Search

Your search keyword '"Nye, Emma"' showing total 350 results
Start Over Author "Nye, Emma"
350 results on '"Nye, Emma"'

1. Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer

Author

Kreuzaler, Peter, Inglese, Paolo, Ghanate, Avinash, Gjelaj, Ersa, Wu, Vincen, Panina, Yulia, Mendez-Lucas, Andres, MacLachlan, Catherine, Patani, Neill, Hubert, Catherine B., Huang, Helen, Greenidge, Gina, Rueda, Oscar M., Taylor, Adam J., Karali, Evdoxia, Kazanc, Emine, Spicer, Amy, Dexter, Alex, Lin, Wei, Thompson, Daria, Silva Dos Santos, Mariana, Calvani, Enrica, Legrave, Nathalie, Ellis, James K., Greenwood, Wendy, Green, Mary, Nye, Emma, Still, Emma, Barry, Simon, Goodwin, Richard J. A., Bruna, Alejandra, Caldas, Carlos, MacRae, James, de Carvalho, Luiz Pedro Sório, Poulogiannis, George, McMahon, Greg, Takats, Zoltan, Bunch, Josephine, and Yuneva, Mariia

Published
2023
Full Text
View/download PDF

2. Student Educational Experiences Relative to Issues Impacting LGBTQPIA+ Patient Care

Author

Eberman, Lindsey E., Rogers, Sean M., Walen, Daniel R., Edler Nye, Jessica R., Nye, Emma, Crossway, Ashley K., and Winkelmann, Zachary K.

Abstract

Context: Athletic trainers have expressed a lack of knowledge and a desire to learn more about the issues impacting lesbian, gay, bisexual, transgender, queer/questioning, pansexual, intersex, asexual/aromantic/agender, two-spirit, and additional community/identity (LGBTQPIA+) patients, yet little is known about how students are prepared. Objective: The purpose of this study was to explore educational experiences relative to LGBTQPIA+ patient care in Commission on Accreditation of Athletic Training Education-accredited, master's-level professional athletic training programs. Design: Cross-sectional study. Setting: Web-based survey. Participants: Students (N = 333) who were currently enrolled in the last 1 to 2 semesters of their respective programs or had recently graduated from a master's-level professional athletic training program within the last year. Main Outcome Measure(s): The survey asked participants to characterize and evaluate the effectiveness of their learning experiences, then rank their confidence in addressing the needs of LGBTQPIA+ patients. We used additional open-ended responses to characterize effective instructional strategies. Data were analyzed using statistics of central tendency and open-ended responses were inductively coded. Results: Participants reported that their learning experiences about LGBTQPIA+ patient needs were moderately effective for formal (38.2%), informal (42.2%), and clinical education (34.0%). Among the areas where participants reported wishing they had learned more were gender incongruence or dysphoria (39.6%), gender-affirming care (43.5%), and providing inclusive health care forms and documentation (38.4%). Participants reported about 15 6 37 hours (range, 0-500 hours) of time dedicated to LGBTQPIA+ patient issues, although only 23.2% indicated that this was enough time. Participants indicated that they were quite confident in addressing the needs of LGBTQPIA+ patients (mode = 3 ["quite confident"], 33.0%); however, 53.7% of participants were only somewhat, slightly, or not at all confident. In the open-ended responses, participants indicated that informal and clinical education experiences providing authentic interactions with LGBTQPIA+ patients were most meaningful. Conclusions: Professional athletic training programs should incorporate more educational experiences to better prepare students to meet the health care needs of LGBTQPIA+ patients. Participants in our study additionally indicated a strong desire to learn more about equitable patient care

Published
2023
Full Text
View/download PDF

3. The evolution of non-small cell lung cancer metastases in TRACERx

Author

Al Bakir, Maise, Huebner, Ariana, Martínez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas B. K., 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 M., 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 A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J., Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2023
Full Text
View/download PDF

4. Integration of an Inclusive Health Care Curriculum for Sexual Health and Gender Minorities

Author

Schulman, Erica H., Eberman, Lindsey E., Crossway, Ashley K., Nye, Emma A., Uriegas, Nancy A., Connell, Spencer A., and Winkelmann, Zachary K.

Abstract

Context: Research suggests that athletic training students lack knowledge and experience providing care to transgender patients. Additionally, research has identified a lack of comfort with sexual health screening in peer health professions. Objective: To assess how a curriculum, including a standardized patient (SP) encounter, influenced attitudes and skills in working with sexual health and gender minorities. Design: Prospective observational study. Setting: Simulation lab. Patients or Other Participants: Twenty cisgender postbaccalaureate professional athletic training students (females = 16, males = 4; age = 23 ± 2 years). Intervention(s): The intervention included a focused curriculum on transgender health care and sexual health. In a culminating SP encounter, one group (n = 10) interacted with a cisgender woman and the second group (n = 10) with a transgender woman. Main Outcome Measure(s): The students completed a postintervention survey. Instruments included the Attitudes Towards Transgender Patients tool, which is divided into 3 subscales: clinician education, transgender sport participation, and clinician comfort; and the the Sexual Health Knowledge and Attitudes and Sexual History--Taking instruments, which evaluated the effectiveness of the sexual health curriculum on knowledge, attitudes, and comfort. The investigator and SP actor evaluated the SP encounters. Data were analyzed using descriptive statistics, nonparametric Mann-Whitney U, and 1-way analyses of variance. Results: We identified a significant difference between those completing a transgender SP encounter (mean = 5.30 ± 2.11) and those completing the cisgender SP encounter (mean = 3.50 ± 0.97) on the clinician education subscale (P = 0.035). There were no differences between groups on the transgender sport participation (P = 0.70) and clinician comfort (P = 0.32) subscales. On the SP actor evaluation, we found no significant differences (P = 0.08). Conclusions: The curriculum and SP encounter influenced knowledge, attitudes, and comfort when working with gender minorities and screening for sexual health.

Published
2022
Full Text
View/download PDF

5. GREM1 is required to maintain cellular heterogeneity in pancreatic cancer

Author

Lan, Linxiang, Evan, Theodore, Li, Huafu, Hussain, Aasia, Ruiz, E. Josue, Zaw Thin, May, Ferreira, Rute M. M., Ps, Hari, Riising, Eva M., Zen, Yoh, Almagro, Jorge, Ng, Kevin W., Soro-Barrio, Pablo, Nelson, Jessica, Koifman, Gabriela, Carvalho, Joana, Nye, Emma L., He, Yulong, Zhang, Changhua, Sadanandam, Anguraj, and Behrens, Axel

Published
2022
Full Text
View/download PDF

6. Vitamin D regulates microbiome-dependent cancer immunity

Author

Giampazolias, Evangelos, primary, Pereira da Costa, Mariana, additional, Lam, Khiem C., additional, Lim, Kok Haw Jonathan, additional, Cardoso, Ana, additional, Piot, Cécile, additional, Chakravarty, Probir, additional, Blasche, Sonja, additional, Patel, Swara, additional, Biram, Adi, additional, Castro-Dopico, Tomas, additional, Buck, Michael D., additional, Rodrigues, Richard R., additional, Poulsen, Gry Juul, additional, Palma-Duran, Susana A., additional, Rogers, Neil C., additional, Koufaki, Maria A., additional, Minutti, Carlos M., additional, Wang, Pengbo, additional, Vdovin, Alexander, additional, Frederico, Bruno, additional, Childs, Eleanor, additional, Lee, Sonia, additional, Simpson, Ben, additional, Iseppon, Andrea, additional, Omenetti, Sara, additional, Kelly, Gavin, additional, Goldstone, Robert, additional, Nye, Emma, additional, Suárez-Bonnet, Alejandro, additional, Priestnall, Simon L., additional, MacRae, James I., additional, Zelenay, Santiago, additional, Patil, Kiran Raosaheb, additional, Litchfield, Kevin, additional, Lee, James C., additional, Jess, Tine, additional, Goldszmid, Romina S., additional, and Reis e Sousa, Caetano, additional

Published
2024
Full Text
View/download PDF

8. USP25 promotes pathological HIF-1-driven metabolic reprogramming and is a potential therapeutic target in pancreatic cancer

Author

Nelson, Jessica K., Thin, May Zaw, Evan, Theodore, Howell, Steven, Wu, Mary, Almeida, Bruna, Legrave, Nathalie, Koenis, Duco S., Koifman, Gabriela, Sugimoto, Yoichiro, Llorian Sopena, Miriam, MacRae, James, Nye, Emma, Howell, Michael, Snijders, Ambrosius P., Prachalias, Andreas, Zen, Yoh, Sarker, Debashis, and Behrens, Axel

Published
2022
Full Text
View/download PDF

10. Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Author

Fendler, Annika, Au, Lewis, Shepherd, Scott T. C., Byrne, Fiona, Cerrone, Maddalena, Boos, Laura Amanda, Rzeniewicz, Karolina, Gordon, William, Shum, Benjamin, Gerard, Camille L., Ward, Barry, Xie, Wenyi, Schmitt, Andreas M., Joharatnam-Hogan, Nalinie, Cornish, Georgina H., Pule, Martin, Mekkaoui, Leila, Ng, Kevin W., Carlyle, Eleanor, Edmonds, Kim, Rosario, Lyra Del, Sarker, Sarah, Lingard, Karla, Mangwende, Mary, Holt, Lucy, Ahmod, Hamid, Stone, Richard, Gomes, Camila, Flynn, Helen R., Agua-Doce, Ana, Hobson, Philip, Caidan, Simon, Howell, Michael, Wu, Mary, Goldstone, Robert, Crawford, Margaret, Cubitt, Laura, Patel, Harshil, Gavrielides, Mike, Nye, Emma, Snijders, Ambrosius P., MacRae, James I., Nicod, Jerome, Gronthoud, Firza, Shea, Robyn L., Messiou, Christina, Cunningham, David, Chau, Ian, Starling, Naureen, Turner, Nicholas, Welsh, Liam, van As, Nicholas, Jones, Robin L., Droney, Joanne, Banerjee, Susana, Tatham, Kate C., Jhanji, Shaman, O’Brien, Mary, Curtis, Olivia, Harrington, Kevin, Bhide, Shreerang, Bazin, Jessica, Robinson, Anna, Stephenson, Clemency, Slattery, Tim, Khan, Yasir, Tippu, Zayd, Leslie, Isla, Gennatas, Spyridon, Okines, Alicia, Reid, Alison, Young, Kate, Furness, Andrew J. S., Pickering, Lisa, Gandhi, Sonia, Gamblin, Steve, Swanton, Charles, Nicholson, Emma, Kumar, Sacheen, Yousaf, Nadia, Wilkinson, Katalin A., Swerdlow, Anthony, Harvey, Ruth, Kassiotis, George, Larkin, James, Wilkinson, Robert J., and Turajlic, Samra

Published
2021
Full Text
View/download PDF

11. Workplace Climate for Sexual and Gender Minorities in Athletic Training.

Author

Eberman, Lindsey E., Edler Nye, Jessica R., and Nye, Emma A.

Subjects
SELF-evaluation, GENDER identity, WORK environment, MEDICAL care, INTERVIEWING, RESEARCH evaluation, LGBTQ+ people, PHYSICAL training & conditioning, INTERNET, DESCRIPTIVE statistics, RESEARCH methodology, SEXUAL minorities, EMPLOYMENT discrimination, WELL-being, INDUSTRIAL safety
Abstract

Sexual and gender minorities (SGMs) are individuals with sexual orientations, gender identities, or expressions (or a combination of these) that differ from cultural norms. Sexual and gender minorities often face workplace discrimination and report decreased physical and emotional well-being from discrimination. To explore the workplace climate of SGM athletic trainers (ATs). Sequential mixed-methods study. Web-based survey and interviews. Criterion sampling of SGM ATs (117 survey participants and 12 interview participants). We modified the LGBTQ Inclusion Assessment and the Organizational Self-Assessment for the survey and developed a semistructured interview script (scale-level content validity index = 0.94). We used means ± SDs, frequencies (%), and the consensual qualitative research tradition to characterize participant responses. Trustworthiness was established through reflexivity (researchers checking bias throughout the research process), member-checking, multianalyst triangulation, and internal and external auditing. Participants indicated their workplace was inclusive (24 [20.5%]), somewhat inclusive (29 [24.8%]), or not inclusive (14 [12.0%]) or did not indicate at all (50 [42.7%]). Respondents most often noted they were unsure of which stage of change their organizations and organizational units were in addressing lesbian, gay, bisexual, transgender, queer, questioning, pansexual, intersex, asexual, 2-spirit, and all within the community of queer and transspectrum identities (LGBTQPIA+) concerns in the workplace as well as specific actions taken for inclusion. Two domains emerged from the interview data: safety and inclusion. The safety domain represented aspects of the workplace climate that made participants feel safe and includes organizational initiatives (12/12), patient-centered policies (7/12), local and federal regulations (7/12), and signaling (12/12). The inclusion domain represented how participants felt a sense of belonging to the organization through their own experience (12/12), through the experiences of their patients (9/12), and through an infrastructure designed for inclusion (12/12). Participants expressed both affirmative and negative feelings of safety and inclusion throughout their responses. Organizations must take both structural and cultural actions to address the concerns of exclusion and lack of safety. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

14. Disruption Of PML Nuclear Bodies Cooperates In The Pathogenesis Of Acute Promyelocytic Leukemia

Author

Moravcsik, Eva, Joannides, Melanie, Voisset, Edwige, Stratford, Eva Wessel, Zeisig, Bernd B, Morris, Jo, Densham, Ruth, Palgrave, Chris, Stamp, Gordon, Nye, Emma, Hills, Robert K, Salomoni, Paolo, Eric So, Chi Wai, Kogan, Scott C, Solomon, Ellen, and Grimwade, David

Subjects
Rare Diseases, Brain Disorders, Hematology, Childhood Leukemia, Stem Cell Research - Nonembryonic - Non-Human, Pediatric, Genetics, Stem Cell Research, Pediatric Cancer, Cancer, 2.1 Biological and endogenous factors, Aetiology, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Paediatrics and Reproductive Medicine, Immunology
Abstract

Abstract Acute promyelocytic leukemia (APL) is characterised by the t(15;17)(q22;q21) leading to fusion of PML to the gene encoding the myeloid transcription factor Retinoic Acid Receptor α (RARα). Chromosomal translocations such as the t(15;17) are considered to be initiating events in leukemogenesis; however, sequencing of APL genomes has provided further evidence that the PML-RARα fusion is insufficient to induce leukemia, which depends upon the acquisition of cooperating mutations. The PML-RARα oncoprotein exerts a profound effect on nuclear architecture, disrupting multiprotein structures known as PML nuclear bodies (NBs). The function of these structures remains an enigma; however, their disruption in PML-RARα+ APL and acute lymphoblastic leukemia with the t(9;15)(p13;q24)/PAX5-PML fusion is associated with delocalisation of a number of component proteins including PML, which have been implicated in growth control and neoplastic transformation. It is now established that the PML moiety contributes to APL pathogenesis by conferring via the translocation a novel dimerisation capacity to RARα, but it has been unclear whether deregulation of PML and other NB components cooperates in leukemic transformation or impacts the response to differentiating agents. To address these questions, we generated a knock-in mouse model with targeted NB disruption achieved through mutation of key zinc-binding cysteine residues in the amino-terminal RING domain of Pml. Homozygous Pml RING mutant mice are viable, with no overt developmental defect; however, analysis of the bone marrow revealed significant expansion of the Lin(-)Sca-1(+)c-Kit(+) (LSK) population compared to wild type (WT) controls (p

Published
2013

15. Data from Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Author

Spain, Lavinia, primary, Coulton, Alexander, primary, Lobon, Irene, primary, Rowan, Andrew, primary, Schnidrig, Desiree, primary, Shepherd, Scott T.C., primary, Shum, Benjamin, primary, Byrne, Fiona, primary, Goicoechea, Maria, primary, Piperni, Elisa, primary, Au, Lewis, primary, Edmonds, Kim, primary, Carlyle, Eleanor, primary, Hunter, Nikki, primary, Renn, Alexandra, primary, Messiou, Christina, primary, Hughes, Peta, primary, Nobbs, Jaime, primary, Foijer, Floris, primary, van den Bos, Hilda, primary, Wardenaar, Rene, primary, Spierings, Diana C.J., primary, Spencer, Charlotte, primary, Schmitt, Andreas M., primary, Tippu, Zayd, primary, Lingard, Karla, primary, Grostate, Lauren, primary, Peat, Kema, primary, Kelly, Kayleigh, primary, Sarker, Sarah, primary, Vaughan, Sarah, primary, Mangwende, Mary, primary, Terry, Lauren, primary, Kelly, Denise, primary, Biano, Jennifer, primary, Murra, Aida, primary, Korteweg, Justine, primary, Lewis, Charlotte, primary, O'Flaherty, Molly, primary, Cattin, Anne-Laure, primary, Emmerich, Max, primary, Gerard, Camille L., primary, Pallikonda, Husayn Ahmed, primary, Lynch, Joanna, primary, Mason, Robert, primary, Rogiers, Aljosja, primary, Xu, Hang, primary, Huebner, Ariana, primary, McGranahan, Nicholas, primary, Al Bakir, Maise, primary, Murai, Jun, primary, Naceur-Lombardelli, Cristina, primary, Borg, Elaine, primary, Mitchison, Miriam, primary, Moore, David A., primary, Falzon, Mary, primary, Proctor, Ian, primary, Stamp, Gordon W.H., primary, Nye, Emma L., primary, Young, Kate, primary, Furness, Andrew J.S., primary, Pickering, Lisa, primary, Stewart, Ruby, primary, Mahadeva, Ula, primary, Green, Anna, primary, Larkin, James, primary, Litchfield, Kevin, primary, Swanton, Charles, primary, Jamal-Hanjani, Mariam, primary, and Turajlic, Samra, primary

Published
2023
Full Text
View/download PDF

16. Supplementary Tables S1-S8 from Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Author

Spain, Lavinia, primary, Coulton, Alexander, primary, Lobon, Irene, primary, Rowan, Andrew, primary, Schnidrig, Desiree, primary, Shepherd, Scott T.C., primary, Shum, Benjamin, primary, Byrne, Fiona, primary, Goicoechea, Maria, primary, Piperni, Elisa, primary, Au, Lewis, primary, Edmonds, Kim, primary, Carlyle, Eleanor, primary, Hunter, Nikki, primary, Renn, Alexandra, primary, Messiou, Christina, primary, Hughes, Peta, primary, Nobbs, Jaime, primary, Foijer, Floris, primary, van den Bos, Hilda, primary, Wardenaar, Rene, primary, Spierings, Diana C.J., primary, Spencer, Charlotte, primary, Schmitt, Andreas M., primary, Tippu, Zayd, primary, Lingard, Karla, primary, Grostate, Lauren, primary, Peat, Kema, primary, Kelly, Kayleigh, primary, Sarker, Sarah, primary, Vaughan, Sarah, primary, Mangwende, Mary, primary, Terry, Lauren, primary, Kelly, Denise, primary, Biano, Jennifer, primary, Murra, Aida, primary, Korteweg, Justine, primary, Lewis, Charlotte, primary, O'Flaherty, Molly, primary, Cattin, Anne-Laure, primary, Emmerich, Max, primary, Gerard, Camille L., primary, Pallikonda, Husayn Ahmed, primary, Lynch, Joanna, primary, Mason, Robert, primary, Rogiers, Aljosja, primary, Xu, Hang, primary, Huebner, Ariana, primary, McGranahan, Nicholas, primary, Al Bakir, Maise, primary, Murai, Jun, primary, Naceur-Lombardelli, Cristina, primary, Borg, Elaine, primary, Mitchison, Miriam, primary, Moore, David A., primary, Falzon, Mary, primary, Proctor, Ian, primary, Stamp, Gordon W.H., primary, Nye, Emma L., primary, Young, Kate, primary, Furness, Andrew J.S., primary, Pickering, Lisa, primary, Stewart, Ruby, primary, Mahadeva, Ula, primary, Green, Anna, primary, Larkin, James, primary, Litchfield, Kevin, primary, Swanton, Charles, primary, Jamal-Hanjani, Mariam, primary, and Turajlic, Samra, primary

Published
2023
Full Text
View/download PDF

17. Supplementary Figures S1-S25 from Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Author

Spain, Lavinia, primary, Coulton, Alexander, primary, Lobon, Irene, primary, Rowan, Andrew, primary, Schnidrig, Desiree, primary, Shepherd, Scott T.C., primary, Shum, Benjamin, primary, Byrne, Fiona, primary, Goicoechea, Maria, primary, Piperni, Elisa, primary, Au, Lewis, primary, Edmonds, Kim, primary, Carlyle, Eleanor, primary, Hunter, Nikki, primary, Renn, Alexandra, primary, Messiou, Christina, primary, Hughes, Peta, primary, Nobbs, Jaime, primary, Foijer, Floris, primary, van den Bos, Hilda, primary, Wardenaar, Rene, primary, Spierings, Diana C.J., primary, Spencer, Charlotte, primary, Schmitt, Andreas M., primary, Tippu, Zayd, primary, Lingard, Karla, primary, Grostate, Lauren, primary, Peat, Kema, primary, Kelly, Kayleigh, primary, Sarker, Sarah, primary, Vaughan, Sarah, primary, Mangwende, Mary, primary, Terry, Lauren, primary, Kelly, Denise, primary, Biano, Jennifer, primary, Murra, Aida, primary, Korteweg, Justine, primary, Lewis, Charlotte, primary, O'Flaherty, Molly, primary, Cattin, Anne-Laure, primary, Emmerich, Max, primary, Gerard, Camille L., primary, Pallikonda, Husayn Ahmed, primary, Lynch, Joanna, primary, Mason, Robert, primary, Rogiers, Aljosja, primary, Xu, Hang, primary, Huebner, Ariana, primary, McGranahan, Nicholas, primary, Al Bakir, Maise, primary, Murai, Jun, primary, Naceur-Lombardelli, Cristina, primary, Borg, Elaine, primary, Mitchison, Miriam, primary, Moore, David A., primary, Falzon, Mary, primary, Proctor, Ian, primary, Stamp, Gordon W.H., primary, Nye, Emma L., primary, Young, Kate, primary, Furness, Andrew J.S., primary, Pickering, Lisa, primary, Stewart, Ruby, primary, Mahadeva, Ula, primary, Green, Anna, primary, Larkin, James, primary, Litchfield, Kevin, primary, Swanton, Charles, primary, Jamal-Hanjani, Mariam, primary, and Turajlic, Samra, primary

Published
2023
Full Text
View/download PDF

19. GREM1 is required to maintain cellular heterogeneity in pancreatic cancer

Author

Lan, Linxiang, Evan, Theodore, Li, Huafu, Hussain, Aasia, Ruiz, E. Josue, Zaw Thin, May, Ferreira, Rute M. M., Ps, Hari, Riising, Eva M., Zen, Yoh, Almagro, Jorge, Ng, Kevin W., Soro-Barrio, Pablo, Nelson, Jessica, Koifman, Gabriela, Carvalho, Joana, Nye, Emma L., He, Yulong, Zhang, Changhua, Sadanandam, Anguraj, and Behrens, Axel

Abstract

Pancreatic ductal adenocarcinoma (PDAC) shows pronounced epithelial and mesenchymal cancer cell populations1–4. Cellular heterogeneity in PDAC is an important feature in disease subtype specification3–5, but how distinct PDAC subpopulations interact, and the molecular mechanisms that underlie PDAC cell fate decisions, are incompletely understood. Here we identify the BMP inhibitor GREM16,7as a key regulator of cellular heterogeneity in pancreatic cancer in human and mouse. Grem1inactivation in established PDAC in mice resulted in a direct conversion of epithelial into mesenchymal PDAC cells within days, suggesting that persistent GREM1 activity is required to maintain the epithelial PDAC subpopulations. By contrast, Grem1overexpression caused an almost complete ‘epithelialization’ of highly mesenchymal PDAC, indicating that high GREM1 activity is sufficient to revert the mesenchymal fate of PDAC cells. Mechanistically, Grem1was highly expressed in mesenchymal PDAC cells and inhibited the expression of the epithelial–mesenchymal transition transcription factors Snai1(also known as Snail) and Snai2(also known as Slug) in the epithelial cell compartment, therefore restricting epithelial–mesenchymal plasticity. Thus, constant suppression of BMP activity is essential to maintain epithelial PDAC cells, indicating that the maintenance of the cellular heterogeneity of pancreatic cancer requires continuous paracrine signalling elicited by a single soluble factor.

Published
2024
Full Text
View/download PDF

20. Body composition and lung cancer-associated cachexia in TRACERx

Author

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

Subjects
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

Published
2023

21. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

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

Subjects
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

Published
2023

22. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author

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

Subjects
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

Published
2023

26. Data Supplement from High-Throughput Time-Resolved FRET Reveals Akt/PKB Activation as a Poor Prognostic Marker in Breast Cancer

Author

Veeriah, Selvaraju, primary, Leboucher, Pierre, primary, de Naurois, Julien, primary, Jethwa, Nirmal, primary, Nye, Emma, primary, Bunting, Tamara, primary, Stone, Richard, primary, Stamp, Gordon, primary, Calleja, Véronique, primary, Jeffrey, Stefanie S., primary, Parker, Peter J., primary, and Larijani, Banafshé, primary

Published
2023
Full Text
View/download PDF

29. Data from Expression Profiling in Progressive Stages of Fumarate-Hydratase Deficiency: The Contribution of Metabolic Changes to Tumorigenesis

Author

Ashrafian, Houman, primary, O'Flaherty, Linda, primary, Adam, Julie, primary, Steeples, Violetta, primary, Chung, Yuen-Li, primary, East, Phil, primary, Vanharanta, Sakari, primary, Lehtonen, Heli, primary, Nye, Emma, primary, Hatipoglu, Emine, primary, Miranda, Melroy, primary, Howarth, Kimberley, primary, Shukla, Deepa, primary, Troy, Helen, primary, Griffiths, John, primary, Spencer-Dene, Bradley, primary, Yusuf, Mohammed, primary, Volpi, Emanuela, primary, Maxwell, Patrick H., primary, Stamp, Gordon, primary, Poulsom, Richard, primary, Pugh, Christopher W., primary, Costa, Barbara, primary, Bardella, Chiara, primary, Di Renzo, Maria Flavia, primary, Kotlikoff, Michael I., primary, Launonen, Virpi, primary, Aaltonen, Lauri, primary, El-Bahrawy, Mona, primary, Tomlinson, Ian, primary, and Pollard, Patrick J., primary

Published
2023
Full Text
View/download PDF

30. Supplementary Figure 1 from Expression Profiling in Progressive Stages of Fumarate-Hydratase Deficiency: The Contribution of Metabolic Changes to Tumorigenesis

Author

Ashrafian, Houman, primary, O'Flaherty, Linda, primary, Adam, Julie, primary, Steeples, Violetta, primary, Chung, Yuen-Li, primary, East, Phil, primary, Vanharanta, Sakari, primary, Lehtonen, Heli, primary, Nye, Emma, primary, Hatipoglu, Emine, primary, Miranda, Melroy, primary, Howarth, Kimberley, primary, Shukla, Deepa, primary, Troy, Helen, primary, Griffiths, John, primary, Spencer-Dene, Bradley, primary, Yusuf, Mohammed, primary, Volpi, Emanuela, primary, Maxwell, Patrick H., primary, Stamp, Gordon, primary, Poulsom, Richard, primary, Pugh, Christopher W., primary, Costa, Barbara, primary, Bardella, Chiara, primary, Di Renzo, Maria Flavia, primary, Kotlikoff, Michael I., primary, Launonen, Virpi, primary, Aaltonen, Lauri, primary, El-Bahrawy, Mona, primary, Tomlinson, Ian, primary, and Pollard, Patrick J., primary

Published
2023
Full Text
View/download PDF

33. Supplementary Methods from Expression Profiling in Progressive Stages of Fumarate-Hydratase Deficiency: The Contribution of Metabolic Changes to Tumorigenesis

Author

Ashrafian, Houman, primary, O'Flaherty, Linda, primary, Adam, Julie, primary, Steeples, Violetta, primary, Chung, Yuen-Li, primary, East, Phil, primary, Vanharanta, Sakari, primary, Lehtonen, Heli, primary, Nye, Emma, primary, Hatipoglu, Emine, primary, Miranda, Melroy, primary, Howarth, Kimberley, primary, Shukla, Deepa, primary, Troy, Helen, primary, Griffiths, John, primary, Spencer-Dene, Bradley, primary, Yusuf, Mohammed, primary, Volpi, Emanuela, primary, Maxwell, Patrick H., primary, Stamp, Gordon, primary, Poulsom, Richard, primary, Pugh, Christopher W., primary, Costa, Barbara, primary, Bardella, Chiara, primary, Di Renzo, Maria Flavia, primary, Kotlikoff, Michael I., primary, Launonen, Virpi, primary, Aaltonen, Lauri, primary, El-Bahrawy, Mona, primary, Tomlinson, Ian, primary, and Pollard, Patrick J., primary

Published
2023
Full Text
View/download PDF

34. Supplementary Table 1 from Expression Profiling in Progressive Stages of Fumarate-Hydratase Deficiency: The Contribution of Metabolic Changes to Tumorigenesis

Author

Ashrafian, Houman, primary, O'Flaherty, Linda, primary, Adam, Julie, primary, Steeples, Violetta, primary, Chung, Yuen-Li, primary, East, Phil, primary, Vanharanta, Sakari, primary, Lehtonen, Heli, primary, Nye, Emma, primary, Hatipoglu, Emine, primary, Miranda, Melroy, primary, Howarth, Kimberley, primary, Shukla, Deepa, primary, Troy, Helen, primary, Griffiths, John, primary, Spencer-Dene, Bradley, primary, Yusuf, Mohammed, primary, Volpi, Emanuela, primary, Maxwell, Patrick H., primary, Stamp, Gordon, primary, Poulsom, Richard, primary, Pugh, Christopher W., primary, Costa, Barbara, primary, Bardella, Chiara, primary, Di Renzo, Maria Flavia, primary, Kotlikoff, Michael I., primary, Launonen, Virpi, primary, Aaltonen, Lauri, primary, El-Bahrawy, Mona, primary, Tomlinson, Ian, primary, and Pollard, Patrick J., primary

Published
2023
Full Text
View/download PDF

35. Supplementary Figure 2 from Expression Profiling in Progressive Stages of Fumarate-Hydratase Deficiency: The Contribution of Metabolic Changes to Tumorigenesis

Author

Ashrafian, Houman, primary, O'Flaherty, Linda, primary, Adam, Julie, primary, Steeples, Violetta, primary, Chung, Yuen-Li, primary, East, Phil, primary, Vanharanta, Sakari, primary, Lehtonen, Heli, primary, Nye, Emma, primary, Hatipoglu, Emine, primary, Miranda, Melroy, primary, Howarth, Kimberley, primary, Shukla, Deepa, primary, Troy, Helen, primary, Griffiths, John, primary, Spencer-Dene, Bradley, primary, Yusuf, Mohammed, primary, Volpi, Emanuela, primary, Maxwell, Patrick H., primary, Stamp, Gordon, primary, Poulsom, Richard, primary, Pugh, Christopher W., primary, Costa, Barbara, primary, Bardella, Chiara, primary, Di Renzo, Maria Flavia, primary, Kotlikoff, Michael I., primary, Launonen, Virpi, primary, Aaltonen, Lauri, primary, El-Bahrawy, Mona, primary, Tomlinson, Ian, primary, and Pollard, Patrick J., primary

Published
2023
Full Text
View/download PDF

37. Late-stage metastatic melanoma emerges through a diversity of evolutionary pathways

Author

Spain, Lavinia, Coulton, Alexander, Lobon, Irene, Rowan, Andrew, Schnidrig, Desiree, Shepherd, Scott TC, Shum, Benjamin, Byrne, Fiona, Goicoechea, Maria, Piperni, Elisa, Au, Lewis, Edmonds, Kim, Carlyle, Eleanor, Hunter, Nikki, Renn, Alexandra, Messiou, Christina, Hughes, Peta, Nobbs, Jaime, Foijer, Floris, van den Bos, Hilda, Wardenaar, Rene, Spierings, Diana CJ, Spencer, Charlotte, Schmitt, Andreas M, Tippu, Zayd, Lingard, Karla, Grostate, Lauren, Peat, Kema, Kelly, Kayleigh, Sarker, Sarah, Vaughan, Sarah, Mangwende, Mary, Terry, Lauren, Kelly, Denise, Biano, Jennifer, Murra, Aida, Korteweg, Justine, Lewis, Charlotte, OFlaherty, Molly, Cattin, Anne-Laure, Emmerich, Max, Gerard, Camille L, Pallikonda, Husayn Ahmed, Lynch, Joanna, Mason, Robert, Rogiers, Aljosja, Xu, Hang, Huebner, Ariana, McGranahan, Nicholas, Al Bakir, Maise, Murai, Jun, Naceur-Lombardelli, Cristina, Borg, Elaine, Mitchison, Miriam, Moore, David A, Falzon, Mary, Proctor, Ian, Stamp, Gordon WH, Nye, Emma L, Young, Kate, Furness, Andrew JS, Pickering, Lisa, Stewart, Ruby, Mahadeva, Ula, Green, Anna, Larkin, James, Litchfield, Kevin, Swanton, Charles, Jamal-Hanjani, Mariam, Consortium, The PEACE, and Turajlic, Samra

Subjects
Chemical Biology & High Throughput, Signalling & Oncogenes, Human Biology & Physiology, Ecology,Evolution & Ethology, Genome Integrity & Repair, Tumour Biology, Genetics & Genomics, Computational & Systems Biology
Abstract

Understanding the evolutionary pathways to metastasis and resistance to immune checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here we present the most comprehensive intra-patient metastatic melanoma dataset assembled to date as part of the PEACE research autopsy programme, including 222 exome, 493 panel-sequenced, 161 RNA-seq, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI non-responders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one of the patients. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.

Published
2023
Full Text
View/download PDF

39. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

Abbosh, Christopher, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Le Quesne, John, Moore, David A., Veeriah, Selvaraju, Rosenthal, Rachel, Marafioti, Teresa, Kirkizlar, Eser, Watkins, Thomas B. K., McGranahan, Nicholas, Ward, Sophia, Martinson, Luke, Riley, Joan, Fraioli, Francesco, Al Bakir, Maise, Grnroos, Eva, Zambrana, Francisco, Endozo, Raymondo, Bi, Wenya Linda, Fennessy, Fiona M., Sponer, Nicole, Johnson, Diana, Laycock, Joanne, Shafi, Seema, Czyzewska-Khan, Justyna, Rowan, Andrew, Chambers, Tim, Matthews, Nik, Turajlic, Samra, Hiley, Crispin, Lee, Siow Ming, Forster, Martin D., Ahmad, Tanya, Falzon, Mary, Borg, Elaine, Lawrence, David, Hayward, Martin, Kolvekar, Shyam, Panagiotopoulos, Nikolaos, Janes, Sam M., Thakrar, Ricky, Ahmed, Asia, Blackhall, Fiona, Summers, Yvonne, Hafez, Dina, Naik, Ashwini, Ganguly, Apratim, Kareht, Stephanie, Shah, Rajesh, Joseph, Leena, Marie Quinn, Anne, Crosbie, Phil A., Naidu, Babu, Middleton, Gary, Langman, Gerald, Trotter, Simon, Nicolson, Marianne, Remmen, Hardy, Kerr, Keith, Chetty, Mahendran, Gomersall, Lesley, Fennell, Dean A., Nakas, Apostolos, Rathinam, Sridhar, Anand, Girija, Khan, Sajid, Russell, Peter, Ezhil, Veni, Ismail, Babikir, Irvin-Sellers, Melanie, Prakash, Vineet, Lester, Jason F., Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Oukrif, Dahmane, Akarca, Ayse U., Hartley, John A., Lowe, Helen L., Lock, Sara, Iles, Natasha, Bell, Harriet, Ngai, Yenting, Elgar, Greg, Szallasi, Zoltan, Schwarz, Roland F., Herrero, Javier, Stewart, Aengus, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Hackshaw, Allan, Shaw, Jacqui A., Zimmermann, Bernhard G., Swanton, Charles, Bosshard-Carter, Leticia, Goh, Gerald, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Horswell, Stuart, Bakir, Maise Al, Mitter, Richard, Escudero, Mickael, Xu, Hang, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Nye, Emma, Graca, Sofia, Joshi, Kroopa, Furness, Andrew, Ben Aissa, Assma, Wong, Yien Ning Sophia, Georgiou, Andy, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Taylor, Magali, Choudhary, Junaid, Califano, Raffaele, Taylor, Paul, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Moss, Stuart, Idries, Faiza, Bishop, Paul, Chaturvedi, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Rogan, Jane, Smith, Elaine, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Djearaman, Madava, Quesne, John Le, Thomas, Anne, Walter, Harriet, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Primrose, Lindsay, Amadi, Anita, Palmer, Shirley, Miller, Joy, Buchan, Keith, Edwards, Alison, Morgan, Fiona, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Dentro, Stefan, and Dessimoz, Christophe

Subjects
Lung cancer -- Genetic aspects -- Development and progression, DNA sequencing -- Methods, Phylogeny -- Observations, Cancer metastasis -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies., Author(s): Christopher Abbosh [1]; Nicolai J. Birkbak [1, 2]; Gareth A. Wilson [1, 2]; Mariam Jamal-Hanjani [1]; Tudor Constantin [3]; Raheleh Salari [3]; John Le Quesne [4]; David A. Moore [...]

Published
2017
Full Text
View/download PDF

41. VE-Cadherin–Mediated Epigenetic Regulation of Endothelial Gene Expression

Author

Morini, Marco F., Giampietro, Costanza, Corada, Monica, Pisati, Federica, Lavarone, Elisa, Cunha, Sara I., Conze, Lei L., O’Reilly, Nicola, Joshi, Dhira, Kjaer, Svend, George, Roger, Nye, Emma, Ma, Anqi, Jin, Jian, Mitter, Richard, Lupia, Michela, Cavallaro, Ugo, Pasini, Diego, Calado, Dinis P., Dejana, Elisabetta, and Taddei, Andrea

Published
2018
Full Text
View/download PDF

44. Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay

Author

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

Subjects
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

Published
2022
Full Text
View/download PDF

45. Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Author

Fendler, Annika, Au, Lewis, Shepherd, Scott TC, Byrne, Fiona, Cerrone, Maddalena, Boos, Laura Amanda, Rzeniewicz, Karolina, Gordon, William, Shum, Benjamin, Gerard, Camille L, Ward, Barry, Xie, Wenyi, Schmitt, Andreas M, Joharatnam-Hogan, Nalinie, Cornish, Georgina H, Pule, Martin, Mekkaoui, Leila, Ng, Kevin W, Carlyle, Eleanor, Edmonds, Kim, Del Rosario, Lyra, Sarker, Sarah, Lingard, Karla, Mangwende, Mary, Holt, Lucy, Ahmod, Hamid, Stone, Richard, Gomes, Camila, Flynn, Helen R, Agua-Doce, Ana, Hobson, Philip, Caidan, Simon, Howell, Michael, Wu, Mary, Goldstone, Robert, Crawford, Margaret, Cubitt, Laura, Patel, Harshil, Gavrielides, Mike, Nye, Emma, Snijders, Ambrosius P, MacRae, James I, Nicod, Jerome, Gronthoud, Firza, Shea, Robyn L, Messiou, Christina, Cunningham, David, Chau, Ian, Starling, Naureen, Turner, Nicholas, Welsh, Liam, van As, Nicholas, Jones, Robin L, Droney, Joanne, Banerjee, Susana, Tatham, Kate C, Jhanji, Shaman, O���Brien, Mary, Curtis, Olivia, Harrington, Kevin, Bhide, Shreerang, Bazin, Jessica, Robinson, Anna, Stephenson, Clemency, Slattery, Tim, Khan, Yasir, Tippu, Zayd, Leslie, Isla, Gennatas, Spyridon, Okines, Alicia, Reid, Alison, Young, Kate, Furness, Andrew JS, Pickering, Lisa, Gandhi, Sonia, Gamblin, Steve, Swanton, Charles, Consortium, The Crick COVID-19, Nicholson, Emma, Kumar, Sacheen, Yousaf, Nadia, Wilkinson, Katalin A, Swerdlow, Anthony, Harvey, Ruth, Kassiotis, George, Larkin, James, Wilkinson, Robert J, Turajlic, Samra, and consortium, The CAPTURE

Subjects
Model organisms, Chemical Biology & High Throughput, Human Biology & Physiology, FOS: Clinical medicine, Stem Cells, Genome Integrity & Repair, Immunology, Neurosciences, Infectious Disease, Cell Biology, Tumour Biology, Biochemistry & Proteomics, Signalling & Oncogenes, Metabolism, Ecology,Evolution & Ethology, Cell Cycle & Chromosomes, Genetics & Genomics, Developmental Biology, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

Published
2022
Full Text
View/download PDF

46. Dendritic cells control fibroblastic reticular network tension and lymph node expansion

Author

Acton, Sophie E., Farrugia, Aaron J., Astarita, Jillian L., Mourao-Sa, Diego, Jenkins, Robert P., Nye, Emma, Hooper, Steven, van Blijswijk, Janneke, Rogers, Neil C., Snelgrove, Kathryn J., Rosewel, Ian, Moita, Luis F., Stamp, Gordon, Turkey, Shannon J., Sahai, Erik, and Sousa, Caetano Reis e.

Subjects
Cell research, Dendritic cells -- Physiological aspects, Cellular signal transduction -- Research, Cell interaction -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

After immunogenic challenge, infiltrating and dividing lymphocytes markedly increase lymph node cellularity, leading to organ expansion (1,2). Here we report that the physical elasticity of lymph nodes is maintained in part by podoplanin (PDPN) signalling in stromal fibroblastic reticular cells (FRCs) and its modulation by CLEC-2 expressed on dendritic cells. We show in mouse cells that PDPN induces actomyosin contractility in FRCs via activation of RhoA/C and downstream Rho-associated protein kinase (ROCK). Engagement by CLEC-2 causes PDPN clustering and rapidly uncouples PDPN from RhoA/C activation, relaxing the actomyosin cytoskeleton and permitting FRC stretching. Notably, administration of CLEC-2 protein to immunized mice augments lymph node expansion. In contrast, lymph node expansion is significantly constrained in mice selectively lacking CLEC-2 expression in dendritic cells. Thus, the same dendritic cells that initiate immunity by presenting antigens to T lymphocytes (3) also initiate remodelling of lymph nodes by delivering CLEC-2 to FRCs. CLEC-2 modulation of PDPN signalling permits FRC network stretching and allows for the rapid lymph node expansion--driven by lymphocyte influx and proliferation--that is the critical hallmark of adaptive immunity., Lymph nodes are meeting places for T lymphocytes and antigen-presenting dendritic cells (1,2). T-cell-dendritic-cell interactions are supported by FRCs (4,5), a complex interconnected network that produces and ensheathes extracellular matrix [...]

Published
2014

48. Renal Cyst Formation in Fh1-Deficient Mice Is Independent of the Hif/Phd Pathway: Roles for Fumarate in KEAP1 Succination and Nrf2 Signaling

Author

Adam, Julie, Hatipoglu, Emine, O'Flaherty, Linda, Ternette, Nicola, Sahgal, Natasha, Lockstone, Helen, Baban, Dilair, Nye, Emma, Stamp, Gordon W., Wolhuter, Kathryn, Stevens, Marcus, Fischer, Roman, Carmeliet, Peter, Maxwell, Patrick H., Pugh, Chris W., Frizzell, Norma, Soga, Tomoyoshi, Kessler, Benedikt M., El-Bahrawy, Mona, Ratcliffe, Peter J., and Pollard, Patrick J.

Published
2011
Full Text
View/download PDF

50. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

Author

Au, Lewis, primary, Hatipoglu, Emine, additional, Robert de Massy, Marc, additional, Litchfield, Kevin, additional, Beattie, Gordon, additional, Rowan, Andrew, additional, Schnidrig, Desiree, additional, Thompson, Rachael, additional, Byrne, Fiona, additional, Horswell, Stuart, additional, Fotiadis, Nicos, additional, Hazell, Steve, additional, Nicol, David, additional, Shepherd, Scott T.C., additional, Fendler, Annika, additional, Mason, Robert, additional, Del Rosario, Lyra, additional, Edmonds, Kim, additional, Lingard, Karla, additional, Sarker, Sarah, additional, Mangwende, Mary, additional, Carlyle, Eleanor, additional, Attig, Jan, additional, Joshi, Kroopa, additional, Uddin, Imran, additional, Becker, Pablo D., additional, Sunderland, Mariana Werner, additional, Akarca, Ayse, additional, Puccio, Ignazio, additional, Yang, William W., additional, Lund, Tom, additional, Dhillon, Kim, additional, Vasquez, Marcos Duran, additional, Ghorani, Ehsan, additional, Xu, Hang, additional, Spencer, Charlotte, additional, López, José I., additional, Green, Anna, additional, Mahadeva, Ula, additional, Borg, Elaine, additional, Mitchison, Miriam, additional, Moore, David A., additional, Proctor, Ian, additional, Falzon, Mary, additional, Pickering, Lisa, additional, Furness, Andrew J.S., additional, Reading, James L., additional, Salgado, Roberto, additional, Marafioti, Teresa, additional, Jamal-Hanjani, Mariam, additional, Kassiotis, George, additional, Chain, Benny, additional, Larkin, James, additional, Swanton, Charles, additional, Quezada, Sergio A., additional, Turajlic, Samra, additional, Abbosh, Chris, additional, Shiu, Kai-Keen, additional, Bridgewater, John, additional, Hochhauser, Daniel, additional, Forster, Martin, additional, Lee, Siow-Ming, additional, Ahmad, Tanya, additional, Papadatos-Pastos, Dionysis, additional, Janes, Sam, additional, Van Loo, Peter, additional, Enfield, Katey, additional, McGranahan, Nicholas, additional, Huebner, Ariana, additional, Beck, Stephan, additional, Parker, Peter, additional, Walczak, Henning, additional, Enver, Tariq, additional, Hynds, Rob, additional, Sinclair, Ron, additional, Lok, Chi-wah, additional, Rhodes, Zoe, additional, Moore, David, additional, Khiroya, Reena, additional, Trevisan, Giorgia, additional, Ellery, Peter, additional, Linch, Mark, additional, Brandner, Sebastian, additional, Hiley, Crispin, additional, Veeriah, Selvaraju, additional, Razaq, Maryam, additional, Shaw, Heather, additional, Attard, Gert, additional, Akther, Mita Afroza, additional, Naceur-Lombardelli, Cristina, additional, Manzano, Lizi, additional, Al-Bakir, Maise, additional, Summan, Simranpreet, additional, Kanu, Nnenna, additional, Ward, Sophie, additional, Asghar, Uzma, additional, Lim, Emilia, additional, Gishen, Faye, additional, Tookman, Adrian, additional, Stone, Paddy, additional, Stirling, Caroline, additional, Hunter, Nikki, additional, Vaughan, Sarah, additional, Spain, Lavinia, additional, Yan, Haixi, additional, Shum, Ben, additional, Yousaf, Nadia, additional, Popat, Sanjay, additional, Curtis, Olivia, additional, Stamp, Gordon, additional, Toncheva, Antonia, additional, Nye, Emma, additional, Murra, Aida, additional, Korteweg, Justine, additional, Josephs, Debra, additional, Chandra, Ashish, additional, Spicer, James, additional, Stewart, Ruby, additional, Iredale, Lara-Rose, additional, Mackay, Tina, additional, Deakin, Ben, additional, Enting, Debra, additional, Rudman, Sarah, additional, Ghosh, Sharmistha, additional, Karapagniotou, Lena, additional, Pintus, Elias, additional, Tutt, Andrew, additional, Howlett, Sarah, additional, Michalarea, Vasiliki, additional, Brenton, James, additional, Caldas, Carlos, additional, Fitzgerald, Rebecca, additional, Jimenez-Linan, Merche, additional, Provenzano, Elena, additional, Cluroe, Alison, additional, Stewart, Grant, additional, Watts, Colin, additional, Gilbertson, Richard, additional, McDermott, Ultan, additional, Tavare, Simon, additional, Beddowes, Emma, additional, Roxburgh, Patricia, additional, Biankin, Andrew, additional, Chalmers, Anthony, additional, Fraser, Sioban, additional, Oien, Karin, additional, Kidd, Andrew, additional, Blyth, Kevin, additional, Krebs, Matt, additional, Blackhall, Fiona, additional, Summers, Yvonne, additional, Dive, Caroline, additional, Marais, Richard, additional, Gomes, Fabio, additional, Carter, Mat, additional, Dransfield, Jo, additional, Le Quesne, John, additional, Fennell, Dean, additional, Shaw, Jacqui, additional, Naidu, Babu, additional, Baijal, Shobhit, additional, Tanchel, Bruce, additional, Langman, Gerald, additional, Robinson, Andrew, additional, Collard, Martin, additional, Cockcroft, Peter, additional, Ferris, Charlotte, additional, Bancroft, Hollie, additional, Kerr, Amy, additional, Middleton, Gary, additional, Webb, Joanne, additional, Kadiri, Salma, additional, Colloby, Peter, additional, Olisemeke, Bernard, additional, Wilson, Rodelaine, additional, Tomlinson, Ian, additional, Jogai, Sanjay, additional, Ottensmeier, Christian, additional, Harrison, David, additional, Loda, Massimo, additional, Flanagan, Adrienne, additional, McKenzie, Mairead, additional, Hackshaw, Allan, additional, Ledermann, Jonathan, additional, Chan, Kitty, additional, Sharp, Abby, additional, Farrelly, Laura, additional, Bridger, Hayley, additional, Challacombe, Ben, additional, Chowdhury, Simon, additional, Drake, William, additional, Fernando, Archana, additional, Harrison-Phipps, Karen, additional, Hill, Peter, additional, Horsfield, Catherine, additional, O'Brien, Tim, additional, Olsburgh, Jonathon, additional, Polson, Alexander, additional, Varia, Mary, additional, and Verma, Hema, additional

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results