120 results on '"Dijkstra, Krijn"'
Search Results
2. Quantifying the impact of immunotherapy on RNA dynamics in cancer
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Usaite, Ieva, primary, Biswas, Dhruva, additional, Dijkstra, Krijn, additional, Watkins, Thomas BK, additional, Pich, Oriol, additional, Puttick, Clare, additional, Angelova, Mihaela, additional, Thakkar, Krupa, additional, Hiley, Crispin, additional, Birkbak, Nicolai, additional, Kok, Marleen, additional, Zaccaria, Simone, additional, Wu, Yin, additional, Litchfield, Kevin, additional, Swanton, Charles, additional, and Kanu, Nnennaya, additional
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- 2023
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3. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers
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Chalabi, Myriam, Fanchi, Lorenzo F., Dijkstra, Krijn K., Van den Berg, José G., Aalbers, Arend G., Sikorska, Karolina, and Lopez-Yurda, Marta
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Colon cancer -- Drug therapy -- Patient outcomes ,Ipilimumab -- Patient outcomes ,Immunotherapy -- Patient outcomes ,Biological sciences ,Health - Abstract
PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: (https://clinicaltrials.gov/ct2/show/NCT03026140)), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86-100%) dMMR tumors, with 19 major pathological responses (MPRs, [less than or equal to]10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8-55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8.sup.+PD-1.sup.+ T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data. Results from the NICHE study show remarkable pathological responses to neoadjuvant combination immunotherapy in patients with early-stage colon cancer and uncover potential biomarkers of response., Author(s): Myriam Chalabi [sup.1] [sup.2] [sup.3] , Lorenzo F. Fanchi [sup.2] [sup.4] , Krijn K. Dijkstra [sup.2] [sup.4] , José G. Van den Berg [sup.5] , Arend G. Aalbers [sup.6] [...]
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- 2020
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4. Tumor organoid–T-cell coculture systems
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Cattaneo, Chiara M., Dijkstra, Krijn K., Fanchi, Lorenzo F., Kelderman, Sander, Kaing, Sovann, van Rooij, Nienke, van den Brink, Stieneke, Schumacher, Ton N., and Voest, Emile E.
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- 2020
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5. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers
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Scheper, Wouter, Kelderman, Sander, Fanchi, Lorenzo F., Linnemann, Carsten, Bendle, Gavin, de Rooij, Marije A. J., Hirt, Christian, Mezzadra, Riccardo, Slagter, Maarten, Dijkstra, Krijn, Kluin, Roelof J. C., Snaebjornsson, Petur, Milne, Katy, Nelson, Brad H., Zijlmans, Henry, Kenter, Gemma, Voest, Emile E., Haanen, John B. A. G., and Schumacher, Ton N.
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- 2019
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6. Data from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
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Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary
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- 2023
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7. Supplementary Figure 4 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
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Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary
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- 2023
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8. Supplementary Figure 5 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
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Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary
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- 2023
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9. Supplementary Figure 1 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
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Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary
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- 2023
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10. Supplementary Table 1 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
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Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary
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- 2023
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11. Supplementary Figure 3 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
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Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary
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- 2023
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12. Supplementary Figure 2 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
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Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary
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- 2023
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13. Cell Model Network-UK from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
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Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary
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- 2023
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14. Tumor Organoids as a Pre-clinical Cancer Model for Drug Discovery
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Weeber, Fleur, Ooft, Salo N., Dijkstra, Krijn K., and Voest, Emile E.
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- 2017
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15. Body composition and lung cancer-associated cachexia in TRACERx
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Al-Sawaf, Othman, Weiss, Jakob, Skrzypski, Marcin, Lam, Jie Min, Karasaki, Takahiro, Zambrana, Francisco, Kidd, Andrew C, Frankell, Alexander M, Watkins, Thomas BK, Martinez-Ruiz, Carlos, Puttick, Clare, Black, James RM, Huebner, Ariana, Al Bakir, Maise, Sokac, Mateo, Collins, Susie, Veeriah, Selvaraju, Magno, Neil, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Ward, Sophia, Jayanth, Nick, Salgado, Roberto, Bridge, Christopher P, Christiani, David C, Mak, Raymond H, Bay, Camden, Rosenthal, Michael, Sattar, Naveed, Welsh, Paul, Liu, Ying, Perrimon, Norbert, Popuri, Karteek, Beg, Mirza Faisal, McGranahan, Nicholas, Hackshaw, Allan, Breen, Danna M, O'Rahilly, Stephen, Birkbak, Nicolai J, Aerts, Hugo JWL, Jamal-Hanjani, Mariam, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Van Loo, Peter, Szallasi, Zoltan, Kisistok, Judit, Diossy, Miklos, Demeulemeester, Jonas, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Abbosh, Christopher, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Hiley, Crispin T, Moore, David A, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Cadieux, Elizabeth Larose, Lim, Emilia L, Colliver, Emma, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Hartley, John A, Peggs, Karl S, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Grigoriadis, Kristiana, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Hill, Mark S, Dietzen, Michelle, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Pich, Oriol, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Zaccaria, Simone, Hessey, Sonya, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew
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Male ,Proteomics ,Cachexia ,Lung Neoplasms ,Antigens, Neoplasm ,Carcinoma, Non-Small-Cell Lung ,Body Weight ,Body Composition ,Humans ,Neoplasm Recurrence, Local ,Muscle, Skeletal ,Neoplasm Proteins - Abstract
Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online
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- 2023
16. The evolution of non-small cell lung cancer metastases in TRACERx
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Al Bakir, Maise, Huebner, Ariana, Martinez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas BK, Pich, Oriol, Moore, David A, Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander, Bunkum, Abigail, Lim, Emilia L, Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T, Hill, Mark S, Cook, Daniel E, Wilson, Gareth A, Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R, Blackhall, Fiona H, Cave, Judith, Blyth, Kevin G, Nair, Arjun, Ahmed, Asia, Taylor, Magali N, Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Papadatos-Pastos, Dionysis, Forster, Martin D, Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio, Peggs, Karl S, Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Benafif, Sarah, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Krebs, Matthew G, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Puttick, Clare, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Black, James RM, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew
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Clonal Evolution ,Cohort Studies ,Evolution, Molecular ,Lung Neoplasms ,Carcinoma, Non-Small-Cell Lung ,Disease Progression ,Humans ,Neoplasm Metastasis ,Neoplasm Recurrence, Local ,Clone Cells - Abstract
Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online
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- 2023
17. The evolution of lung cancer and impact of subclonal selection in TRACERx
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Frankell, Alexander M, Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L, Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S, Grigoriadis, Kristiana, Moore, David A, Black, James RM, Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas BK, Naceur-Lombardelli, Cristina, Cook, Daniel E, Salgado, Roberto, Wilson, Gareth A, Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martinez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G, Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Blyth, Kevin G, Fennell, Dean A, Forster, Martin D, Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J, Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G, Lester, Jason F, Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M, Lawrence, David, Navani, Neal, Janes, Sam M, Dive, Caroline, Blackhall, Fiona H, Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A, Peggs, Karl S, Schwarz, Roland F, Van Loo, Peter, Miedema, Daniel M, Birkbak, Nicolai J, Hiley, Crispin T, Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joa, Primrose, Lindsay, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Kaufmann, Tom L, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran L, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Rane, Jayant K, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Danson, Sarah, Robinson, Lily, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew
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Lung Neoplasms ,Treatment Outcome ,DNA Copy Number Variations ,Mutagenesis ,Carcinoma, Non-Small-Cell Lung ,Mutation ,Smoking ,Humans ,Adenocarcinoma of Lung ,Neoplasm Recurrence, Local ,Phylogeny - Abstract
Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online
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- 2023
18. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx
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Karasaki, Takahiro, Moore, David A, Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Al Bakir, Maise, Watkins, Thomas BK, Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S, Frankell, Alexander M, Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L, Martinez-Ruiz, Carlos, Black, James RM, Biswas, Dhruva, Campbell, Brittany B, Lee, Claudia, Colliver, Emma, Enfield, Katey SS, Hessey, Sonya, Hiley, Crispin T, Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J, Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad R, Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R, Rekhtman, Natasha, Travis, William D, Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G, McGranahan, Nicholas, Swanton, Charles, Jamal-Hanjani, Mariam, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Castignani, Carla, Bailey, Chris, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Peggs, Karl S, Selvaraju, Kayalvizhi, Thol, Kerstin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Prymas, Paulina, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew
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TRACERx Consortium - Abstract
Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and 'tumor spread through air spaces' were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online
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- 2023
19. The Effects of Clonal Heterogeneity on Cancer Immunosurveillance
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Dijkstra, Krijn K., primary, Wu, Yin, additional, and Swanton, Charles, additional
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- 2023
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20. Open questions in human lung organoid research
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Hughes, Tessa, primary, Dijkstra, Krijn K., additional, Rawlins, Emma L., additional, and Hynds, Robert E., additional
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- 2023
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21. Open questions in human lung organoid research
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Hughes, Tessa, Dijkstra, Krijn K, Rawlins, Emma L, Hynds, Robert E, Apollo - University of Cambridge Repository, and Hynds, Robert E [0000-0002-2170-8791]
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Chemical Biology & High Throughput ,Pharmacology ,3D cell culture ,Human Biology & Physiology ,Genome Integrity & Repair ,Tumour Biology ,epithelial cells ,respiratory biology ,Signalling & Oncogenes ,Ecology,Evolution & Ethology ,Pharmacology (medical) ,lung stem cells ,Genetics & Genomics ,Computational & Systems Biology ,in vitro models - Abstract
Peer reviewed: True, Organoids have become a prominent model system in pulmonary research. The ability to establish organoid cultures directly from patient tissue has expanded the repertoire of physiologically relevant preclinical model systems. In addition to their derivation from adult lung stem/progenitor cells, lung organoids can be derived from fetal tissue or induced pluripotent stem cells to fill a critical gap in modelling pulmonary development in vitro. Recent years have seen important progress in the characterisation and refinement of organoid culture systems. Here, we address several open questions in the field, including how closely organoids recapitulate the tissue of origin, how well organoids recapitulate patient cohorts, and how well organoids capture diversity within a patient. We advocate deeper characterisation of models using single cell technologies, generation of more diverse organoid biobanks and further standardisation of culture media.
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- 2023
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22. Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases
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Weeber, Fleur, van de Wetering, Marc, Hoogstraat, Marlous, Dijkstra, Krijn K., Krijgsman, Oscar, Kuilman, Thomas, Gadellaa-van Hooijdonk, Christa G. M., van der Velden, Daphne L., Peeper, Daniel S., Cuppen, Edwin P. J. G., Vries, Robert G., Clevers, Hans, and Voest, Emile E.
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- 2015
23. Evasion of G1 Checkpoints in Cancer
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Dijkstra, Krijn K., Blanchetot, Cristophe, Boonstra, Johannes, and Siddik, Zahid H., editor
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- 2009
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24. Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
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Picco, Gabriele, Cattaneo, Chiara Maria, van Vliet, Esmee J, Crisafulli, Giovanni, Rospo, Giuseppe, Consonni, Sarah, Vieira, Sara Filipa, Sanchez Rodriguez, Inigo, Cancelliere, Carlotta, Banerjee, Ruby, Schipper, Luuk Johan, Oddo, Daniele, Dijkstra, Krijn Kristian, Cinatl, Jindrich, Michaelis, Martin, Yang, Fengtang, Uk Group, Cell Model Network, Di Nicolantonio, Federica, Sartore-Bianchi, Andrea, Siena, Salvatore, Arena, Sabrina, Voest, Emile E, Bardelli, Alberto, and Garnett, Mathew J
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Oncology ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Werner Syndrome Helicase ,Colorectal cancer ,medicine.medical_treatment ,Synthetic lethality ,Disease ,DNA Mismatch Repair ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Drug Therapy ,Internal medicine ,Humans ,Medicine ,Molecular Targeted Therapy ,030304 developmental biology ,Werner syndrome ,0303 health sciences ,Chemotherapy ,business.industry ,nutritional and metabolic diseases ,Immunotherapy ,medicine.disease ,3. Good health ,DNA mismatch repair ,Colorectal Neoplasms ,business ,030217 neurology & neurosurgery - Abstract
Targeted therapies, chemotherapy, and immunotherapy are used to treat patients with mismatch repair–deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer. The clinical effectiveness of targeted therapy and chemotherapy is limited by resistance and drug toxicities, and about half of patients receiving immunotherapy have disease that is refractory to immune checkpoint inhibitors. Loss of Werner syndrome ATP-dependent helicase (WRN) is a synthetic lethality in dMMR/MSI-H cells. To inform the development of WRN as a therapeutic target, we performed WRN knockout or knockdown in 60 heterogeneous dMMR colorectal cancer preclinical models, demonstrating that WRN dependency is an almost universal feature and a robust marker for patient selection. Furthermore, models of resistance to clinically relevant targeted therapy, chemotherapy, and immunotherapy retain WRN dependency. These data show the potential of therapeutically targeting WRN in patients with dMMR/MSI-H colorectal cancer and support WRN as a therapeutic option for patients with dMMR/MSI-H cancers refractory to current treatment strategies. Significance: We found that a large, diverse set of dMMR/MSI-H colorectal cancer preclinical models, including models of treatment-refractory disease, are WRN-dependent. Our results support WRN as a promising synthetic-lethal target in dMMR/MSI-H colorectal cancer tumors as a monotherapy or in combination with targeted agents, chemotherapy, or immunotherapy. This article is highlighted in the In This Issue feature, p. 1861
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- 2021
25. Abstract 1394: Pervasive allele specific transcriptional repression of the class I and II HLA genes in TRACERx non-small cell lung cancer
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Puttick, Clare, primary, Pich, Oriol, additional, Leung, Michelle, additional, Martinez-Ruiz, Carlos, additional, Bentham, Robert, additional, Rosenthal, Rachel, additional, Hessey, Sonya, additional, Black, James R., additional, Lim, Emilia L., additional, Enfield, Katey, additional, Colliver, Emma, additional, Dijkstra, Krijn, additional, Hiley, Crispin T., additional, Karasaki, Takahiro, additional, Huebner, Ariana, additional, Bakir, Maise Al, additional, Watkins, Thomas B., additional, Frankell, Alexander M., additional, Zaccaria, Simone, additional, Jamal-Hanjani, Mariam, additional, McGranahan, Nicholas, additional, and Swanton, Charles, additional
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- 2022
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26. Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay
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Orlando, Francesco, Romanel, Alessandro, Trujillo, Blanca, Sigouros, Michael, Wetterskog, Daniel, Quaini, Orsetta, Leone, Gianmarco, Xiang, Jenny Z, Wingate, Anna, Tagawa, Scott, Jayaram, Anuradha, Linch, Mark, Swanton, Charles, Jamal-Hanjani, Mariam, Abbosh, Chris, Zaccaria, Simone, Hessey, Sonya, Shiu, Kai-Keen, Bridgewater, John, Hochhauser, Daniel, Forster, Martin, Lee, Siow-Ming, Ahmad, Tanya, Papadatos-Pastos, Dionysis, Janes, Sam, Van Loo, Peter, Enfield, Katey, McGranahan, Nicholas, Huebner, Ariana, Quezada, Sergio, Beck, Stephan, Parker, Peter, Enver, Tariq, Hynds, Robert E, Dijkstra, Krijn, Pearce, David R, Falzon, Mary, Proctor, Ian, Sinclair, Ron, Lok, Chi-wah, Rhodes, Zoe, Moore, David, Marafioti, Teresa, Mitchison, Miriam, Ellery, Peter, Sivakumar, Monica, Brandner, Sebastian, Rowan, Andrew, Hiley, Crispin, Veeriah, Selvaraju, Shaw, Heather, Attard, Gert, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Prymas, Paulina, Watkins, Tom, Bailey, Chris, Ruiz, Carlos Martinez, Litchfield, Kevin, Al-Bakir, Maise, Kanu, Nnenna, Ward, Sophie, Lim, Emilia, Reading, James, Chain, Benny, Alba, Blanca Trujillo, Akay, Melek, Flanagan, Adrienne, Biswas, Dhruva, Pich, Oriol, Dietzen, Michelle, Puttick, Clare, Colliver, Emma, Magness, Alistair, Angelova, Mihaela, Black, James, Lucas, Olivia, Hill, William, Liu, Wing-Kin, Frankell, Alexander, Magno, Neil, Athanasopoulou, Foteini, Wilson, Gareth, Rosenthal, Rachel, Salgado, Roberto, Lee, Claudia, Grigoriadis, Kristiana, Al-Sawaf, Othman, Karasaki, Takahiro, Bunkum, Abigail, Noorani, Imran, Benafif, Sarah, Barbe, Vittorio, Bola, Supreet, Vainauskas, Osvaldas, Hasan, Mahedi, Lise, Stefano, Leone, GianMarco, Alifrangis, Constantine, McGovern, Ursula, Thol, Kerstin, Gamble, Samuel, Ung, Seng Kuong, Sahwangarrom, Teerapon, Marin, Claudia Peinador, Wong, Sophia, Pawlik, Piotr, Gishen, Faye, Tookman, Adrian, Stone, Paddy, Stirling, Caroline, Turajlic, Samra, Larkin, James, Pickering, Lisa, Furness, Andrew, Young, Kate, Drake, Will, Edmonds, Kim, Hunter, Nikki, Mangwende, Mary, Pearce, Karla, Grostate, Lauren, Au, Lewis, Spain, Lavinia, Shepherd, Scott, Yan, Haixi, Shum, Ben, Tippu, Zayd, Hanley, Brian, Spencer, Charlotte, Emmerich, Max, Gerard, Camille, Schmitt, Andreas Michael, Del Rosario, Lyra, Carlyle, Eleanor, Lewis, Charlotte, Holt, Lucy, Lucanas, Analyn, O'Flaherty, Molly, Hazell, Steve, Mudhar, Hardeep, Messiou, Christina, Latifoltojar, Arash, Fendler, Annika, Byrne, Fiona, Pallinkonda, Husayn, Lobon, Irene, Coulton, Alex, Cattin, Anne Laure, Deng, Daqi, Feng, Geoffrey Hugang, Rowan, Andew, Yousaf, Nadia, Popat, Sanjay, Curtis, Olivia, Milner-Watts, Charlotte, Stamp, Gordon, Nye, Emma, Murra, Aida, Korteweg, Justine, Kelly, Denise, Terry, Lauren, Biano, Jennifer, Peat, Kema, Kelly, Kayleigh, Hill, Peter, Josephs, Debra, Irshad, Sheeba, Chandra, Ashish, Spicer, James, Mahadeva, Ula, Green, Anna, Stewart, Ruby, Iredale, Lara-Rose, Mackay, Tina, Deakin, Ben, Enting, Debra, Rudman, Sarah, Ghosh, Sharmistha, Karapagniotou, Lena, Pintus, Elias, Tutt, Andrew, Howlett, Sarah, Michalarea, Vasiliki, Brenton, James, Caldas, Carlos, Fitzgerald, Rebecca, Jimenez-Linan, Merche, Provenzano, Elena, Cluroe, Alison, Paterson, Anna, Aitken, Sarah, Allinson, Kieren, Stewart, Grant, McDermott, Ultan, Beddowes, Emma, Maughan, Tim, Ansorge, Olaf, Campbell, Peter, Roxburgh, Patricia, Fraser, Sioban, Kidd, Andrew, Blyth, Kevin, Le Quesne, John, Krebs, Matthew, Blackhall, Fiona, Summers, Yvonne, Oliveira, Pedro, Ortega-Franco, Ana, Dive, Caroline, Gomes, Fabio, Carter, Mat, Dransfield, Jo, Thomas, Anne, Fennell, Dean, Shaw, Jacqui, Naidu, Babu, Baijal, Shobhit, Tanchel, Bruce, Langman, Gerald, Robinson, Andrew, Collard, Martin, Cockcroft, Peter, Ferris, Charlotte, Bancroft, Hollie, Kerr, Amy, Middleton, Gary, Webb, Joanne, Kadiri, Salma, Colloby, Peter, Olisemeke, Bernard, Wilson, Rodelaine, Tomlinson, Ian, McNeish, Iain, Jogai, Sanjay, Holden, Samantha, Fernandes, Tania, Hampton, Blanche, McKenzie, Mairead, Hackshaw, Allan, Sharp, Abby, Chan, Kitty, Farrelly, Laura, Bridger, Hayley, Leslie, Rachel, Consortium, PEACE, Rubin, Mark A, Wyatt, Alexander W, Beltran, Himisha, Attard, Gerhardt, and Demichelis, Francesca
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Chemical Biology & High Throughput ,Signalling & Oncogenes ,Human Biology & Physiology ,Ecology,Evolution & Ethology ,Genome Integrity & Repair ,Tumour Biology ,Genetics & Genomics ,Computational & Systems Biology - Abstract
Sequencing of cell-free DNA (cfDNA) in cancer patients’ plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with
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- 2022
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27. Patient-Derived Organoid Models of Human Neuroendocrine Carcinoma
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Dijkstra, Krijn K., primary, van den Berg, José G., additional, Weeber, Fleur, additional, van de Haar, Joris, additional, Velds, Arno, additional, Kaing, Sovann, additional, Peters, Dennis D. G. C., additional, Eskens, Ferry A. L. M., additional, de Groot, Derk-Jan A., additional, Tesselaar, Margot E. T., additional, and Voest, Emile E., additional
- Published
- 2021
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28. Misuse of SARS-CoV-2 testing in symptomatic health-care staff in the UK – Authors' reply
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Black, James R M, primary, Bailey, Chris, additional, Przewrocka, Joanna, additional, Dijkstra, Krijn K, additional, Gandhi, Sonia, additional, Gamblin, Steve, additional, Barrell, Sam, additional, and Swanton, Charles, additional
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- 2020
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29. Patterns and predictors of atypical language representation in epilepsy
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Dijkstra, Krijn Kristian and Ferrier, Cyrille Henri
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- 2013
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30. The biogenesis and characterization of mammalian microRNAs of mirtron origin
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Sibley, Christopher R., Seow, Yiqi, Saayman, Sheena, Dijkstra, Krijn K., El Andaloussi, Samir, Weinberg, Marc S., and Wood, Matthew J. A.
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- 2012
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31. Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine
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Dijkstra, Krijn K., primary, Monkhorst, Kim, additional, Schipper, Luuk J., additional, Hartemink, Koen J., additional, Smit, Egbert F., additional, Kaing, Sovann, additional, de Groot, Rosa, additional, Wolkers, Monika C., additional, Clevers, Hans, additional, Cuppen, Edwin, additional, and Voest, Emile E., additional
- Published
- 2020
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32. COVID-19: the case for health-care worker screening to prevent hospital transmission
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Black, James R M, primary, Bailey, Chris, additional, Przewrocka, Joanna, additional, Dijkstra, Krijn K, additional, and Swanton, Charles, additional
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- 2020
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33. TH17 differentiation capacity develops within the first 3 months of life
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Dijkstra, Krijn K., Hoeks, Sanne B.E.A., Prakken, Berent J., and de Roock, Sytze
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- 2014
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34. Tumor organoid–T-cell coculture systems
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Cattaneo, Chiara M., primary, Dijkstra, Krijn K., additional, Fanchi, Lorenzo F., additional, Kelderman, Sander, additional, Kaing, Sovann, additional, van Rooij, Nienke, additional, van den Brink, Stieneke, additional, Schumacher, Ton N., additional, and Voest, Emile E., additional
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- 2019
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35. Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients
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Ooft, Salo N., primary, Weeber, Fleur, additional, Dijkstra, Krijn K., additional, McLean, Chelsea M., additional, Kaing, Sovann, additional, van Werkhoven, Erik, additional, Schipper, Luuk, additional, Hoes, Louisa, additional, Vis, Daniel J., additional, van de Haar, Joris, additional, Prevoo, Warner, additional, Snaebjornsson, Petur, additional, van der Velden, Daphne, additional, Klein, Michelle, additional, Chalabi, Myriam, additional, Boot, Henk, additional, van Leerdam, Monique, additional, Bloemendal, Haiko J., additional, Beerepoot, Laurens V., additional, Wessels, Lodewyk, additional, Cuppen, Edwin, additional, Clevers, Hans, additional, and Voest, Emile E., additional
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- 2019
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36. Long‐term expanding human airway organoids for disease modeling
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Sachs, Norman, primary, Papaspyropoulos, Angelos, additional, Zomer‐van Ommen, Domenique D, additional, Heo, Inha, additional, Böttinger, Lena, additional, Klay, Dymph, additional, Weeber, Fleur, additional, Huelsz‐Prince, Guizela, additional, Iakobachvili, Nino, additional, Amatngalim, Gimano D, additional, de Ligt, Joep, additional, van Hoeck, Arne, additional, Proost, Natalie, additional, Viveen, Marco C, additional, Lyubimova, Anna, additional, Teeven, Luc, additional, Derakhshan, Sepideh, additional, Korving, Jeroen, additional, Begthel, Harry, additional, Dekkers, Johanna F, additional, Kumawat, Kuldeep, additional, Ramos, Emilio, additional, van Oosterhout, Matthijs FM, additional, Offerhaus, G Johan, additional, Wiener, Dominique J, additional, Olimpio, Eduardo P, additional, Dijkstra, Krijn K, additional, Smit, Egbert F, additional, van der Linden, Maarten, additional, Jaksani, Sridevi, additional, van de Ven, Marieke, additional, Jonkers, Jos, additional, Rios, Anne C, additional, Voest, Emile E, additional, van Moorsel, Coline HM, additional, van der Ent, Cornelis K, additional, Cuppen, Edwin, additional, van Oudenaarden, Alexander, additional, Coenjaerts, Frank E, additional, Meyaard, Linde, additional, Bont, Louis J, additional, Peters, Peter J, additional, Tans, Sander J, additional, van Zon, Jeroen S, additional, Boj, Sylvia F, additional, Vries, Robert G, additional, Beekman, Jeffrey M, additional, and Clevers, Hans, additional
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- 2019
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37. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers
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Scheper, Wouter, primary, Kelderman, Sander, additional, Fanchi, Lorenzo F., additional, Linnemann, Carsten, additional, Bendle, Gavin, additional, de Rooij, Marije A. J., additional, Hirt, Christian, additional, Mezzadra, Riccardo, additional, Slagter, Maarten, additional, Dijkstra, Krijn, additional, Kluin, Roelof J. C., additional, Snaebjornsson, Petur, additional, Milne, Katy, additional, Nelson, Brad H., additional, Zijlmans, Henry, additional, Kenter, Gemma, additional, Voest, Emile E., additional, Haanen, John B. A. G., additional, and Schumacher, Ton N., additional
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- 2018
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38. Modelling the moisture vapour transmission rate through segmented block co-poly(ether–ester) based breathable films
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Stroeks, Alexander and Dijkstra, Krijn
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- 2001
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39. Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids
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Dijkstra, Krijn K., primary, Cattaneo, Chiara M., additional, Weeber, Fleur, additional, Chalabi, Myriam, additional, van de Haar, Joris, additional, Fanchi, Lorenzo F., additional, Slagter, Maarten, additional, van der Velden, Daphne L., additional, Kaing, Sovann, additional, Kelderman, Sander, additional, van Rooij, Nienke, additional, van Leerdam, Monique E., additional, Depla, Annekatrien, additional, Smit, Egbert F., additional, Hartemink, Koen J., additional, de Groot, Rosa, additional, Wolkers, Monika C., additional, Sachs, Norman, additional, Snaebjornsson, Petur, additional, Monkhorst, Kim, additional, Haanen, John, additional, Clevers, Hans, additional, Schumacher, Ton N., additional, and Voest, Emile E., additional
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- 2018
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40. Long-term expanding human airway organoids for disease modelling
- Author
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Sachs, Norman, primary, Zomer-van Ommen, Domenique D., additional, Papaspyropoulos, Angelos, additional, Heo, Inha, additional, Böttinger, Lena, additional, Klay, Dymph, additional, Weeber, Fleur, additional, Huelsz-Prince, Guizela, additional, Iakobachvili, Nino, additional, Viveen, Marco C., additional, Lyubimova, Anna, additional, Teeven, Luc, additional, Derakhshan, Sepideh, additional, Korving, Jeroen, additional, Begthel, Harry, additional, Kumawat, Kuldeep, additional, Ramos, Emilio, additional, van Oosterhout, Matthijs F.M., additional, Olimpio, Eduardo P., additional, de Ligt, Joep, additional, Dijkstra, Krijn K., additional, Smit, Egbert F., additional, van der Linden, Maarten, additional, Voest, Emile E., additional, van Moorsel, Coline H.M., additional, van der Ent, Cornelis K., additional, Cuppen, Edwin, additional, van Oudenaarden, Alexander, additional, Coenjaerts, Frank E., additional, Meyaard, Linde, additional, Bont, Louis J., additional, Peters, Peter J., additional, Tans, Sander J., additional, van Zon, Jeroen S., additional, Boj, Sylvia F., additional, Vries, Robert G., additional, Beekman, Jeffrey M., additional, and Clevers, Hans, additional
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- 2018
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41. Genomics- and Transcriptomics-Based Patient Selection for Cancer Treatment With Immune Checkpoint Inhibitors
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Dijkstra, Krijn K., primary, Voabil, Paula, additional, Schumacher, Ton N., additional, and Voest, Emile E., additional
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- 2016
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42. High Treg development in the first year of life gives insight into immune regulation
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De Roock, Sytze, primary, Dijkstra, Krijn, additional, Hoeks, Sanne, additional, and Prakken, Berent, additional
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- 2014
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43. Ductile to brittle transition in blends of polyamide-6 and rubber
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Gaymans, R.J., Dijkstra, Krijn, and Materials Science and Technology of Polymers
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METIS-106971 - Published
- 1996
44. The biogenesis and characterization of mammalian microRNAs of mirtron origin
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Sibley, Christopher R., primary, Seow, Yiqi, additional, Saayman, Sheena, additional, Dijkstra, Krijn K., additional, El Andaloussi, Samir, additional, Weinberg, Marc S., additional, and Wood, Matthew J. A., additional
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- 2011
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45. Thermal blunting in PA-6-rubber blends
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Gaymans, R.J., Dijkstra, Krijn, and Materials Science and Technology of Polymers
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METIS-107491 - Published
- 1994
46. Cavitation in rubber modified thermoplastics
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Dijkstra, Krijn, Gaymans, R.J., and Materials Science and Technology of Polymers
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METIS-107476 - Published
- 1994
47. Polyamide-rubber blends: influence of deformation speed on crack propagation process
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Gaymans, R.J., Dijkstra, Krijn, Janik-Jakubowska, H.Z., and Materials Science and Technology of Polymers
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METIS-107490 - Published
- 1994
48. Revealing the deformed structure of nylon rubber blends by electron microscopy studies
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Janik-Jakubowska, H.Z., Dijkstra, Krijn, Gaymans, R.J., and Materials Science and Technology of Polymers
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METIS-107493 - Published
- 1993
49. The importance of thermal blunting in the toughening process of PA-rubber blends
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Dijkstra, Krijn, Gaymans, R.J., and Materials Science and Technology of Polymers
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METIS-107494 - Published
- 1993
50. Deformation and fracture of nylon 6-rubber blends
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Dijkstra, Krijn, Struik, L.C.E., Gaymans, Reinoud J., and Materials Science and Technology of Polymers
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METIS-105222 - Published
- 1993
Catalog
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