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1,165 results on '"Llovet, Josep M."'

1. WNTinib is a multi-kinase inhibitor with specificity against β-catenin mutant hepatocellular carcinoma

Author

Rialdi, Alex, Duffy, Mary, Scopton, Alex P, Fonseca, Frank, Zhao, Julia Nanyi, Schwarz, Megan, Molina-Sanchez, Pedro, Mzoughi, Slim, Arceci, Elisa, Abril-Fornaguera, Jordi, Meadows, Austin, Ruiz de Galarreta, Marina, Torre, Denis, Reyes, Kyna, Lim, Yan Ting, Rosemann, Felix, Khan, Zaigham M, Mohammed, Kevin, Wang, Xuedi, Yu, Xufen, Lakshmanan, Manikandan, Rajarethinam, Ravisankar, Tan, Soo Yong, Jin, Jian, Villanueva, Augusto, Michailidis, Eleftherios, De Jong, Ype P, Rice, Charles M, Marazzi, Ivan, Hasson, Dan, Llovet, Josep M, Sobota, Radoslaw M, Lujambio, Amaia, Guccione, Ernesto, and Dar, Arvin C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Rare Diseases, Liver Disease, Biotechnology, Liver Cancer, Genetics, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Humans, Mice, Animals, Carcinoma, Hepatocellular, beta Catenin, Liver Neoplasms, Transcription Factors, Antineoplastic Agents, Protein Kinase Inhibitors, Immunology, Oncology and carcinogenesis
Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. β-Catenin (CTNNB1)-mutated HCC represents 30% of cases of the disease with no precision therapeutics available. Using chemical libraries derived from clinical multi-kinase inhibitor (KI) scaffolds, we screened HCC organoids to identify WNTinib, a KI with exquisite selectivity in CTNNB1-mutated human and murine models, including patient samples. Multiomic and target engagement analyses, combined with rescue experiments and in vitro and in vivo efficacy studies, revealed that WNTinib is superior to clinical KIs and inhibits KIT/mitogen-activated protein kinase (MAPK) signaling at multiple nodes. Moreover, we demonstrate that reduced engagement on BRAF and p38α kinases by WNTinib relative to several multi-KIs is necessary to avoid compensatory feedback signaling-providing a durable and selective transcriptional repression of mutant β-catenin/Wnt targets through nuclear translocation of the EZH2 transcriptional repressor. Our studies uncover a previously unknown mechanism to harness the KIT/MAPK/EZH2 pathway to potently and selectively antagonize CTNNB1-mutant HCC with an unprecedented wide therapeutic index.

Published
2023

7. Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer

Author

Ortiz-Barahona, Vanessa, Soler, Marta, Davalos, Veronica, García-Prieto, Carlos A., Janin, Maxime, Setien, Fernando, Fernández-Rebollo, Irene, Bech-Serra, Joan J., De La Torre, Carolina, Guil, Sonia, Villanueva, Alberto, Zhang, Pei-Hong, Yang, Li, Guarnacci, Marco, Schumann, Ulrike, Preiss, Thomas, Balaseviciute, Ugne, Montal, Robert, Llovet, Josep M., and Esteller, Manel

Published
2023
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8. Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

Author

Llovet, Josep M, Pinyol, Roser, Kelley, Robin K, El-Khoueiry, Anthony, Reeves, Helen L, Wang, Xin Wei, Gores, Gregory J, and Villanueva, Augusto

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Liver Cancer, Rare Diseases, Liver Disease, Clinical Research, Digestive Diseases, Cancer, Carcinoma, Hepatocellular, Combined Modality Therapy, Humans, Immunotherapy, Liver Neoplasms, Molecular Targeted Therapy, Immunology, Oncology and carcinogenesis
Abstract

Hepatocellular carcinoma (HCC) remains one of the most prevalent and deadliest cancers. The poor outcome associated with HCC is dramatically changing due to the advent of effective systemic therapies. Here we discuss the molecular pathogenesis of HCC, molecular classes and determinants of heterogeneity. In addition, effective single-agent and combination systemic therapies involving immunotherapies as standard of care are analyzed. Finally, we propose a flowchart of sequential therapies, explore mechanisms of resistance and address the need for predictive biomarkers.

Published
2022

9. Oncogenic role of PMEPA1 and its association with immune exhaustion and TGF-β activation in HCC☆

Author

Piqué-Gili, Marta, Andreu-Oller, Carmen, Mesropian, Agavni, Esteban-Fabró, Roger, Bárcena-Varela, Marina, Ruiz de Galarreta, Marina, Montironi, Carla, Martinez-Quetglas, Iris, Cappuyns, Sarah, Peix, Judit, Keraite, Ieva, Gris-Oliver, Albert, Fernández-Martínez, Elisa, Mauro, Ezequiel, Torres-Martin, Miguel, Abril-Fornaguera, Jordi, Lindblad, Katherine E., Lambrechts, Diether, Dekervel, Jeroen, Thung, Swan, Sia, Daniela, Lujambio, Amaia, Pinyol, Roser, and Llovet, Josep M.

Published
2024
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11. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations

Author

Affo, Silvia, Nair, Ajay, Brundu, Francesco, Ravichandra, Aashreya, Bhattacharjee, Sonakshi, Matsuda, Michitaka, Chin, LiKang, Filliol, Aveline, Wen, Wen, Song, Xinhua, Decker, Aubrianna, Worley, Jeremy, Caviglia, Jorge Matias, Yu, Lexing, Yin, Deqi, Saito, Yoshinobu, Savage, Thomas, Wells, Rebecca G, Mack, Matthias, Zender, Lars, Arpaia, Nicholas, Remotti, Helen E, Rabadan, Raul, Sims, Peter, Leblond, Anne-Laure, Weber, Achim, Riener, Marc-Oliver, Stockwell, Brent R, Gaublomme, Jellert, Llovet, Josep M, Kalluri, Raghu, Michalopoulos, George K, Seki, Ekihiro, Sia, Daniela, Chen, Xin, Califano, Andrea, and Schwabe, Robert F

Subjects
Genetics, Liver Disease, Cancer, Digestive Diseases - (Gallbladder), Chronic Liver Disease and Cirrhosis, Digestive Diseases, Liver Cancer, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Aged, Animals, Bile Duct Neoplasms, Bile Ducts, Intrahepatic, Cancer-Associated Fibroblasts, Cholangiocarcinoma, Collagen Type I, Female, Hepatic Stellate Cells, Hepatocyte Growth Factor, Humans, Hyaluronan Synthases, Hyaluronic Acid, Male, Mice, Transgenic, Middle Aged, Proto-Oncogene Proteins c-met, Tumor Microenvironment, CellPhoneDB, HGF, KRAS, YAP, cholangiocarcinoma, immune, mechanosensitive, single cell, stiffness, tumor microenvironment, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high panCAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, but not type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen.

Published
2021

12. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial

Author

Strasser, Simone, Thompson, Alexander, Roohullah, Aflah, Sievert, William, Andelkovic, Vladimir, Knox, Jennifer, Davies, Janine, Asselah, Jamil, Brahmania, Mayur, Majeed, Habeeb, Villanueva, Luis, Yanez Weber, Patricio, Garrido, Marcelo, Pizarro, Gonzalo Ignacio, Yanez, Nicolas, Xu, Ruocai, Ou, Shuangyan, Ren, Zhenggang, Pan, Hongming, Meng, Zhiqiang, Gu, Kangsheng, Chen, Xi, Zhang, Tao, Hao, Chunyi, Cao, Peiguo, Guo, Yabing, Qin, Shukui, Xiao, Juxiang, Fang, Weijia, Wang, Xin, Bai, Yuxian, Chen, Xiaoming, Yan, Dong, Zhao, Hong, Ying, Jieer, Bonilla, Carlos, Urrego, Olga, Zambrano, Angela, Lema, Mauricio, Restrepo Gutierrez, Juan Carlos, Cardona, Andres, Franco Millan, Sandra, Oscar, Madiedo, Ramos, Victor, Merle, Philippe, LeSourd, Samuel, Edeline, Julien, Bronowicki, Jean-Pierre, Bourliere, Marc, Cattan, Stephane, Bouattour, Mohamed, Mineur, Laurent, Regnault, Helene, Dauvois, Barbara, Schulze, Kornelius, Folprecht, Gunnar, Geier, Andreas, Waidmann, Oliver, Finkelmeier, Fabian, Venerito, Marino, Berres, Marie-Luise, Berg, Thomas, Lange, Christian, Schmidt, Hartmut, Waldschmidt, Dirk T, Bitzer, Michael, McDermott, Ray, Duffy, Austin, Masi, Gianluca, Zagonel, Vittorina, Tonini, Giuseppe, Piscaglia, Fabio, Gori, Stefania, Rizzo, Mimma, Biscaldi, Elisa, Foltran, Luisa, Cabibbo, Giuseppe, Ikeda, Masafumi, Kudo, Masatoshi, Aikata, Hiroshi, Numata, Kazushi, Marusawa, Hiroyuki, Kato, Naoya, Kurosaki, Masayuki, Morimoto, Manabu, Yamashita, Tatsuya, Koga, Hironori, Masaki, Tsutomu, Tateishi, Ryosuke, Inaba, Yoshitaka, Arakawa, Tomohiro, Suzuki, Yoshiyuki, Akua, Norio, Kobayashi, Masahiro, Hosaka, Tetsuya, Nakamuta, Makoto, Oza, Noriko, Kondo, Shunsuke, Furuse, Junji, Nagashima, Fumio, Kitano, Masayuki, Takaguchi, Koichi, Ryoo, Baek-Yeol, Lim, Ho Yeong, Kim, Jee Hyun, Kim, Tae-You, Kim, Han Sang, Hernandez Hernandez, Carlos, Motola Kuba, Daniel, Segura Gonzalez, Manuel, Cabrera Luviano, Jesus, Huitzil Melendez, Fidel, Ramirez Godinez, Francisco, Silva-Bravo, Fernando, Gane, Edward, Stedman, Catherine, Kwiatkowski, Mariusz, Wyrwicz, Lucjan, Nowakowska-Zajdel, Ewa, Kraj, Leszek, Janczewska, Ewa, Surma-Wlodarczyk, Renata, Breder, Valeriy, Sekacheva, Marina, Orlova, Rashida, Vasilyev, Alexander, Zukov, Ruslan, Vladimirov, Vladimir, Minguez, Beatriz, Matilla Pena, Ana, Fernandez Castroagudin, Javier, Romero Gomez, Manuel, Luis Lledo, Jose, Rubin, Angel, Garcia Sanchez, Araceli, Calleja Panero, Jose, Yu, Ming-Chin, Shen, Ying-Chun, Huang, Yi-Hsiang, Jeng, Long-Bin, Chang, Ting-Tsung, Yang, Sheng-Shun, Chen, Shinn-Cherng, Dechaphunkul, Arunee, Tanwandee, Tawesak, Leerapun, Apinya, Seker, Mesut, Harputluoglu, Hakan, Cicin, Irfan, Oksuzoglu, Berna, Bilici, Mehmet, Sezgin Goksu, Sema, Artac, Mehmet, Cil, Timucin, Yalcin, Suayib, Meyer, Tim, Sarker, Debashis, Rao, Ankit, Palmer, Daniel, Evans, Jeff, Hubner, Richard, Finn, Richard, Ulahannan, Susanna, Zakari, Ahmed, Feun, Lynn, Al-Rajabi, Raed, Sung, Max, He, Aiwu, Kardosh, Adel, Goyal, Lipika, Li, Daneng, Choi, Minsig, Posada, Juan, Dodlapati, Jyothi, Shroff, Rachna, Agrawal, Saurabh, Gopaluni, Srivalli, Akce, Mehmet, Alese, Olatunji, Baron, Ari, Dunne, Richard, Loaiza-Bonilla, Arturo, Frenette, Catherine, Llovet, Josep M, Kumada, Hiromitsu, Cheng, Ann-Lii, Galle, Peter R, Kaneko, Shuichi, Wang, Anran, Mody, Kalgi, Dutcus, Corina, Dubrovsky, Leonid, Siegel, Abby B, and Finn, Richard S

Published
2023
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13. Sublethal necroptosis signaling promotes inflammation and liver cancer

Author

Vucur, Mihael, Ghallab, Ahmed, Schneider, Anne T., Adili, Arlind, Cheng, Mingbo, Castoldi, Mirco, Singer, Michael T., Büttner, Veronika, Keysberg, Leonie S., Küsgens, Lena, Kohlhepp, Marlene, Görg, Boris, Gallage, Suchira, Barragan Avila, Jose Efren, Unger, Kristian, Kordes, Claus, Leblond, Anne-Laure, Albrecht, Wiebke, Loosen, Sven H., Lohr, Carolin, Jördens, Markus S., Babler, Anne, Hayat, Sikander, Schumacher, David, Koenen, Maria T., Govaere, Olivier, Boekschoten, Mark V., Jörs, Simone, Villacorta-Martin, Carlos, Mazzaferro, Vincenzo, Llovet, Josep M., Weiskirchen, Ralf, Kather, Jakob N., Starlinger, Patrick, Trauner, Michael, Luedde, Mark, Heij, Lara R., Neumann, Ulf P., Keitel, Verena, Bode, Johannes G., Schneider, Rebekka K., Tacke, Frank, Levkau, Bodo, Lammers, Twan, Fluegen, Georg, Alexandrov, Theodore, Collins, Amy L., Nelson, Glyn, Oakley, Fiona, Mann, Derek A., Roderburg, Christoph, Longerich, Thomas, Weber, Achim, Villanueva, Augusto, Samson, Andre L., Murphy, James M., Kramann, Rafael, Geisler, Fabian, Costa, Ivan G., Hengstler, Jan G., Heikenwalder, Mathias, and Luedde, Tom

Published
2023
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14. Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma

Author

Haber, Philipp K., Castet, Florian, Torres-Martin, Miguel, Andreu-Oller, Carmen, Puigvehí, Marc, Miho, Maeda, Radu, Pompilia, Dufour, Jean-Francois, Verslype, Chris, Zimpel, Carolin, Marquardt, Jens U., Galle, Peter R., Vogel, Arndt, Bathon, Melanie, Meyer, Tim, Labgaa, Ismail, Digklia, Antonia, Roberts, Lewis R., Mohamed Ali, Mohamed A., Mínguez, Beatriz, Citterio, Davide, Mazzaferro, Vincenzo, Finkelmeier, Fabian, Trojan, Jörg, Özdirik, Burcin, Müller, Tobias, Schmelzle, Moritz, Bejjani, Anthony, Sung, Max W., Schwartz, Myron E., Finn, Richard S., Thung, Swan, Villanueva, Augusto, Sia, Daniela, and Llovet, Josep M.

Published
2023
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16. Recent Developments and Therapeutic Strategies against Hepatocellular Carcinoma

Author

Yarchoan, Mark, Agarwal, Parul, Villanueva, Augusto, Rao, Shuyun, Dawson, Laura A, Karasic, Thomas, Llovet, Josep M, Finn, Richard S, Groopman, John D, El-Serag, Hashem B, Monga, Satdarshan P, Wang, Xin Wei, Karin, Michael, Schwartz, Robert E, Tanabe, Kenneth K, Roberts, Lewis R, Gunaratne, Preethi H, Tsung, Allan, Brown, Kimberly A, Lawrence, Theodore S, Salem, Riad, Singal, Amit G, Kim, Amy K, Rabiee, Atoosa, Resar, Linda, Meyer, Jeffrey, Hoshida, Yujin, He, Aiwu Ruth, Ghoshal, Kalpana, Ryan, Patrick B, Jaffee, Elizabeth M, Guha, Chandan, Mishra, Lopa, Coleman, C Norman, and Ahmed, Mansoor M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Liver Disease, Liver Cancer, Cancer, Orphan Drug, Rare Diseases, Chronic Liver Disease and Cirrhosis, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Anilides, Antibodies, Monoclonal, Humanized, Carcinoma, Hepatocellular, Chemoembolization, Therapeutic, Clinical Trials as Topic, Humans, Immunotherapy, Liver Neoplasms, Molecular Targeted Therapy, Mutation, Phenylurea Compounds, Protein Kinase Inhibitors, Pyridines, Quinolines, beta Catenin, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.

Published
2019

22. Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

Author

Kudo, Masatoshi, Galle, Peter R., Brandi, Giovanni, Kang, Yoon-Koo, Yen, Chia-Jui, Finn, Richard S., Llovet, Josep M., Assenat, Eric, Merle, Philippe, Chan, Stephen L., Palmer, Daniel H., Ikeda, Masafumi, Yamashita, Tatsuya, Vogel, Arndt, Huang, Yi-Hsiang, Abada, Paolo B., Yoshikawa, Reigetsu, Shinozaki, Kenta, Wang, Chunxiao, Widau, Ryan C., and Zhu, Andrew X.

Published
2021
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24. Molecular portraits of patients with intrahepatic cholangiocarcinoma who diverge as rapid progressors or long survivors on chemotherapy

Author

O'Rourke, Colm J., Salati, Massimiliano, Rae, Colin, Carpino, Guido, Leslie, Holly, Pea, Antonio, Prete, Maria G., Bonetti, Luca R., Amato, Francesco, Montal, Robert, Upstill-Goddard, Rosie, Nixon, Colin, Sanchon-Sanchez, Paula, Kunderfranco, Paolo, Sia, Daniela, Gaudio, Eugenio, Overi, Diletta, Cascinu, Stefano, Hogdall, Dan, Pugh, Sian, Domingo, Enric, Primrose, John N., Bridgewater, John, Spallanzani, Andrea, Gelsomino, Fabio, Llovet, Josep M., Calvisi, Diego F., Boulter, Luke, Caputo, Francesco, Lleo, Ana, Jamieson, Nigel B., Luppi, Gabriele, Dominici, Massimo, Andersen, Jesper B., Braconi, Chiara, O'Rourke, Colm J., Salati, Massimiliano, Rae, Colin, Carpino, Guido, Leslie, Holly, Pea, Antonio, Prete, Maria G., Bonetti, Luca R., Amato, Francesco, Montal, Robert, Upstill-Goddard, Rosie, Nixon, Colin, Sanchon-Sanchez, Paula, Kunderfranco, Paolo, Sia, Daniela, Gaudio, Eugenio, Overi, Diletta, Cascinu, Stefano, Hogdall, Dan, Pugh, Sian, Domingo, Enric, Primrose, John N., Bridgewater, John, Spallanzani, Andrea, Gelsomino, Fabio, Llovet, Josep M., Calvisi, Diego F., Boulter, Luke, Caputo, Francesco, Lleo, Ana, Jamieson, Nigel B., Luppi, Gabriele, Dominici, Massimo, Andersen, Jesper B., and Braconi, Chiara

Abstract

Objective: Cytotoxic agents are the cornerstone of treatment for patients with advanced intrahepatic cholangiocarcinoma (iCCA), despite heterogeneous benefit. We hypothesised that the pretreatment molecular profiles of diagnostic biopsies can predict patient benefit from chemotherapy and define molecular bases of innate chemoresistance. Design: We identified a cohort of advanced iCCA patients with comparable baseline characteristics who diverged as extreme outliers on chemotherapy (survival <6 m in rapid progressors, RP; survival >23 m in long survivors, LS). Diagnostic biopsies were characterised by digital pathology, then subjected to whole-transcriptome profiling of bulk and geospatially macrodissected tissue regions. Spatial transcriptomics of tumour-infiltrating myeloid cells was performed using targeted digital spatial profiling (GeoMx). Transcriptome signatures were evaluated in multiple cohorts of resected cancers. Signatures were also characterised using in vitro cell lines, in vivo mouse models and single cell RNA-sequencing data. Results: Pretreatment transcriptome profiles differentiated patients who would become RPs or LSs on chemotherapy. Biologically, this signature originated from altered tumour-myeloid dynamics, implicating tumour-induced immune tolerogenicity with poor response to chemotherapy. The central role of the liver microenviroment was confrmed by the association of the RPLS transcriptome signature with clinical outcome in iCCA but not extrahepatic CCA, and in liver metastasis from colorectal cancer, but not in the matched primary bowel tumours. Conclusions: The RPLS signature could be a novel metric of chemotherapy outcome in iCCA. Further development and validation of this transcriptomic signature is warranted to develop precision chemotherapy strategies in these settings.

Published
2024

25. NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Author

Pfister, Dominik, Núñez, Nicolás Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Müller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jörn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D’Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jörg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rössler, Fabian, Siebenhüner, Alexander, De Dosso, Sara, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Müller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kütting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, Ruiz de Galarreta, Marina, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., and Heikenwalder, Mathias

Published
2021
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26. Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Author

Zhu, Andrew X., Finn, Richard S., Kang, Yoon-Koo, Yen, Chia-Jui, Galle, Peter R., Llovet, Josep M., Assenat, Eric, Brandi, Giovanni, Motomura, Kenta, Ohno, Izumi, Daniele, Bruno, Vogel, Arndt, Yamashita, Tatsuya, Hsu, Chih-Hung, Gerken, Guido, Bilbruck, John, Hsu, Yanzhi, Liang, Kun, Widau, Ryan C., Wang, Chunxiao, Abada, Paolo, and Kudo, Masatoshi

Published
2021
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27. A Phase 1b Study of Lenvatinib plus Pembrolizumab in Patients with Unresectable Hepatocellular Carcinoma: Extended Analysis of Study 116.

Author

Kudo, Masatoshi, Finn, Richard S., Ikeda, Masafumi, Sung, Max W., Baron, Ari D., Okusaka, Takuji, Kobayashi, Masahiro, Kumada, Hiromitsu, Kaneko, Shuichi, Pracht, Marc, Meyer, Tim, Nagao, Satoshi, Saito, Kenichi, Mody, Kalgi, Ramji, Zahra, Dubrovsky, Leonid, and Llovet, Josep M.

Subjects
PROGRESSION-free survival, OVERALL survival, HEPATOCELLULAR carcinoma, PATIENT safety, ANTINEOPLASTIC agents
Abstract

Introduction: Lenvatinib (dosing for patients who weigh ≥60 kg was 12 mg/day; for patients who weigh <60 kg, the dose was 8 mg/day) plus pembrolizumab 200 mg once every 3 weeks demonstrated antitumor activity and a manageable safety profile in patients with first-line unresectable hepatocellular carcinoma (uHCC) in the open-label phase 1b Study 116/KEYNOTE-524 (primary analysis data cutoff date: October 31, 2019; median follow-up: 10.6 months). This analysis (updated data cutoff date: March 31, 2021) reports efficacy results from 17 months of additional follow-up time. Methods: 100 patients with uHCC were included in the primary analysis (median follow-up: 27.6 months). Endpoints included overall survival (OS), investigator-assessed progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) per modified RECIST. Landmark analyses of OS by the best response at 3 and 9 months were performed. Pembrolizumab antidrug antibodies (ADAs) and concentrations were also measured (cutoff date: August 7, 2020). Results: ORR was 43.0% (95% CI 33.1–53.3%) and median DOR was 17.1 months (95% CI 6.9–19.3 months). Median PFS and OS were 9.3 months (95% CI 7.4–9.8 months) and 20.4 months (95% CI 14.4–25.9 months), respectively. No treatment-emergent ADAs were detected. Conclusion: Results show a sustained treatment effect with lenvatinib plus pembrolizumab in patients with uHCC in the first-line setting. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Coformulated quavonlimab and pembrolizumab (pembro) in combination with lenvatinib (lenva) as first-line (1L) therapy for patients (pts) with advanced hepatocellular carcinoma (HCC): Phase 2 KEYSTEP-004 study.

Author

Rimassa, Lorenza, primary, Li, Daneng, additional, Ikeda, Masafumi, additional, Yarchoan, Mark, additional, Ryoo, Baek-Yeol, additional, Kossler, Thibaud, additional, Lim, Ho-Yeong, additional, Kwiatkowski, Mariusz, additional, Chang, Ting-Tsung, additional, Kim, Jee Hyun, additional, Casadei-Gardini, Andrea, additional, Kudo, Masatoshi, additional, Ren, Zhenggang, additional, Varela Calvo, Maria, additional, Llovet, Josep M, additional, Zhang, Yayan, additional, Hatogai, Ken, additional, Siegel, Abby B., additional, and Cheng, Ann-Lii, additional

Published
2024
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31. Lenvatinib plus pembrolizumab versus lenvatinib alone as first-line therapy for advanced hepatocellular carcinoma: Longer-term efficacy and safety results from the phase 3 LEAP-002 study.

Author

Finn, Richard S., primary, Kudo, Masatoshi, additional, Merle, Philippe, additional, Meyer, Tim, additional, Qin, Shukui, additional, Ikeda, Masafumi, additional, Xu, Ruocai, additional, Edeline, Julien, additional, Ryoo, Baek-Yeol, additional, Ren, Zhenggang, additional, Cheng, Ann-Lii, additional, Galle, Peter R., additional, Kaneko, Shuichi, additional, Kumada, Hiromitsu, additional, Wang, Anran, additional, Mody, Kalgi, additional, Dubrovsky, Leonid, additional, Siegel, Abby B., additional, and Llovet, Josep M, additional

Published
2024
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34. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial

Author

Llovet, Josep M, primary, Kudo, Masatoshi, additional, Merle, Philippe, additional, Meyer, Tim, additional, Qin, Shukui, additional, Ikeda, Masafumi, additional, Xu, Ruocai, additional, Edeline, Julien, additional, Ryoo, Baek-Yeol, additional, Ren, Zhenggang, additional, Masi, Gianluca, additional, Kwiatkowski, Mariusz, additional, Lim, Ho Yeong, additional, Kim, Jee Hyun, additional, Breder, Valeriy, additional, Kumada, Hiromitsu, additional, Cheng, Ann-Lii, additional, Galle, Peter R, additional, Kaneko, Shuichi, additional, Wang, Anran, additional, Mody, Kalgi, additional, Dutcus, Corina, additional, Dubrovsky, Leonid, additional, Siegel, Abby B, additional, Finn, Richard S, additional, Strasser, Simone, additional, Thompson, Alexander, additional, Roohullah, Aflah, additional, Sievert, William, additional, Andelkovic, Vladimir, additional, Knox, Jennifer, additional, Davies, Janine, additional, Asselah, Jamil, additional, Brahmania, Mayur, additional, Majeed, Habeeb, additional, Villanueva, Luis, additional, Yanez Weber, Patricio, additional, Garrido, Marcelo, additional, Pizarro, Gonzalo Ignacio, additional, Yanez, Nicolas, additional, Ou, Shuangyan, additional, Pan, Hongming, additional, Meng, Zhiqiang, additional, Gu, Kangsheng, additional, Chen, Xi, additional, Zhang, Tao, additional, Hao, Chunyi, additional, Cao, Peiguo, additional, Guo, Yabing, additional, Xiao, Juxiang, additional, Fang, Weijia, additional, Wang, Xin, additional, Bai, Yuxian, additional, Chen, Xiaoming, additional, Yan, Dong, additional, Zhao, Hong, additional, Ying, Jieer, additional, Bonilla, Carlos, additional, Urrego, Olga, additional, Zambrano, Angela, additional, Lema, Mauricio, additional, Restrepo Gutierrez, Juan Carlos, additional, Cardona, Andres, additional, Franco Millan, Sandra, additional, Oscar, Madiedo, additional, Ramos, Victor, additional, LeSourd, Samuel, additional, Bronowicki, Jean-Pierre, additional, Bourliere, Marc, additional, Cattan, Stephane, additional, Bouattour, Mohamed, additional, Mineur, Laurent, additional, Regnault, Helene, additional, Dauvois, Barbara, additional, Schulze, Kornelius, additional, Folprecht, Gunnar, additional, Geier, Andreas, additional, Waidmann, Oliver, additional, Finkelmeier, Fabian, additional, Venerito, Marino, additional, Berres, Marie-Luise, additional, Berg, Thomas, additional, Lange, Christian, additional, Schmidt, Hartmut, additional, Waldschmidt, Dirk T, additional, Bitzer, Michael, additional, McDermott, Ray, additional, Duffy, Austin, additional, Zagonel, Vittorina, additional, Tonini, Giuseppe, additional, Piscaglia, Fabio, additional, Gori, Stefania, additional, Rizzo, Mimma, additional, Biscaldi, Elisa, additional, Foltran, Luisa, additional, Cabibbo, Giuseppe, additional, Aikata, Hiroshi, additional, Numata, Kazushi, additional, Marusawa, Hiroyuki, additional, Kato, Naoya, additional, Kurosaki, Masayuki, additional, Morimoto, Manabu, additional, Yamashita, Tatsuya, additional, Koga, Hironori, additional, Masaki, Tsutomu, additional, Tateishi, Ryosuke, additional, Inaba, Yoshitaka, additional, Arakawa, Tomohiro, additional, Suzuki, Yoshiyuki, additional, Akua, Norio, additional, Kobayashi, Masahiro, additional, Hosaka, Tetsuya, additional, Nakamuta, Makoto, additional, Oza, Noriko, additional, Kondo, Shunsuke, additional, Furuse, Junji, additional, Nagashima, Fumio, additional, Kitano, Masayuki, additional, Takaguchi, Koichi, additional, Kim, Tae-You, additional, Kim, Han Sang, additional, Hernandez Hernandez, Carlos, additional, Motola Kuba, Daniel, additional, Segura Gonzalez, Manuel, additional, Cabrera Luviano, Jesus, additional, Huitzil Melendez, Fidel, additional, Ramirez Godinez, Francisco, additional, Silva-Bravo, Fernando, additional, Gane, Edward, additional, Stedman, Catherine, additional, Wyrwicz, Lucjan, additional, Nowakowska-Zajdel, Ewa, additional, Kraj, Leszek, additional, Janczewska, Ewa, additional, Surma-Wlodarczyk, Renata, additional, Sekacheva, Marina, additional, Orlova, Rashida, additional, Vasilyev, Alexander, additional, Zukov, Ruslan, additional, Vladimirov, Vladimir, additional, Minguez, Beatriz, additional, Matilla Pena, Ana, additional, Fernandez Castroagudin, Javier, additional, Romero Gomez, Manuel, additional, Luis Lledo, Jose, additional, Rubin, Angel, additional, Garcia Sanchez, Araceli, additional, Calleja Panero, Jose, additional, Yu, Ming-Chin, additional, Shen, Ying-Chun, additional, Huang, Yi-Hsiang, additional, Jeng, Long-Bin, additional, Chang, Ting-Tsung, additional, Yang, Sheng-Shun, additional, Chen, Shinn-Cherng, additional, Dechaphunkul, Arunee, additional, Tanwandee, Tawesak, additional, Leerapun, Apinya, additional, Seker, Mesut, additional, Harputluoglu, Hakan, additional, Cicin, Irfan, additional, Oksuzoglu, Berna, additional, Bilici, Mehmet, additional, Sezgin Goksu, Sema, additional, Artac, Mehmet, additional, Cil, Timucin, additional, Yalcin, Suayib, additional, Sarker, Debashis, additional, Rao, Ankit, additional, Palmer, Daniel, additional, Evans, Jeff, additional, Hubner, Richard, additional, Finn, Richard, additional, Ulahannan, Susanna, additional, Zakari, Ahmed, additional, Feun, Lynn, additional, Al-Rajabi, Raed, additional, Sung, Max, additional, He, Aiwu, additional, Kardosh, Adel, additional, Goyal, Lipika, additional, Li, Daneng, additional, Choi, Minsig, additional, Posada, Juan, additional, Dodlapati, Jyothi, additional, Shroff, Rachna, additional, Agrawal, Saurabh, additional, Gopaluni, Srivalli, additional, Akce, Mehmet, additional, Alese, Olatunji, additional, Baron, Ari, additional, Dunne, Richard, additional, Loaiza-Bonilla, Arturo, additional, and Frenette, Catherine, additional

Published
2023
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35. A Phase 1b Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma: Extended Analysis of Study 116

Author

Kudo, Masatoshi, primary, Finn, Richard S., additional, Ikeda, Masafumi, additional, Sung, Max W., additional, Baron, Ari D., additional, Okusaka, Takuji, additional, Kobayashi, Masahiro, additional, Kumada, Hiromitsu, additional, Kaneko, Shuichi, additional, Pracht, Marc, additional, Meyer, Tim, additional, Nagao, Satoshi, additional, Saito, Kenichi, additional, Mody, Kalgi, additional, Ramji, Zahra, additional, Dubrovsky, Leonid, additional, and Llovet, Josep M., additional

Published
2023
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36. Hepatocellular carcinoma

Author

Llovet, Josep M., Kelley, Robin Kate, Villanueva, Augusto, Singal, Amit G., Pikarsky, Eli, Roayaie, Sasan, Lencioni, Riccardo, Koike, Kazuhiko, Zucman-Rossi, Jessica, and Finn, Richard S.

Published
2021
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40. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Zhu, Andrew X, Kang, Yoon-Koo, Yen, Chia-Jui, Finn, Richard S, Galle, Peter R, Llovet, Josep M, Assenat, Eric, Brandi, Giovanni, Pracht, Marc, Lim, Ho Yeong, Rau, Kun-Ming, Motomura, Kenta, Ohno, Izumi, Merle, Philippe, Daniele, Bruno, Shin, Dong Bok, Gerken, Guido, Borg, Christophe, Hiriart, Jean-Baptiste, Okusaka, Takuji, Morimoto, Manabu, Hsu, Yanzhi, Abada, Paolo B, and Kudo, Masatoshi

Published
2019
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41. Molecular portraits of patients with intrahepatic cholangiocarcinoma who diverge as rapid progressors or long survivors on chemotherapy

Author

O'Rourke, Colm J, primary, Salati, Massimiliano, additional, Rae, Colin, additional, Carpino, Guido, additional, Leslie, Holly, additional, Pea, Antonio, additional, Prete, Maria G, additional, Bonetti, Luca R, additional, Amato, Francesco, additional, Montal, Robert, additional, Upstill-Goddard, Rosie, additional, Nixon, Colin, additional, Sanchon-Sanchez, Paula, additional, Kunderfranco, Paolo, additional, Sia, Daniela, additional, Gaudio, Eugenio, additional, Overi, Diletta, additional, Cascinu, Stefano, additional, Hogdall, Dan, additional, Pugh, Sian, additional, Domingo, Enric, additional, Primrose, John N, additional, Bridgewater, John, additional, Spallanzani, Andrea, additional, Gelsomino, Fabio, additional, Llovet, Josep M, additional, Calvisi, Diego F, additional, Boulter, Luke, additional, Caputo, Francesco, additional, Lleo, Ana, additional, Jamieson, Nigel B, additional, Luppi, Gabriele, additional, Dominici, Massimo, additional, Andersen, Jesper B, additional, and Braconi, Chiara, additional

Published
2023
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43. Author Correction: Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer

Author

Malehmir, Mohsen, Pfister, Dominik, Gallage, Suchira, Szydlowska, Marta, Inverso, Donato, Kotsiliti, Elena, Leone, Valentina, Peiseler, Moritz, Surewaard, Bas G. J., Rath, Dominik, Ali, Adnan, Wolf, Monika Julia, Drescher, Hannah, Healy, Marc E., Dauch, Daniel, Kroy, Daniela, Krenkel, Oliver, Kohlhepp, Marlene, Engleitner, Thomas, Olkus, Alexander, Sijmonsma, Tjeerd, Volz, Julia, Deppermann, Carsten, Stegner, David, Helbling, Patrick, Nombela-Arrieta, César, Rafiei, Anahita, Hinterleitner, Martina, Rall, Marcel, Baku, Florian, Borst, Oliver, Wilson, Caroline L., Leslie, Jack, O’Connor, Tracy, Weston, Christopher J., Chauhan, Abhishek, Adams, David H., Sheriff, Lozan, Teijeiro, Ana, Prinz, Marco, Bogeska, Ruzhica, Anstee, Natasha, Bongers, Malte N., Notohamiprodjo, Mike, Geisler, Tobias, Withers, Dominic J., Ware, Jerry, Mann, Derek A., Augustin, Hellmut G., Vegiopoulos, Alexandros, Milsom, Michael D., Rose, Adam J., Lalor, Patricia F., Llovet, Josep M., Pinyol, Roser, Tacke, Frank, Rad, Roland, Matter, Matthias, Djouder, Nabil, Kubes, Paul, Knolle, Percy A., Unger, Kristian, Zender, Lars, Nieswandt, Bernhard, Gawaz, Meinrad, Weber, Achim, and Heikenwalder, Mathias

Published
2022
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45. Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer

Author

Malehmir, Mohsen, Pfister, Dominik, Gallage, Suchira, Szydlowska, Marta, Inverso, Donato, Kotsiliti, Elena, Leone, Valentina, Peiseler, Moritz, Surewaard, Bas G. J., Rath, Dominik, Ali, Adnan, Wolf, Monika Julia, Drescher, Hannah, Healy, Marc E., Dauch, Daniel, Kroy, Daniela, Krenkel, Oliver, Kohlhepp, Marlene, Engleitner, Thomas, Olkus, Alexander, Sijmonsma, Tjeerd, Volz, Julia, Deppermann, Carsten, Stegner, David, Helbling, Patrick, Nombela-Arrieta, César, Rafiei, Anahita, Hinterleitner, Martina, Rall, Marcel, Baku, Florian, Borst, Oliver, Wilson, Caroline L., Leslie, Jack, O’Connor, Tracy, Weston, Christopher J., Chauhan, Abhishek, Adams, David H., Sheriff, Lozan, Teijeiro, Ana, Prinz, Marco, Bogeska, Ruzhica, Anstee, Natasha, Bongers, Malte N., Notohamiprodjo, Mike, Geisler, Tobias, Withers, Dominic J., Ware, Jerry, Mann, Derek A., Augustin, Hellmut G., Vegiopoulos, Alexandros, Milsom, Michael D., Rose, Adam J., Lalor, Patricia F., Llovet, Josep M., Pinyol, Roser, Tacke, Frank, Rad, Roland, Matter, Matthias, Djouder, Nabil, Kubes, Paul, Knolle, Percy A., Unger, Kristian, Zender, Lars, Nieswandt, Bernhard, Gawaz, Meinrad, Weber, Achim, and Heikenwalder, Mathias

Published
2019
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46. AASLD practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma

Author

Singal, Amit G., primary, Llovet, Josep M., additional, Yarchoan, Mark, additional, Mehta, Neil, additional, Heimbach, Julie K., additional, Dawson, Laura A., additional, Jou, Janice H., additional, Kulik, Laura M., additional, Agopian, Vatche G., additional, Marrero, Jorge A., additional, Mendiratta-Lala, Mishal, additional, Brown, Daniel B., additional, Rilling, William S., additional, Goyal, Lipika, additional, Wei, Alice C., additional, and Taddei, Tamar H., additional

Published
2023
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47. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Bruix, Jordi, Qin, Shukui, Merle, Philippe, Granito, Alessandro, Huang, Yi-Hsiang, Bodoky, György, Pracht, Marc, Yokosuka, Osamu, Rosmorduc, Olivier, Breder, Valeriy, Gerolami, René, Masi, Gianluca, Ross, Paul J, Song, Tianqiang, Bronowicki, Jean-Pierre, Ollivier-Hourmand, Isabelle, Kudo, Masatoshi, Cheng, Ann-Lii, Llovet, Josep M, Finn, Richard S, LeBerre, Marie-Aude, Baumhauer, Annette, Meinhardt, Gerold, and Han, Guohong

Published
2017
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48. Intratumoral heterogeneity and clonal evolution in liver cancer

Author

Losic, Bojan, Craig, Amanda J., Villacorta-Martin, Carlos, Martins-Filho, Sebastiao N., Akers, Nicholas, Chen, Xintong, Ahsen, Mehmet E., von Felden, Johann, Labgaa, Ismail, DʹAvola, Delia, Allette, Kimaada, Lira, Sergio A., Furtado, Glaucia C., Garcia-Lezana, Teresa, Restrepo, Paula, Stueck, Ashley, Ward, Stephen C., Fiel, Maria I., Hiotis, Spiros P., Gunasekaran, Ganesh, Sia, Daniela, Schadt, Eric E., Sebra, Robert, Schwartz, Myron, Llovet, Josep M., Thung, Swan, Stolovitzky, Gustavo, and Villanueva, Augusto

Published
2020
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50. A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma

Author

Labgaa, Ismail, Villacorta-Martin, Carlos, D’Avola, Delia, Craig, Amanda J., von Felden, Johann, Martins-Filho, Sebastiao N., Sia, Daniela, Stueck, Ashley, Ward, Stephen C., Fiel, M. Isabel, Mahajan, Milind, Tabrizian, Parissa, Thung, Swan N., Ang, Celina, Friedman, Scott L., Llovet, Josep M., Schwartz, Myron, and Villanueva, Augusto

Published
2018
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