👤 K. Freeman

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6
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6
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Also published as: BA Freeman, CD Freeman, GJ Freeman, R.H. Freeman, T.N. Carder Freeman
articles
F Fadlallah, K Elshiwy, Y Elkeraie +1388 more · 2024 · World Journal of Clinical Oncology · added 2026-04-20
F Fadlallah, K Elshiwy, Y Elkeraie, Z Merjaneh, G Khoudari, MT Sarmini, M Gad, M Al-Husseini, A Saad, RL Siegel, KD Miller, NS Wagle, A Jemal, A Kumar, V Gautam, A Sandhu, K Rawat, A Sharma, L Saha, M Bretthauer, M Løberg, P Wieszczy, M Kalager, L Emilsson, K Garborg, M Rupinski, E Dekker, M Spaander, M Bugajski, Ø Holme, AG Zauber, ND Pilonis, A Mroz, EJ Kuipers, J Shi, MA Hernán, HO Adami, J Regula, G Hoff, MF Kaminski, S Shinji, T Yamada, A Matsuda, H Sonoda, R Ohta, T Iwai, K Takeda, K Yonaga, Y Masuda, H Yoshida, M Zajkowska, B Mroczko, GJ Poston, J Figueras, F Giuliante, G Nuzzo, AF Sobrero, JF Gigot, B Nordlinger, R Adam, T Gruenberger, MA Choti, AJ Bilchik, Cutsem EJ Van, JM Chiang, MI D'Angelica, GJ Chang, AM Kaiser, S Mills, JF Rafferty, WD Buie, JR Monson, MR Weiser, J Rafferty, AE Blackmore, MT Wong, CL Tang, BL Green, HC Marshall, F Collinson, P Quirke, P Guillou, DG Jayne, JM Brown, J Mar, A Anton-Ladislao, O Ibarrondo, A Arrospide, S Lázaro, N Gonzalez, M Bare, D Callejo, M Redondo, JM Quintana, S Kitano, M Inomata, J Mizusawa, H Katayama, M Watanabe, S Yamamoto, M Ito, S Saito, S Fujii, F Konishi, Y Saida, H Hasegawa, T Akagi, K Sugihara, T Yamaguchi, T Masaki, Y Fukunaga, K Murata, M Okajima, Y Moriya, Y Shimada, P Gavriilidis, K Katsanos, K Toritani, J Watanabe, K Nakagawa, Y Suwa, H Suwa, A Ishibe, M Ota, C Kunisaki, I Endo, T Matsuda, Y Sumi, K Yamashita, M Yamamoto, Y Matsuda, S Kanaji, T Oshikiri, T Nakamura, S Suzuki, Y Kakeji, RK Cleary, AM Morris, AL Halverson, KA Mirkin, AS Kulaylat, CS Hollenbeak, E Messaris, S Atallah, B Martin-Perez, M Albert, T deBeche-Adams, G Nassif, L Hunter, S Larach, MX Bjørn, SK Perdawood, Z Shen, Y Ye, Q Xie, K Jiang, S Wang, G Wang, Z Wang, Z Jiang, J Liu, J Zhao, J Li, A Arezzo, MA Bonino, F Ris, L Boni, E Cassinotti, DCC Foo, NF Shum, A Brolese, F Ciarleglio, DS Keller, R Rosati, Nardi P De, U Elmore, Romario U Fumagalli, MD Jafari, A Pigazzi, E Rybakov, M Alekseev, N Vettoretto, R Cirocchi, R Passera, E Forcignanò, M Morino, SH Park, HM Park, KR Baek, HM Ahn, IY Lee, GM Son, FA Vuijk, DE Hilling, JSD Mieog, AL Vahrmeijer, A Hiroishi, T Morimoto, K Horikoshi, Y Nakajima, KL Baglan, RC Frazier, D Yan, RR Huang, AA Martinez, JM Robertson, JG Letschert, JV Lebesque, Boer RW de, AA Hart, H Bartelink, JY Wo, CJ Anker, JB Ashman, NA Bhadkamkar, L Bradfield, DT Chang, J Dorth, J Garcia-Aguilar, D Goff, D Jacqmin, P Kelly, NB Newman, J Olsen, AC Raldow, E Ruiz-Garcia, KB Stitzenberg, CR Jr Thomas, QJ Wu, P Das, V Paroder, TJ Fraum, S Nougaret, I Petkovska, GM Rauch, H Kaur, C Bascoul-Mollevi, S Gourgou, C Borg, PL Etienne, E Rio, E Rullier, B Juzyna, F Castan, T Conroy, RR Bahadoer, EA Dijkstra, Etten B van, CAM Marijnen, H Putter, EM Kranenbarg, AGH Roodvoets, ID Nagtegaal, RGH Beets-Tan, LK Blomqvist, T Fokstuen, Tije AJ Ten, J Capdevila, MP Hendriks, I Edhemovic, A Cervantes, PJ Nilsson, B Glimelius, de Velde CJH van, GAP Hospers, P Goffredo, FF Quezada-Diaz, JJ Smith, A Cercek, CSD Roxburgh, P Strombom, LKF Temple, GM Nash, JG Guillem, PB Paty, R Yaeger, ZK Stadler, K Seier, M Gonen, NH Segal, DL Reidy, A Varghese, J Shia, E Vakiani, AJ Wu, CH Crane, MJ Gollub, LB Saltz, V Vendrely, J Asselineau, P Rouanet, JJ Tuech, A Valverde, Chaisemartin C de, M Rivoire, B Trilling, M Jafari, G Portier, B Meunier, I Sieleznieff, M Bertrand, F Marchal, A Dubois, M Pocard, A Rullier, D Smith, N Frulio, E Frison, Q Denost, CC Fossum, JY Alabbad, LB Romak, CL Hallemeier, MG Haddock, M Huebner, EJ Dozois, DW Larson, J Simpson, JH Scholefield, L Feo, M Polcino, E Vinet, N Joharatnam-Hogan, W Wilson, KK Shiu, GK Fusai, B Davidson, D Hochhauser, J Bridgewater, K Khan, JY Luh, KV Albuquerque, C Cheng, RP Ermoian, N Nabavizadeh, H Parsai, JC Roeske, SE Weiss, RB Wynn, Y Yu, SA Rosenthal, A Hartford, S Gwynne, R Webster, R Adams, S Mukherjee, B Coles, J Staffurth, AC Hartford, JM Galvin, DC Beyer, TJ Eichler, GS Ibbott, B Kavanagh, CJ Schultz, ST Chao, LK Dad, LA Dawson, NB Desai, M Pacella, R Rengan, Y Xiao, KM Yenice, BS Teh, SY Woo, EB Butler, SS Lo, AJ Fakiris, EL Chang, NA Mayr, JZ Wang, L Papiez, RC McGarry, HR Cardenes, RD Timmerman, AB Sharabi, PT Tran, M Lim, CG Drake, TL Deweese, E Lavrova, MD Garrett, YF Wang, C Chin, C Elliston, M Savacool, M Price, LA Kachnic, DP Horowitz, KK Brock, CH Chiang, TY Chao, MY Huang, M Haque, MS Shakil, KM Mahmud, EJ Vaios, J Yan, C Wang, X Jiang, Y Wei, Q Wang, K Cui, X Xu, F Wang, L Zhang, T Mitin, AL Zietman, X Tian, K Liu, Y Hou, J Cheng, J Zhang, Y Hiroshima, H Ishikawa, M Murakami, M Nakamura, S Shimizu, T Enomoto, T Oda, M Mizumoto, K Nakai, T Okumura, H Sakurai, G Kraft, S Yamada, H Takiyama, Y Isozaki, M Shinoto, H Makishima, N Yamamoto, H Tsuji, DK Ebner, T Kamada, EG Chiorean, G Nandakumar, T Fadelu, S Temin, AE Alarcon-Rozas, S Bejarano, AE Croitoru, S Grover, PV Lohar, A Odhiambo, ER Garcia, C Teh, A Rose, B Zaki, MD Chamberlin, Dominguez O Hernandez, S Yilmaz, SR Steele, D Duarte, N Vale, XH You, YH Jiang, Z Fang, F Sun, Y Li, W Wang, ZJ Xia, XZ Wang, HQ Ying, L Xiong, Y Lou, L Wang, NN Baxter, EB Kennedy, E Bergsland, J Berlin, TJ George, S Gill, PJ Gold, A Hantel, L Jones, C Lieu, N Mahmoud, YN You, JA Meyerhardt, WJ Thompson, GA Piazza, H Li, L Liu, J Fetter, B Zhu, G Sperl, D Ahnen, R Pamukcu, BN Islam, DD Browning, M Cruz-Burgos, A Losada-Garcia, CD Cruz-Hernández, SA Cortés-Ramírez, I Camacho-Arroyo, V Gonzalez-Covarrubias, M Morales-Pacheco, SI Trujillo-Bornios, M Rodríguez-Dorantes, P Dent, L Booth, JL Roberts, A Poklepovic, JF Hancock, N Arber, CJ Eagle, J Spicak, I Rácz, P Dite, J Hajer, M Zavoral, MJ Lechuga, P Gerletti, J Tang, RB Rosenstein, K Macdonald, P Bhadra, R Fowler, J Wittes, SD Solomon, B Levin, J Peñarando, A Cañas, LM López-Sánchez, F Conde, S Guil-Luna, V Hernández, C Villar, C Morales-Estévez, la Haba-Rodríguez J de, E Aranda, A Rodríguez-Ariza, RK Phillips, MH Wallace, PM Lynch, E Hawk, GB Gordon, BP Saunders, N Wakabayashi, Y Shen, S Zimmerman, L Godio, M Rodrigues-Bigas, LK Su, J Sherman, G Kelloff, G Steinbach, CA Burke, R Phillips, JS Morris, R Slack, X Wang, S Patterson, FA Sinicrope, MA Rodriguez-Bigas, E Half, S Bulow, A Latchford, S Clark, WA Ross, B Malone, H Hasson, E Richmond, D Fina, L Franchi, R Caruso, I Peluso, GC Naccari, S Bellinvia, R Testi, F Pallone, G Monteleone, A Reinacher-Schick, A Schoeneck, U Graeven, I Schwarte-Waldhoff, W Schmiegel, C Stolfi, J Słoka, M Madej, B Strzalka-Mrozik, AF Slater, JH Choi, JS Yoon, YW Won, BB Park, YY Lee, K Sasaki, NH Tsuno, E Sunami, K Kawai, K Hongo, M Hiyoshi, M Kaneko, K Murono, N Tada, T Nirei, K Takahashi, J Kitayama, M Selvakumaran, RK Amaravadi, IA Vasilevskaya, PJ O'Dwyer, LE Anselmino, MV Baglioni, G Reynoso, VR Rozados, OG Scharovsky, MJ Rico, M Menacho-Márquez, T André, C Boni, L Mounedji-Boudiaf, M Navarro, J Tabernero, T Hickish, C Topham, M Zaninelli, P Clingan, I Tabah-Fisch, Gramont A de, A Bonetti, F Rivera, JP Kuebler, HS Wieand, MJ O'Connell, RE Smith, LH Colangelo, G Yothers, NJ Petrelli, MP Findlay, TE Seay, JN Atkins, JL Zapas, JW Goodwin, L Fehrenbacher, RK Ramanathan, BA Conley, PJ Flynn, G Soori, LK Colman, EA Levine, KS Lanier, N Wolmark, A Figer, M Seymour, M Homerin, A Hmissi, J Cassidy, H Cortes-Funes, G Freyer, D Papamichael, Bail N Le, C Louvet, D Hendler, Braud F de, C Wilson, F Morvan, A Mohammed, NB Janakiram, M Brewer, K Vedala, VE Steele, CV Rao, AR Brás, P Fernandes, T Moreira, J Morales-Sanfrutos, E Sabidó, AMM Antunes, A Valente, A Preto, C Teixeira-Guedes, RG Teixeira, Garcia M Helena, TS Morais, P Florindo, MF Piedade, V Moreno, C Ciudad, V Noe, YT Lee, YJ Tan, CE Oon, VV Padma, Z Koveitypour, F Panahi, M Vakilian, M Peymani, Forootan F Seyed, Esfahani MH Nasr, K Ghaedi, N Valeri, C Dearman, S Rao, D Watkins, N Starling, I Chau, D Cunningham, J Neumann, L Wehweck, S Maatz, J Engel, T Kirchner, A Jung, Y Humblet, S Siena, D Khayat, H Bleiberg, A Santoro, D Bets, M Mueser, A Harstrick, C Verslype, Cutsem E Van, G Fornasier, S Francescon, P Baldo, CH Köhne, E Hitre, J Zaluski, Chien CR Chang, A Makhson, G D'Haens, T Pintér, R Lim, G Bodoky, JK Roh, G Folprecht, P Ruff, C Stroh, S Tejpar, M Schlichting, J Nippgen, P Rougier, I Láng, MP Nowacki, S Cascinu, I Shchepotin, J Maurel, A Zubel, I Celik, F Ciardiello, TS Maughan, RA Adams, CG Smith, AM Meade, MT Seymour, RH Wilson, S Idziaszczyk, R Harris, D Fisher, SL Kenny, E Kay, JK Mitchell, A Madi, B Jasani, MD James, MJ Kennedy, B Claes, D Lambrechts, R Kaplan, JP Cheadle, CJ Allegra, RB Rumble, SR Hamilton, PB Mangu, N Roach, RL Schilsky, VK Morris, AB 3rd Benson, M Cho, KK Ciombor, C Cremolini, A Davis, DA Deming, MG Fakih, S Gholami, TS Hong, I Jaiyesimi, K Klute, H Sanoff, JH Strickler, S White, JA Willis, C Eng, F Petrelli, R Ardito, A Ghidini, A Zaniboni, M Ghidini, S Barni, G Tomasello, L Lo, D Patel, AR Townsend, TJ Price, JY Douillard, R Burkes, M Barugel, J Jassem, I Kocákova, M Błasińska-Morawiec, M Šmakal, JL Canon, M Rother, KS Oliner, M Wolf, J Gansert, TW Kim, A Elme, JO Park, AA Udrea, SY Kim, JB Ahn, RV Valencia, S Krishnan, N Manojlovic, X Guan, C Lofton-Day, AS Jung, E Vrdoljak, D Rossini, A Boccaccino, M Carullo, C Antoniotti, G Dima, P Ciracì, F Marmorino, R Moretto, G Masi, T Liu, S Jiang, X Teng, L Zhong, M Liu, Y Jin, M Dong, Y Zhang, JY Zou, Y Wang, A Dasari, S Lonardi, R Garcia-Carbonero, E Elez, T Yoshino, A Sobrero, J Yao, P García-Alfonso, J Kocsis, Gracian A Cubillo, A Sartore-Bianchi, T Satoh, V Randrian, J Tomasek, G Chong, AS Paulson, T Masuishi, J Jones, T Csőszi, F Ghiringhelli, A Shergill, HS Hochster, J Krauss, A Bassam, M Ducreux, L Faugeras, S Kasper, D Arnold, S Nanda, Z Yang, WR Schelman, M Kania, D Dakowicz, R Bhattacharya, XC Ye, R Wang, X Ling, M McManus, F Fan, D Boulbes, LM Ellis, X Ye, L Xia, J Garcia, HI Hurwitz, AB Sandler, D Miles, RL Coleman, R Deurloo, OL Chinot, H Hurwitz, W Novotny, T Cartwright, J Hainsworth, W Heim, A Baron, S Griffing, E Holmgren, N Ferrara, G Fyfe, B Rogers, R Ross, F Kabbinavar, C Zhang, Y Lv, C Cao, J Lu, B Du, X Yang, Y Cui, Y Guo, R Lakomy, H Prenen, J Prausová, T Macarulla, Hazel GA van, V Moiseyenko, D Ferry, J McKendrick, J Polikoff, A Tellier, R Castan, C Allegra, A Thakur, MR Chorawala, RS Patel, AL Cohn, R Obermannova, TE Ciuleanu, DC Portnoy, A Grothey, P Garcia-Alfonso, K Yamazaki, PR Clingan, L Simms, SC Chang, F Nasroulah, P Ge, N Wan, X Han, X Long, Y Bian, Z Gao, Y Bao, Y Fan, G Chen, P Fu, J Ros, M Rodríguez-Castells, N Saoudi, I Baraibar, F Salva, E Élez, H Wasan, J Desai, F Loupakis, YS Hong, N Steeghs, TK Guren, HT Arkenau, A Gollerkeri, K Maharry, J Christy-Bittel, S Kopetz, DY Oh, YJ Bang, SJ Casak, MN Horiba, M Yuan, SJ Lemery, YL Shen, W Fu, JN Moore, Y Bi, D Auth, N Fesenko, PG Kluetz, R Pazdur, LA Fashoyin-Aje, T Vu, FX Claret, K Ng, C Wu, JM Hubbard, AL Coveler, C Fountzilas, A Kardosh, PM Kasi, HJ Lenz, DL Bajor, F Sanchez, M Stecher, W Feng, TS Bekaii-Saab, J Koury, M Lucero, C Cato, L Chang, J Geiger, D Henry, J Hernandez, F Hung, P Kaur, G Teskey, A Tran, Z Zhang, AS Shimu, HX Wei, Q Li, X Zheng, B Li, J Zheng, DM Pardoll, Y Shiravand, F Khodadadi, SMA Kashani, SR Hosseini-Fard, S Hosseini, H Sadeghirad, R Ladwa, K O'Byrne, A Kulasinghe, JA Seidel, A Otsuka, K Kabashima, HB Jie, Y Lei, N Gildener-Leapman, S Trivedi, T Green, LP Kane, RL Ferris, ME Keir, MJ Butte, GJ Freeman, AH Sharpe, M Wu, Q Huang, Y Xie, X Wu, H Ma, Y Xia, for Colorectal Cancer Immunotherapy, C for DE Research, LA Jr Diaz, BV Jensen, LH Jensen, C Punt, M Benavides, P Gibbs, la Fourchardiere C de, DT Le, WY Zhong, D Fogelman, P Marinello, T Andre, F Hirano, K Kaneko, H Tamura, H Dong, M Ichikawa, C Rietz, DB Flies, JS Lau, G Zhu, K Tamada, L Chen, MJ Overman, R McDermott, JL Leach, MA Morse, A Hill, M Axelson, RA Moss, MV Goldberg, ZA Cao, JM Ledeine, GA Maglinte, O Kooshkaki, A Derakhshani, N Hosseinkhani, M Torabi, S Safaei, O Brunetti, V Racanelli, N Silvestris, B Baradaran, V Singh, A Sheikh, MAS Abourehab, P Kesharwani, A GSK, M Lumish, J Sinopoli, J Weiss, M Lamendola-Essel, Dika IH El, N Segal, M Shcherba, R Sugarman, Z Stadler, B Rousseau, G Argiles, M Patel, A Desai, M Widmar, K Iyer, N Gianino, C Crane, PB Romesser, EP Pappou, P Paty, M Gollub, KA Schalper, T Watanabe, T Ishino, Y Ueda, J Nagasaki, T Sadahira, H Dansako, M Araki, Y Togashi, S Hashemzadeh, Z Asadzadeh, MA Shadbad, F Rasibonab, H Safarpour, V Jafarlou, AG Solimando, PK Singh, S Najafi, D Javadrashid, A Tarhini, KYM Wong, F Gelsomino, M Aglietta, MB Sawyer, A Hendlisz, B Neyns, S Abdullaev, A Memaj, M Lei, M Dixon, PM Boland, WW Ma, CH June, SR Riddell, TN Schumacher, A Mitra, A Barua, L Huang, S Ganguly, Q Feng, B He, H Du, J Yang, Q Zhang, J Shen, X Huang, M Wang, Y Huang, J Chen, Y Xu, W Zhao, Y Qi, Y Ou, C Qian, DJ Juat, SJ Hachey, J Billimek, Rosario MP Del, EL Nelson, CCW Hughes, JA Zell, E Martinis, C Ricci, C Trevisan, G Tomadini, S Tonon, Z Wu, M Yang, Y Cao, W Jia, T Zhang, H Huang, H Feng, Z Guo, Z Luo, X Ji, X Cheng, R Zhao, E Janssen, B Subtil, la Jara Ortiz F de, HMW Verheul, DVF Tauriello, Therapeutics Tizona, LLC Inc, Sankyo Co Daiichi, SE BioNTech, DS Neel, TG Bivona, A Bardelli, S Corso, A Bertotti, S Hobor, E Valtorta, G Siravegna, E Scala, A Cassingena, D Zecchin, M Apicella, G Migliardi, F Galimi, C Lauricella, C Zanon, T Perera, S Veronese, G Corti, A Amatu, M Gambacorta, M Sausen, VE Velculescu, P Comoglio, L Trusolino, Nicolantonio F Di, S Giordano, A Jahangiri, Lay M De, LM Miller, WS Carbonell, YL Hu, K Lu, MW Tom, J Paquette, TA Tokuyasu, S Tsao, R Marshall, A Perry, KM Bjorgan, MM Chaumeil, SM Ronen, G Bergers, MK Aghi, CJ LaFargue, P Amero, K Noh, LS Mangala, Y Wen, E Bayraktar, S Umamaheswaran, E Stur, SK Dasari, C Ivan, S Pradeep, W Yoo, C Lu, NB Jennings, V Vathipadiekal, W Hu, A Chelariu-Raicu, Z Ku, H Deng, W Xiong, HJ Choi, M Hu, T Kiyama, CA Mao, R Ali-Fehmi, MJ Birrer, N Zhang, G Lopez-Berestein, Franciscis V de, Z An, AK Sood, M Hao, S Hou, W Li, K Li, L Xue, Q Hu, L Zhu, Y Chen, H Sun, C Ju, YL Tang, DD Li, JY Duan, LM Sheng, J Manzi, CO Hoff, R Ferreira, A Pimentel, J Datta, AS Livingstone, R Vianna, P Abreu, GM Ramzy, M Norkin, T Koessler, L Voirol, M Tihy, D Hany, T McKee, N Buchs, M Docquier, C Toso, L Rubbia-Brandt, G Bakalli, S Guerrier, J Huelsken, P Nowak-Sliwinska, JD Fumet, A Hoos, AM Eggermont, S Janetzki, FS Hodi, R Ibrahim, A Anderson, R Humphrey, B Blumenstein, L Old, J Wolchok, F Tartari, M Santoni, L Burattini, P Mazzanti, A Onofri, R Berardi, J Zugazagoitia, C Guedes, S Ponce, I Ferrer, S Molina-Pinelo, L Paz-Ares, Velzen MJM van, S Derks, Grieken NCT van, Mohammad N Haj, Laarhoven HWM van, N Huyghe, P Baldin, den Eynde M Van, G Trimaglio, AF Tilkin-Mariamé, V Feliu, F Lauzéral-Vizcaino, M Tosolini, C Valle, M Ayyoub, O Neyrolles, N Vergnolle, Y Rombouts, C Devaud, AD Kostic, E Chun, L Robertson, JN Glickman, CA Gallini, M Michaud, TE Clancy, DC Chung, P Lochhead, GL Hold, EM El-Omar, D Brenner, CS Fuchs, M Meyerson, WS Garrett, LS Pessoa, M Heringer, VP Ferrer, Maghvan P Vaseghi, S Jeibouei, ME Akbari, V Niazi, F Karami, A Rezvani, N Ansarinejad, M Abbasinia, G Sarvari, H Zali, R Talaie, A Dey, S Pathak, S Prasad, AS Zhang, H Zhang, XF Sun, A Banerjee Show less
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000 Show more
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000, accounting for 10% of all cancer deaths worldwide. Accordingly, there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and mortality. Current management strategies for CRC include surgical procedures for resectable cases, and radiotherapy, chemotherapy, and immunotherapy, in addition to their combination, for non-resectable tumors. Despite these options, CRC remains incurable in 50% of cases. Nonetheless, significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated, leading to the availability of new drugs and therapeutic strategies. This review summarizes the most recent therapeutic approaches for CRC, with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC. Show less
📄 PDF DOI: 10.5306/wjco.v15.i9.1136
review
S. Hangan, J. Lodge, A. Odani +529 more · 2024 · Molecules · MDPI · added 2026-04-20
S. Hangan, J. Lodge, A. Odani, T. Yamaguchi, I. Persson, N. Hadjiliadis, E. Sletten, S.A. Mehrdad, A. Cucchiarini, J.L. Mergny, S.K. Noureini, S. Muthaiah, A. Bhatia, M. Kannan, A.N. Srivastva, M. Stankovic, J. Kljun, N.L.J. Stevanovic, J. Lazic, S.S. Bogojevic, S. Vojnovic, M. Zlatar, J. Nikodinovic-Runic, I. Turel, M.I. Djuran, I. Aleksic, A. Veselinovic, B.D. Glisic, H. Alshater, A.I. Al-Sulami, S.A. Aly, E.M. Abdalla, M.A. Sakr, S.S. Hassan, S. de la Mata Moratilla, S. Casado Angulo, N. Gómez-Casanova, J.L. Copa-Patiño, I. Heredero-Bermejo, F.J. de la Mata, S. García-Gallego, A. Hangan, A. Turza, R.L. Lucaciu, B. Sevastre, E. Pall, L.S. Oprean, G. Borodi, D. Rusu, A. Stănilă, I.O. Marian, C.O. Marian, M. Rusu, R. Lucaciu, T.J. Hubin, P.N. Amoyaw, K.D. Roewe, N.C. Simpson, R.D. Maples, T.N. Carder Freeman, A.N. Cain, J.G. Le, S.J. Archibald, S.I. Khan, E. Bortolamiol, F. Visentin, T. Scattolin, I. Kostova, A.C. Hangan, L. Dican, E. Páll, R.L. Stan, S. Gheorghe-Cetean, A. Tsoupras, S. Pafli, C. Stylianoudakis, K. Ladomenou, C.A. Demopoulos, A. Philippopoulos, J. Wlodarczyk, J. Krajewska, L. Szeleszczuk, P. Szalwinska, A. Gurba, S. Lipiec, P. Taciak, R. Szczepaniak, I. Mlynarzuk-Bialy, J. Fichna, C. Abate, F. Carnamucio, O. Giuffre, C. Foti, C. Chuong, C.M. DuChane, E.M. Webb, P. Rai, J.M. Marano, C.M. Bernier, J.S. Merola, J. Weger-Lucarelli, L. Oprean, P. Kumar, S. Gorai, M.K. Santra, B. Mondal, D. Manna, M. Sirajuddin, S. Ali, A. Badshah, J.D. Watson, F.H.C. Crick, B. Maddox, P.J. Kennelly, K.M. Botham, O. McGuinness, V.W. Rodwell, P.A. Weil, R.A. Harvey, D.R. Ferrier, J.M. Berg, J.L. Tymoczko, G.J. Gatto, L. Stryer, J.A. Cowan, P. Yakovchuk, E. Protozanova, M.D. Frank-Kamenetskii, M.J. Hannon, I. Bertini, H.B. Gray, S.J. Lippard, J.S. Valentine, Z. Shakked, G. Guerstein-Guzikevich, M. Eisenstein, F. Frolow, D. Rabinovich, J.C. Garcia-Ramos, R. Galindo-Murillo, F. Cortez-Guzman, L. Ruiz-Azuara, S. Neidle, M. Hägerlöf, P. Papsai, C.S. Chow, S.K.C. Elmroth, J. François, N.T. Thuong, C. Hélène, J.L. Huppert, T.A. Brooks, S. Kendrick, L. Hurley, X. Li, Y. Peng, J. Ren, X. Qu, Y. Akiyama, S.M. Hecht, L.H. Hurley, J. Zhou, C. Wei, G. Jia, X. Wang, Z. Feng, C. Li, A. Mukherjee, K.M. Vasquez, E. Marian, L.G. Vicas, J. Tunde, M. Muresan, Z. Diaconeasa, C. Ionescu, R.G. Pearson, G. Barone, A. Terenzi, A. Lauria, A.M. Almerico, J.M. Leal, N. Busto, B. Garcia, J. Vinje, J.A. Parkinson, P.J. Sadler, T. Brown, A.A. Almaqwashi, T. Paramanathan, I. Rouzina, M.C. Williams, F.R. Keene, J.A. Smith, J.G. Collins, A. Rilak, R. Masnikosa, I. Bratsos, E. Alessio, S.K. Srivastava, T.C. Johnstone, K. Suntharalingam, S. Cetean, T. Ciuleanu, D.C. Leucuta, C. Cainap, A.M. Constantin, I. Cazacu, S. Cainap, A. Gherman, Y. He, Y. Ding, D. Wang, W. Zhang, W. Chen, X. Liu, W. Qin, X. Qian, H. Chen, Z. Guo, E. Stefàno, F. De Castro, A. Ciccarese, A. Muscella, S. Marsigliante, M. Benedetti, F.P. Fanizzi, P.M. Takahara, A.C. Rosenzweig, C.A. Frederick, M. Demeunynck, C. Bailly, W.D. Wilson, K. Nakamoto, M. Tsuboi, G.D. Strahan, B.M. Zeglis, V.C. Pierre, J.K. Barton, C. Shobha Devi, B. Thulasiram, R.R. Aerva, P. Nagababu, T. Biver, F. Secco, M. Venturini, C.E. Maciel-Flores, J.A. Lozano-Alvarez, E.Y. Bivián-Castro, F. Jia, S. Wang, Y. Man, B. Liu, P. Modrich, A. Erxleben, E. Dumont, A. Monari, D.L. Morris, G.S. Khan, A. Shah, D. Zia-ur-Rehman, B.J. Pages, D.L. Ang, E.P. Wright, J.R. Aldrich-Wright, S.M. Nelson, L.R. Ferguson, W.A. Denny, L. Winkler, F. Cortes-Guzman, T.E. Cheatham, O. Sarpataki, N.K. Olah, M. Taulescu, I. Marcus, C. Cătoi, M.M. González-Ballesteros, L. Sánchez-Sánchez, A. Espinoza-Guillén, J. Espinal-Enríquez, C. Mejía, E. Hernández-Lemus, P.H. von Hippel, A.H. Marcus, S. Komeda, T. Moulaei, K. Kruger Woods, M. Chikuma, N.P. Farrell, L.D. Williams, T. Jany, A. Moreth, C. Gruschka, A. Sischka, A. Spiering, M. Dieding, Y. Wang, S. Haji Samo, A. Stammler, H. Bögge, S. Li, B. Yuan, J. Zhang, L. Yue, H. Hou, J. Hu, S. Chen, B.R. Kirthan, M.C. Prabhakara, H.S. Bhojya Naik, P.H.A. Nayak, E.I. Naik, U. Saha, S. Chatterjee, M. Dolai, G.S. Kumar, A.M. Abu-Dief, N.H. Alotaibi, E.S. Al-Farraj, H.A. Qasem, S. Alzahrani, M.K. Mahfouz, A. Abdou, B. Kurt, H. Temel, M. Atlan, S. Kaya, H.A. Kiwaan, A.S. El-Mowafy, A.A. El-Bindary, S. Baskaran, M.N. Krishnan, M. Arumugham, R. Kumar, N. Kumar, R. Kaushal, P. Awasthi, A. Kellett, Z. Molphy, C. Slator, V. McKee, V.G. Vaidyanathan, B.U. Nair, R. Vijayalakshmi, P. Karacan, O. Okay, S. Phukan, S. Mitra, S. Nafisi, A.A. Saboury, N. Keramat, J.F. Neault, H.A. Tajmir-Riahi, P. Sathyadevi, P. Krishnamoorthy, R.R. Butorac, A.H. Cowley, N.S.P. Bhuvanesh, N. Dharmaraj, F. Arjmand, S. Parveen, M. Afzal, M. Shahid, J.B. Lepecq, C. Paoletti, J.L. Garcia-Gimenez, M. Gonzalez-Alvarez, M. Liu-Gonzalez, B. Macias, J. Borras, G. Alzuet, M. Aslanoglu, M. Zaheer, R. Qureshi, Z. Akhter, M.F. Nazar, M. Ngoepe, H. Clayton, P. Mucha, P. Hikisz, K. Gwoździński, U. Krajewska, A. Leniart, E. Budzisz, E.F. Garman, J.R. Helliwell, E.P. Mitchell, A.N. Boynton, K.M. Boyle, M.J. Waring, S. Da Vela, D.I. Svergun, L.A. Feigin, P.P.P. Kumar, D.K. Lim, T.H. Jensen, M. Bech, O. Bunk, M. Thomsen, A. Menzel, A. Bouchet, G. Le Duc, R. Feidenhans, F. Pfeiffer, S. Sidhu, G. Falzon, S.A. Hart, J.G. Fox, R.A. Lewis, K.K.W. Siu, D.A. Jacques, J. Trewhella, N. Allec, M. Choi, N. Yesupriya, B. Szychowski, M.R. White, M.G. Kann, E.D. Garcin, M.C. Daniel, A. Badano, Y. Qu, J.B. Mangrum, A. Hegmans, S.J. Berners-Price, L. Ronconi, X. Filip, C. Tripon, C. Morari, C. Filip, T. Urathamakul, D.J. Waller, J.L. Beck, S.F. Ralph, X. Fan, J. Wang, X. Zhang, Z. Yang, J.C. Zhang, L. Zhao, H. Peng, J. Lei, H.W. Wang, J.L. Rubinstein, X. Benjin, L. Ling, A. Punjani, D.J. Fleet, M.A. Brubaker, A. Goldstein, Y. Soroka, M. Frušic-Zlotkin, I. Popov, R. Kohen, M. Havrdova, K. Polakova, J. Skopalik, M. Vujtek, A. Mokdad, M. Homolkova, J. Tucek, J. Nebesarova, R. Zboril, M. Malatesta, M.R. Rodríguez, M.J. Lavecchia, B.Z. Parajón-Costa, A.C. González-Baró, M.R. González-Baró, E. Cattáneo, A.N. Alaghaz, S. Aldulmani, A. Yadav, K. Poonia, R. Ștefan, K.R. Fox, M.V. Villa, R. Lapresa, J. Hernandez-Gil, F. Sanz, J.B. Chaires, M. Mudasir, E.T. Wahyuni, D.H. Tjahjono, N. Yoshioka, H. Inoue, P. Jaividhya, R. Dhivya, M.A. Akbarsha, M. Palaniandavar, N. Raman, R. Jeyamurugan, A. Sakthivel, L. Mitu, A. Prisecaru, R.G. Kipping, E.J. Peterson, J.L. García-Giménez, J. Hernández-Gil, A. Martínez-Ruíz, A. Castiñeiras, M. Liu-Gonzáles, F.V. Pallardó, J. Borrás, G. Alzuet Piña, M. Swathi, D.S. Shankar, S. Daravath, N. Ganji, P.V.A. Lakshmi, R. Shivaraj, A. Pérez, F.J. Luque, M. Orozco, N.M. Henriksen, D.R. Davis, D.A. Case, T.E.I. Cheatham, T. Darden, H. Gohlke, R. Luo, K.M. Merz, A. Onufriev, C. Simmerling, B. Wang, R.J. Woods, M.B. Peters, Y. Yang, L. Füsti-Molnár, M.N. Weaver, M. Sahadevan, M. Sundaram, K. Subramanian Show less
DNA structure has many potential places where endogenous compounds and xenobiotics can bind. Therefore, xenobiotics bind along the sites of the nucleic acid with the aim of changing its structure, its Show more
DNA structure has many potential places where endogenous compounds and xenobiotics can bind. Therefore, xenobiotics bind along the sites of the nucleic acid with the aim of changing its structure, its genetic message, and, implicitly, its functions. Currently, there are several mechanisms known to be involved in DNA binding. These mechanisms are covalent and non-covalent interactions. The covalent interaction or metal base coordination is an irreversible binding and it is represented by an intra-/interstrand cross-link. The non-covalent interaction is generally a reversible binding and it is represented by intercalation between DNA base pairs, insertion, major and/or minor groove binding, and electrostatic interactions with the sugar phosphate DNA backbone. In the present review, we focus on the types of DNA–metal complex interactions (including some representative examples) and on presenting the methods currently used to study them. Show less
📄 PDF DOI: 10.3390/molecules29184361
DNA-binding coordination-chemistry review
TA Kalyanaraman, N Daver, M Mahendra +242 more · 2023 · Expert opinion on therapeutic targets · Taylor & Francis · added 2026-04-20
TA Kalyanaraman, N Daver, M Mahendra, X Zhang, CV Dang, TM Ashton, WG McKenna, LA Kunz-Schughart, Y Xu, D Xue, A Bankhead, M Huang, CR Myers, Y Wang, B Kalyanaraman, SK Biswas, RAJ Smith, CM Porteous, AM Gane, MP Murphy, RC Hartley, E Fokas, M Benej, X Hong, S Vibhute, M Nishida, N Yamashita, T Ogawa, K Chandran, D Aggarwal, RQ Migrino, D Graham, NN Huynh, CA Hamilton, T Capeloa, J Krzystyniak, D d’Hose, JA Van de Velde, AC Rodriguez, NG Yoon, H Lee, SY Kim, S Yoshida, S Tsutsumi, G Muhlebach, A Rasola, L Neckers, D Picard, G Cheng, H Karoui, M Hardy, F Weinberg, R Hamanaka, WW Wheaton, B Fink, L Coppey, E Davidson, EM Gottwald, M Duss, M Bugarski, J Pan, Y Lee, JR Molina, Y Sun, M Protopopova, J Zielonka, M AbuEid, DM McAllister, L McOlash, IK Srivastava, H Rottenberg, AB Vaidya, PD Radloff, J Philipps, M Nkeyi, W Hughes, G Leoung, F Kramer, CD Freeman, NE Klutman, KC Lamp, A Darade, S Pathak, S Sharma, R Dixon, AL Pozniak, HM Watt, GL Nixon, DM Moss, AE Shone, M Fry, M Pudney, MW Mather, E Darrouzet, M Valkova-Valchanova, M Fiorillo, R Lamb, HB Tanowitz, M Xiang, H Kim, VT Ho, N Gupta, SK Srivastava, S Tian, H Chen, W Tan, D Xiong, P Topchyan, RM Loftus, DK Finlay, G Andrejeva, JC Rathmell, X Li, M Wenes, P Romero, T Gaber, C Strehl, F Buttgereit, A Tasdogan, JM Ubellacker, SJ Morrison, B Faubert, V Ramesh, Q Zhang, LP Burton, G Deng, CD Yanes, SR Lord, AL Harris, ME McGuinness, RL Talbert, H Zhao, KD Swanson, B Zheng, L Di Magno, S Manni, F Di Pastena, SR Veiga, X Ge, CA Mercer, R Masoud, G Reyes-Castellanos, S Lac, F Janku, SH Beom, YW Moon, O Ouari, KA Boyle, J Van Wickle, RB Hill, RF Keyes, D McAllister, Z Bielcikova, J Stursa, L Krizova, K Rohlenova, K Sachaphibulkij, KER Hollinshead, SJ Parker, VV Eapen, S Stemberkova-Hubackova, R Zobalova, M Dubisova, CA Reddy, V Somepalli, T Golakoti, S Jayakumar, RS Patwardhan, D Pal, A Mattarei, M Romio, A Managò, RK Pathak, S Marrache, DA Harn, DR Boulware, MF Pullen, AS Bangdiwala, S Crunkhorn, LD Zorova, VA Popkov, EY Plotnikov, J Joseph, A Sikora, L Dong, J Neuzil, A Solmonson, RJ DeBerardinis, V Gouirand, F Guillaumond, S Vasseur, GM Fischer, A Jalali, DA Kircher, VS LeBleu, JT O’Connell, KN Gonzalez Herrera, JH Park, S Vithayathil, S Kumar, F Sotgia, D Whitaker-Menezes, UE Martinez-Outschoorn, CR Bartman, DR Weilandt, Y Shen, YG Najjar, AV Menk, C Sander, AR Jaiswal, AJ Liu, S Pudakalakatti, MJ McManus, JL Franklin, RA Smith, B Mathieu, L Mignion, M Skwarski, DR McGowan, E Belcher, M Zielonka, B Dranka, HR Bridges, JG Fedor, JN Blaza, A Naguib, G Mathew, CR Reczek, SE Weinberg, BD Singer, EM Steinert, Z Zhao, Y Mei, Z Wang, K Vasan, M Werner, NS Chandel, EM De Francesco, B Ózsvári, S Izreig, A Gariepy, I Kaymak, D Kolb, N Kolishetti, B Surnar Show less
Introduction: Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity. Developing mitochondria- Show more
Introduction: Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity. Developing mitochondria-targeted modified natural compounds and US FDA-approved drugs with increased therapeutic index in cancer is discussed as an alternative strategy. Areas Covered: Triphenylphosphonium cation (TPP + )-based drugs selectively accumulate in the mitochondria of cancer cells due to their increased negative membrane potential, target the oxidative phosphorylation proteins, inhibit mitochondrial respiration, and inhibit tumor proliferation. TPP + -based drugs exert minimal toxic side effects in rodents and humans. These drugs can sensitize radiation and immunotherapies. Expert Opinion: TPP + -based drugs targeting the tumor mitochondrial electron transport chain are a new class of oxidative phosphorylation inhibitors with varying antiproliferative and antimetastatic potencies. Some of these TPP + -based agents, which are synthesized from naturally occurring molecules and FDA-approved drugs, have been tested in mice and did not show notable toxicity, including neurotoxicity, when used at doses under the maximally tolerated dose. Thus, more effort should be directed toward the clinical translation of TPP + -based OXPHOS-inhibiting drugs in cancer prevention and treatment. Show less
no PDF DOI: 10.1080/14728222.2023.2261631
anticancer mitochondria synthesis
S. Trapotsi, G. Drakakis, A. Koutsoukas +1688 more · 2022 · RSC Chemical Biology · Royal Society of Chemistry · added 2026-04-20
S. Trapotsi, G. Drakakis, A. Koutsoukas, I. Cortes–Ciriano, P. Martínez–Alonso, T. E. Malliavin, A. Velazquez-Campoy, S. C. Brewerton, M. J. Bodkin, D. A. Evans, R. C. Glen, J. A. Carrodeguas, A. Bender, S. W. Page, J. E. Maddison, M. R. Trusheim, E. R. Berndt, F. L. Douglas, L. Rovin, C. J. Bailey, G. Zhou, R. Myers, Y. Li, Y. Chen, X. Shen, J. Fenyk-Melody, M. Wu, J. Ventre, T. Doebber, N. Fujii, N. Musi, M. F. Hirshman, L. J. Goodyear, D. E. Moller, I. Bezprozvanny, J. Wu, Q. Li, A. C. Lai, C. M. Crews, J. Downward, F. Ardito, M. Giuliani, D. Perrone, G. Troiano, L. L. Muzio, H. Lodish, A. Berk, S. L. Zipursky, P. Matsudaira, D. Baltimore, J. Darnell, N. Ammeux, B. E. Housden, A. Georgiadis, Y. Hu, N. Perrimon, J. E. Dumont, S. Dremier, I. Pirson, C. Maenhaut, T. Vu, F. X. Claret, H. S. Camp, O. Li, S. C. Wise, Y. H. Hong, C. L. Frankowski, R. Vanbogelen, T. Leff, K. Kores, J. Konc, U. Bren, M.-A. Trapotsi, L. H. Mervin, A. M. Afzal, N. Sturm, O. Engkvist, I. P. Barrett, B. Baillif, J. Wichard, O. Méndez-Lucio, D. Rouquié, J. Inglese, D. S. Auld, B. A. Wetmore, J. F. Wambaugh, S. S. Ferguson, M. A. Sochaski, D. M. Rotroff, K. Freeman, H. J. Clewell III, D. J. Dix, M. E. Andersen, K. A. Houck, B. Allen, R. S. Judson, R. Singh, R. J. Kavlock, A. M. Richard, R. S. Thomas, M. Schenone, V. Dančík, B. K. Wagner, P. A. Clemons, A. Subramanian, R. Narayan, S. M. Corsello, D. D. Peck, T. E. Natoli, X. Lu, J. Gould, J. F. Davis, A. A. Tubelli, J. K. Asiedu, D. L. Lahr, J. E. Hirschman, Z. Liu, M. Donahue, B. Julian, M. Khan, D. Wadden, I. C. Smith, D. Lam, A. Liberzon, C. Toder, M. Bagul, M. Orzechowski, O. M. Enache, F. Piccioni, S. A. Johnson, N. J. Lyons, A. H. Berger, A. F. Shamji, A. N. Brooks, A. Vrcic, C. Flynn, J. Rosains, D. Y. Takeda, R. Hu, D. Davison, J. Lamb, K. Ardlie, L. Hogstrom, P. Greenside, N. S. Gray, S. Silver, X. Wu, W.-N. Zhao, W. Read-Button, S. J. Haggarty, L. V. Ronco, J. S. Boehm, S. L. Schreiber, J. G. Doench, J. A. Bittker, D. E. Root, B. Wong, T. R. Golub, J. M. Raser, E. K. O’Shea, A. A. Kalaitzis, N. D. Lawrence, D. P. Nusinow, J. Szpyt, M. Ghandi, C. M. Rose, E. R. McDonald, M. Kalocsay, J. Jané-Valbuena, E. Gelfand, D. K. Schweppe, M. Jedrychowski, J. Golji, D. A. Porter, T. Rejtar, Y. K. Wang, G. V. Kryukov, F. Stegmeier, B. K. Erickson, L. A. Garraway, W. R. Sellers, S. P. Gygi, M.-A. Bray, S. Singh, H. Han, C. T. Davis, B. Borgeson, C. Hartland, M. Kost-Alimova, S. M. Gustafsdottir, C. C. Gibson, A. E. Carpenter, A. X. Lu, O. Z. Kraus, S. Cooper, A. M. Moses, S. N. Chandrasekaran, H. Ceulemans, J. D. Boyd, M. J. Cox, S. Jaensch, J. Van de Waeter, L. Cougnaud, D. Seynaeve, S. Benalla, S. J. Koo, I. Van Den Wyngaert, J.-M. Neefs, D. Malkov, M. Bittremieux, M. Steemans, P. J. Peeters, J. K. Wegner, E. Gustin, Y. T. Chong, H. W. H. Göhlmann, I. Nassiri, M. N. McCall, P. D. Piehowski, V. A. Petyuk, D. J. Orton, F. Xie, M. Ramirez-Restrepo, A. Engel, A. P. Lieberman, R. L. Albin, D. G. Camp, R. D. Smith, A. J. Myers, M. Medo, D. M. Aebersold, M. Medová, C. H. Johnson, F. J. Gonzalez, T. Ramirez, M. Daneshian, H. Kamp, F. Y. Bois, M. R. Clench, M. Coen, B. Donley, S. M. Fischer, D. R. Ekman, E. Fabian, C. Guillou, J. Heuer, H. T. Hogberg, H. Jungnickel, H. C. Keun, G. Krennrich, E. Krupp, A. Luch, F. Noor, E. Peter, B. Riefke, M. Seymour, N. Skinner, L. Smirnova, E. Verheij, S. Wagner, T. Hartung, B. van Ravenzwaay, M. Leist, A. M. D. Livera, M. Sysi-Aho, L. Jacob, J. A. Gagnon-Bartsch, S. Castillo, J. A. Simpson, T. P. Speed, R. Chaleckis, I. Meister, P. Zhang, C. E. Wheelock, J. G. Abelin, J. Patel, C. M. Feeney, L. Fagbami, A. L. Creech, L. Pino, J. W. Qiao, E. Kuhn, A. Officer, J. Li, S. Abbatiello, R. Sidman, E. Snyder, S. A. Carr, J. D. Jaffe, Y. A. Chen, S. A. Eschrich, L. Litichevskiy, R. Peckner, C. M. Dunning, J. D. Egertson, S. Egri, T. Ko, B. X. MacLean, A. E. Mungenast, M. Papanastasiou, V. Sharma, J. Z. Young, M. J. MacCoss, L.-H. Tsai, R. Lewis, Z. Tanoli, U. Seemab, A. 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Moore, D. G. Murray, B. Steiner, P. Tucker, V. Vasudevan, P. Warden, M. Wicke, Y. Yu, X. Zheng, A. Paszke, S. Gross, F. Massa, A. Lerer, G. Chanan, T. Killeen, Z. Lin, N. Gimelshein, L. Antiga, A. Desmaison, A. Köpf, E. Yang, Z. DeVito, M. Raison, A. Tejani, S. Chilamkurthy, L. Fang, S. Chintala, P. Zakeri, T. Haber, K. C. Bulusu, L. Kalash, M. A. Firth, Z. Ji, J. Su, H. Wang, D. Huang, X. Zhou, O. Weinreb, T. Amit, M. B. H. Youdim, N. L. Patel-Murray, M. Adam, N. Huynh, B. T. Wassie, P. Milani, E. Fraenkel, J. Vialard, P. Buijnsters, I. Velter, A. Vapirev, M. F. Cuccarese, B. A. Earnshaw, K. Heiser, B. Fogelson, P. F. McLean, H. B. Gordon, K.-R. Skelly, F. L. Weathersby, V. Rodic, I. K. Quigley, E. D. Pastuzyn, B. M. Mendivil, N. H. Lazar, C. A. Brooks, J. Carpenter, B. L. Probst, P. Jacobson, S. W. Glazier, J. Ford, J. D. Jensen, N. D. Campbell, M. A. Statnick, A. S. Low, K. R. Thomas, S. S. Hegde, R. W. Alfa, M. L. Victors, I. S. Haque, M. Kibble, N. Saarinen, F. Iorio, S. Mäkelä, T. Aittokallio, M. Iwata, R. Sawada, H. Iwata, M. Kotera, Y. Yamanishi, E. Dazert, M. Colombi, T. Boldanova, S. Moes, D. Adametz, L. Quagliata, V. Roth, L. Terracciano, M. H. Heim, P. Jenoe, M. N. Hall, D. Carrella, F. Napolitano, R. Rispoli, M. Miglietta, A. Carissimo, L. Cutillo, F. Sirci, F. Gregoretti, D. Di Bernardo, A. Conesa, S. Beck Show less
The elucidation of a compound's Mechanism of Action (MoA) is a challenging task in the drug discovery process, but it is important in order to rationalise phenotypic findings and to anticipate potenti Show more
The elucidation of a compound's Mechanism of Action (MoA) is a challenging task in the drug discovery process, but it is important in order to rationalise phenotypic findings and to anticipate potential side-effects. Bioinformatic approaches, advances in machine learning techniques and the increasing deposition of high-throughput data in public databases have significantly contributed to recent advances in the field, but it is not straightforward to decide which data and methods are most suitable to use in a given case. In this review, we focus on these methods and data and their applications in generating MoA hypotheses for subsequent experimental validation. We discuss compound-specific data such as -omics, cell morphology and bioactivity data, as well as commonly used supplementary prior knowledge such as network and pathway data, and provide information on databases where this data can be accessed. In terms of methodologies, we discuss both well-established methods (connectivity mapping, pathway enrichment) as well as more developing methods (neural networks and multi-omics integration). Finally, we review case studies where the MoA of a compound was successfully suggested from computational analysis by incorporating multiple data modalities and/or methodologies. Our aim for this review is to provide researchers with insights into the benefits and drawbacks of both the data and methods in terms of level of understanding, biases and interpretation – and to highlight future avenues of investigation which we foresee will improve the field of MoA elucidation, including greater public access to -omics data and methodologies which are capable of data integration. Show less
📄 PDF DOI: 10.1039/d1cb00069a
ML review
R.R. Zhou, C. Alarcón, C. Nadal +374 more · 2021 · Cancers · MDPI · added 2026-04-20
R.R. Zhou, C. Alarcón, C. Nadal, C. Van Poznak, J. Massagué, J.M. Angelastro, P.D. Canoll, J. Kuo, M. Weicker, A. Costa, J.N. Bruce, L. A Greene, R. Piva, E. Pellegrino, M. Mattioli, L. Agnelli, L. Lombardi, F. Boccalatte, G. Costa, B.A. Ruggeri, M. Cheng, R. Chiarle, S.E. Monaco, M. Szabolcs, L.A. Greene, W.J. Oh, V. Rishi, A. Orosz, M.J. Gerdes, C. Vinson, Z. Sheng, L. Li, L.J. Zhu, T.W. Smith, A. Demers, A.H. Ross, R.P. Moser, M.R. Green, M.S. Carro, W.K. Lim, M.J. Alvarez, R.J. Bollo, X. Zhao, E.Y. Snyder, E.P. Sulman, S.L. Anne, F. Doetsch, H. Colman, J. Rousseau, V. Gagné, M. Labuda, C. Beaubois, D. Sinnett, C. Laverdière, A. Moghrabi, S.E. Sallan, L.B. Silverman, D. Neuberg, T.R. Sarkar, S. Sharan, J. Wang, S.A. Pawar, C.A. Cantwell, P.F. Johnson, D.K. Morrison, J.-M. Wang, E. Sterneck, M. Hu, B. Wang, D. Qian, L. Zhang, X. Song, D.X. Liu, Y.-H. Wang, W.-J. Wu, W.-J. Wang, H.-Y. Huang, W.-M. Li, B.-W. Yeh, T.-F. Wu, Y.-L. Shiue, J.J.-C. Sheu, S. Ishihara, M. Yasuda, A. Ishizu, M. Ishikawa, H. Shirato, H. Haga, A. Nukuda, H. Endoh, T. Mizutani, K. Kawabata, S. Banerjee, N. Aykin-Burns, K.J. Krager, S.K. Shah, S.B. Melnyk, M. Hauer-Jensen, J.D. Gardiner, L.M. Abegglen, X. Huang, B.E. Carter, E.A. Schackmann, M. Stucki, C.N. Paxton, R.L. Randall, J.F. Amatruda, A.R. Putnam, Y. Zhang, H.-R. Wang, J.L. Wrana, S. Ben-Shmuel, R. Rashed, R. Rostoker, E. Isakov, Z. Shen-Orr, D. Leroith, C.-F. Li, Y.-Y. Chu, T.-C. Hour, C.-J. Yen, W.-C. Chang, Z.J. Messenger, J.R. Hall, D.D. Jima, J.S. House, H.W. Tam, D.A. Tokarz, R.C. Smart, D. Liu, X.-X. Zhang, M.-C. Li, C.-H. Cao, D.-Y. Wan, B.-X. Xi, J.-H. Tan, Z.-Y. Yang, X.-X. Feng, J. Feldheim, A.F. Kessler, D. Schmitt, L. Wilczek, T. Linsenmann, M. Dahlmann, C.M. Monoranu, R.-I. Ernestus, C. Hagemann, M. Löhr, F. Wang, Y. Gao, L. Tang, K. Ning, N. Geng, H. Zhang, Y. Li, F. Liu, F. Li, Q. Du, Z. Tan, F. Shi, M. Tang, L. Xie, L. Zhao, J. Hu, M. Zhou, A. Bode, D. Wang, X. Cheng, M. Guo, W. Zhao, J. Qiu, Y. Zheng, M. Meng, X. Ping, X. Chen, X. Ruan, X. Liu, Y. Xue, L. Shao, C. Yang, L. Zhu, Y. Yang, Z. Li, B. Yu, H. Wu, J. Gu, D. Zhou, W. Cheng, Y. Wang, Q. Wang, X. Wang, T. Kudo, M.T. Prentzell, S.R. Mohapatra, F. Sahm, Z. Zhao, I. Grummt, W. Wick, C.A. Opitz, M. Platten, E.W. Green, Z.-Y. Hua, J.N. Hansen, M. He, S.-K. Dai, Y. Choi, M.D. Fulton, S.M. Lloyd, M. Szemes, J. Sen, H.-F. Ding, A. Arias, M.W. Lamé, L. Santarelli, R. Hen, C.C. Cates, A.D. Arias, L.S.N. Wong, M. Sidorov, G. Cayanan, D.J. Rowland, J. Fung, G. Karpel-Massler, M.D. Siegelin, B.A. Horst, C. Shu, L. Chau, T. Tsujiuchi, P. Canoll, X. Sun, P. Jefferson, Q. Zhou, M. Olive, S.C. Williams, C. Dezan, A.W. Reinke, J. Baek, O. Ashenberg, A.E. Keating, C.R. Vinson, T. Hai, S.M. Boyd, E. Dupont, A. Prochiantz, A. Joliot, A.M. Sonabend, J. Yun, L. Lei, R. Leung, C. Soderquist, C. Crisman, B.J. Gill, A. Carminucci, J. Sisti, M. Castelli, J.-F. Beaulieu, D. Ménard, W. Chai, I. Ullah, K. Chung, S. Bae, C. Kim, B. Choi, H.Y. Nam, S.H. Kim, C.-O. Yun, K.Y. Lee, S. Rodrigues-Ferreira, H. Moindjie, M.M. Haykal, C. Nahmias, R. Xu, Z. Ji, C. Xu, J. Zhu, N.J. Caron, S.P. Quenneville, J.P. Tremblay, S.Y. Van Der Zanden, X. Qiao, J. Neefjes, F. A Fornari, W.D. Jarvis, S. Grant, M.S. Orr, J.K. Randolph, F.K. White, V.R. Mumaw, E.T. Lovings, R.H. Freeman, D. A Gewirtz, A. Bojko, J. Czarnecka-Herok, A. Charzynska, M. Dabrowski, E. Sikora, T. Kuilman, C. Michaloglou, L.C. Vredeveld, S. Douma, R. Van Doorn, C.J. Desmet, L.A. Aarden, W.J. Mooi, D.S. Peeper, E.S. Hungness, G.-J. Luo, T.A. Pritts, B.W. Robb, D. Hershko, P.-O. Hasselgren, M.Y. Taher, D.M. Davies, J. Maher, J. David, C. Dominguez, D.H. Hamilton, C. Palena, J. Al Sarraj, G. Thiel, F. Siu, C. Chen, C. Zhong, M.S. Kilberg, M. Chiu, G. Taurino, M.G. Bianchi, O. Bussolati, S.P. Wheatley, D.C. Altieri, N.M. Warrier, P. Agarwal, P. Kumar, D.M. García, N. Manero-Rupérez, R. Quesada, L. Korrodi-Gregório, V. Soto-Cerrato, D. Merino, D. Dluzen, G. Li, D. Tacelosky, M. Moreau, W. Li, C. Fiorese, A.M. Schulz, Y.-F. Lin, N. Rosin, M.W. Pellegrino, C.M. Haynes, B. Madarampalli, Y. Yuan, K. Lengel, Y. Xu, J. Yang, Z. Lu, I.K. Mann, R. Chatterjee, J. Zhao, X. He, M.T. Weirauch, T.R. Hughes, M.A. Summers, M.M. McDonald, P.I. Croucher, S.-Y. Park, J.-S. Nam, K.J. Kurppa, Y. Liu, C. To, T. Zhang, M. Fan, A. Vajdi, E.H. Knelson, Y. Xie, K. Lim, P. Cejas Show less
Simple Summary The gene-regulatory factors ATF5, CEBPB and CEBPD promote survival, growth, metastasis and treatment resistance of a range of cancer cell types. Presently, no drugs target all three at Show more
Simple Summary The gene-regulatory factors ATF5, CEBPB and CEBPD promote survival, growth, metastasis and treatment resistance of a range of cancer cell types. Presently, no drugs target all three at once. Here, with the aim of treating cancers, we designed novel cell-penetrating peptides that interact with and inactivate all three. The peptides Bpep and Dpep kill a range of cancer cell types in culture and in animals. In animals with tumors, they also significantly increase survival time. In contrast, they do not affect survival of non-cancer cells and have no apparent side effects in animals. The peptides work in combination with other anti-cancer treatments. Mechanism studies of how the peptides kill cancer cells indicate a decrease in survival proteins and increase in death proteins. These studies support the potential of Bpep and Dpep as novel, safe agents for the treatment of a variety of cancer types, both as mono- and combination therapies. Abstract Transcription factors are key players underlying cancer formation, growth, survival, metastasis and treatment resistance, yet few drugs exist to directly target them. Here, we characterized the in vitro and in vivo anti-cancer efficacy of novel synthetic cell-penetrating peptides (Bpep and Dpep) designed to interfere with the formation of active leucine-zipper-based dimers by CEBPB and CEBPD, transcription factors implicated in multiple malignancies. Both peptides similarly promoted apoptosis of multiple tumor lines of varying origins, without such effects on non-transformed cells. Combined with other treatments (radiation, Taxol, chloroquine, doxorubicin), the peptides acted additively to synergistically and were fully active on Taxol-resistant cells. The peptides suppressed expression of known direct CEBPB/CEBPD targets IL6 , IL8 and asparagine synthetase ( ASNS ), supporting their inhibition of transcriptional activation. Mechanisms by which the peptides trigger apoptosis included depletion of pro-survival survivin and a required elevation of pro-apoptotic BMF. Bpep and Dpep significantly slowed tumor growth in mouse models without evident side effects. Dpep significantly prolonged survival in xenograft models. These findings indicate the efficacy and potential of Bpep and Dpep as novel agents to treat a variety of cancers as mono- or combination therapies. Show less
📄 PDF DOI: 10.3390/cancers13102504
JP Ježek, AGW Leslie, R Lutter +1993 more · 2018 · Antioxidants & redox signaling · added 2026-04-20
JP Ježek, AGW Leslie, R Lutter, JE Walker, AE Adams, AM Carroll, PG Fallon, RK Porter, O Hanrahan, DN Nolan, HP Voorheis, P Fallon, OM Kelly, C Affourtit, MD Brand, M Jastroch, C Aguer, BD Piccolo, O Fiehn, SH Adams, ME Harper, L Alán, K Smolková, E Kronusová, J Šantorová, P Ježek, EM Allister, CA Robson-Doucette, KJ Prentice, AB Hardy, S Sultan, HY Gaisano, D Kong, P Gilon, PL Herrera, BB Lowell, MB Wheeler, R Amat, G Solanes, M Giralt, F Villarroya, ZB Andrews, ZW Liu, N Walllingford, DM Erion, E Borok, JM Friedman, MH Tschöp, M Shanabrough, G Cline, GI Shulman, A Coppola, XB Gao, TL Horvath, S Diano, MA Aon, S Cortassa, E Marbán, B O'Rourke, H Aquila, TA Link, M Klingenberg, D Arsenijevic, H Onuma, C Pecqueur, S Raimbault, BS Manning, B Miroux, E Couplan, MC Alves-Guerra, M Goubern, R Surwit, F Bouillaud, D Richard, S Collins, D Ricquier, V Ayyasamy, KM Owens, MM Desouki, P Liang, A Bakin, K Thangaraj, DJ Buchsbaum, AF LoBuglio, KK Singh, V Azzu, EP Breen, N Parker, G Baffy, Z Derdak, SC Robson, Y Bai, X Bai, AV Medvedev, M Misukonis, JB Weinberg, W Cao, J Robidoux, LM Floering, KW Daniel, KA Ball, AW Nelson, DG Foster, RO Poyton, J Barlow, V Hirschberg Jensen, CJ Barnstable, R Reddy, H Li, W Basu Ball, S Kar, M Mukherjee, AG Chande, R Mukhopadhyaya, PK Das, JM Baughman, F Perocchi, HS Girgis, M Plovanich, CA Belcher-Timme, Y Sancak, XR Bao, L Strittmatter, O Goldberger, RL Bogorad, V Koteliansky, VK Mootha, V Beck, M Jabůrek, EE Pohl, T Demina, A Rupprecht, EL Bell, TA Klimova, J Eisenbart, CT Moraes, MP Murphy, GRS Budinger, NS Chandel, MJ Berardi, JJ Chou, WM Shih, SC Harrison, M Bertolotti, G Farinelli, M Galli, A Aiuti, R Sitia, J Blanc, B Esposito, S Rousset, P Gourdy, A Tedgui, Z Mallat, L Bleier, S Dröse, M Board, C Lopez, C van den Bos, R Callaghan, K Clarke, C Carr, AI Bondarenko, W Parichatikanond, CT Madreiter, R Rost, M Waldeck-Weiermair, R Malli, WF Graier, J Borecký, D Siemen, O Boss, S Samec, A Paoloni-Giacobino, C Rossier, A Dulloo, J Seydoux, P Muzzin, JP Giacobino, S Boudina, S Sena, BT O'Neill, P Tathireddy, ME Young, ED Abel, H Theobald, X Sheng, JJ Wright, XH Xia, S Aziz, JI Johnson, H Bugger, VG Zaha, TC Esteves, J Brandi, D Cecconi, M Cordani, M Torrens-Mas, R Pacchiana, E Dalla Pozza, G Butera, M Manfredi, E Marengo, J Oliver, P Roca, I Dando, M Donadelli, MO Breckwoldt, FMJ Pfister, PM Bradley, P Marinković, PR Williams, MS Brill, B Plomer, A Schmalz, DK St Clair, R Naumann, O Griesbeck, M Schwarzländer, L Godinho, FM Bareyre, TP Dick, M Kerschensteiner, T Misgeld, W Pilgrim, KJ Clarke, C Yssel, M Farrell, J Zhou, PV Murphy, PS Brookes, JA Buckingham, A Vidal-Puig, AP Halestrap, TE Gunter, DG Nicholls, P Bernardi, JJ Lemasters, A Bugge, M Siersbæk, MS Madsen, A Göndör, C Rougier, S Mandrup, C Guzman, C Zechner, M Palmeri, KS Russell, RR Russell, JA Cabrera, EA Ziemba, R Colbert, RF Kelly, M Kuskowski, EA Arriaga, W Sluiter, DJ Duncker, HB Ward, EO McFalls, V Calegari, CC Zoppi, L Rezende, L Silveira, E Carneiro, AC Boschero, B Cannon, IG Shabalina, TV Kramarova, N Petrovic, J Nedergaard, A Caron, SM Labbé, S Carter, MC Roy, R Lecomte, F Picard, LR Haines, TW Pearson, CM Walsh, CM Brennan, E Casanova, L Baselga-Escudero, A Ribas-Latre, A Arola-Arnal, C Bladé, L Arola, MJ Salvadó, HZ Chae, H Oubrahim, JW Park, SG Rhee, PB Chock, CB Chan, SL Chan, D Liu, GA Kyriazis, P Bagsiyao, X Ouyang, MP Mattson, L Chaudhuri, RK Srivastava, F Kos, PA Shrikant, M Che, R Wang, X Li, HY Wang, XFS Zheng, C Chen, K Wang, J Chen, J Guo, Y Yin, X Cai, X Guo, G Wang, R Yang, L Zhu, Y Zhang, J Wang, Y Xiang, C Weng, K Zen, J Zhang, CY Zhang, Y Chen, J Liu, Y Zheng, Z Wang, S Gu, J Tan, Q Jing, H Yang, J Cheng, G Nanayakkara, Y Shao, R Cueto, L Wang, WY Yang, Y Tian, H Wang, X Yang, N Cheurfa, D Dubois-Laforgue, DAF Ferrarezi, AF Reis, GM Brenner, C Bouche, C Le Feuvre, F Fumeron, J Timsit, M Marre, G Velho, SY Cho, D Seo, WG Kim, S Lee, YS Cho, JH Lee, KH Jung, SH Moon, YS Choe, KH Lee, ET Chouchani, L Kazak, MP Jedrychowski, GZ Lu, BK Erickson, J Szpyt, KA Pierce, D Laznik-Bogoslavski, R Vetrivelan, CB Clish, AJ Robinson, SP Gygi, BM Spiegelman, C Methner, G Buonincontri, CH Hu, A Logan, SJ Sawiak, T Krieg, VR Pell, E Gaude, D Aksentijević, SY Sundier, EL Robb, SM Nadtochiy, ENJ Ord, AC Smith, F Eyassu, R Shirley, C-H Hu, AJ Dare, AM James, S Rogatti, RC Hartley, S Eaton, ASH Costa, SM Davidson, MR Duchen, K Saeb-Parsy, MJ Shattock, LM Work, C Frezza, YC Chuang, TK Lin, HY Huang, WN Chang, CW Liou, SD Chen, AY Chang, SH Chan, L Contreras, E Rial, S Cerdan, J Satrustegui, E Paradis, A Corcoran, TG Cotter, D Cosentino-Gomes, N Rocco-Machado, JR Meyer-Fernandes, LF Costa Rosa, R Curi, C Murphy, P Newsholme, MDM Gonzalez-Barroso, PG Crichton, Y Lee, ERS Kunji, MD Cruz, S Ledbetter, S Chowdhury, AK Tiwari, N Momi, RK Wali, C Bliss, C Huang, D Lichtenstein, S Bhattacharya, A Varma-Wilson, V Backman, HK Roy, M D'Adamo, L Perego, M Cardellini, MA Marini, S Frontoni, F Andreozzi, A Sciacqua, D Lauro, P Sbraccia, M Federici, M Paganelli, AE Pontiroli, R Lauro, F Perticone, F Folli, G Sesti, A Daiber, F Di Lisa, M Oelze, S Kröller-Schön, S Steven, E Schulz, T Münzel, LT Dalgaard, G Andersen, LH Larsen, TIA Sørensen, T Andersen, T Drivsholm, K Borch-Johnsen, J Fleckner, T Hansen, N Din, O Pedersen, C Fiorini, ED Pozza, C Padroni, C Costanzo, M Palmieri, S Dato, F De Rango, P Crocco, G Passarino, G Rose, PBM De Andrade, M Casimir, P Maechler, P De Lange, A Feola, M Ragni, R Senese, M Moreno, A Lombardi, E Silvestri, F Goglia, A Lanni, U De Marchi, C Castelbou, N Demaurex, R De Simone, MA Ajmone-Cat, M Pandolfi, A Bernardo, C De Nuccio, L Minghetti, S Visentin, D De Stefani, A Raffaello, E Teardo, I Szabò, R Rizzuto, T Pozzan, G Den Besten, A Bleeker, A Gerding, K Van Eunen, R Havinga, TH Van Dijk, MH Oosterveer, JW Jonker, AK Groen, DJ Reijngoud, BM Bakker, Z Derdák, P Fülöp, E Sabo, R Tavares, EP Berthiaume, MB Resnick, G Paragh, JR Wands, NM Mark, G Beldi, SS Dhamrait, JW Stephens, JA Cooper, J Acharya, AR Mani, K Moore, GJ Miller, SE Humphries, SJ Hurel, HE Montgomery, JK Jeong, MO Dietrich, HB Ruan, E Kim, S Suyama, K Kelly, E Gyengesi, JL Arbiser, DD Belsham, DA Sarruf, MW Schwartz, AM Bennett, CV Mobbs, WX Ding, M Li, JM Biazik, DG Morgan, F Guo, HM Ni, M Goheen, EL Eskelinen, XM Yin, AS Divakaruni, A Dlasková, L Hlavatá, J Ježek, T Špacek, E Škobisová, U Brandt, RH Du, FF Wu, M Lu, X dong Shu, JH Ding, G Wu, G Hu, CM Duffy, H Xu, JP Nixon, DA Bernlohr, TA Butterick, D Duteil, C Chambon, F Ali, R Malivindi, J Zoll, S Kato, B Geny, P Chambon, D Metzger, C Duval, A Nègre-Salvayre, A Doglio, R Salvayre, L Pénicaud, L Casteilla, F Echeverría, M Ortiz, R Valenzuela, LA Videla, KS Echtay, JL Pakay, MB Jekabsons, AJ Lambert, M Portero-Otín, R Pamplona, AJ Vidal-Puig, S Wang, SJ Roebuck, V Eisner, RR Cupo, E Gao, G Csordás, WS Slovinsky, M Paillard, L Cheng, J Ibetti, SRW Chen, JK Chuprun, JB Hoek, WJ Koch, G Hajnóczky, A Elorza, B Hyde, HK Mikkola, OS Shirihai, Y Emre, C Hurtaud, T Nübel, F Criscuolo, AM Cassard-Doulcier, H Esterbauer, C Schneitler, H Oberkofler, C Ebenbichler, B Paulweber, F Sandhofer, G Ladurner, E Hell, AD Strosberg, JR Patsch, F Krempler, W Patsch, P Esteves, C Ransy, C Esnous, V Lenoir, AL Bulteau, A Lombès, C Prip-Buus, Y Fan, K Futawaka, R Koyama, Y Fukuda, M Hayashi, M Imamoto, T Miyawaki, M Kasahara, T Tagami, K Moriyama, A Fedorenko, PV Lishko, Y Kirichok, C Fleury, M Neverova, O Champigny, C Levi-Meyrueis, MF Seldin, RS Surwit, CH Warden, S Freigang, F Ampenberger, A Weiss, T-D Kanneganti, Y Iwakura, M Hersberger, M Kopf, R Fukumori, T Takarada, Y Kambe, R Nakazato, K Fujikawa, Y Yoneda, M Kou, E Hinoi, DR Gable, S Galetti, A Sarre, H Perreten, N Produit-Zengaffinen, F Assimacopoulos-Jeannet, S Gargiulo, MP Petretta, A Greco, M Panico, M Larobina, M Gramanzini, GG Schiattarella, G Esposito, M Petretta, A Brunetti, A Cuocolo, AO Garlid, JP Jacobs, KD Garlid, ADT Costa, CL Quinlan, SV Pierre, P Dos Santos, 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Hou, Y Ding, T Zhang, C Shi, W Fu, Z Cai, F Yin, H Sancheti, E Cadenas, H Yoshitomi, K Yamazaki, I Tanaka, T Liu, SB Jin, C Ning, U Lendahl, M Nistér, SX Yu, CT Du, W Chen, QQ Lei, N Li, S Qi, XJ Zhang, GQ Hu, XM Deng, WY Han, YJ Yang, XX Yu, W Mao, A Zhong, P Schow, J Brush, SW Sherwood, G Pan, P Perret, O Peroni, YB Kim, XX Zheng, R Shen, CT Lin, JA Porco, HJ Zhang, W Zhao, S Venkataraman, MEC Robbins, GR Buettner, KC Kregel, LW Oberley, I Khvorostov, JS Hong, Y Oktay, L Vergnes, E Nuebel, PN Wahjudi, K Setoguchi, A Do, HJ Jung, JM McCaffery, IJ Kurland, K Reue, WNP Lee, CM Koehler, MA Teitell, K Zhang, Z Song, G Zheng, J Lyu, S Liu, J Huang, C Liu, D Xiang, M Xie, Q Zeng, M Zhou, PKH Tam, KSL Lam, B Huang, Y Liang, D Wu, Y Zhou, T Cai, J Xu, L Jiang, J Wu, Q Sun, R Zhu, A Ebner, T Haselgrübler, HJ Gruber, P Hinterdorfer Show less
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology Show more
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology state are integrated by the protonmotive force Δ p or its potential component, Δ Ψ , which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1–5) play an eminent role in the regulation of each of the mentioned aspects, being involved in numerous physiological events including redox signaling. Recent Advances: UCP2 structure, including purine nucleotide and fatty acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels FA anions, whereas uncoupling is achieved by the membrane backflux of protonated FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting Δ p dissipation decreases superoxide formation dependent on Δ p . UCP-mediated antioxidant protection and its impairment are expected to play a major role in cell physiology and pathology. Moreover, UCP2-mediated aspartate, oxaloacetate, and malate antiport with phosphate is expected to alter metabolism of cancer cells. Critical Issues: A wide range of UCP antioxidant effects and participations in redox signaling have been reported; however, mechanisms of UCP activation are still debated. Switching off/on the UCP2 protonophoretic function might serve as redox signaling either by employing/releasing the extra capacity of cell antioxidant systems or by directly increasing/decreasing mitochondrial superoxide sources. Rapid UCP2 degradation, FA levels, elevation of purine nucleotides, decreased Mg 2+ , or increased pyruvate accumulation may initiate UCP-mediated redox signaling. Future Directions: Issues such as UCP2 participation in glucose sensing, neuronal (synaptic) function, and immune cell activation should be elucidated. Antioxid. Redox Signal. 29, 667–714. Show less
📄 PDF DOI: 10.1089/ars.2017.7225
mitochondria