Reiter, Robert E, Steinberg, Michael L, Elashoff, David, Horwitz, Eric M, Tendulkar, Rahul D, and Kishan, Amar U

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prevention, Urologic Diseases, Prostate Cancer, Cancer, Clinical Research, Aging, Brachytherapy, Humans, Male, Neoplasm Grading, Prostate, Prostatic Neoplasms, Salvage Therapy, Biochemical recurrence, Brachytherapy boost, EBRT, External beam radiation therapy, High-risk prostate cancer, Prostate cancer, Radiorecurrence, Recurrent prostate cancer, Urology & Nephrology, Clinical sciences
Abstract

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p

Published
2021

16. Computer extracted gland features from H&E predicts prostate cancer recurrence comparably to a genomic companion diagnostic test: a large multi-site study.

Author

Leo, Patrick, Janowczyk, Andrew, Elliott, Robin, Janaki, Nafiseh, Bera, Kaustav, Shiradkar, Rakesh, Farré, Xavier, Fu, Pingfu, El-Fahmawi, Ayah, Shahait, Mohammed, Kim, Jessica, Lee, David, Yamoah, Kosj, Rebbeck, Timothy R, Khani, Francesca, Robinson, Brian D, Eklund, Lauri, Jambor, Ivan, Merisaari, Harri, Ettala, Otto, Taimen, Pekka, Aronen, Hannu J, Boström, Peter J, Tewari, Ashutosh, Magi-Galluzzi, Cristina, Klein, Eric, Purysko, Andrei, Nc Shih, Natalie, Feldman, Michael, Gupta, Sanjay, Lal, Priti, and Madabhushi, Anant

Abstract

Existing tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p

Published
2021

18. Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Author

Graff, Mariaelisa, Justice, Anne E, Young, Kristin L, Marouli, Eirini, Zhang, Xinruo, Fine, Rebecca S, Lim, Elise, Buchanan, Victoria, Rand, Kristin, Feitosa, Mary F, Wojczynski, Mary K, Yanek, Lisa R, Shao, Yaming, Rohde, Rebecca, Adeyemo, Adebowale A, Aldrich, Melinda C, Allison, Matthew A, Ambrosone, Christine B, Ambs, Stefan, Amos, Christopher, Arnett, Donna K, Atwood, Larry, Bandera, Elisa V, Bartz, Traci, Becker, Diane M, Berndt, Sonja I, Bernstein, Leslie, Bielak, Lawrence F, Blot, William J, Bottinger, Erwin P, Bowden, Donald W, Bradfield, Jonathan P, Brody, Jennifer A, Broeckel, Ulrich, Burke, Gregory, Cade, Brian E, Cai, Qiuyin, Caporaso, Neil, Carlson, Chris, Carpten, John, Casey, Graham, Chanock, Stephen J, Chen, Guanjie, Chen, Minhui, Chen, Yii-Der I, Chen, Wei-Min, Chesi, Alessandra, Chiang, Charleston WK, Chu, Lisa, Coetzee, Gerry A, Conti, David V, Cooper, Richard S, Cushman, Mary, Demerath, Ellen, Deming, Sandra L, Dimitrov, Latchezar, Ding, Jingzhong, Diver, W Ryan, Duan, Qing, Evans, Michele K, Falusi, Adeyinka G, Faul, Jessica D, Fornage, Myriam, Fox, Caroline, Freedman, Barry I, Garcia, Melissa, Gillanders, Elizabeth M, Goodman, Phyllis, Gottesman, Omri, Grant, Struan FA, Guo, Xiuqing, Hakonarson, Hakon, Haritunians, Talin, Harris, Tamara B, Harris, Curtis C, Henderson, Brian E, Hennis, Anselm, Hernandez, Dena G, Hirschhorn, Joel N, McNeill, Lorna Haughton, Howard, Timothy D, Howard, Barbara, Hsing, Ann W, Hsu, Yu-Han H, Hu, Jennifer J, Huff, Chad D, Huo, Dezheng, Ingles, Sue A, Irvin, Marguerite R, John, Esther M, Johnson, Karen C, Jordan, Joanne M, Kabagambe, Edmond K, Kang, Sun J, Kardia, Sharon L, Keating, Brendan J, Kittles, Rick A, Klein, Eric A, Kolb, Suzanne, and Kolonel, Laurence N

Subjects
Human Genome, Genetics, Africa, Black or African American, Black People, Body Height, Europe, Female, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, African ancestry, fine-mapping, genome-wide, height, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

Published
2021

19. Intratumoral androgen biosynthesis associated with 3[beta]-hydroxysteroid dehydrogenase 1 promotes resistance to radiotherapy in prostate cancer

Author

Ganguly, Shinjini, Lone, Zaeem, Muskara, Andrew, Imamura, Jarrell, Hardaway, Aimalie, Patel, Mona, Berk, Mike, Smile, Timothy D., Davicioni, Elai, Stephans, Kevin L., Ciezki, Jay, Weight, Christopher J., Gupta, Shilpa, Reddy, Chandana A., Tendulkar, Rahul D., Chakraborty, Abhishek A., Klein, Eric A., Sharifi, Nima, and Mian, Omar Y.

Subjects
Thermo Fisher Scientific Inc., Life Technologies Corp., DNA repair -- Genetic aspects -- Research -- Physiological aspects, Dehydroepiandrosterone -- Research, Scientific equipment and supplies industry -- Physiological aspects -- Genetic aspects -- Research, Gene expression -- Research -- Physiological aspects -- Genetic aspects, Prostate cancer -- Development and progression -- Research -- Genetic aspects, Genes -- Physiological aspects -- Genetic aspects -- Research, Biotechnology industry -- Physiological aspects -- Research -- Genetic aspects, Androgens -- Research, DNA damage -- Physiological aspects -- Genetic aspects -- Research, Radiotherapy -- Physiological aspects -- Research, Health care industry, Cleveland Clinic
Abstract

Half of all men with advanced prostate cancer (PCa) inherit at least 1 copy of an adrenal-permissive HSD3B1 (1245C) allele, which increases levels of 3[beta]-hydroxysteroid dehydrogenase 1 (3[beta]HSD1) and promotes intracellular androgen biosynthesis. Germline inheritance of the adrenally permissive allele confers worse outcomes in men with advanced PCa. We investigated whether H5D3S7 (1245C) drives resistance to combined androgen deprivation and radiotherapy. Adrenally permissive 3[beta]HSD1 enhanced resistance to radiotherapy in PCa cell lines and xenograft models engineered to mimic the human adrenal/gonadal axis during androgen deprivation. The allele-specific effects on radiosensitivity were dependent on availability of DHEA, the substrate for 3[beta]HSD1. In lines expressing the HSD3B1 (1245C) allele, enhanced expression of DNA damage response (DDR) genes and more rapid DNA double-strand break (DSB) resolution were observed. A correlation between androgen receptor (AR) expression and increased DDR gene expression was confirmed in 680 radical prostatectomy specimens. Treatment with the nonsteroidal antiandrogen enzalutamide reversed the resistant phenotype of HSD3B1 (1245C) PCa in vitro and in vivo. In conclusion, 3[beta]HSD1 promotes prostate cancer resistance to combined androgen deprivation and radiotherapy by upregulating ?NA DSB repair. This work supports prospective validation of early combined androgen blockade for high-risk men harboring the HSD3B1 (1245C) allele., Introduction In men with high-grade prostate cancer (PCa) treated with curative-intent radiotherapy, the addition of androgen-deprivation therapy (ADT) confers a clear and sustained benefit in terms of local control, metastasis-free [...]

Published
2023
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22. A novel imaging based Nomogram for predicting post-surgical biochemical recurrence and adverse pathology of prostate cancer from pre-operative bi-parametric MRI

Author

Li, Lin, Shiradkar, Rakesh, Leo, Patrick, Algohary, Ahmad, Fu, Pingfu, Tirumani, Sree Harsha, Mahran, Amr, Buzzy, Christina, Obmann, Verena C, Mansoori, Bahar, El-Fahmawi, Ayah, Shahait, Mohammed, Tewari, Ashutosh, Magi-Galluzzi, Cristina, Lee, David, Lal, Priti, Ponsky, Lee, Klein, Eric, Purysko, Andrei S, and Madabhushi, Anant

Subjects
Aging, Prostate Cancer, Cancer, Biomedical Imaging, Patient Safety, Urologic Diseases, Good Health and Well Being, Aged, Aged, 80 and over, Biomarkers, Tumor, Clinical Decision-Making, Diagnostic Imaging, Disease Management, Humans, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Nomograms, Patient Selection, Perioperative Care, Prognosis, Prostatectomy, Prostatic Neoplasms, Retrospective Studies, Workflow, Prostate cancer, Biochemical recurrence, Adverse pathology, Radiomic, MRI, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundWe developed and validated an integrated radiomic-clinicopathologic nomogram (RadClip) for post-surgical biochemical recurrence free survival (bRFS) and adverse pathology (AP) prediction in men with prostate cancer (PCa). RadClip was further compared against extant prognostics tools like CAPRA and Decipher.MethodsA retrospective study of 198 patients with PCa from four institutions who underwent pre-operative 3 Tesla MRI followed by radical prostatectomy, between 2009 and 2017 with a median 35-month follow-up was performed. Radiomic features were extracted from prostate cancer regions on bi-parametric magnetic resonance imaging (bpMRI). Cox Proportional-Hazards (CPH) model warped with minimum redundancy maximum relevance (MRMR) feature selection was employed to select bpMRI radiomic features for bRFS prediction in the training set (D1, N = 71). In addition, a bpMRI radiomic risk score (RadS) and associated nomogram, RadClip, were constructed in D1 and then compared against the Decipher, pre-operative (CAPRA), and post-operative (CAPRA-S) nomograms for bRFS and AP prediction in the testing set (D2, N = 127).Findings"RadClip yielded a higher C-index (0.77, 95% CI 0.65-0.88) compared to CAPRA (0.68, 95% CI 0.57-0.8) and Decipher (0.51, 95% CI 0.33-0.69) and was found to be comparable to CAPRA-S (0.75, 95% CI 0.65-0.85). RadClip resulted in a higher AUC (0.71, 95% CI 0.62-0.81) for predicting AP compared to Decipher (0.66, 95% CI 0.56-0.77) and CAPRA (0.69, 95% CI 0.59-0.79)."InterpretationRadClip was more prognostic of bRFS and AP compared to Decipher and CAPRA. It could help pre-operatively identify PCa patients at low risk of biochemical recurrence and AP and who therefore might defer additional therapy.FundingThe National Institutes of Health, the U.S. Department of Veterans Affairs, and the Department of Defense.

Published
2021

23. When to order genomic tests: development and external validation of a model to predict high-risk prostate cancer at the genotypic level

Author

Falagario, Ugo Giovanni, Chakravarty, Dimple, Martini, Alberto, Shahait, Mohammed, El-Fahmawi, Ayah, Jambor, Ivan, Lantz, Anna, Grannas, David, Ratnani, Parita, Parekh, Sneha, Lundon, Dara, Haines, Kenneth, Cormio, Luigi, Carrieri, Giuseppe, Kyprianou, Natasha, Kattan, Michael W., Klein, Eric A., Wiklund, Peter, Lee, David I., and Tewari, Ash

Published
2023
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24. Performance of clinicopathologic models in men with high risk localized prostate cancer: impact of a 22-gene genomic classifier

Author

Tosoian, Jeffrey J, Birer, Samuel R, Jeffrey Karnes, R, Zhang, Jingbin, Davicioni, Elai, Klein, Eric E, Freedland, Stephen J, Weinmann, Sheila, Trock, Bruce J, Dess, Robert T, Zhao, Shuang G, Jackson, William C, Yamoah, Kosj, Dal Pra, Alan, Mahal, Brandon A, Morgan, Todd M, Mehra, Rohit, Kaffenberger, Samuel, Salami, Simpa S, Kane, Christopher, Pollack, Alan, Den, Robert B, Berlin, Alejandro, Schaeffer, Edward M, Nguyen, Paul L, Feng, Felix Y, and Spratt, Daniel E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prostate Cancer, Prevention, Patient Safety, Cancer, Aging, Urologic Diseases, Biotechnology, Aged, Biomarkers, Tumor, Cohort Studies, Disease Progression, Humans, Kallikreins, Male, Middle Aged, Models, Statistical, Neoplasm Metastasis, Nomograms, Prognosis, Prostate-Specific Antigen, Prostatectomy, Prostatic Neoplasms, ROC Curve, Retrospective Studies, Risk Factors, Transcriptome, Urology & Nephrology, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundProstate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date.MethodsA multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed. Cox proportional hazards models were used to determine the hazard ratios (HR) for the development of metastatic disease based on clinico-pathologic variables, risk groups, and GC score. The area under the receiver operating characteristic curve (AUC) was determined for regression models without and with the GC score.ResultsOver a median follow-up of 82 months, 104 patients (26%) developed metastatic disease. On univariable analysis, increasing GC score was significantly associated with metastatic disease ([HR]: 1.34 per 0.1 unit increase, 95% confidence interval [CI]: 1.19-1.50, p  0.05). On multivariable analysis, GC score (HR: 1.33 per 0.1 unit increase, 95% CI: 1.19-1.48, p

Published
2020

25. Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Author

Chen, Fei, Madduri, Ravi K., Rodriguez, Alex A., Darst, Burcu F., Chou, Alisha, Sheng, Xin, Wang, Anqi, Shen, Jiayi, Saunders, Edward J., Rhie, Suhn K., Bensen, Jeannette T., Ingles, Sue A., Kittles, Rick A., Strom, Sara S., Rybicki, Benjamin A., Nemesure, Barbara, Isaacs, William B., Stanford, Janet L., Zheng, Wei, Sanderson, Maureen, John, Esther M., Park, Jong Y., Xu, Jianfeng, Wang, Ying, Berndt, Sonja I., Huff, Chad D., Yeboah, Edward D., Tettey, Yao, Lachance, Joseph, Tang, Wei, Rentsch, Christopher T., Cho, Kelly, Mcmahon, Benjamin H., Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Sellers, Thomas A., Yamoah, Kosj, Murphy, Adam B., Crawford, Dana C., Patel, Alpa V., Bush, William S., Aldrich, Melinda C., Cussenot, Olivier, Petrovics, Gyorgy, Cullen, Jennifer, Neslund-Dudas, Christine M., Stern, Mariana C., Kote-Jarai, Zsofia, Govindasami, Koveela, Cook, Michael B., Chokkalingam, Anand P., Hsing, Ann W., Goodman, Phyllis J., Hoffmann, Thomas J., Drake, Bettina F., Hu, Jennifer J., Keaton, Jacob M., Hellwege, Jacklyn N., Clark, Peter E., Jalloh, Mohamed, Gueye, Serigne M., Niang, Lamine, Ogunbiyi, Olufemi, Idowu, Michael O., Popoola, Olufemi, Adebiyi, Akindele O., Aisuodionoe-Shadrach, Oseremen I., Ajibola, Hafees O., Jamda, Mustapha A., Oluwole, Olabode P., Nwegbu, Maxwell, Adusei, Ben, Mante, Sunny, Darkwa-Abrahams, Afua, Mensah, James E., Diop, Halimatou, Van Den Eeden, Stephen K., Blanchet, Pascal, Fowke, Jay H., Casey, Graham, Hennis, Anselm J., Lubwama, Alexander, Thompson, Ian M., Jr., Leach, Robin, Easton, Douglas F., Preuss, Michael H., Loos, Ruth J., Gundell, Susan M., Wan, Peggy, Mohler, James L., Fontham, Elizabeth T., Smith, Gary J., Taylor, Jack A., Srivastava, Shiv, Eeles, Rosaline A., Carpten, John D., Kibel, Adam S., Multigner, Luc, Parent, Marie-Élise, Menegaux, Florence, Cancel-Tassin, Geraldine, Klein, Eric A., Andrews, Caroline, Rebbeck, Timothy R., Brureau, Laurent, Ambs, Stefan, Edwards, Todd L., Watya, Stephen, Chanock, Stephen J., Witte, John S., Blot, William J., Michael Gaziano, J., Justice, Amy C., Conti, David V., and Haiman, Christopher A.

Published
2023
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26. Using IsoPSA With Prostate Imaging Reporting and Data System Score May Help Refine Biopsy Decision Making in Patients With Elevated PSA

Author

Benidir, Tarik, Lone, Zaeem, Wood, Andrew, Abdallah, Nour, Campbell, Rebecca, Bajic, Petar, Purysko, Andrei, Nguyen, Jane K., Kaouk, Jihad, Haber, Georges-Pascal, Eltemamy, Mohamed, Stein, Robert, Haywood, Samuel, Klein, Eric A, Almassi, Nima, Campbell, Steven C., Abouassaly, Robert, and Weight, Christopher J.

Published
2023
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29. Transcriptomic Heterogeneity of Gleason Grade Group 5 Prostate Cancer

Author

Kishan, Amar U, Romero, Tahmineh, Alshalalfa, Mohammed, Liu, Yang, Tran, Phuoc T, Nickols, Nicholas G, Ye, Huihui, Sajed, Dipti, Rettig, Matthew B, Reiter, Robert E, Garraway, Isla P, Spratt, Daniel E, Freedland, Steven J, Zhao, Xin, Li, Ziwen, Deek, Matthew, Livingstone, Julie, Mahal, Brandon A, Nguyen, Paul L, Feng, Felix Y, Den, Robert B, Schaeffer, Edward M, Lotan, Tamara L, Karnes, R Jeffrey, Klein, Eric A, Ross, Ashley E, Grogan, Tristan, Davicioni, Elai, Elashoff, David, Boutros, Paul C, and Weidhaas, Joanne B

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Prostate Cancer, Aging, Biotechnology, Clinical Trials and Supportive Activities, Genetics, Human Genome, Clinical Research, Urologic Diseases, Aetiology, 2.1 Biological and endogenous factors, Aged, Cohort Studies, Genetic Variation, Humans, Male, Middle Aged, Neoplasm Grading, Prostatic Neoplasms, Transcriptome, Gleason grade group 5, Gleason score 9, Gleason score 10, Biomarkers, Transcriptomics, Urology & Nephrology, Clinical sciences
Abstract

Gleason grade group (GG) 5 prostate cancer has been associated with an aggressive natural history, and retrospective data support a role for treatment intensification. However, clinical outcomes remain heterogeneous in this cohort, and intensified treatments carry an increased risk of adverse events. We sought to explore the transcriptomic heterogeneity of GG 5 tumors by querying transcriptomic data from the tumors of 2138 patients with GG 5 disease who underwent prostatectomy. Four distinct consensus clusters were identified with respect to differential transcriptional activation of hallmark pathways, with distinct molecular subtyping profiles and different average genomic risks (AGRs). One cluster, accounting for 325 tumors (15.2% of the population), was enriched for genes related to the cell cycle/proliferation, metabolic pathways, androgen response pathways, and DNA repair, and had a higher AGR than the other clusters (p

Published
2020

30. A neuronal signature for monogamous reunion

Author

Scribner, Jennifer L, Vance, Eric A, Protter, David SW, Sheeran, William M, Saslow, Elliott, Cameron, Ryan T, Klein, Eric M, Jimenez, Jessica C, Kheirbek, Mazen A, and Donaldson, Zoe R

Subjects
Neurosciences, Neurological, Animals, Arvicolinae, Female, Male, Mating Preference, Animal, Neurons, Nucleus Accumbens, Pair Bond, Sexual Behavior, Animal, Social Behavior, prairie vole, nucleus accumbens, pair bond, ensemble, calcium imaging
Abstract

Pair-bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using 1-photon in vivo Ca2+ imaging in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca2+ activity. Instead, we identified distinct ensembles of neurons in this region that are recruited during approach to either a partner or a novel vole. The partner-approach neuronal ensemble increased in size following bond formation, and differences in the size of approach ensembles for partner and novel voles predict bond strength. In contrast, neurons comprising departure ensembles do not change over time and are not correlated with bond strength, indicating that ensemble plasticity is specific to partner approach. Furthermore, the neurons comprising partner and novel-approach ensembles are nonoverlapping while departure ensembles are more overlapping than chance, which may reflect another key feature of approach ensembles. We posit that the features of the partner-approach ensemble and its expansion upon bond formation potentially make it a key neuronal substrate associated with bond formation and maturation.

Published
2020

31. Decipher identifies men with otherwise clinically favorable-intermediate risk disease who may not be good candidates for active surveillance.

Author

Herlemann, Annika, Huang, Huei-Chung, Alam, Ridwan, Tosoian, Jeffery J, Kim, Hyung L, Klein, Eric A, Simko, Jeffry P, Chan, June M, Lane, Brian R, Davis, John W, Davicioni, Elai, Feng, Felix Y, McCue, Peter, Kim, Hyun, Den, Robert B, Bismar, Tarek A, Carroll, Peter R, and Cooperberg, Matthew R

Subjects
Humans, Prostatic Neoplasms, Biopsy, Neoplasm Staging, Prognosis, Odds Ratio, Risk Assessment, Risk Factors, Patient Selection, Aged, Middle Aged, Disease Management, Male, Watchful Waiting, Neoplasm Grading, Biomarkers, Tumor, Biomarkers, Tumor, Oncology and Carcinogenesis, Urology & Nephrology
Abstract

BackgroundWe aimed to validate Decipher to predict adverse pathology (AP) at radical prostatectomy (RP) in men with National Comprehensive Cancer Network (NCCN) favorable-intermediate risk (F-IR) prostate cancer (PCa), and to better select F-IR candidates for active surveillance (AS).MethodsIn all, 647 patients diagnosed with NCCN very low/low risk (VL/LR) or F-IR prostate cancer were identified from a multi-institutional PCa biopsy database; all underwent RP with complete postoperative clinicopathological information and Decipher genomic risk scores. The performance of all risk assessment tools was evaluated using logistic regression model for the endpoint of AP, defined as grade group 3-5, pT3b or higher, or lymph node invasion.ResultsThe median age was 61 years (interquartile range 56-66) for 220 patients with NCCN F-IR disease, 53% classified as low-risk by Cancer of the Prostate Risk Assessment (CAPRA 0-2) and 47% as intermediate-risk (CAPRA 3-5). Decipher classified 79%, 13% and 8% of men as low-, intermediate- and high-risk with 13%, 10%, and 41% rate of AP, respectively. Decipher was an independent predictor of AP with an odds ratio of 1.34 per 0.1 unit increased (p value = 0.002) and remained significant when adjusting by CAPRA. Notably, F-IR with Decipher low or intermediate score did not associate with significantly higher odds of AP compared to VL/LR.ConclusionsNCCN risk groups, including F-IR, are highly heterogeneous and should be replaced with multivariable risk-stratification. In particular, incorporating Decipher may be useful for safely expanding the use of AS in this patient population.

Published
2020

32. A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry

Author

Du, Zhaohui, Weinhold, Niels, Song, Gregory Chi, Rand, Kristin A, Van Den Berg, David J, Hwang, Amie E, Sheng, Xin, Hom, Victor, Ailawadhi, Sikander, Nooka, Ajay K, Singhal, Seema, Pawlish, Karen, Peters, Edward S, Bock, Cathryn, Mohrbacher, Ann, Stram, Alexander, Berndt, Sonja I, Blot, William J, Casey, Graham, Stevens, Victoria L, Kittles, Rick, Goodman, Phyllis J, Diver, W Ryan, Hennis, Anselm, Nemesure, Barbara, Klein, Eric A, Rybicki, Benjamin A, Stanford, Janet L, Witte, John S, Signorello, Lisa, John, Esther M, Bernstein, Leslie, Stroup, Antoinette M, Stephens, Owen W, Zangari, Maurizio, Van Rhee, Frits, Olshan, Andrew, Zheng, Wei, Hu, Jennifer J, Ziegler, Regina, Nyante, Sarah J, Ingles, Sue Ann, Press, Michael F, Carpten, John David, Chanock, Stephen J, Mehta, Jayesh, Colditz, Graham A, Wolf, Jeffrey, Martin, Thomas G, Tomasson, Michael, Fiala, Mark A, Terebelo, Howard, Janakiraman, Nalini, Kolonel, Laurence, Anderson, Kenneth C, Le Marchand, Loic, Auclair, Daniel, Chiu, Brian C-H, Ziv, Elad, Stram, Daniel, Vij, Ravi, Bernal-Mizrachi, Leon, Morgan, Gareth J, Zonder, Jeffrey A, Huff, Carol Ann, Lonial, Sagar, Orlowski, Robert Z, Conti, David V, Haiman, Christopher A, and Cozen, Wendy

Subjects
Hematology, Rare Diseases, Genetics, Cancer, Clinical Research, Prevention, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Multiple Myeloma, Polymorphism, Single Nucleotide, Transcriptional Elongation Factors
Abstract

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

Published
2020

33. Development of Treatments for Localized Prostate Cancer in Patients Eligible for Active Surveillance: U.S. Food and Drug Administration Oncology Center of Excellence Public Workshop.

Author

Weinstock, Chana, Suzman, Daniel, Kluetz, Paul, Baxley, John, Viviano, Charles, Ibrahim, Amna, Jarow, Jonathan, Sridhara, Raejshwari, Liu, Ke, Carroll, Peter, Eggener, Scott, Hu, Jim C, Hussain, Maha, King, Martin, Klein, Eric, Kungel, Terry, Makarov, Danil, Pinto, Peter A, Rini, Brian, Roach, Mack, Sandler, Howard, Schlegel, Peter N, Song, Daniel, Goldberg, Kirsten, Pazdur, Richard, and Beaver, Julia A

Subjects
Humans, Prostatic Neoplasms, Diagnostic Imaging, Endpoint Determination, Population Surveillance, Genomics, Research Design, United States Food and Drug Administration, Education, United States, Male, Clinical Trials as Topic, Watchful Waiting, drug development, equipment design, prostatic neoplasms, research design, Urologic Diseases, Cancer, Prostate Cancer, Aging, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, United States Food and Drug, Administration, Clinical Sciences, Urology & Nephrology
Abstract

PurposeThe following is a summary of discussion at a United States FDA (Food and Drug Administration) public workshop reviewing potential trial designs and end points to develop therapies to treat localized prostate cancer.Materials and methodsThe workshop focused on the challenge that drug and device development to treat localized prostate cancer has been limited by the large trial sizes and lengthy timelines required to demonstrate an improvement in overall or metastasis-free survival and by the lack of agreed on alternative end points. Additionally, evolving treatment paradigms in the management of localized prostate cancer include the widespread use of active surveillance of patients with low and some intermediate risk prostate cancer, and the availability of advances in imaging and genomics.ResultsThe workshop addressed issues related to trial design in this setting. Attendees discussed several potential novel end points such as a delay of morbidity due to radiation or prostatectomy and pathological end points such as Gleason Grade Group upgrade.ConclusionsThe workshop provided an open forum for multiple stakeholder engagement to advance the development of effective treatment options for men with localized prostate cancer.

Published
2020

34. Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis

Author

Sandler, Kiri A, Cook, Ryan R, Ciezki, Jay P, Ross, Ashley E, Pomerantz, Mark M, Nguyen, Paul L, Shaikh, Talha, Tran, Phuoc T, Stock, Richard G, Merrick, Gregory S, Demanes, David Jeffrey, Spratt, Daniel E, Abu-Isa, Eyad I, Wedde, Trude B, Lilleby, Wolfgang, Krauss, Daniel J, Shaw, Grace K, Alam, Ridwan, Reddy, Chandana A, Song, Daniel Y, Klein, Eric A, Stephenson, Andrew J, Tosoian, Jeffrey J, Hegde, John V, Yoo, Sun Mi, Fiano, Ryan, D'Amico, Anthony V, Nickols, Nicholas G, Aronson, William J, Sadeghi, Ahmad, Greco, Stephen C, Deville, Curtiland, McNutt, Todd, DeWeese, Theodore L, Reiter, Robert E, Said, Jonathan W, Steinberg, Michael L, Horwitz, Eric M, Kupelian, Patrick A, King, Christopher R, and Kishan, Amar U

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Clinical Trials and Supportive Activities, Prostate Cancer, Clinical Research, Urologic Diseases, Aging, Aged, Brachytherapy, Hemibody Irradiation, Humans, Male, Neoplasm Grading, Pelvis, Prostate, Prostatic Neoplasms, Retrospective Studies, Survival Rate, Gleason grade group 5, Prostate cancer, Radiation therapy, Whole-pelvis irradiation, Urology & Nephrology, Clinical sciences
Abstract

BackgroundThe role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases.ObjectiveTo assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).Design, setting, and participantsWe identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT).Outcome measurements and statistical analysisBiochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment.Results and limitationsA total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS).ConclusionsWPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted.Patient summaryWhen men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.

Published
2020

38. Elevated periprostatic venous testosterone correlates with prostate cancer progression after radical prostatectomy

Author

Alyamani, Mohammad, Michael, Patrick, Hettel, Daniel, Thomas, Lewis, Lundy, Scott D., Berk, Mike, Patel, Mona, Li, Jianbo, Rashidi, Hooman, McKenney, Jesse K., Klein, Eric A., and Sharifi, Nima

Subjects
Prostate cancer -- Development and progression -- Prognosis -- Care and treatment -- Patient outcomes, Prostatectomy -- Patient outcomes, Testosterone -- Measurement -- Health aspects, Health care industry
Abstract

BACKGROUND. Generally, clinical assessment of gonadal testosterone (T) in human physiology is determined using concentrations measured in peripheral blood. Prostatic T exposure is similarly thought to be determined from peripheral T exposure. Despite the fact that androgens drive prostate cancer, peripheral T has had no role in the clinical evaluation or treatment of men with localized prostate cancer. METHODS. To assess the role of local androgen delivery in prostate cancer, we obtained blood from the (periprostatic) prostatic dorsal venous complex in 266 men undergoing radical prostatectomy from July 2014 to August 2021 and compared dorsal T (DT) levels with those in circulating peripheral blood (PT) and prostatic tissue. Comprehensive targeted steroid analysis and unbiased metabolomics analyses were performed. The association between the DT/PT ratio and progression-free survival after prostatectomy was assessed. RESULTS. Surprisingly, in some men, DT levels were enriched several-fold compared with PT levels. For example, 20% of men had local T concentrations that were at least 2-fold higherthan peripheral T concentrations. Isocaproic acid, a byproduct of androgen biosynthesis, and 17-OH-progesterone, a marker of intratesticular T, were also enriched in the dorsal vein of these men, consistent with testicular shunting. Men with enriched DT had higher rates of prostate cancer recurrence. DT/PT concentration ratios predicted worse outcomes even when accounting for known clinical predictors. CONCLUSIONS. These data suggest that a large proportion of men have a previously unappreciated exposure to an undiluted and highly concentrated T supply. Elevated periprostatic T exposure was associated with worse clinical outcomes after radical prostatectomy. FUNDING. National Cancer Institute (NCI), NIH grants R01CA172382, R01CA236780, R01CA261995, R01CA249279, and R50CA251961; US Army Medical Research and Development Command grants W81XWH2010137 and W81XWH-22-1-0082., Introduction Androgens and androgen receptor (AR) signaling are essential for normal prostate development, the initiation of prostate cancer, and tumor progression even at very advanced stages (1). Gonadal testosterone (T), [...]

Published
2023
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39. Cohort-Specific Online Discussion Experiences: A Collaborative and Multidisciplinary Approach to Improving Student Learning

Author

Selhorst, Adam L., Klein, Eric, and Harrison, Justin

Abstract

Research addressing the effects of cohort size on student success in asynchronous online discussions is sparse. As such, the following study attempted to determine an optimal student cohort size to enhance success and engagement within online discussions in general education courses at a large post-secondary university consisting of predominately adult learners. Experimental courses split mandatory discussions into one, two, or three cohorts to maintain a discussion size of no more than ten students per cohort per week. The effects of cohort size on student grade-point-average (GPA), withdraw rate, fail rate, and progression rate was evaluated in addition to effects on student satisfaction as measured by end-of-course surveys (EoCS). Results showed no significant difference in either student success or student satisfaction between courses with one, two, or three online discussion cohorts. Future online education research should focuses on upper division courses where students might benefit from smaller group discussions.d

Published
2017

40. Independent blinded validation of an AI-based digital histology classifier for prostate cancer recurrence and metastasis risk prediction.

Author

Fay, Magdalena, primary, Liao, Ross, additional, Lone, Zaeem M, additional, Reddy, Chandana A., additional, Muhammad, Hassan, additional, Xie, Chensu, additional, Jain, Parag, additional, Huang, Wei, additional, Basu, Hirak S, additional, Nguyen, Jane, additional, Nair, Sujit S., additional, Chakravarty, Dimple, additional, Williamson, Sean R., additional, Gupta, Shilpa, additional, Weight, Christopher, additional, Roy, Rajat, additional, Wilding, George, additional, Tewari, Ashutosh K., additional, Klein, Eric A., additional, and Mian, Omar Y., additional

Published
2024
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41. Impact of cancer screening results on patient-reported outcomes (PRO) and behavioral intentions.

Author

Patrick, Donald, primary, Ross, Melissa, additional, Mulnick, Sarah, additional, Samuelson, Ashley, additional, Cong, Ze, additional, Chung, Karen, additional, Klein, Eric A., additional, Reid, Robert Lawrence, additional, Lopatin, Margarita, additional, Fung, Eric T., additional, Dilaveri, Christina A., additional, Marinac, Catherine, additional, and McDonnell, Charles H, additional

Published
2024
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42. Multi-cancer early detection (MCED) test performance in cancer survivors.

Author

Marinac, Catherine, primary, O'Donnell, Elizabeth, additional, Shaknovich, Rita, additional, Clarke, Christina A., additional, Walia, Guneet, additional, Chung, Karen, additional, Farese, Jennifer, additional, Lopatin, Margarita, additional, Fung, Eric T., additional, Venstrom, Jeffrey M., additional, Klein, Eric A., additional, and Karlitz, Jordan J., additional

Published
2024
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43. PD26-02 THE PROLONGED LOW RISK OF CLINICALLY SIGNIFICANT PROSTATE CANCER DIAGNOSIS IN MEN WITH AN ELEVATED PSA BUT LOW IsoPSA

Author

Abdallah, Nour, primary, Campbell, Rebecca, additional, Benidir, Tarik, additional, Wood, Andrew, additional, Lone, Zaeem, additional, Zhang, Ao, additional, Ergun, Onuralp, additional, Curry, Caleb, additional, Michael, Patrick, additional, Chavali, Jay, additional, Haywood, Samuel, additional, Schwen, Zeyad, additional, Olivares, Ruben, additional, Kaouk, Jihad, additional, Abouassaly, Robert, additional, Klein, Eric, additional, and Weight, Christopher, additional

Published
2024
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44. MP77-12 ARTIFICIAL INTELLIGENCE-BASED MORPHOLOGIC MODEL FOR PREDICTION OF IMMUNOTHERAPY RESPONSE IN LOCALLY ADVANCED AND METASTATIC UROTHELIAL CARCINOMA OF THE BLADDER

Author

Liao, Ross S., primary, Nair, Monica, additional, Jain, Parag, additional, Xie, Chensu, additional, Muhammad, Hassan, additional, Huang, Wei, additional, Basu, Hirak, additional, Wilding, George, additional, Roy, Rajat, additional, Diaz-Montero, Claudia Marcela, additional, Hwang, Tae Hyun, additional, Dawsey, Scott, additional, Nguyen, Jane, additional, Klein, Eric, additional, Gupta, Shilpa, additional, and Mian, Omar, additional

Published
2024
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45. PD14-01 ORTHOTOPIC MURINE MODEL OF NEUROENDOCRINE BLADDER CANCER ELUCIDATES POTENTIAL MOLECULAR DRIVERS OF SMALL CELL BLADDER CANCER (SCBC)

Author

Liao, Ross, primary, Imamura, Jarrell, additional, Ruan Li, Hui Ting, additional, Muskara, Andrew, additional, Ganguly, Shinjini, additional, McFarland, Chris, additional, Balyimez, Aysegul, additional, Ornstein, Moshe, additional, Gupta, Shilpa, additional, McKenney, Jesse, additional, Klein, Eric, additional, Weight, Christopher, additional, Almassi, Nima, additional, and Mian, Omar, additional

Published
2024
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46. Evaluation of cell-free DNA approaches for multi-cancer early detection

Author

Jamshidi, Arash, Liu, Minetta C., Klein, Eric A., Venn, Oliver, Hubbell, Earl, Beausang, John F., Gross, Samuel, Melton, Collin, Fields, Alexander P., Liu, Qinwen, Zhang, Nan, Fung, Eric T., Kurtzman, Kathryn N., Amini, Hamed, Betts, Craig, Civello, Daniel, Freese, Peter, Calef, Robert, Davydov, Konstantin, Fayzullina, Saniya, Hou, Chenlu, Jiang, Roger, Jung, Byoungsok, Tang, Susan, Demas, Vasiliki, Newman, Joshua, Sakarya, Onur, Scott, Eric, Shenoy, Archana, Shojaee, Seyedmehdi, Steffen, Kristan K., Nicula, Virgil, Chien, Tom C., Bagaria, Siddhartha, Hunkapiller, Nathan, Desai, Mohini, Dong, Zhao, Richards, Donald A., Yeatman, Timothy J., Cohn, Allen L., Thiel, David D., Berry, Donald A., Tummala, Mohan K., McIntyre, Kristi, Sekeres, Mikkael A., Bryce, Alan, Aravanis, Alexander M., Seiden, Michael V., and Swanton, Charles

Published
2022
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