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2. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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Klionsky, DJ, Abdel-Aziz, AK, Abdelfatah, S, Abdellatif, M, Abdoli, A, Abel, S, Abeliovich, H, Abildgaard, MH, Abudu, YP, Acevedo-Arozena, A, Adamopoulos, IE, Adeli, K, Adolph, TE, Adornetto, A, Aflaki, E, Agam, G, Agarwal, A, Aggarwal, BB, Agnello, M, Agostinis, P, Agrewala, JN, Agrotis, A, Aguilar, PV, Ahmad, ST, Ahmed, ZM, Ahumada-Castro, U, Aits, S, Aizawa, S, Akkoc, Y, Akoumianaki, T, Akpinar, HA, Al-Abd, AM, Al-Akra, L, Al-Gharaibeh, A, Alaoui-Jamali, MA, Alberti, S, Alcocer-Gómez, E, Alessandri, C, Ali, M, Alim Al-Bari, MA, Aliwaini, S, Alizadeh, J, Almacellas, E, Almasan, A, Alonso, A, Alonso, GD, Altan-Bonnet, N, Altieri, DC, Álvarez, ÉMC, Alves, S, Alves da Costa, C, Alzaharna, MM, Amadio, M, Amantini, C, Amaral, C, Ambrosio, S, Amer, AO, Ammanathan, V, An, Z, Andersen, SU, Andrabi, SA, Andrade-Silva, M, Andres, AM, Angelini, S, Ann, D, Anozie, UC, Ansari, MY, Antas, P, Antebi, A, Antón, Z, Anwar, T, Apetoh, L, Apostolova, N, Araki, T, Araki, Y, Arasaki, K, Araújo, WL, Araya, J, Arden, C, Arévalo, M-A, Arguelles, S, Arias, E, Arikkath, J, Arimoto, H, Ariosa, AR, Armstrong-James, D, Arnauné-Pelloquin, L, Aroca, A, Arroyo, DS, Arsov, I, Artero, R, Asaro, DML, Aschner, M, Ashrafizadeh, M, Ashur-Fabian, O, Atanasov, AG, Au, AK, Auberger, P, Auner, HW, Aurelian, L, Autelli, R, Avagliano, L, Ávalos, Y, Aveic, S, Aveleira, CA, Avin-Wittenberg, T, Aydin, Y, Ayton, S, Ayyadevara, S, Azzopardi, M, Baba, M, Backer, JM, Backues, SK, Bae, D-H, Bae, O-N, Bae, SH, Baehrecke, EH, Baek, A, Baek, S-H, Baek, SH, Bagetta, G, Bagniewska-Zadworna, A, Bai, H, Bai, J, Bai, X, Bai, Y, Bairagi, N, Baksi, S, Balbi, T, Baldari, CT, Balduini, W, Ballabio, A, Ballester, M, Balazadeh, S, Balzan, R, Bandopadhyay, R, Banerjee, S, Bánréti, Á, Bao, Y, Baptista, MS, Baracca, A, Barbati, C, Bargiela, A, Barilà, D, Barlow, PG, Barmada, SJ, Barreiro, E, Barreto, GE, Bartek, J, Bartel, B, Bartolome, A, Barve, GR, Basagoudanavar, SH, Bassham, DC, Bast, RC, Basu, A, Batoko, H, Batten, I, Baulieu, EE, Baumgarner, BL, Bayry, J, Beale, R, Beau, I, Beaumatin, F, Bechara, LRG, Beck, GR, Beers, MF, Begun, J, Behrends, C, Behrens, GMN, Bei, R, Bejarano, E, Bel, S, Behl, C, Belaid, A, Belgareh-Touzé, N, Bellarosa, C, Belleudi, F, Belló Pérez, M, Bello-Morales, R, Beltran, JSDO, Beltran, S, Benbrook, DM, Bendorius, M, Benitez, BA, Benito-Cuesta, I, Bensalem, J, Berchtold, MW, Berezowska, S, Bergamaschi, D, Bergami, M, Bergmann, A, Berliocchi, L, Berlioz-Torrent, C, Bernard, A, Berthoux, L, Besirli, CG, Besteiro, S, Betin, VM, Beyaert, R, Bezbradica, JS, Bhaskar, K, Bhatia-Kissova, I, Bhattacharya, R, Bhattacharya, S, Bhattacharyya, S, Bhuiyan, MS, Bhutia, SK, Bi, L, Bi, X, Biden, TJ, Bijian, K, Billes, VA, Binart, N, Bincoletto, C, Birgisdottir, AB, Bjorkoy, G, Blanco, G, Blas-Garcia, A, Blasiak, J, Blomgran, R, Blomgren, K, Blum, JS, Boada-Romero, E, Boban, M, Boesze-Battaglia, K, Boeuf, P, Boland, B, Bomont, P, Bonaldo, P, Bonam, SR, Bonfili, L, Bonifacino, JS, Boone, BA, Bootman, MD, Bordi, M, Borner, C, Bornhauser, BC, Borthakur, G, Bosch, J, Bose, S, Botana, LM, Botas, J, Boulanger, CM, Boulton, ME, Bourdenx, M, Bourgeois, B, Bourke, NM, Bousquet, G, Boya, P, Bozhkov, PV, Bozi, LHM, Bozkurt, TO, Brackney, DE, Brandts, CH, Braun, RJ, Braus, GH, Bravo-Sagua, R, Bravo-San Pedro, JM, Brest, P, Bringer, M-A, Briones-Herrera, A, Broaddus, VC, Brodersen, P, Brodsky, JL, Brody, SL, Bronson, PG, Bronstein, JM, Brown, CN, Brown, RE, Brum, PC, Brumell, JH, Brunetti-Pierri, N, Bruno, D, Bryson-Richardson, RJ, Bucci, C, Buchrieser, C, Bueno, M, Buitrago-Molina, LE, Buraschi, S, Buch, S, Buchan, JR, Buckingham, EM, Budak, H, Budini, M, Bultynck, G, Burada, F, Burgoyne, JR, Burón, MI, Bustos, V, Büttner, S, Butturini, E, Byrd, A, Cabas, I, Cabrera-Benitez, S, Cadwell, K, Cai, J, Cai, L, Cai, Q, Cairó, M, Calbet, JA, Caldwell, GA, Caldwell, KA, Call, JA, Calvani, R, Calvo, AC, Calvo-Rubio Barrera, M, Camara, NO, Camonis, JH, Camougrand, N, Campanella, M, Campbell, EM, Campbell-Valois, F-X, Campello, S, Campesi, I, Campos, JC, Camuzard, O, Cancino, J, Candido de Almeida, D, Canesi, L, Caniggia, I, Canonico, B, Cantí, C, Cao, B, Caraglia, M, Caramés, B, Carchman, EH, Cardenal-Muñoz, E, Cardenas, C, Cardenas, L, Cardoso, SM, Carew, JS, Carle, GF, Carleton, G, Carloni, S, Carmona-Gutierrez, D, Carneiro, LA, Carnevali, O, Carosi, JM, Carra, S, Carrier, A, Carrier, L, Carroll, B, Carter, AB, Carvalho, AN, Casanova, M, Casas, C, Casas, J, Cassioli, C, Castillo, EF, Castillo, K, Castillo-Lluva, S, Castoldi, F, Castori, M, Castro, AF, Castro-Caldas, M, Castro-Hernandez, J, Castro-Obregon, S, Catz, SD, Cavadas, C, Cavaliere, F, Cavallini, G, Cavinato, M, Cayuela, ML, Cebollada Rica, P, Cecarini, V, Cecconi, F, Cechowska-Pasko, M, Cenci, S, Ceperuelo-Mallafré, V, Cerqueira, JJ, Cerutti, JM, Cervia, D, Cetintas, VB, Cetrullo, S, Chae, H-J, Chagin, AS, Chai, C-Y, Chakrabarti, G, Chakrabarti, O, Chakraborty, T, Chami, M, Chamilos, G, Chan, DW, Chan, EYW, Chan, ED, Chan, HYE, Chan, HH, Chan, H, Chan, MTV, Chan, YS, Chandra, PK, Chang, C-P, Chang, C, Chang, H-C, Chang, K, Chao, J, Chapman, T, Charlet-Berguerand, N, Chatterjee, S, Chaube, SK, Chaudhary, A, Chauhan, S, Chaum, E, Checler, F, Cheetham, ME, Chen, C-S, Chen, G-C, Chen, J-F, Chen, LL, Chen, L, Chen, M, Chen, M-K, Chen, N, Chen, Q, Chen, R-H, Chen, S, Chen, W, Chen, X-M, Chen, X-W, Chen, X, Chen, Y, Chen, Y-G, Chen, Y-J, Chen, Y-Q, Chen, ZS, Chen, Z, Chen, Z-H, Chen, ZJ, Cheng, H, Cheng, J, Cheng, S-Y, Cheng, W, Cheng, X, Cheng, X-T, Cheng, Y, Cheng, Z, Cheong, H, Cheong, JK, Chernyak, BV, Cherry, S, Cheung, CFR, Cheung, CHA, Cheung, K-H, Chevet, E, Chi, RJ, Chiang, AKS, Chiaradonna, F, Chiarelli, R, Chiariello, M, Chica, N, Chiocca, S, Chiong, M, Chiou, S-H, Chiramel, AI, Chiurchiù, V, Cho, D-H, Choe, S-K, Choi, AMK, Choi, ME, Choudhury, KR, Chow, NS, Chu, CT, Chua, JP, Chua, JJE, Chung, H, Chung, KP, Chung, S, Chung, S-H, Chung, Y-L, Cianfanelli, V, Ciechomska, IA, Cifuentes, M, Cinque, L, Cirak, S, Cirone, M, Clague, MJ, Clarke, R, Clementi, E, Coccia, EM, Codogno, P, Cohen, E, Cohen, MM, Colasanti, T, Colasuonno, F, Colbert, RA, Colell, A, Čolić, M, Coll, NS, Collins, MO, Colombo, MI, Colón-Ramos, DA, Combaret, L, Comincini, S, Cominetti, MR, Consiglio, A, Conte, A, Conti, F, Contu, VR, Cookson, MR, Coombs, KM, Coppens, I, Corasaniti, MT, Corkery, DP, Cordes, N, Cortese, K, Costa, MDC, Costantino, S, Costelli, P, Coto-Montes, A, Crack, PJ, Crespo, JL, Criollo, A, Crippa, V, Cristofani, R, Csizmadia, T, Cuadrado, A, Cui, B, Cui, J, Cui, Y, Culetto, E, Cumino, AC, Cybulsky, AV, Czaja, MJ, Czuczwar, SJ, D'Adamo, S, D'Amelio, M, D'Arcangelo, D, D'Lugos, AC, D'Orazi, G, da Silva, JA, Dafsari, HS, Dagda, RK, Dagdas, Y, Daglia, M, Dai, X, Dai, Y, Dal Col, J, Dalhaimer, P, Dalla Valle, L, Dallenga, T, Dalmasso, G, Damme, M, Dando, I, Dantuma, NP, Darling, AL, Das, H, Dasarathy, S, Dasari, SK, Dash, S, Daumke, O, Dauphinee, AN, Davies, JS, Dávila, VA, Davis, RJ, Davis, T, Dayalan Naidu, S, De Amicis, F, De Bosscher, K, De Felice, F, De Franceschi, L, De Leonibus, C, de Mattos Barbosa, MG, De Meyer, GRY, De Milito, A, De Nunzio, C, De Palma, C, De Santi, M, De Virgilio, C, De Zio, D, Debnath, J, DeBosch, BJ, Decuypere, J-P, Deehan, MA, Deflorian, G, DeGregori, J, Dehay, B, Del Rio, G, Delaney, JR, Delbridge, LMD, Delorme-Axford, E, Delpino, MV, Demarchi, F, Dembitz, V, Demers, ND, Deng, H, Deng, Z, Dengjel, J, Dent, P, Denton, D, DePamphilis, ML, Der, CJ, Deretic, V, Descoteaux, A, Devis, L, Devkota, S, Devuyst, O, Dewson, G, Dharmasivam, M, Dhiman, R, di Bernardo, D, Di Cristina, M, Di Domenico, F, Di Fazio, P, Di Fonzo, A, Di Guardo, G, Di Guglielmo, GM, Di Leo, L, Di Malta, C, Di Nardo, A, Di Rienzo, M, Di Sano, F, Diallinas, G, Diao, J, Diaz-Araya, G, Díaz-Laviada, I, Dickinson, JM, Diederich, M, Dieudé, M, Dikic, I, Ding, S, Ding, W-X, Dini, L, Dinić, J, Dinic, M, Dinkova-Kostova, AT, Dionne, MS, Distler, JHW, Diwan, A, Dixon, IMC, Djavaheri-Mergny, M, Dobrinski, I, Dobrovinskaya, O, Dobrowolski, R, Dobson, RCJ, Đokić, J, Dokmeci Emre, S, Donadelli, M, Dong, B, Dong, X, Dong, Z, Dorn Ii, GW, Dotsch, V, Dou, H, Dou, J, Dowaidar, M, Dridi, S, Drucker, L, Du, A, Du, C, Du, G, Du, H-N, Du, L-L, du Toit, A, Duan, S-B, Duan, X, Duarte, SP, Dubrovska, A, Dunlop, EA, Dupont, N, Durán, RV, Dwarakanath, BS, Dyshlovoy, SA, Ebrahimi-Fakhari, D, Eckhart, L, Edelstein, CL, Efferth, T, Eftekharpour, E, Eichinger, L, Eid, N, Eisenberg, T, Eissa, NT, Eissa, S, Ejarque, M, El Andaloussi, A, El-Hage, N, El-Naggar, S, Eleuteri, AM, El-Shafey, ES, Elgendy, M, Eliopoulos, AG, Elizalde, MM, Elks, PM, Elsasser, H-P, Elsherbiny, ES, Emerling, BM, Emre, NCT, Eng, CH, Engedal, N, Engelbrecht, A-M, Engelsen, AST, Enserink, JM, Escalante, R, Esclatine, A, Escobar-Henriques, M, Eskelinen, E-L, Espert, L, Eusebio, M-O, Fabrias, G, Fabrizi, C, Facchiano, A, Facchiano, F, Fadeel, B, Fader, C, Faesen, AC, Fairlie, WD, Falcó, A, Falkenburger, BH, Fan, D, Fan, J, Fan, Y, Fang, EF, Fang, Y, Fanto, M, Farfel-Becker, T, Faure, M, Fazeli, G, Fedele, AO, Feldman, AM, Feng, D, Feng, J, Feng, L, Feng, Y, Feng, W, Fenz Araujo, T, Ferguson, TA, Fernández, ÁF, Fernandez-Checa, JC, Fernández-Veledo, S, Fernie, AR, Ferrante, AW, Ferraresi, A, Ferrari, MF, Ferreira, JCB, Ferro-Novick, S, Figueras, A, Filadi, R, Filigheddu, N, Filippi-Chiela, E, Filomeni, G, Fimia, GM, Fineschi, V, Finetti, F, Finkbeiner, S, Fisher, EA, Fisher, PB, Flamigni, F, Fliesler, SJ, Flo, TH, Florance, I, Florey, O, Florio, T, Fodor, E, Follo, C, Fon, EA, Forlino, A, Fornai, F, Fortini, P, Fracassi, A, Fraldi, A, Franco, B, Franco, R, Franconi, F, Frankel, LB, Friedman, SL, Fröhlich, LF, Frühbeck, G, Fuentes, JM, Fujiki, Y, Fujita, N, Fujiwara, Y, Fukuda, M, Fulda, S, Furic, L, Furuya, N, Fusco, C, Gack, MU, Gaffke, L, Galadari, S, Galasso, A, Galindo, MF, Gallolu Kankanamalage, S, Galluzzi, L, Galy, V, Gammoh, N, Gan, B, Ganley, IG, Gao, F, Gao, H, Gao, M, Gao, P, Gao, S-J, Gao, W, Gao, X, Garcera, A, Garcia, MN, Garcia, VE, García-Del Portillo, F, Garcia-Escudero, V, Garcia-Garcia, A, Garcia-Macia, M, García-Moreno, D, Garcia-Ruiz, C, García-Sanz, P, Garg, AD, Gargini, R, Garofalo, T, Garry, RF, Gassen, NC, Gatica, D, Ge, L, Ge, W, Geiss-Friedlander, R, Gelfi, C, Genschik, P, Gentle, IE, Gerbino, V, Gerhardt, C, Germain, K, Germain, M, Gewirtz, DA, Ghasemipour Afshar, E, Ghavami, S, Ghigo, A, Ghosh, M, Giamas, G, Giampietri, C, Giatromanolaki, A, Gibson, GE, Gibson, SB, Ginet, V, Giniger, E, Giorgi, C, Girao, H, Girardin, SE, Giridharan, M, Giuliano, S, Giulivi, C, Giuriato, S, Giustiniani, J, Gluschko, A, Goder, V, Goginashvili, A, Golab, J, Goldstone, DC, Golebiewska, A, Gomes, LR, Gomez, R, Gómez-Sánchez, R, Gomez-Puerto, MC, Gomez-Sintes, R, Gong, Q, Goni, FM, González-Gallego, J, Gonzalez-Hernandez, T, Gonzalez-Polo, RA, Gonzalez-Reyes, JA, González-Rodríguez, P, Goping, IS, Gorbatyuk, MS, Gorbunov, NV, Görgülü, K, Gorojod, RM, Gorski, SM, Goruppi, S, Gotor, C, Gottlieb, RA, Gozes, I, Gozuacik, D, Graef, M, Gräler, MH, Granatiero, V, Grasso, D, Gray, JP, Green, DR, Greenhough, A, Gregory, SL, Griffin, EF, Grinstaff, MW, Gros, F, Grose, C, Gross, AS, Gruber, F, Grumati, P, Grune, T, Gu, X, Guan, J-L, Guardia, CM, Guda, K, Guerra, F, Guerri, C, Guha, P, Guillén, C, Gujar, S, Gukovskaya, A, Gukovsky, I, Gunst, J, Günther, A, Guntur, AR, Guo, C, Guo, H, Guo, L-W, Guo, M, Gupta, P, Gupta, SK, Gupta, S, Gupta, VB, Gupta, V, Gustafsson, AB, Gutterman, DD, H B, R, Haapasalo, A, Haber, JE, Hać, A, Hadano, S, Hafrén, AJ, Haidar, M, Hall, BS, Halldén, G, Hamacher-Brady, A, Hamann, A, Hamasaki, M, Han, W, Hansen, M, Hanson, PI, Hao, Z, Harada, M, Harhaji-Trajkovic, L, Hariharan, N, Haroon, N, Harris, J, Hasegawa, T, Hasima Nagoor, N, Haspel, JA, Haucke, V, Hawkins, WD, Hay, BA, Haynes, CM, Hayrabedyan, SB, Hays, TS, He, C, He, Q, He, R-R, He, Y-W, He, Y-Y, Heakal, Y, Heberle, AM, Hejtmancik, JF, Helgason, GV, Henkel, V, Herb, M, 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Tuxworth, RI, Tyler, JK, Tyutereva, EV, Uchiyama, Y, Ugun-Klusek, A, Uhlig, HH, Ułamek-Kozioł, M, Ulasov, IV, Umekawa, M, Ungermann, C, Unno, R, Urbe, S, Uribe-Carretero, E, Üstün, S, Uversky, VN, Vaccari, T, Vaccaro, MI, Vahsen, BF, Vakifahmetoglu-Norberg, H, Valdor, R, Valente, MJ, Valko, A, Vallee, RB, Valverde, AM, Van den Berghe, G, van der Veen, S, Van Kaer, L, van Loosdregt, J, van Wijk, SJL, Vandenberghe, W, Vanhorebeek, I, Vannier-Santos, MA, Vannini, N, Vanrell, MC, Vantaggiato, C, Varano, G, Varela-Nieto, I, Varga, M, Vasconcelos, MH, Vats, S, Vavvas, DG, Vega-Naredo, I, Vega-Rubin-de-Celis, S, Velasco, G, Velázquez, AP, Vellai, T, Vellenga, E, Velotti, F, Verdier, M, Verginis, P, Vergne, I, Verkade, P, Verma, M, Verstreken, P, Vervliet, T, Vervoorts, J, Vessoni, AT, Victor, VM, Vidal, M, Vidoni, C, Vieira, OV, Vierstra, RD, Viganó, S, Vihinen, H, Vijayan, V, Vila, M, Vilar, M, Villalba, JM, Villalobo, A, Villarejo-Zori, B, Villarroya, F, Villarroya, J, Vincent, O, Vindis, 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Woehlbier, U, Wollert, T, Wong, E, Wong, JH, Wong, RW, Wong, VKW, Wong, WW-L, Wu, A-G, Wu, C, Wu, J, Wu, KK, Wu, M, Wu, S-Y, Wu, S, Wu, WKK, Wu, X, Wu, Y-W, Wu, Y, Xavier, RJ, Xia, H, Xia, L, Xia, Z, Xiang, G, Xiang, J, Xiang, M, Xiang, W, Xiao, B, Xiao, G, Xiao, H, Xiao, H-T, Xiao, J, Xiao, L, Xiao, S, Xiao, Y, Xie, B, Xie, C-M, Xie, M, Xie, Y, Xie, Z, Xilouri, M, Xu, C, Xu, E, Xu, H, Xu, J, Xu, L, Xu, WW, Xu, X, Xue, Y, Yakhine-Diop, SMS, Yamaguchi, M, Yamaguchi, O, Yamamoto, A, Yamashina, S, Yan, S, Yan, S-J, Yan, Z, Yanagi, Y, Yang, C, Yang, D-S, Yang, H, Yang, H-T, Yang, J-M, Yang, J, Yang, L, Yang, M, Yang, P-M, Yang, Q, Yang, S, Yang, S-F, Yang, W, Yang, WY, Yang, X, Yang, Y, Yao, H, Yao, S, Yao, X, Yao, Y-G, Yao, Y-M, Yasui, T, Yazdankhah, M, Yen, PM, Yi, C, Yin, X-M, Yin, Y, Yin, Z, Ying, M, Ying, Z, Yip, CK, Yiu, SPT, Yoo, YH, Yoshida, K, Yoshii, SR, Yoshimori, T, Yousefi, B, Yu, B, Yu, H, Yu, J, Yu, L, Yu, M-L, Yu, S-W, Yu, VC, Yu, WH, Yu, Z, Yuan, J, Yuan, L-Q, Yuan, S, Yuan, S-SF, Yuan, Y, Yuan, Z, Yue, J, Yue, Z, Yun, J, Yung, RL, Zacks, DN, Zaffagnini, G, Zambelli, VO, Zanella, I, Zang, QS, Zanivan, S, Zappavigna, S, Zaragoza, P, Zarbalis, KS, Zarebkohan, A, Zarrouk, A, Zeitlin, SO, Zeng, J, Zeng, J-D, Žerovnik, E, Zhan, L, Zhang, B, Zhang, DD, Zhang, H, Zhang, H-L, Zhang, J, Zhang, J-P, Zhang, KYB, Zhang, LW, Zhang, L, Zhang, M, Zhang, P, Zhang, S, Zhang, W, Zhang, X, Zhang, X-W, Zhang, XD, Zhang, Y, Zhang, Y-D, Zhang, Y-Y, Zhang, Z, Zhao, H, Zhao, L, Zhao, S, Zhao, T, Zhao, X-F, Zhao, Y, Zheng, G, Zheng, K, Zheng, L, Zheng, S, Zheng, X-L, Zheng, Y, Zheng, Z-G, Zhivotovsky, B, Zhong, Q, Zhou, A, Zhou, B, Zhou, C, Zhou, G, Zhou, H, Zhou, J, Zhou, K, Zhou, R, Zhou, X-J, Zhou, Y, Zhou, Z-Y, Zhou, Z, Zhu, B, Zhu, C, Zhu, G-Q, Zhu, H, Zhu, W-G, Zhu, Y, Zhuang, H, Zhuang, X, Zientara-Rytter, K, Zimmermann, CM, Ziviani, E, Zoladek, T, Zong, W-X, Zorov, DB, Zorzano, A, Zou, W, Zou, Z, Zuryn, S, Zwerschke, W, Brand-Saberi, B, Dong, XC, Kenchappa, CS, Lin, Y, Oshima, S, Rong, Y, Sluimer, JC, Stallings, CL, and Tong, C-K
- Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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- 2021
3. Neuroendocrine differentiation in a large series of genetically-confirmed Ewing's sarcoma family tumor: Does it provide any diagnostic or prognostic information?
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Machado I, Navarro S, López-Guerrero JA, Verdini L, Picci P, Giner F, and Llombart-Bosch A
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CD56 and INSM1, Chromogranin-A, Ewing’s sarcoma, Neuroendocrine differentiation, Synaptophysin - Abstract
Given the potential for neuroendocrine differentiation in Ewing's sarcoma family of tumors (ESFT), we aimed to determine neuroendocrine expression in a large series of genetically-confirmed ESFT and its prognostic significance in clinically-localised neoplasms (n = 176). Slides prepared from tissue microarrays were stained for Insulinoma-associated protein 1 (INSM1), CD56, chromogranin-A and synaptophysin. INSM1 expression was present in 59% of ESFT, while synaptophysin, chromogranin-A and CD56 were expressed in only 13%, 8% and 5% of ESFT, respectively. Histological subtypes were only significantly correlated with INSM1 (p = 0.032) or CD56 (p = 0.016) immunoexpression. Regarding prognosis, no significant association was found between INSM1, synaptophysin or chromogranin-A immunoexpression and progression-free survival (PFS) or overall survival (OS). Despite the low proportion of tumors with CD56 immunoreactivity, CD56 expression was shown to correlate with both poor PFS (p < 0.001) and poor OS (p < 0.001) in the present series. In conclusion, neuroendocrine differentiation is often present in ESFT, and in the present study INSM1 expression in particular was found to be higher than previously described in Ewing's tumors. Nevertheless, this finding does not distinguish these tumors from other round cell tumors that may show focal or diffuse neuroendocrine differentiation. CD56 expression could be used as a prognostic factor in ESFT, although given the results herein obtained, we recommend a prospective validation in independent series including localized and disseminated tumors in ESFT.
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- 2021
4. Distribution and clinical role of KIT gene mutations in melanoma according to subtype: a study of 492 Spanish patients
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Millán-Esteban D, García-Casado Z, Manrique-Silva E, Virós A, Kumar R, Furney S, López-Guerrero JA, Requena C, Bañuls J, Traves V, and Nagore E
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subtype ,melanoma ,KIT ,aggressiveness ,mutation - Abstract
BACKGROUND: KIT mutations are primarily associated with acral and mucosal melanoma, and have been reported to show higher prevalence in chronic sun-damaged (CSD) than non-CSD melanomas. OBJECTIVES: To investigate the prevalence of KIT mutations in melanoma according to subtype, and determine the clinical role of such mutations. MATERIALS & METHODS: We present results from a study of a Spanish population of 492 melanomas, classified according to the latest World Health Organization (WHO) guidelines. We analysed the mutational status of KIT and correlated with different clinical variables related to sun exposure and family history. RESULTS: KIT mutations were significantly more frequent in acral (3/36; 8.3%) and mucosal (4/8; 50%) melanomas than non-acral cutaneous melanomas. No significant difference was observed in KIT mutational status between CSD and non-CSD melanomas. CONCLUSION: Our results suggest that KIT mutations in melanoma tumours are unrelated to the development of nevi or chronic sun damage, but their presence is associated with aggressive melanomas which show ulceration, vascular invasiveness, and increased Breslow thickness. These findings are consistent with those reported by The Cancer Genome Atlas network.
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- 2021
5. Angiosarcomas: histology, immunohistochemistry and molecular insights with implications for differential diagnosis
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Machado I, Giner F, Lavernia J, Cruz J, Traves V, Requena C, Llombart B, López-Guerrero JA, and Llombart-Bosch A
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Molecular biology ,Differential diagnosis ,Angiosarcomas ,Immunohistochemistry - Abstract
Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. AS share an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging, especially in poorly-differentiated tumors. Although molecular studies provide significant clues, especially in the differential diagnosis with other vascular neoplasms, a thorough hematoxylin and eosin analysis remains an essential tool in AS diagnosis. In this review, we discuss pathological and molecular insights with emphasis on implications for differential diagnosis in cutaneous, breast, soft tissue and visceral AS.
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- 2021
6. Angiosarcomas: histology, immunohistochemistry and molecular insights with implications for differential diagnosis
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Machado I, Giner F, Lavernia J, Cruz J, Traves V, Requena C, Llombart B, López-Guerrero JA, and Llombart-Bosch A
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Molecular biology ,Differential diagnosis ,Angiosarcomas ,Immunohistochemistry - Abstract
Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. AS share an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging, especially in poorly-differentiated tumors. Although molecular studies provide significant clues, especially in the differential diagnosis with other vascular neoplasms, a thorough hematoxylin and eosin analysis remains an essential tool in AS diagnosis. In this review, we discuss pathological and molecular insights with emphasis on implications for differential diagnosis in cutaneous, breast, soft tissue and visceral AS.
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- 2020
7. The Frequency and Prognostic Significance of the Histologic Type in Early-stage Ovarian Carcinoma: A Reclassification Study by the Spanish Group For Ovarian Cancer Research (GEICO)
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Leskela S, Romero I, Cristobal E, Pérez-Mies B, Rosa-Rosa JM, Gutierrez-Pecharroman A, Santón A, Gonzalez BO, López-Reig R, Hardisson D, Vera-Sempere F, Illueca C, Vieites B, López-Guerrero JA, Palacios J, and Poveda A
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tumor classification ,endocrine system diseases ,early-stage ovarian carcinoma ,histologic type ,biomarkers ,female genital diseases and pregnancy complications - Abstract
The frequency and prognostic significance of the histologic type in early-stage ovarian cancer (OC) is not as well established as in advanced stages. In addition, histologic typing based only on morphologic features may be difficult, especially in high-grade tumors. In this study, we have analyzed a prospective cohort of 502 early-stage OCs to investigate their frequency, immunohistochemical characteristics, and survival of the 5 main histologic types. Histotype was assigned according to not only the morphologic features but also according to the expression pattern of WT1, p53, Napsin A, and progesterone receptors. In addition, an extended panel including p16, -catenin, HER2, Arid1A, HINF1B, CK7, CDX2, and CK20 was used to refine the diagnosis in difficult cases. In this series, the frequency of the 5 major histologic types was as follows: endometrioid carcinoma, 32.7%; clear cell carcinoma, 25.1%; high-grade serous carcinoma (HGSC), 24.7%; mucinous carcinoma, 10.2%; low-grade serous carcinoma, 4.6%; and others, 2.8%. The combination of morphology and immunohistochemistry allowed the reclassification of 23% of OCs. The lowest concordance was found between samples initially diagnosed as endometrioid, but finally classified as high-grade serous tumors (22% error rate). Endometrioid carcinoma was the most favorable histologic type, whereas HGSC and low-grade serous carcinoma had the worst prognosis. Clear cell carcinoma with abnormal p53 immunostaining pattern also had poor prognosis. Although histologic grade was not a prognostic factor among early-stage endometrioid OCs, distinction between grade 3 endometrioid OC and HGSC is recommended, taking into account differences in prognosis and molecular alterations that can guide different treatments.
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- 2020
8. A Tetra-Panel of Serum Circulating miRNAs for the Diagnosis of the Four Most Prevalent Tumor Types
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Pastor-Navarro B, García-Flores M, Fernández-Serra A, Blanch-Tormo S, Martínez de Juan F, Martínez-Lapiedra C, Maia de Alcantara F, Peñalver JC, Cervera-Deval J, Rubio-Briones J, García-Rupérez J, and López-Guerrero JA
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Early diagnosis, breast cancer, circulating microRNAs, colorectal cancer, lung cancer, prostate cancer - Abstract
The purpose of this study is to clinically validate a series of circulating miRNAs that distinguish between the 4 most prevalent tumor types (lung cancer (LC); breast cancer (BC); colorectal cancer (CRC); and prostate cancer (PCa)) and healthy donors (HDs). A total of 18 miRNAs and 3 housekeeping miRNA genes were evaluated by qRT-PCR on RNA extracted from serum of cancer patients, 44 LC, 45 BC, 27 CRC, and 40 PCa, and on 45 HDs. The cancer detection performance of the miRNA expression levels was evaluated by studying the area under the curve (AUC) of receiver operating characteristic (ROC) curves at univariate and multivariate levels. miR-21 was significantly overexpressed in all cancer types compared with HDs, with accuracy of 67.5% ( p = 0.001) for all 4 tumor types and of 80.8% ( p < 0.0001) when PCa cases were removed from the analysis. For each tumor type, a panel of miRNAs was defined that provided cancer-detection accuracies of 91%, 94%, 89%, and 77%, respectively. In conclusion, we have described a series of circulating miRNAs that define different tumor types with a very high diagnostic performance. These panels of miRNAs would constitute the basis of different approaches of cancer-detection systems for which clinical utility should be validated in prospective cohorts.
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- 2020
9. Expiratory airflow obstruction due to tracheostomy tube: A spirometric study in 50 patients
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Sanchez-Guerrero, JA, Guerlain, J, Iranzo, MACI, Baujat, B, St Guily, JL, and Perie, S
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head neck cancer ,expiratory flow limitation ,decannulation ,weaning ,upper airway obstruction ,tracheostomy - Abstract
Objectives Tracheostomy is commonly used in intensive care units and in head and neck departments. Airway obstruction due to occluded cuffless tracheostomy tubes themselves remains unknown, although capping trials are commonly used before decannulation. The aim of this study was to evaluate the extent to which airway obstruction can be caused by occluded cuffless tubes in patients who underwent head and neck surgery. Design Prospective Research Outcome. Settings University teaching hospital. Participants Fifty patients requiring transient tracheostomy after head and neck surgery. Main outcome measures A flow-volume loop (FVL) through the mouth using a portable spirometer, with the occluded fenestrated cuffless tube, was measured before and immediately after decannulation, by obstructing the orifice of tracheostomy tube. The measurement of FVL recorded the forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), forced expiratory flow at 50% of FVC, peak inspiratory flow (PIF) and forced inspiratory flow at 50% of FVC. Results A statistically significant difference between all spirometric parameters was found. Mean PEF and PIF, respectively, increased from 2.8 to 4.5 L/s (P < .0001) and 2.3 to 2.7 L/s (P < .01) before and after decannulation, with a strong positive correlation (r = 0.7; P < .05). A mean expiratory (34%) and inspiratory (9%) airflow reduction was observed due to cannula. Conclusions Occluded cuffless tracheostomy tubes cause a dramatic airflow obstruction, mainly in the expiratory phase of FVL. This should be taken into account during capping trials.
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- 2020
10. Prognostic Impact of let-7e MicroRNA and Its Target Genes in Localized High-Risk Intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study
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Fernandez-Serra A, Moura DS, Sanchez-Izquierdo MD, Calabuig-Fariñas S, Lopez-Alvarez M, Martínez-Martínez A, Carrasco-Garcia I, Ramírez-Calvo M, Blanco-Alcaina E, López-Reig R, Obrador-Hevia A, Alemany R, Gutierrez A, Hindi N, Poveda A, Lopez-Guerrero JA, and Martin-Broto J
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GIST, caspase-3, let-7e, miR-550, prognostic biomarkers - Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, and they have been described as being associated with tumor prognosis. Here, miRNA profiling was planned to explore new molecular prognostic biomarkers in localized intestinal high-risk GIST. Paraffin tumor blocks of 14 and 86 patients were used in the discovery and expansion sets, respectively. GeneChip miRNA v3.0 was employed to identify the miRNAs differentially expressed between relapsed and non-relapsed patient samples, which were validated in the expansion set, by qRT-PCR. RT2 Profiler PCR Array was used for the screening of let-7e targets. Expression levels were correlated with relapse-free survival and overall survival. In the discovery set, 39 miRNAs were significantly deregulated, let-7e and miR-550 being the most underexpressed and overexpressed miRNAs in the relapsed group, respectively. In the expansion set, the underexpression of let-7e or the overexpression of 4 of its target genes ( ACVR1B , CASP3 , COL3A1, and COL5A2 ) were statistically associated with worse relapse-free survival. The expression of let-7e and 4 of its target genes are potential prognostic biomarkers in high-risk localized intestinal GIST. The expression of these genes is a potential molecular tool useful for a more accurate prognosis in this subset of GIST patients.
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- 2020
11. Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma
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Hervás-Marín D, Higgins F, Sanmartín O, López-Guerrero JA, Bañó MC, Igual JC, Quilis I, and Sandoval J
- Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although most cSCCs have good prognosis, a subgroup of high-risk cSCC has a higher frequency of recurrence and mortality. Therefore, the identification of molecular risk factors associated with this aggressive subtype is of major interest. In this work we carried out a global-scale approach to investigate the DNA-methylation profile in patients at different stages, from premalignant actinic keratosis to low-risk invasive and high-risk non-metastatic and metastatic cSCC. The results showed massive non-sequential changes in DNA-methylome and identified a minimal methylation signature that discriminates between stages. Importantly, a direct comparison of low-risk and high-risk stages revealed epigenetic traits characteristic of high-risk tumours. Finally, a prognostic prediction model in cSCC patients identified a methylation signature able to predict the overall survival of patients. Thus, the analysis of DNA-methylation in cSCC revealed changes during the evolution of the disease through the different stages that can be of great value not only in the diagnosis but also in the prognosis of the disease.
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- 2019
12. Metabolomics Contributions to the Discovery of Prostate Cancer Biomarkers
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Gómez-Cebrián N, Rojas-Benedicto A, Albors-Vaquer A, López-Guerrero JA, Pineda-Lucena A, and Puchades-Carrasco L
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biomarker ,prognosis ,prostate cancer ,metabolomics ,metabolism ,early diagnosis - Abstract
Prostate cancer (PCa) is one of the most frequently diagnosed cancers and a leading cause of death among men worldwide. Despite extensive efforts in biomarker discovery during the last years, currently used clinical biomarkers are still lacking enough specificity and sensitivity for PCa early detection, patient prognosis, and monitoring. Therefore, more precise biomarkers are required to improve the clinical management of PCa patients. In this context, metabolomics has shown to be a promising and powerful tool to identify novel PCa biomarkers in biofluids. Thus, changes in polyamines, tricarboxylic acid (TCA) cycle, amino acids, and fatty acids metabolism have been reported in different studies analyzing PCa patients' biofluids. The review provides an up-to-date summary of the main metabolic alterations that have been described in biofluid-based studies of PCa patients, as well as a discussion regarding their potential to improve clinical PCa diagnosis and prognosis. Furthermore, a summary of the most significant findings reported in these studies and the connections and interactions between the different metabolic changes described has also been included, aiming to better describe the specific metabolic signature associated to PCa.
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- 2019
13. Impacto de las consultas y triajes telefónicos pediátricos en el uso del servicio de urgencias hospitalario
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Sarria-Guerrero JA, Luaces-Cubells C, Jiménez-Fàbrega FX, Villamor-Ordozgoiti A, Isla Pera P, and Guix-Comellas EM
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Teleconsulta ,Emergency health services ,Pediatría ,Telephone triage ,Triaje telefónico ,Urgencias ,Triage ,Triaje ,Pediatrics ,Remote consultation - Abstract
OBJECTIVES: To analyze the characteristics of remote telephone consultations (televisits) and triage of pediatric emergencies attended by the 24-hour emergency service of Catalonia (CatSalut Respon), and to describe the impact of televisits on callers' decisions about whether or not to come to the emergency department and their opinion of the call service. MATERIAL AND METHODS: Observational cross-sectional study. During the call, cases were classified according the Spanish and Andorran triage system. Patients who were sent to the hospital underwent triage again, and the 2 assigned triage levels were compared. The families were later called to check data and ask their opinion of the service. Sociodemographic and clinical data related to the cases were recorded. RESULTS: A total of 370 televisits were made. Most cases (300, 81%) were not emergencies. Seventy-five callers (20.3%) were advised to go to an emergency department. Fever (P = .002) and questions about medication (P < .001) were the problems significantly associated with nonurgent cases. Nearly 46% of the cases classified as serious during telephone triage were also considered serious when the child was brought to the emergency department. The rate of agreement between the 2 triage levels was moderate. Over half the parents stated they had intended to go to the hospital before calling the service; 46% changed their mind based on the call. CONCLUSION: Fever and questions about medication were significantly associated with televisits for nonurgent cases. Nearly half the parents changed their mind about going to the emergency department after a televisit.
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- 2019
14. Polyvinylpyrrolidone/hyaluronic acid-based bilayer constructs for sequential delivery of cutaneous antiseptic and antibiotic
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Contardi, M, Russo, D, Suarato, G, Heredia Guerrero, J, Ceseracciu, L, Penna, I, Margaroli, N, Summa, M, Spano, R, Tassistro, G, Vezzulli, L, Bandiera, T, Bertorelli, R, Athanassiou, A, Bayer, I, Heredia Guerrero, JA, Bayer, IS, Contardi, M, Russo, D, Suarato, G, Heredia Guerrero, J, Ceseracciu, L, Penna, I, Margaroli, N, Summa, M, Spano, R, Tassistro, G, Vezzulli, L, Bandiera, T, Bertorelli, R, Athanassiou, A, Bayer, I, Heredia Guerrero, JA, and Bayer, IS
- Abstract
After a skin injury, many complex metabolic events are triggered to ensure proper wound healing. Particularly for chronic, non-healing wounds or burns several risk factors such as persistent bacterial infections and fast dehydration can counteract the healing process. Intelligent wound dressings should help accelerate the healing process, while maintaining the wound bed clean and disinfected for several days at a time. Ideally, they should be self-adherent to both moist and dry skin surfaces and be transparent enough to allow prolonged wound inspection. These requirements pose challenges both in terms of materials science and pharmaceutics. Herein, we describe fabrication of a transparent bilayer construct for the sequential release and delivery of a cutaneous antiseptic and a widely used antibiotic, potentially suitable for wound dressing applications. The fabrication is a scalable waterborne and ecofriendly solution casting process. The first layer (for direct wound contact) is polyvinylpyrrolidone (PVP) containing a commercial antiseptic, Neomercurocromo® (Neo), while the second layer is a blend of hyaluronic acid (HA) and PVP containing ciprofloxacin. We show that the bilayer films have satisfactory self-adhering strength to human skin and that PVP and HA can interact via hydrogen bonds causing sustained release of the antibiotic over a period of 5 days. Biocompatibility was demonstrated on human foreskin fibroblast HFF-1 cells. Antibacterial activity was evaluated against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa while the wound resorption behavior was assessed through an in vivo full-thickness excisional wound healing mice model. These observations indicate that such bilayer constructs can be potentially implemented as wound care products for diverse range of skin wounds, including large area skin infections.
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- 2019
15. Suitability of melanoma FFPE samples for NGS libraries: time and quality thresholds for downstream molecular tests
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Millán-Esteban D, Reyes-García D, García-Casado Z, Bañuls J, López-Guerrero JA, Requena C, Rodríguez-Hernández A, Traves V, and Nagore E
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library ,threshold ,QC ,FFPE ,melanoma ,time ,quality ,DIN ,NGS - Abstract
The use of NGS in clinical practice for precision diagnosis requires a quality starting material. Despite the broadly established use of formalin-fixed paraffin-embedded (FFPE) samples in molecular testing, these usually have low-quality DNA. We established a method to determine the suitability of melanoma FFPE samples for an amplicon-based NGS custom panel analysis. DNA was extracted from unstained melanoma samples and wide local excision samples. Amplicon-based libraries were constructed and tested using time and quality parameters as variables. Time elapsed from sample retrieval >7 years, a quality control value > 5.63 and a DNA integrity value
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- 2018
16. Prognostic Value of Tumour-Infiltrating Lymphocytes Changes between Pre and Post-Neoadjuvant Treatment and in Residual Disease in Triple Negative Breast Cancer
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Herrero-Vicent, C, primary, Calatrava, A, additional, Ramírez, M, additional, Gavilá, J, additional, Guerrero, A, additional, Hernández-Serra, A, additional, Lopez-Guerrero, JA, additional, Guillem-Porta, V, additional, and Ruiz-Simón, A, additional
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- 2019
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17. Abstract P2-09-27: Integrated analysis of PTEN protein expression and PI3KCA mutations as predictors for pathological complete response in HER2-positive breast cancer
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Gavila, J, primary, Gozalbo, F, additional, Climent, MA, additional, Guerrero, AL, additional, Sandiego, S, additional, Blanch, S, additional, Algarra, MA, additional, Soriano, V, additional, Guillem, V, additional, Ruiz, A, additional, and Lopez Guerrero, JA, additional
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- 2018
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18. Guidance Statement On BRCA1/2 Tumor Testing in Ovarian Cancer Patients
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Capoluongo, Ettore Domenico, Ellison, G, Lopez-Guerrero, Ja, Penault-Llorca, F, Ligtenberg, Mjl, Banerjee, S, Singer, C, Friedman, E, Markiefka, B, Schirmacher, P, Buttner, R, van Asperen, Cj, Ray-Coquard, I, Endris, V, Kamel-Reid, S, Percival, N, Bryce, J, Rothlisberger, B, Soong, R, de Castro, Dg, Capoluongo, E (ORCID:0000-0001-9872-0572), Capoluongo, Ettore Domenico, Ellison, G, Lopez-Guerrero, Ja, Penault-Llorca, F, Ligtenberg, Mjl, Banerjee, S, Singer, C, Friedman, E, Markiefka, B, Schirmacher, P, Buttner, R, van Asperen, Cj, Ray-Coquard, I, Endris, V, Kamel-Reid, S, Percival, N, Bryce, J, Rothlisberger, B, Soong, R, de Castro, Dg, and Capoluongo, E (ORCID:0000-0001-9872-0572)
- Abstract
The approval, in 2015, of the first poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi; olaparib, Lynparza) for platinum sensitive relapsed high grade ovarian cancer with either germline or somatic BRCA1/2 deleterious mutations is changing the way that BRCA1/2 testing services are offered to patients with ovarian cancer. Ovarian cancer patients are now being referred for BRCA1/2 genetic testing for treatment decisions, in addition to familial risk estimation, and irrespective of a family history of breast or ovarian cancer. Furthermore, testing of tumor samples to identify the estimated 3%-9% of patients with somatic BRCA1/2 mutations who, in addition to germline carriers, could benefit from PARPi therapy is also now being considered. This new testing paradigm poses some challenges, in particular the technical and analytical difficulties of analyzing chemically challenged DNA derived from formalin fixed, paraffin embedded specimens. The current manuscript reviews some of these challenges and technical recommendations to consider when undertaking BRCA1/2 testing in tumor tissue samples to detect both germline and somatic BRCA1/2 mutations. Also provided are considerations for incorporating genetic analysis of ovarian tumor samples into the patient pathway and ethical requirements.
- Published
- 2017
19. Relationship of immunohistochemistry, copy number aberrations and epigenetic disorders with BRCAness pattern in hereditary and sporadic breast cancer
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Murria Estal R, Palanca Suela S, de Juan Jiménez I, Alenda Gonzalez C, Egoavil Rojas C, García-Casado Z, López Guerrero JA, Juan Fita MJ, Sánchez Heras AB, Segura Huerta Á, Santaballa Bertrán A, Chirivella González I, Llop García M, Pérez Simó G, Barragán González E, and Bolufer Gilabert P
- Subjects
BRCAness, Copy number aberrations, Immunohistochemical markers, Promoter methylation, microRNA expression - Abstract
The study aims to identify the relevance of immunohistochemistry (IHC), copy number aberrations (CNA) and epigenetic disorders in BRCAness breast cancers (BCs). We studied 95 paraffin included BCs, of which 41 carried BRCA1/BRCA2 germline mutations and 54 were non hereditary (BRCAX/Sporadic). Samples were assessed for BRCA1ness and CNAs by Multiplex Ligation-dependent Probe Amplification (MLPA); promoter methylation (PM) was assessed by methylation-specific-MLPA and the expression of miR-4417, miR-423-3p, miR-590-5p and miR-187-3p by quantitative RT-PCR. IHC markers Ki67, ER, PR, HER2, CK5/6, EGFR and CK18 were detected with specific primary antibodies (DAKO, Denmark). BRCAness association with covariates was performed using multivariate binary logistic regression (stepwise backwards Wald option). BRCA1/2 mutational status (p = 0.027), large tumor size (p = 0.041) and advanced histological grade (p = 0.017) among clinic-pathological variables; ER (p < 0.001) among IHC markers; MYC (p < 0.001) among CNA; APC (p = 0.065), ATM (p = 0.014) and RASSF1 (p = 0.044) among PM; and miR-590-5p (p = 0.001), miR-4417 (p = 0.019) and miR-423 (p = 0.013) among microRNA expression, were the selected parameters significantly related with the BRCAness status. The logistic regression performed with all these parameters selected ER+ as linked with the lack of BRCAness (p = 0.001) and MYC CNA, APC PM and miR-590-5p expression with BRCAness (p = 0.014, 0.045 and 0.007, respectively). In conclusion, the parameters ER expression, APC PM, MYC CNA and miR-590-5p expression, allowed detection of most BRCAness BCs. The identification of BRCAness can help establish a personalized medicine addressed to predict the response to specific treatments.
- Published
- 2016
20. Novel and recurrent BRCA1/BRCA2 mutations in early onset and familial breast and ovarian cancer detected in the Program of Genetic Counseling in Cancer of Valencian Community (eastern Spain). Relationship of family phenotypes with mutation prevalence
- Author
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de Juan Jiménez I, García Casado Z, Palanca Suela S, Esteban Cardeñosa E, López Guerrero JA, Segura Huerta Á, Chirivella González I, Sánchez Heras AB, Juan Fita MJ, Tena García I, Guillen Ponce C, Martínez de Dueñas E, Romero Noguera I, Salas Trejo D, Goicoechea Sáez M, and Bolufer Gilabert P
- Subjects
endocrine system diseases ,skin and connective tissue diseases - Abstract
During the first 6 years of the Program of Genetic Counselling in Cancer of Valencia (eastern Spain), 310 mutations (155 in BRCA1 and 155 in BRCA2) in 1,763 hereditary breast (BC) and ovarian cancer (OC) families were identified. Of the mutations found 105 were distinct (53 in BRCA1 and 52 in BRCA2), eight new and 37 recurrent. Two of the novel mutations were frame-shift placed in exons 2 and 11 of BRCA1 and the remaining six were placed in BRCA2; four frame-shift (three in exon 11 and one in exon 23), one deletion of the entire exon 19 and one in the intervening sequence of exon 22. The BRCA1 mutations with higher recurrence were c.66_68delAG, c.5123C > A, c.1961delA, c.3770_3771delAG and c.5152+5G > A that covered 45.2% of mutations of this gene. The age of onset of BCs of c.68_69delAG mutation carriers occurs later than for the other recurrent mutations of this gene (45 vs. 37 years; p = 0.008). The BRCA2 mutations with higher recurrence were c.9026_9030delATCAT, c.3264insT and c.8978_8991del14 which represented 43.2% of all mutations in this gene, being the most recurrent mutation by far c.9026_9030delATCAT that represents 21.3% of BRCA2 mutations and 10.6% of all mutations. Probands with family histories of BC and OC, or OC and/or BC in at least two first degree relatives, were the more likely to have BRCA1/BRCA2 mutations (35.2% of the total mutations). And that most BRCA1mutations (73.19% mutations) occurred in probands with early-onset BC or with family history of OC.
- Published
- 2013
21. Differential effects of quercetin, apigenin and genistein on signalling pathways of protease-activated receptors PAR1 and PAR4 in platelets
- Author
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Navarro-Núñez, L, Rivera, J, Guerrero, JA, Martínez, C, Vicente, V, and Lozano, ML
- Subjects
Flavonoids ,Serotonin ,Platelet Aggregation ,Thrombin ,Research Papers ,Genistein ,Radioligand Assay ,Humans ,Calcium ,Quercetin ,Receptor, PAR-1 ,Receptors, Thrombin ,Apigenin ,Platelet Aggregation Inhibitors ,Signal Transduction - Abstract
The modulation by flavonoids of platelet responses induced by thrombin has been little investigated, and the antiplatelet activity, as well as possible inhibitory mechanisms of these compounds on thrombin signalling, has not yet been elucidated. We explored whether flavonoids affect platelet signalling pathways triggered by thrombin and by the selective activation of its protease-activated receptors (PARs) 1 and 4, and analysed the antagonism of these polyphenols at thrombin receptors.We investigated the effect of a range of polyphenolic compounds on platelet aggregation, 5-HT secretion, intracellular calcium mobilization, protein kinase activity and tyrosine phosphorylation, triggered by thrombin and PAR agonist peptides (PAR-APs). The ability of these flavonoids to bind to thrombin receptors was investigated by competitive radioligand binding assays using (125)I-thrombin.Quercetin, apigenin and genistein impaired platelet aggregation, as well as 5-HT release and calcium mobilization, induced by thrombin and PAR-APs. Quercetin and apigenin were inhibitors of protein kinases, but genistein exhibited a minimal ability to suppress platelet phosphorylation. Binding assays did not establish any kind of interaction between thrombin receptors and any of the flavonoids tested.Quercetin, apigenin and genistein did not inhibit thrombin responses by interacting with thrombin receptors, but by interfering with intracellular signalling. While inhibition by genistein may be a consequence of affecting calcium mobilization, subsequent platelet secretion and aggregation, for quercetin and apigenin, inhibition of kinase activation may also be involved in the impairment of platelet responses.
- Published
- 2009
22. Virtual microscopy in virtual tumor banking
- Author
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Isabelle, M, Teodorovic, I, Oosterhuis, Wolter, Riegman, Peter, Passioukov, A, Lejeune, S, Therasse, P, Dinjens, Winand, Lam, King, Oomen, Monique, Ratcliffe, C, Knox, K, Mager, R, Kerr, D, Pezzella, F, van Damme, B, van de Vijver, M, van Boven, H, Morente, MM, Alonso, S, Kerjaschki, D, Pammer, J, Lopez-Guerrero, JA, Llombart-Bosch, A, Carbone, A, Gloghini, A, van Veen, EB, and Pathology
- Published
- 2006
23. TuBaFrost 4: access rules and incentives for a European tumour bank
- Author
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Lopez-Guerrero, JA, Riegman, Peter, Oosterhuis, Wolter, Lam, King, Oomen, Monique, Spatz, A, Ratcliffe, C, Knox, K, Mager, R, Kerr, D, Pezzella, F, van Damme, B, van de Vijver, MJ, van Boven, H, Morente, MM, Alonso, S, Kerjaschki, D, Pammer, J, Carbone, A, Gloghini, A, Teodorovic, I, Isabelle, M, Passioukov, A, Lejeune, S, Therasse, P, van Veen, EB, Dinjens, Winand, Llombart-Bosch, A, Lopez-Guerrero, JA, Riegman, Peter, Oosterhuis, Wolter, Lam, King, Oomen, Monique, Spatz, A, Ratcliffe, C, Knox, K, Mager, R, Kerr, D, Pezzella, F, van Damme, B, van de Vijver, MJ, van Boven, H, Morente, MM, Alonso, S, Kerjaschki, D, Pammer, J, Carbone, A, Gloghini, A, Teodorovic, I, Isabelle, M, Passioukov, A, Lejeune, S, Therasse, P, van Veen, EB, Dinjens, Winand, and Llombart-Bosch, A
- Published
- 2006
24. Differential effects of quercetin, apigenin and genistein on signalling pathways of protease-activated receptors PAR1 and PAR4 in platelets
- Author
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Navarro-Núñez, L, primary, Rivera, J, additional, Guerrero, JA, additional, Martínez, C, additional, Vicente, V, additional, and Lozano, ML, additional
- Published
- 2009
- Full Text
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25. Atrophic dermatofibrosarcoma protuberans with the fusion gene COL1A1‐PDGFB
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Llombart, B, primary, Sanmartin, O, additional, Requena, C, additional, Monteagudo, C, additional, Botella‐Estrada, R, additional, Nagore, E, additional, Serra, C, additional, Alfaro, A, additional, Pellín, A, additional, Llombart‐Bosch, A, additional, Guillén, C, additional, and López‐Guerrero, JA, additional
- Published
- 2007
- Full Text
- View/download PDF
26. Discussion on: Adaptive and Predictive Path Tracking Control for Off-road Mobile Robots
- Author
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Macek, Kristijan, primary, Matsuko, Jadranko, additional, Martinelli, Agostino, additional, Siegwart, Roland, additional, Guerrero, JA, additional, and Lozano, Rogelio, additional
- Published
- 2007
- Full Text
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27. Spatial and temporal composition of the avifauna from small coastal wetlands and adjacent habitats in northwestern Baja California, Mexico
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Ruiz-Campos, G, primary, Palacios, E, additional, Castillo-Guerrero, JA, additional, González-Guzmán, S, additional, and Batche-González, EH, additional
- Published
- 2005
- Full Text
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28. Dermatofibrosarcoma protuberans: a clinicopathological, immunohistochemical, genetic (COL1A1-PDGFB), and therapeutic study of low-grade versus high-grade (fibrosarcomatous) tumors.
- Author
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Llombart B, Monteagudo C, Sanmartín O, López-Guerrero JA, Serra-Guillén C, Poveda A, Jorda E, Fernandez-Serra A, Pellín A, Guillén C, Llombart-Bosch A, Llombart, Beatriz, Monteagudo, Carlos, Sanmartín, Onofre, López-Guerrero, José Antonio, Serra-Guillén, Carlos, Poveda, Andrés, Jorda, Esperanza, Fernandez-Serra, Antonio, and Pellín, Antonio
- Abstract
Background: Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous tumor, usually low grade, except for the fibrosarcomatous variant (DFSP-FS).Objectives: We sought to compare the clinicopathological, immunohistochemical, genetic, and therapeutic features between DFSP and DFSP-FS.Methods: The clinicopathological features were reviewed in 63 DFSP and 12 DFSP-FS. Immunohistochemistry and multiplex reverse transcriptase-polymerase chain reaction were carried out using formalin-fixed, paraffin-embedded tissue, using specific primers for collagen type I alpha 1 (COL1A1) and platelet-derived growth factor beta (PDGFB).Results: DFSP-FS was associated with tumor history longer than 5 years (P = .009), tumor size greater than 4 cm (P = .001), more stages of modified Mohs micrographic surgery (P = .005), expansive subcutaneous infiltration (P = .005), muscular invasion (P = .0001), absence of CD34 staining (P = .018), p53 positivity (P = .006), and increased proliferative activity (P = .004) compared with DFSP. The COL1A1-PDGFB fusion transcript was found in 100% DFSP-FS and 72% DFSP. No association was found between the different COL1A1-PDGFB fusion transcripts and the different histologic subtypes. Wide local excision (2 cm) was performed in 47% of cases and modified Mohs micrographic surgery in 53%. After a mean follow-up of 73 months (range 21-235), 6 patients had local recurrence (5 DFSP, 1 DFSP-FS) and one died of disease (DFSP-FS). The only factor related to local recurrence was the type of surgery (17% wide local excision vs 0% modified Mohs micrographic surgery) (P = .006).Limitations: Our study is retrospective. Prospective studies are necessary to confirm our results.Conclusions: DFSP-FS reflects tumor progression in DFSP, with larger size, particular invasive patterns, p53 expression, and increased proliferative activity. However, as in low-grade DFSP, appropriate surgery permits a tumor-free excision. COL1A1-PDGFB is a useful tool for diagnosis of DFSP and particularly for DFSP-FS. [ABSTRACT FROM AUTHOR]- Published
- 2011
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29. Imatinib plus low-dose doxorubicin in patients with advanced gastrointestinal stromal tumors refractory to high-dose imatinib: a phase I-II study by the Spanish Group for Research on Sarcomas.
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Maurel J, Martins AS, Poveda A, López-Guerrero JA, Cubedo R, Casado A, Martínez-Trufero J, Ramón Ayuso J, Lopez-Pousa A, Garcia-Albeniz X, Garcia Del Muro X, de Alava E, Maurel, Joan, Martins, Ana Sofia, Poveda, Andrés, López-Guerrero, José Antonio, Cubedo, Ricardo, Casado, Antonio, Martínez-Trufero, Javier, and Ramón Ayuso, Juan
- Abstract
Background: In KIT-expressing Ewing sarcoma cell lines, the addition of doxorubicin to imatinib increases apoptosis, compared with imatinib or doxorubicin alone. On the basis of these in vitro data, the authors conducted a phase 1-2 trial of doxorubicin with imatinib in patients with gastrointestinal sarcoma tumors refractory to high-dose imatinib therapy.Methods: Patients with metastatic gastrointestinal sarcoma tumor resistant to imatinib at 400 mg by mouth (p.o.) twice a day were eligible for this multicenter study, and received imatinib (400 mg p.o. every day [q.d.]) concomitantly with doxorubicin 15-20 mg/m2/weekly for 4 cycles (monthly cycles), followed by imatinib (400 mg p.o. q.d.) maintenance in nonprogressive patients. Spiral computed tomography and positron emission tomography with F18-fluorodeoxyglucose were done basally and after 2 months of therapy to evaluate response. An in vitro study assessed the effect of combining imatinib and doxorubicin.Results: Twenty-six patients with progressive gastrointestinal sarcoma tumor were entered in the study. Treatment was well tolerated. Three (14%) of 22 evaluable patients had partial responses per Response Evaluation Criteria in Solid Tumors, and 8 (36%) had clinical benefit (partial response or stable disease for >or=6 months). Median progression-free survival (PFS) was 100 days (95% confidence interval [CI], 62-138), and median survival was 390 days (95% CI, 264-516). Interestingly, PFS was 211 days (95% CI, 52-370) in patients with wild type (WT) KIT and 82 days (95% CI, 53-111) in non-WT patients (10 mutant, 6 not assessed). A synergistic effect on cell line proliferation and apoptosis was found with imatinib and doxorubicin combination.Conclusions: Low-dose chemobiotherapy combination showed promising activity in heavily pretreated gastrointestinal sarcoma tumor patients, especially in those with WT-KIT genotype. [ABSTRACT FROM AUTHOR]- Published
- 2010
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30. Biological assessment of aspirin efficacy on healthy individuals: heterogeneous response or aspirin failure?
- Author
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Gonzalez-Conejero R, Rivera J, Corral J, Acuña C, Guerrero JA, Vicente V, Gonzalez-Conejero, Rocio, Rivera, Jose, Corral, Javier, Acuña, Carmen, Guerrero, Jose A, and Vicente, Vincente
- Published
- 2005
- Full Text
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31. OECI TuBaFrost Tumor Biobanking
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Riegman, Peter HJ, Bosch, Antonio Llombart, Riegman, PHJ, Dinjens, WNM, Oomen, MHA, Spatz, A, Ratcliffe, C, Knox, K, Mager, R, Kerr, D, Pezzella, F., van Damme, B, van de Vijver, M, van Boven, H, Morente, MM, Alonso, S, Kerjaschki, D, Pammer, J, Lopez-Guerrero, JA, Bosch, A Llombart, Carbone, A, Gloghini, A, Teodorovic, I, Isabelle, M, Jaminé, D, Passioukov, A, Lejeune, S, Therasse, P, van Veen, EB, Lam, KH, and Oosterhuis, JW
- Abstract
OECI TuBaFrost harbors a complete infrastructure for the exchange of frozen tumor samples between European countries. OECI TuBaFrost consists of: •A code of conduct on how to exchange human residual samples in Europe•A central database application accessible over the Internet (www.tubafrost.org) where data can be uploaded and searched from samples that can be selected and ordered•Access rules with incentives for collectors•Standardization needed to enable the analysis of high quality samples derived from different centers•Virtual Microscopy to support sample selection with difficult pathologyThe entire infrastructure was, after completion, which was entirely financed by the European Commission, implemented in the OECI. But so far it has not been used to its capacity. A recent survey held amongst the OECI members shed light on the causes. The main conclusion is that all responders see OECI TuBaFrost as a good platform for exchange of samples, however, the biggest bottleneck found was that potential users are too unfamiliar with the communication between their own biobank tracking system and the TuBaFrost central database application. Therefore, new future plans are drawn. In addition, new infrastructure plans have been developed and the first preparatory steps have been set. For biobanks the BBMRI project has started aiming for Pan-European Biobanking and Biomolecular Resources Research Infrastructure.
- Published
- 2008
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32. Successful resection of carcinoma of the common hepatic duct at its superior bifurcation
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R. Camprodon, Guerrero Ja, Jornet J, and Salva Ja
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Male ,Photomicrography ,medicine.medical_specialty ,medicine.medical_treatment ,Hilum (biology) ,Hepatic Duct, Common ,Punctures ,Bile Duct Neoplasm ,Cholangiography ,Preoperative Care ,medicine ,Humans ,Cholecystectomy ,Common Bile Duct ,Palpation ,medicine.diagnostic_test ,Common bile duct ,business.industry ,General Medicine ,Middle Aged ,Surgery ,Dissection ,Bile Ducts, Intrahepatic ,medicine.anatomical_structure ,Bile Duct Neoplasms ,Diagnostic Techniques, Surgical ,Common hepatic duct ,Biliary tract ,business - Abstract
A case of carcinoma of the common hepatic duct at its superior bifurcation is presented in which surgical treatment was based on a previous diagnosis of neoplasia of the biliary tract. The regional diagnosis was made at operation during difficult dissection of the hepatic hilum and with the aid of retrograde cholangiographic exploration of the principal biliary tract through transhepatic puncture. Resection was performed at a level above the tumor with the hepatotomy being performed at the level of the umbilical notch. A Roux-en-Y hepaticojejunostomy was performed. At the time of this writing the patient has survived over sixteen months in quite satisfactory health.
- Published
- 1974
- Full Text
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33. Reservoir characterization by multiattribute analysis: The Orito field case
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Montes Luis, Vargas Carlos Alberto, and Guerrero Jairo G.
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Geology ,QE1-996.5 - Abstract
In order to characterize the Caballos formation reservoir in the Orito field in the Putumayo basin - Colombia, a multiattribute analysis was applied to a 50 km2 seismic volume along with 16 boreholes. Some properties of the reservoir were reliably estimated and very accurate when compared with well data. The porosity, permeability and volume of shale were calculated in the seismic volume by at least second order multivariate polynomial. A good correlation between porosity and acoustic impedance was observed by means of crossplot analysis performed on properties measured and estimated in cores or borehole logs as well as on properties calculated in the seismic volume. The estimated property values were well behaved according to the rocks physics analysis. With the property maps generated and the geological environments of the reservoir a new interpretation of the Caballos formation was established. High correlation coefficients and low estimated errors point out competence to calculate these three reservoir properties in places far from the influence of the wells. The multiple equation system was established through weighted hierarchical grouping of attributes and their coefficients calculated applying the inverse generalized matrix method.
- Published
- 2010
34. Molecular alterations of the G1/S checkpoint genes and cytogenetics in human osteosarcoma
- Author
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Pellin, A., Carmen Carda Batalla, Lopez-Gines, C., Lopez-Guerrero, Ja, and Llombart-Bosch, A.
35. Immunohistochemical and molecular profiling of human synovial sarcomas xenotransplanted into nude mice. A tissue microarray-based study
- Author
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Sabater, Plg, Heredia, Ja, Carda, C., Lopez-Guerrero, Ja, Pellin, A., Navarro, S., Subramaniam, M., and Llombart-Bosch, A.
36. Estudio de residuos de permetrina en un cultivo de tomate
- Author
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Farias Diana María, Guerrero Jairo Arturo, Lozano Amanda, and Piedrahita Wilson
- Subjects
Residuos de plaguicidas, dosis, frecuencia ,Plant ecology ,QK900-989 - Abstract
Con base en los resultados de una encuestade patrones de uso y manejo se evaluó el contenido delinsecticida permetrina mediante cromatografía de gasescon un detector μ-ECD en muestras de tomate provenientesde un ensayo bajo invernadero realizado en elCentro Agropecuario Marengo de la Universidad Nacionalde Colombia, ubicado en el municipio de Mosquera,Cundinamarca. Un 96% de las muestras presentaronresiduos de permetrina que superaron el límite máximode residuos (LMR). El análisis estadístico mostró que lafrecuencia de aplicación es el factor de uso que más influyeen la presencia de residuos, así como su interacciónsimple con el tiempo transcurrido entre la última aplicacióny la cosecha, además de la interacción de segundoorden entre los tres patrones de manejo más relevantes:la frecuencia de aplicación, el período de tiempo entre laúltima aplicación y la cosecha, y la dosis
- Published
- 2004
37. Estudio de residuos de plaguicidas en frutas y hortalizas en áreas específicas de Colombia
- Author
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Guerrero Jairo Arturo
- Subjects
Plant ecology ,QK900-989 - Abstract
La utilización incorrecta de los plaguicidas, debida principalmente a la sobredosificación y la aplicación inadecuada por parte de los agricultores, entre otros factores, puede ocasionar la presencia de residuos de plaguicidas en las frutas y las hortalizas. Ello origina riesgos para la salud humana y también afecta la comercialización en diferentes mercados mundiales. El presente estudio tiene por objeto evaluar la presencia de residuos de plaguicidas de alto riesgo en los cultivos de fresa, repollo, uchuva y tomate, representativos de diferentes regiones de Colombia, y determinar la calidad de estos alimentos, requisito importante para satisfacer convenios internacionales relacionados con la inocuidad de alimentos y su comercialización. El estudio de campo se efectuó en varios municipios de Cundinamarca y Huila, Colombia. En la mayoría de las muestras (95,4%) no se encontraron residuos que sobrepasaran los límites máximos de residuos, LMRs. Se encontraron dos muestras positivas con residuos de plaguicidas de clorpirifos en tomate (4,7%). Para la evaluación de las muestras se diseñaron y validaron metodologías multirresiduo por cromatografía de gases con detectores de μ-ECD y NPD para compuestos organoclorados, organofosforados y piretroides. Estas metodologías permitieron determinar concentraciones de estos compuestos cercanas a los límites máximos de residuos permisibles para cada una de la matrices.
- Published
- 2003
38. A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole.
- Author
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Garcia-Casado Z, Guerrero-Zotano A, Llombart-Cussac A, Calatrava A, Fernandez-Serra A, Ruiz-Simon A, Gavila J, Climent MA, Almenar S, Cervera-Deval J, Campos J, Albaladejo CV, Llombart-Bosch A, Guillem V, Lopez-Guerrero JA, Garcia-Casado, Zaida, Guerrero-Zotano, Angel, Llombart-Cussac, Antonio, Calatrava, Ana, and Fernandez-Serra, Antonio
- Abstract
Background: Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC.Methods: We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood.Results: Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009).Conclusions: Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients. [ABSTRACT FROM AUTHOR]- Published
- 2010
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39. The fecal microbiota of the mouse-eared bat (Myotis velifer) with new records of microbial taxa for bats.
- Author
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Arellano-Hernández HD, Montes-Carreto LM, Guerrero JA, and Martinez-Romero E
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- Animals, Female, Male, Bacteria classification, Bacteria genetics, Bacteria isolation & purification, Microbiota genetics, Mexico, Phylogeny, Gastrointestinal Microbiome genetics, Chiroptera microbiology, Feces microbiology, RNA, Ribosomal, 16S genetics
- Abstract
Studies on the fecal microbiome of wild animals reveal valuable information on the feeding habits of the host and the possible roles of bacteria in digestion. In this work we characterized the fecal microbiota of seven male and seven female Myotis velifer bats using the V3-V4 regions of the 16S rRNA gene. Fecal samples were collected at the El Salitre cave in Mexico. We obtained 81 amplicon sequence variants, identifying four phyla, 12 families and 14 genera for females and seven phyla, 21 families and 26 genera for males. The phylum Synergistota is reported for the first time in bats. The most abundant phyla were Pseudomonadota and Fusobacteriota. Male feces showed a greater taxonomic richness than those from females. This study revealed that the fecal microbiota of M. velifer had a unique and more diverse composition compared to the microbiota reported for other bats. We identified 24 families and two abundant genera Cetobacterium and Haematospirillum in both males and females. Cetobacterium may produce vitamin B12 that is not produced by animals and Haematospirillum, which has been reported as an emerging human pathogen, may produce non-volatile organic acids. These genera had not been previously reported in the bat microbiota., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arellano-Hernández et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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40. Extracranial Carotid Artery Aneurysms: A Comprehensive Analysis of its Epidemiology, Pathogenesis, Diagnosis, and Management: A Scoping Review.
- Author
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Martinez-Rodriguez HR, Acevedo-Castillo CD, Macias-Cruz HM, Bautista-Coronado UA, Ortega-Ruiz OR, Cornejo-Hernandez A, Naranjo-Hernández P, Tabera-Tarello PM, Moran-Guerrero JA, and Figueroa-Sanchez JA
- Abstract
Introduction: Extracranial carotid artery aneurysms (ECAAs) are extraordinarily rare, representing approximately 0.4-4% of all extracranial artery aneurysms. As medical technology has advanced, new approaches for ECCAs treatment can be performed. Nevertheless, there is currently no consensus on the best therapeutic approach due to the information scarcity., Methods: We performed a systematic review of all published ECAA cases in Scopus, Medline, Web of Science, and Google Scholar to retrieve all available studies up to March 2024., Results: Eighty-eight studies reporting on a total of 359 patients presenting ECAAs were included. The mean age at diagnosis was 53 years. Most patients were male (58.4%). The primary presenting symptoms were pulsatile mass (31.2%), ischemia (24.7%), pain (9.75%), and dizziness (8.36%). Overall, the leading etiologies of aneurysms were atherosclerosis (34.2%), trauma (10%), and vasculitis (5.57%). Surgery was performed in 68.5% of patients, 26.7% underwent endovascular procedures, and 3.9% received conservative management., Conclusion: ECAAs are a rare clinical condition. However, a great percentage of patients could present with ischemic symptoms. Similarly, cardiovascular risk factors present as the most prevalent comorbid conditions associated with these vascular aberrancies. With this systematic review, we seek to provide insight into extracranial carotid aneurysms, identifying areas of opportunity in both the diagnosis and management of this pathology and the standardization of clinical reporting and case classification. These findings underscore the need for future research to improve the understanding and approach to this complex clinical condition., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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41. Predictive and Dynamic Signature for Antiangiogenics in Combination with a PD1 Inhibitor in Soft-Tissue Sarcoma: Correlative Studies Linked to the IMMUNOSARC Trial.
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Moura DS, Lopez-Marti JM, Benesova I, de Andrea C, di Lernia D, Lacerenza S, Mondaza-Hernandez JL, Martin-Ruiz M, Ramirez-Calvo M, Grignani G, Martinez-Trufero J, Redondo A, Valverde C, Stacchiotti S, Lopez-Pousa A, Lopez-Guerrero JA, Gutierrez A, Encinas-Tobajas V, Hindi N, Sangiolo D, Lopez-Martin JA, Strizova ZO, and Martin-Broto J
- Subjects
- Humans, Female, Male, Angiogenesis Inhibitors therapeutic use, Angiogenesis Inhibitors administration & dosage, Middle Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Nivolumab therapeutic use, Nivolumab administration & dosage, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes metabolism, Adult, Aged, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Lymphocytes, Tumor-Infiltrating drug effects, Biomarkers, Tumor, Tumor Microenvironment drug effects, Tumor Microenvironment immunology, Prognosis, Sarcoma drug therapy, Sarcoma pathology, Sarcoma genetics
- Abstract
Purpose: The IMMUNOSARC trial combined an antiangiogenic agent (sunitinib) with a PD1 inhibitor (nivolumab) in advanced sarcomas. Here, we present the first correlative studies of the soft-tissue sarcoma cohort enrolled in this trial., Experimental Design: Formalin-fixed paraffin-embedded and peripheral blood samples were collected at baseline and week 13. Formalin-fixed paraffin-embedded samples were used for transcriptomics and multiplex immunofluorescence, whereas peripheral blood samples were used for multiplexed immunoassays. Flow cytometry and Luminex assays were performed to validate translational findings in tumor-isolated cells and peripheral blood mononuclear cells derived from patients., Results: The density of intratumoral CD8+ T cells, measured by multiplexed immunophenotyping, was significantly increased after treatment. This augment was accompanied by the dynamic significant increase in the gene expressions of CD86, CHI3L1, CXCL10, CXCL9, LAG3, and VCAM1 and the decrease in the expression levels of NR4A1. In peripheral blood, 12 proteins were significantly modulated by treatment at week 13. A score integrating the dynamic expression of the 7 genes and the 12 soluble factors separated 2 groups with distinct progression-free survival (PFS): 4.1 months [95% confidence interval, 3.5-not reached (NR)] versus 17 months (95% confidence interval, 12.0-NR), P = 0.014. This molecular score was predictive of PFS when applied to the normalized data determined in the baseline samples., Conclusions: Treatment with sunitinib and nivolumab inflamed the sarcoma microenvironment, increasing CD8+ T-cell density and the expression of several genes/proteins with relevance in the response to PD1 inhibitors. A molecular signature identified two groups of patients with distinct PFS for the combination of antiangiogenics plus PD1 inhibitor therapy., (©2024 American Association for Cancer Research.)
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- 2024
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42. Exploratory analysis of immunomodulatory factors identifies L1CAM as a prognostic marker in alveolar soft-part sarcoma.
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Mondaza-Hernandez JL, Hindi N, Fernandez-Serra A, Ramos R, Gonzalez-Cámpora R, Gómez-Mateo MC, Martinez-Trufero J, Lavernia J, Lopez-Pousa A, Laínez N, Martinez-Garcia J, Valverde C, Vaz-Salgado MÁ, Garcia-Plaza G, Marin-Borrero I, Carrillo-Garcia J, Martin-Ruiz M, Romero P, Gutierrez A, López-Guerrero JA, Moura DS, and Martin-Broto J
- Abstract
Background: Alveolar soft-part sarcoma (ASPS) is a rare tumor driven by the ASPSCR1-TFE3 fusion protein, with a propensity for metastasis. Prognostic factors remain poorly understood, and traditional chemotherapies are largely ineffective. Recent interest lies in immune checkpoint inhibitors (ICIs), yet predictive biomarkers for treatment response are lacking. Previous studies have shown promising results with ICIs in ASPS, indicating a need for further investigation into biomarkers associated with immune response., Objectives: To identify prognostic biomarkers in ASPS and to explore the role of immune-related markers, particularly L1CAM, in predicting patient outcomes., Design: A retrospective cohort study of 19 ASPS patients registered in the GEIS database. The study involved the collection of clinical and histopathological data, followed by an analysis of immune markers and gene expression profiles to identify potential prognostic indicators., Methods: Clinical and histopathological data were retrospectively collected from the GEIS-26 study cohort of 19 ASPS patients. Immunohistochemistry was performed to evaluate immune markers programmed death-1 ligand (PD-L1), programmed death-1, FAS, FASL, CD8, CD3, and CD4. An HTG ImmunOncology panel was conducted on formalin-fixed paraffin-embedded samples to explore gene expression. Effects of differentially expressed genes on survival were explored by Kaplan-Meier., Results: PD-L1 positivity was widely observed (63%) in tumors, and CD8+ lymphocytic infiltration was common. High CD8 density correlated with greater overall survival (OS) while not statistically significant. No associations were found for other immune markers. L1CAM was identified as differentially expressed in patients with low CD8 infiltration and correlated negatively with OS., Conclusion: High L1CAM expression correlated with poorer OS, highlighting its potential as a prognostic marker and therapeutic target in ASPS. Immunomodulatory interventions may hold promise, as evidenced by PD-L1 expression and CD8+ infiltration. Further research, including larger cohorts and international collaborations, is needed to validate these findings and explore therapeutic strategies targeting L1CAM in ASPS., Competing Interests: N.H. reports grants, personal fees, and non-financial support from PharmaMar, personal fees from Lilly, grants from Eisai, and Novartis, outside the submitted work and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint, Nektar, Forma, Amgen, and Daiichi-Sankyo. D.S.M. reports institutional research grants from PharmaMar, Eisai, Immix BioPharma, and Novartis outside the submitted work; travel support from PharmaMar, Eisai, Celgene, Bayer, and Pfizer. J.M.-B. reports research grants from PharmaMar, Eisai, Immix BioPharma, and Novartis outside the submitted work; honoraria for advisory board participation and expert testimony from PharmaMar, Eli Lilly and Company, Bayer, GSK, Novartis, Boehringer Ingelheim, Amgen, Roche, Tecnofarma, and Asofarma; and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, BMS, Pfizer, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Celgene, Novartis, Blueprint, Adaptinmune, Nektar, Forma, Amgen, Daiichi-Sankyo, Ran Therapeutics, INHIBRX, Ayala Pharmaceuticals, Philogen, Cebiotex, PTC Therapeutics, Inc., and SpringWorks therapeutics. The other authors declare no potential conflicts of interest., (© The Author(s), 2024.)
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- 2024
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43. Epiploic Appendagitis: Systematic Review of a Distinctive Pathology.
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Acevedo-Castillo CD, Macias-Cruz HM, Ramirez-Cisneros A, Bautista-Coronado UA, Moran-Guerrero JA, and Guzman EA
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- Adult, Female, Humans, Male, Appendicitis complications, Appendicitis diagnosis, Colitis complications, Colitis diagnosis, Diagnosis, Differential, Diverticulitis complications, Diverticulitis diagnosis, Abdomen, Acute diagnosis, Abdomen, Acute etiology, Abdomen, Acute surgery, Abdominal Pain diagnosis, Abdominal Pain etiology, Abdominal Pain surgery
- Abstract
Introduction: Epiploic appendagitis (EA) is an essential cause of abdominal pain that can be confused with more typical causes such as acute diverticulitis and appendicitis. Epiploic appendagitis accounts for 1% of all cases of abdominal pain in adults. The scarcity of information has limited its recognition as an essential nonsurgical cause of acute abdominal pain. Methods: We performed a systematic review of all EA cases published. We searched Scopus, Medline, Web of Science, and Google Scholar to retrieve all available studies from January 2000 to November 2023. Results: 196 case reports and case series were analyzed, with 371 patients with EA included. The mean age at the time of diagnosis was 39 years. Most patients were male (59%). The primary presenting symptoms were pain (100%), tenderness (59.5%), and rebound tenderness (27.4%). The left abdomen was the most common localization of pain (53%). The most frequently identified differential diagnoses were acute appendicitis (26.4%) and acute diverticulitis (16.1%). Most patients (53%) were treated conservatively, and 98 (26.4%) underwent surgical treatment. A significant difference in the choice of treatment was found for signs and symptoms such as rebound tenderness, nausea, anorexia, and diarrhea. Conclusions: Acute EA is an essential clinical condition of rare occurrence that might present a diagnostic challenge, as it can masquerade as another acute abdominal pain etiology. The optimal management of EA is conservative, so a higher recognition by surgeons and emergency physicians is essential to avoid unnecessary surgical interventions and their associated consequences., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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44. The Impact of Tube Type, Centrifugation Conditions, and Hemolysis on Plasma Circulating MicroRNAs.
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Pastor-Navarro B, Ramírez-Calvo M, Gil-Aldea I, Cortell-Granero I, and López-Guerrero JA
- Abstract
Background: In recent years, liquid biopsy has emerged as a promising tool for the diagnosis and prognosis of numerous diseases, including cancer. Among the biomolecules analyzed in liquid biopsies are plasma circulating microRNAs (miRNAs), small non-coding RNAs that have proven to be crucial in the regulation of gene expression and the pathobiology of different health conditions, making them useful as biomarkers. However, variations in preanalytical conditions during biospecimen collection and processing can affect the analytical results., Objectives: Herein, we determined how the type of collection tube, the number of centrifugations, and the degree of hemolysis can affect plasma circulating miRNA levels., Methods: A cohort of 11 healthy donors was included. Whole blood was collected and handled in three different conditions, and miRNAs levels were analyzed using quantitative RT-PCR., Results: Our results show that the differences in the type of preservative tubes influence hemolysis, measured as OD at 414 nm. Moreover, the number of centrifugations performed also altered miRNAs levels, increasing or decreasing them depending on the miRNA analyzed. Hence, our study shows that alterations in preanalytical conditions affect miRNAs levels, particularly the number of centrifugations and the type of collection tubes., Conclusions: In our work, we highlight the importance of registering the preanalytical conditions in a standardized way that might be considered when analytical results are obtained.
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- 2024
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45. GLUT1 overexpression in CAR-T cells induces metabolic reprogramming and enhances potency.
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Guerrero JA, Klysz DD, Chen Y, Malipatlolla M, Lone J, Fowler C, Stuani L, May A, Bashti M, Xu P, Huang J, Michael B, Contrepois K, Dhingra S, Fisher C, Svensson KJ, Davis KL, Kasowski M, Feldman SA, Sotillo E, and Mackall CL
- Subjects
- Humans, Animals, Mice, Tumor Microenvironment immunology, Immunotherapy, Adoptive methods, Receptors, Chimeric Antigen metabolism, Receptors, Chimeric Antigen immunology, Receptors, Chimeric Antigen genetics, Oxidative Phosphorylation, Reactive Oxygen Species metabolism, Cell Differentiation, Cell Line, Tumor, Lymphocyte Activation immunology, Th17 Cells immunology, Th17 Cells metabolism, Cytokines metabolism, Cellular Reprogramming genetics, Metabolic Reprogramming, Glucose Transporter Type 1 metabolism, Glucose Transporter Type 1 genetics, Glucose metabolism, Glycolysis, T-Lymphocytes immunology, T-Lymphocytes metabolism
- Abstract
The intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise the prospect that glucose availability may limit CAR-T cell function. Here, we seek to test the hypothesis that stable overexpression (OE) of the glucose transporter GLUT1 in primary human CAR-T cells would improve their function and antitumor potency. We observe that GLUT1OE in CAR-T cells increases glucose consumption, glycolysis, glycolytic reserve, and oxidative phosphorylation, and these effects are associated with decreased T cell exhaustion and increased Th
17 differentiation. GLUT1OE also induces broad metabolic reprogramming associated with increased glutathione-mediated resistance to reactive oxygen species, and increased inosine accumulation. When challenged with tumors, GLUT1OE CAR-T cells secrete more proinflammatory cytokines and show enhanced cytotoxicity in vitro, and demonstrate superior tumor control and persistence in mouse models. Our collective findings support a paradigm wherein glucose availability is rate limiting for effector CAR-T cell function and demonstrate that enhancing glucose availability via GLUT1OE could augment antitumor immune function., (© 2024. The Author(s).)- Published
- 2024
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46. In Reply to the Letter to the Editor Regarding "Backup Frontal Drainage System for Urgent Tension Pneumocephalus Management After Chronic Subdural Hematoma Surgery: A Retrospective Cohort Study".
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Moran-Guerrero JA, Martínez HR, Gonzalez-Sanchez DG, Perez-Martinez LE, Flores-Salcido RE, Ferrigno AS, Caro-Osorio E, Salazar-Alejo M, Avalos-Montes PJ, and Figueroa-Sanchez JA
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- 2024
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47. Comparing the Need and Development of Pediatric Palliative Care in Mexico: A Geographical Analysis.
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Ramos-Guerrero JA, Correa-Morales JE, Sánchez-Cárdenas MA, Andrade-Fonseca D, Hernández-Flores LM, López-Jiménez EJ, and Zuniga-Villanueva G
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- Humans, Mexico, Child, Infant, Child, Preschool, Adolescent, Pediatrics, Infant, Newborn, Male, Palliative Care, Health Services Accessibility, Health Services Needs and Demand
- Abstract
Context: The Global Atlas of Palliative Care (GAPC) ranked Mexico's palliative care services at a preliminary integration stage into mainstream healthcare services. However, this data does not reflect pediatric palliative care (PPC) development., Objectives: To analyze the current need and level of development of PPC within Mexico., Methods: PPC need was estimated using causes of death associated with serious health-related suffering from national mortality data from the General Directorate of Health Information. The level of development was measured through six indicators involving access to PPC services and opioids, then classified using the GAPC development categories adapted to regional territories based on available data., Results: In 2021, 37,444 children died in Mexico. Of those, 10,677 (28.29%) died from conditions with serious health-related suffering, averaging a need for PPC of 25/100,000 children. Out of Mexico's 32 states, two (6.2%) had no PPC activity (category 1), twenty (62.6%) were in a capacity-building phase (category 2), eight (25%) had isolated PPC provision (category 3a), while two (6.2%) had generalized PPC provision (category 3b). No state had early (category 4a) or advanced PPC integration (category 4b). Overall, Mexico was classified as category 2., Conclusions: PPC services are distributed unevenly across the country, leading to inequitable access to care and an inability to meet the needs of patients and families. There is a disparity between the level of development of adult palliative care services and the underdevelopment of PPC in Mexico. This information can help stakeholders guide the development of PPC where it is needed most., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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48. Human Coronavirus 229E Uses Clathrin-Mediated Endocytosis as a Route of Entry in Huh-7 Cells.
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Andreu S, Ripa I, López-Guerrero JA, and Bello-Morales R
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- Humans, Cell Line, Tumor, Adaptor Protein Complex 2 metabolism, Clathrin-Coated Vesicles metabolism, Endocytosis, Virus Internalization, Clathrin metabolism, Coronavirus 229E, Human physiology
- Abstract
Human coronavirus 229E (HCoV-229E) is an endemic coronavirus responsible for approximately one-third of "common cold" cases. To infect target cells, HCoV-229E first binds to its receptor on the cell surface and then can follow different pathways, entering by direct fusion or by taking advantage of host cell mechanisms such as endocytosis. Based on the role of clathrin, the process can be classified into clathrin-dependent or -independent endocytosis. This study characterizes the role of clathrin-mediated endocytosis (CME) in HCoV-229E infection of the human hepatoma cell line Huh-7. Using specific CME inhibitory drugs, we demonstrated that blocking CME significantly reduces HCoV-229E infection. Additionally, CRISPR/Cas9-mediated knockout of the µ subunit of adaptor protein complex 2 (AP-2) further corroborated the role of CME, as KOs showed over a 50% reduction in viral infection. AP-2 plays an important role in clathrin recruitment and the maturation of clathrin-coated vesicles. Our study also confirmed that in Huh-7 cells, HCoV-229E requires endosomal acidification for successful entry, as viral entry decreased when treated with lysomotropic agents. Furthermore, the colocalization of HCoV-229E with early endosome antigen 1 (EEA-1), only present in early endosomes, suggested that the virus uses an endosomal route for entry. These findings highlight, for the first time, the role of CME in HCoV-229E infection and confirm previous data of the use of the endosomal route at a low pH in the experimental cell model Huh-7. Our results provide new insights into the mechanisms of entry of HCoV-229E and provide a new basis for the development of targeted antiviral therapies.
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- 2024
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49. Enhancing the Performance of Nanocrystalline SnO 2 for Solar Cells through Photonic Curing Using Impedance Spectroscopy Analysis.
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Slimani MA, Benavides-Guerrero JA, Cloutier SG, and Izquierdo R
- Abstract
Wide-bandgap tin oxide (SnO2) thin-films are frequently used as an electron-transporting layers in perovskite solar cells due to their superior thermal and environmental stabilities. However, its crystallization by conventional thermal methods typically requires high temperatures and long periods of time. These post-processing conditions severely limit the choice of substrates and reduce the large-scale manufacturing capabilities. This work describes the intense-pulsed-light-induced crystallization of SnO2 thin-films using only 500 μs of exposure time. The thin-films' properties are investigated using both impedance spectroscopy and photoconductivity characteristic measurements. A Nyquist plot analysis establishes that the process parameters have a significant impact on the electronic and ionic behaviors of the SnO2 films. Most importantly, we demonstrate that light-induced crystallization yields improved topography and excellent electrical properties through enhanced charge transfer, improved interfacial morphology, and better ohmic contact compared to thermally annealed (TA) SnO2 films.
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- 2024
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50. HER2DX Genomic Assay in HER2-Positive Early Breast Cancer Treated with Trastuzumab and Pertuzumab: A Correlative Analysis from the PHERGain Phase II Trial.
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Llombart-Cussac A, Pérez-García J, Brasó-Maristany F, Paré L, Villacampa G, Gion M, Schmid P, Colleoni M, Borrego MR, Galván P, Parker JS, Buckingham W, Perou CM, Villagrasa P, Guerrero JA, Sampayo-Cordero M, Mancino M, Prat A, and Cortés J
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- Humans, Female, Middle Aged, Adult, Aged, Retrospective Studies, Neoplasm Staging, Treatment Outcome, Biomarkers, Tumor genetics, Trastuzumab therapeutic use, Trastuzumab administration & dosage, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms pathology, Breast Neoplasms mortality, Receptor, ErbB-2 metabolism, Receptor, ErbB-2 genetics, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Purpose: The purpose of this study was to assess the predictive capability of HER2DX assay following (neo)adjuvant trastuzumab-pertuzumab (HP)-based therapy in HER2-positive (HER2+) early breast cancer., Experimental Design: HER2DX was analyzed in baseline pretreatment tumors from the PHERGain trial. Patients with stage I-IIIA HER2+ early breast cancer were randomized to group A [docetaxel, carboplatin, and HP (TCHP)] and group B (HP ± endocrine therapy). PET response was evaluated after two cycles. Group A received TCHP for six cycles regardless of PET response. Group B continued with HP ± endocrine therapy for six cycles (PET responders) or with TCHP for six cycles (PET nonresponders). The primary objective of this retrospective study was to associate the HER2DX pathologic complete response (pCR) score with pCR. The secondary objective was the association of the HER2DX risk score with 3-year invasive disease-free survival (iDFS)., Results: HER2DX was performed on 292 (82.0%) tumors. The overall pCR rate was 38.0%, with pCR rates of 56.4% in group A and 33.8% in group B. In multivariable analysis including treatment and clinicopathologic factors, the HER2DX pCR score (continuous variable) significantly correlated with pCR [OR, 1.29; 95% confidence interval (CI), 1.10-1.54; P < 0.001]. HER2DX-defined pCR-high, -med, and -low groups exhibited pCR rates of 50.4%, 35.8%, and 23.2%, respectively (pCR-high vs. pCR-low OR, 3.27; 95% CI, 1.54-7.09; P < 0.001). In patients with residual disease, the HER2DX high-risk group demonstrated numerically worse 3-year iDFS than the low-risk group (89.8% vs. 100%; HR, 2.70; 95% CI, 0.60-12.18; P = 0.197)., Conclusions: HER2DX predicts pCR in the context of neoadjuvant HP-based therapy, regardless of chemotherapy addition, and might identify patients at higher risk of recurrence among patients with residual disease., (©2024 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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