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4. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Author

Loibl, S., primary, André, F., additional, Bachelot, T., additional, Barrios, C.H., additional, Bergh, J., additional, Burstein, H.J., additional, Cardoso, M.J., additional, Carey, L.A., additional, Dawood, S., additional, Del Mastro, L., additional, Denkert, C., additional, Fallenberg, E.M., additional, Francis, P.A., additional, Gamal-Eldin, H., additional, Gelmon, K., additional, Geyer, C.E., additional, Gnant, M., additional, Guarneri, V., additional, Gupta, S., additional, Kim, S.B., additional, Krug, D., additional, Martin, M., additional, Meattini, I., additional, Morrow, M., additional, Janni, W., additional, Paluch-Shimon, S., additional, Partridge, A., additional, Poortmans, P., additional, Pusztai, L., additional, Regan, M.M., additional, Sparano, J., additional, Spanic, T., additional, Swain, S., additional, Tjulandin, S., additional, Toi, M., additional, Trapani, D., additional, Tutt, A., additional, Xu, B., additional, Curigliano, G., additional, and Harbeck, N., additional

Published
2024
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5. Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer

Author

Harvey-Jones, E., primary, Raghunandan, M., additional, Robbez-Masson, L., additional, Magraner-Pardo, L., additional, Alaguthurai, T., additional, Yablonovitch, A., additional, Yen, J., additional, Xiao, H., additional, Brough, R., additional, Frankum, J., additional, Song, F., additional, Yeung, J., additional, Savy, T., additional, Gulati, A., additional, Alexander, J., additional, Kemp, H., additional, Starling, C., additional, Konde, A., additional, Marlow, R., additional, Cheang, M., additional, Proszek, P., additional, Hubank, M., additional, Cai, M., additional, Trendell, J., additional, Lu, R., additional, Liccardo, R., additional, Ravindran, N., additional, Llop-Guevara, A., additional, Rodriguez, O., additional, Balmana, J., additional, Lukashchuk, N., additional, Dorschner, M., additional, Drusbosky, L., additional, Roxanis, I., additional, Serra, V., additional, Haider, S., additional, Pettitt, S.J., additional, Lord, C.J., additional, and Tutt, A.N.J., additional

Published
2024
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6. Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials

Author

Taylor, Carolyn, primary, Dodwell, David, additional, McGale, Paul, additional, Hills, Robert K, additional, Berry, Richard, additional, Bradley, Rosie, additional, Braybrooke, Jeremy, additional, Clarke, Mike, additional, Gray, Richard, additional, Holt, Francesca, additional, Liu, Zulian, additional, Pan, Hongchao, additional, Peto, Richard, additional, Straiton, Ewan, additional, Coles, Charlotte, additional, Duane, Fran, additional, Hennequin, Christophe, additional, Jones, Glenn, additional, Kühn, Thorsten, additional, Oliveros, Sileida, additional, Overgaard, Jens, additional, Pritchard, Kathy I, additional, Suh, Chang-Ok, additional, Beake, Graham, additional, Boddington, Clare, additional, Davies, Christina, additional, Davies, Lucy, additional, Evans, Vaughan, additional, Gay, Jo, additional, Gettins, Lucy, additional, Godwin, Jon, additional, James, Sam, additional, Kerr, Amanda, additional, Liu, Hui, additional, MacKinnon, Elizabeth, additional, Mannu, Gurdeep, additional, McHugh, Theresa, additional, Morris, Philip, additional, Nakahara, Mariko, additional, Read, Simon, additional, Taylor, Hannah, additional, Ferguson, John, additional, Scheurlen, Hans, additional, Zurrida, Stefano, additional, Galimberti, Viviana, additional, Ingle, James, additional, Valagussa, Pinuccia, additional, Veronesi, Umberto, additional, Anderson, Stewart, additional, Tang, Gong, additional, Fisher, Bernard, additional, Fossa, Sophie, additional, Valborg Reinertsen, Kristin, additional, Host, Herman, additional, Muss, Hyman, additional, Holli, Kaija, additional, Albain, Kathy, additional, Arriagada, Rodrigo, additional, Bartlett, John, additional, Bergsten-Nordström, Elizabeth, additional, Bliss, Judith, additional, Brain, Etienne, additional, Carey, Lisa, additional, Coleman, Robert, additional, Cuzick, Jack, additional, Davidson, Nancy, additional, Del Mastro, Lucia, additional, Di Leo, Angelo, additional, Dignam, James, additional, Dowsett, Mitch, additional, Ejlertsen, Bent, additional, Francis, Prue, additional, García-Sáenz, José Angel, additional, Gelber, Rich, additional, Gnant, Michael, additional, Goetz, Matthew, additional, Goodwin, Pam, additional, Halpin-Murphy, Pat, additional, Hayes, Dan, additional, Hill, Catherine, additional, Jagsi, Reshma, additional, Janni, Wolfgang, additional, Loibl, Sibylle, additional, Mamounas, Eleftherios, additional, Martín, Miguel, additional, McIntosh, Stuart, additional, Mukai, Hirofumi, additional, Nekljudova, Valentina, additional, Norton, Larry, additional, Ohashi, Yasuo, additional, Piccart, Martine, additional, Pierce, Lori, additional, Raina, Vinod, additional, Rea, Daniel, additional, Regan, Meredith, additional, Robertson, John, additional, Rutgers, Emiel, additional, Salgado, Roberto, additional, Slamon, Dennis, additional, Spanic, Tanja, additional, Sparano, Joseph, additional, Steger, Guenther, additional, Toi, Masakazu, additional, Tutt, Andrew, additional, Viale, Giuseppe, additional, Wang, Xiang, additional, Wilcken, Nicholas, additional, Wolmark, Norman, additional, Yu, Ke-Da, additional, Cameron, David, additional, Bergh, Jonas, additional, Swain, Sandra, additional, Whelan, Tim, additional, and Poortmans, Philip, additional

Published
2023
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7. Systemic Therapy for Hereditary Breast Cancers

Author

Elizabeth J. Harvey-Jones, Christopher J. Lord, and Andrew N.J. Tutt

Subjects
DNA Repair, Oncology, Genes, BRCA2, Humans, Female, Breast Neoplasms, Hematology, Poly(ADP-ribose) Polymerase Inhibitors
Abstract

Approximately 5% to 10% of all breast cancers are hereditary; many of which are caused by pathogenic variants in genes required for homologous recombination, including BRCA1 and BRCA2. Here we discuss systemic treatment for such breast cancers, including approved chemotherapeutic approaches and also targeted treatment approaches using poly-(ADP ribose) polymerase inhibitors. We also discuss experimental approaches to treating hereditary breast cancer, including new small molecule DNA repair inhibitors and also immunomodulatory agents. Finally, we discuss how drug resistance emerges in patients with hereditary breast cancer, how this might be delayed or prevented, and how biomarker-adapted treatment is molding the future management of hereditary breast cancer.

Published
2023

8. Utilizing video simulation in interprofessional education to teach IPEC competencies and social determinants of health: A universal IPE teaching tool

Author

Batteson, Tamzin J., primary, Chirica, Marianne G., additional, Fox, Kelli S., additional, Froehlich, Jan, additional, Garber, Sarah S., additional, Lambdin-Pattavina, Carol, additional, McCormack Tutt, Sally A., additional, Ochs, Leslie, additional, Rodriguez, Kira, additional, Ross, Nancy Jo, additional, and Thuente, Lori, additional

Published
2023
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9. MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells

Author

Zelceski, Anabel, primary, Francica, Paola, additional, Lingg, Lea, additional, Mutlu, Merve, additional, Stok, Colin, additional, Liptay, Martin, additional, Alexander, John, additional, Baxter, Joseph S., additional, Brough, Rachel, additional, Gulati, Aditi, additional, Haider, Syed, additional, Raghunandan, Maya, additional, Song, Feifei, additional, Sridhar, Sandhya, additional, Forment, Josep V., additional, O’Connor, Mark J., additional, Davies, Barry R., additional, van Vugt, Marcel A.T.M., additional, Krastev, Dragomir B., additional, Pettitt, Stephen J., additional, Tutt, Andrew N.J., additional, Rottenberg, Sven, additional, and Lord, Christopher J., additional

Published
2023
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11. Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials

Author

Braybrooke, Jeremy, primary, Bradley, Rosie, additional, Gray, Richard, additional, Hills, Robert K, additional, Pan, Hongchao, additional, Peto, Richard, additional, Dodwell, David, additional, McGale, Paul, additional, Taylor, Carolyn, additional, Aihara, Tomohiko, additional, Anderson, Stewart, additional, Blum, Joanne, additional, Cardoso, Fatima, additional, Chen, Xiaosong, additional, Crown, John P, additional, Ejlertsen, Bent, additional, Friedl, Thomas W P, additional, Harbeck, Nadia, additional, Janni, Wolfgang, additional, Jensen, Maj-Britt, additional, Mamounas, Eleftherios, additional, Narui, Kazutaka, additional, Nitz, Ulrike, additional, Norton, Larry, additional, O'Shaughnessy, Joyce, additional, Piccart, Martine, additional, Robert, Nicholas, additional, Shao, Zhi-Ming, additional, Slamon, Dennis, additional, Sparano, Joseph, additional, Watanabe, Toru, additional, Yothers, Greg, additional, Yu, Ke-Da, additional, Berry, Richard, additional, Boddington, Clare, additional, Clarke, Mike, additional, Davies, Christina, additional, Davies, Lucy, additional, Duane, Fran, additional, Evans, Vaughan, additional, Gay, Jo, additional, Gettins, Lucy, additional, Godwin, Jon, additional, James, Sam, additional, Lui, Hui, additional, Lui, Zulian, additional, MacKinnon, Elizabeth, additional, Mannu, Gurdeep, additional, McHugh, Theresa, additional, Morris, Philip, additional, Read, Simon, additional, Straiton, Ewan, additional, Buzdar, Aman, additional, Suman, Vera J, additional, Hunt, Kelly K, additional, Leonard, Robert C F, additional, Mansi, Janine, additional, Delbaldo, Catherine, additional, Piedbois, Pascal, additional, Quinaux, Emmanuel, additional, Fesl, Christian, additional, Gnant, Michael, additional, Sölkner, Lidija, additional, Steger, Guenther, additional, Eikesdal, Hans Petter, additional, Lønning, Per Eystein, additional, Bee, Valerie, additional, Fung, Helena, additional, Mackey, John, additional, Martin, Miguel, additional, Press, Michael, additional, De Azambuja, Evandro, additional, Gelber, Richard, additional, Regan, Meredith, additional, Di Leo, Angelo, additional, Van Dooren, Veerle, additional, Nogaret, Jean Marie, additional, Bartlett, John, additional, Chen, Bingshu E, additional, Gelmon, Karen, additional, Goss, Paul E, additional, Levine, Mark N, additional, Parulekar, Wendy, additional, Pritchard, Kathleen I, additional, Shepherd, Lois, additional, Berry, Donald, additional, Cirrincione, Constance, additional, Shulman, Lawrence N, additional, Winer, Eric, additional, Gelman, Rebecca S, additional, Harris, Jay R, additional, Henderson, Craig, additional, Shapiro, Charles L, additional, Christiansen, Peer, additional, Ewertz, Marianne, additional, Mouridsen, Henning T, additional, Van Leeuwen, Elise, additional, Linn, Sabine, additional, Van Rossum, Annelot G J, additional, Van Tinteren, Harm, additional, Van Werkhoven, Erik, additional, Goldstein, Lori, additional, Gray, Robert, additional, Eiermann, Wolfgang, additional, Gianni, Luca, additional, Valagussa, Pinuccia, additional, Bogaerts, Jan, additional, Bonnefoi, Herve, additional, Poncet, Coralie, additional, Huovinen, Riikka, additional, Joensuu, Heikki, additional, Bonneterre, Jacques, additional, Fargeot, Pierre, additional, Fumoleau, Pierre, additional, Kerbrat, Pierre, additional, Luporsi, Elisabeth, additional, Namer, Moïse, additional, Carrasco, Eva M, additional, Segui, Miguel Angel, additional, Meisner, Christoph, additional, Loibl, Sibylle, additional, Nekljudova, Valentina, additional, Thomssen, Christoph, additional, Von Minckwitz, Gunter, additional, Kümmel, Sherko, additional, Lopez, Massimo, additional, Vici, Patrizia, additional, Fountzilas, George, additional, Koliou, Georgia, additional, Mavroudis, Dimitrios, additional, Saloustros, Emmanouil, additional, Brain, Etienne, additional, Delaloge, Suzette, additional, Michiels, Stefan, additional, Mathoulin-Pelissier, Simone, additional, Bines, Jose, additional, Sarmento, Roberta M B, additional, Bonadonna, Gianni, additional, Brambilla, Cristina, additional, Rossi, Anna, additional, Bliss, Judith, additional, Coombes, Raoul Charles, additional, Kilburn, Lucy, additional, Marty, Michel, additional, Amadori, Dino, additional, Boccardo, Francesco, additional, Nanni, Oriana, additional, Rubagotti, Alessandra, additional, Scarpi, Emanuela, additional, Masuda, Norikazu, additional, Toi, Masakazu, additional, Ueno, Takayuki, additional, Ishikawa, Takashi, additional, Matsumoto, Koji, additional, Takao, Shintaro, additional, Sommer, Harald, additional, Foroglou, Pericles, additional, Giokas, George, additional, Kondylis, D, additional, Lissaios, Byron, additional, Reinisch, Mattea, additional, Lee, Keun Seok, additional, Nam, Byung-Ho, additional, Ro, Jung Sil, additional, De Matteis, Andrea, additional, Perrone, Francesco, additional, Tang, Gong, additional, Wolmark, Norman, additional, Hozumi, Yasuo, additional, Nomura, Yasuo, additional, Earl, Helena, additional, Hiller, Louise, additional, Vallier, Anne-Laure, additional, De Mastro, Lucia, additional, Venturini, Macro, additional, Delozier, Thierry, additional, Lemonnier, Jerome, additional, Martin, Anne-Laure, additional, Roché, Henri, additional, Spielmann, Marc, additional, Chen, Xiasong, additional, Shen, Kunwei, additional, Albain, Kathy, additional, Barlow, William, additional, Budd, George T, additional, Gralow, Julie, additional, Hayes, Dan, additional, Bartlett-Lee, Peter, additional, Ellis, Paul, additional, Bianco, Angelo Raffaele, additional, De Laurentiis, Michelino, additional, De Placido, Sabino, additional, Wildiers, Hans, additional, Hsu, Limin, additional, Eremin, Oleg, additional, Walker, Leslie G, additional, Ahlgren, Johan, additional, Blomqvist, Carl, additional, Holmberg, Lars, additional, Lindman, Henrik, additional, Asmar, Lina, additional, Jones, Stephen E, additional, Gluz, Oleg, additional, Liedtke, Cornelia, additional, Arriagada, Rodrigo, additional, Bergsten-Nordström, Elizabeth, additional, Carey, Lisa, additional, Coleman, Robert, additional, Cuzick, Jack, additional, Davidson, Nancy, additional, Dignam, James, additional, Dowsett, Mitch, additional, Francis, Prudence A, additional, Goetz, Matthew P, additional, Goodwin, Pam, additional, Halpin-Murphy, Pat, additional, Hill, Catherine, additional, Jagsi, Reshma, additional, Mukai, Hirofumi, additional, Ohashi, Yasuo, additional, Pierce, Lori, additional, Poortmans, Philip, additional, Raina, Vinod, additional, Rea, Daniel, additional, Robertson, John, additional, Rutgers, Emiel, additional, Salgado, Roberto, additional, Spanic, Tanja, additional, Tutt, Andrew, additional, Viale, Giuseppe, additional, Wang, Xiang, additional, Whelan, Tim, additional, Wilcken, Nicholas, additional, Cameron, David, additional, Bergh, Jonas, additional, and Swain, Sandra M, additional

Published
2023
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17. The anion channel GPR89 is a novel oncogene associated with tumour specific dependency in breast cancer

Author

Ferro, R., primary, Carroll, A., additional, Mendes-Pereira, A., additional, Reen, V., additional, Roxanis, I., additional, Annunziato, S., additional, Jonkers, J., additional, Liv, N., additional, Alexander, J., additional, Quist, J., additional, Pardo, M., additional, Roumeliotis, T.I., additional, Choudhary, J.S., additional, Weekes, D., additional, Marra, P., additional, Natrajan, R., additional, Grigoriadis, A., additional, Haider, S., additional, Lord, C.J., additional, and Tutt, A.J., additional

Published
2022
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20. REX: X-ray experiment on the water recovery rocket

Author

Vladimir Daniel, Martin Urban, Ladislav Sieger, Adolf Inneman, Daniela Doubravova, Ladislav Pina, James H. Tutt, Ted Schultz, Randall L. McEntaffer, Ondřej Nentvich, V. Marsikova, Ivo Veřtát, Tomas Baca, and Drew M. Miles

Subjects
Physics, 020301 aerospace & aeronautics, business.product_category, Sounding rocket, Infrared, Detector, FOS: Physical sciences, Aerospace Engineering, 02 engineering and technology, 01 natural sciences, law.invention, Telescope, 0203 mechanical engineering, Rocket, law, 0103 physical sciences, Focal length, Satellite, Astrophysics - Instrumentation and Methods for Astrophysics, Supernova remnant, business, Instrumentation and Methods for Astrophysics (astro-ph.IM), 010303 astronomy & astrophysics, Remote sensing
Abstract

This paper presents Rocket Experiment (REX) that was part of a dual payload rocket campaign for NASA's sounding rocket Black Brant IX with water recovery technology. This mission was a suborbital sounding rocket flight that was launched and recovered on April 4, 2018 and targeted the Vela supernova remnant. The purpose of REX was to classify the Technology Readiness Level of onboard devices designed for space applications. The devices were two wide-field X-ray telescopes consisting of a combination of Lobster-Eye (LE) optics with an uncooled Timepix detector (256 x 256 px @ 55 um), and additional sensors. The first telescope uses a two-dimensional combination of LE modules with a focal length of 1 m and a Field of View (FOV) of 1.0 x 1.2 deg and operates in the energy range of 3 - 60 keV. The second telescope was a one-dimensional LE with a focal length of 250 mm and a FOV of 2.7 x 8.0 deg for the energy range 3 - 40 keV. The X-ray telescopes were supplemented by a camera in the visible spectrum with 1,280 x 1,024 px resolution, which was used to obtain images of the observed sources and to verify the resulting pointing of the rocket carrier. Other devices also include infrared array sensors and inertial measurement units tested for future small satellite missions. The data handler and communication system were built using the Robot Operating System, and both the system and the electronics were deployed and operated in flight. The hardware was successfully recovered after the launch and the data were extracted., Comment: Submitted to Acta Astronautica

Published
2021

23. FcγRIIB controls antibody-mediated target cell depletion by ITIM-independent mechanisms

Author

Simpson, Alexander P., primary, Roghanian, Ali, additional, Oldham, Robert J., additional, Chan, H.T. Claude, additional, Penfold, Christine A., additional, Kim, Hyung J., additional, Inzhelevskaya, Tatyana, additional, Mockridge, C. Ian, additional, Cox, Kerry L., additional, Bogdanov, Yury D., additional, James, Sonya, additional, Tutt, Alison L., additional, Rycroft, Daniel, additional, Morley, Peter, additional, Dahal, Lekh N., additional, Teige, Ingrid, additional, Frendeus, Björn, additional, Beers, Stephen A., additional, and Cragg, Mark S., additional

Published
2022
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25. Analysis of bovine blastocysts indicates ovarian stimulation does not induce chromosome errors, nor discordance between inner-cell mass and trophectoderm lineages

Author

Giuseppe Silvestri, R.J. Simmons, G. Guven-Ates, Carla Canedo-Ribeiro, Rémi Labrecque, Alan H. Handyside, Patrick Blondin, Darren K. Griffin, Wing Yee Kwong, Kevin D. Sinclair, Desmond A. R. Tutt, and María Serrano-Albal

Subjects
medicine.medical_specialty, Biopsy, Theriogenology, Cattle Diseases, Aneuploidy, Aneuploidy, Cattle, Ovarian stimulation, In vitro culture, Blastocyst, Biopsy, Biology, Chromosomes, Article, In vitro culture, Andrology, 03 medical and health sciences, 0302 clinical medicine, Ovulation Induction, Food Animals, Meiosis, Pregnancy, Follicular phase, medicine, Animals, Inner cell mass, Blastocyst, Small Animals, Preimplantation Diagnosis, 030219 obstetrics & reproductive medicine, Equine, 0402 animal and dairy science, Embryo, 04 agricultural and veterinary sciences, Abortion, Veterinary, medicine.disease, Oocyte, 040201 dairy & animal science, medicine.anatomical_structure, embryonic structures, Cattle, Female, Animal Science and Zoology, Ovarian stimulation
Abstract

Contemporary systems for oocyte retrieval and culture of both cattle and human embryos are suboptimal with respect to pregnancy outcomes following transfer. In humans, chromosome abnormalities are the leading cause of early pregnancy loss in assisted reproduction. Consequently, pre-implantation genetic testing for aneuploidy (PGT-A) is widespread and there is considerable interest in its application to identify suitable cattle IVP embryos for transfer. Here we report on the nature and extent of chromosomal abnormalities following transvaginal follicular aspiration (OPU) and IVP in cattle. Nine sexually mature Holstein heifers underwent nine sequential cycles of OPU-IVP (six non-stimulated and three stimulated cycles), generating 459 blastocysts from 783 oocytes. We adopted a SNP-array approach normally employed in genomic evaluations but reanalysed (Turner et al., 2019; Theriogenology125: 249) to detect levels of meiotic aneuploidy. Specifically, we asked whether ovarian stimulation increased the level of aneuploidy in either trophectoderm (TE) or inner-cell mass (ICM) lineages of blastocysts generated from OPU-IVP cycles. The proportion of Day 8 blastocysts of inseminated was greater (P, Highlights • In vitro oocyte maturation rather than ovarian stimulation contributes to aneuploidy. • Trophectoderm biopsies accurately represent the ploidy status of the overall embryo. • SNP-array analyses facilitate simultaneous genomic evaluation and aneuploidy screening. • Incidence of aneuploidy declines in developmentally more advanced embryos. • High degree of variability in the incidence of aneuploidy exists between donors.

Published
2021

26. Assessment of structural chromosomal instability phenotypes as biomarkers of carboplatin response in triple negative breast cancer: the TNT trial

Author

Cheryl Gillett, C. Toms, Julie Owen, Sarah Kernaghan, Holly Tovey, Andrew Tutt, Patrycja Gazinska, Judith M Bliss, Sarah Maguire, Sabine C. Linn, Maggie C.U. Cheang, Orsolya Sipos, Sarah E Pinder, Salpie Nowinski, Syed Haider, Nick Orr, Anita Grigoriadis, and Jelmar Quist

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Triple Negative Breast Neoplasms, Loss of heterozygosity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Chromosomal Instability, Chromosome instability, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Allele, neoplasms, Triple-negative breast cancer, business.industry, Hematology, genomic instability, Phenotype, Carboplatin, 030104 developmental biology, Docetaxel, chemistry, allelic imbalance, 030220 oncology & carcinogenesis, carboplatin, Allelic Imbalance, Original Article, metastatic triple negative breast cancer, business, Biomarkers, medicine.drug
Abstract

Background In the TNT trial of triple negative breast cancer (NCT00532727), germline BRCA1/2 mutations were present in 28% of carboplatin responders. We assessed quantitative measures of structural chromosomal instability (CIN) to identify a wider patient subgroup within TNT with preferential benefit from carboplatin over docetaxel. Patients and methods Copy number aberrations (CNAs) were established from 135 formalin-fixed paraffin-embedded primary carcinomas using Illumina OmniExpress SNP-arrays. Seven published [allelic imbalanced CNA (AiCNA); allelic balanced CNA (AbCNA); copy number neutral loss of heterozygosity (CnLOH); number of telomeric allelic imbalances (NtAI); BRCA1-like status; percentage of genome altered (PGA); homologous recombination deficiency (HRD) scores] and two novel [Shannon diversity index (SI); high-level amplifications (HLAMP)] CIN-measurements were derived. HLAMP was defined based on the presence of at least one of the top 5% amplified cytobands located on 1q, 8q and 10p. Continuous CIN-measurements were divided into tertiles. All nine CIN-measurements were used to analyse objective response rate (ORR) and progression-free survival (PFS). Results Patients with tumours without HLAMP had a numerically higher ORR and significantly longer PFS in the carboplatin (C) than in the docetaxel (D) arm [56% (C) versus 29% (D), PHLAMP,quiet = 0.085; PFS 6.1 months (C) versus 4.1 months (D), Pinteraction/HLAMP = 0.047]. In the carboplatin arm, patients with tumours showing intermediate telomeric NtAI and AiCNA had higher ORR [54% (C) versus 20% (D), PNtAI,intermediate = 0.03; 62% (C) versus 33% (D), PAiCNA,intermediate = 0.076]. Patients with high AiCNA and PGA had shorter PFS in the carboplatin arm [3.4 months (high) versus 5.7 months (low/intermediate); and 3.8 months (high) versus 5.6 months (low/intermediate), respectively; Pinteraction/AiCNA = 0.027, Padj.interaction/AiCNA = 0.125 and Pinteraction/PGA = 0.053, Padj.interaction/PGA = 0.176], whilst no difference was observed in the docetaxel arm. Conclusions Patients with tumours lacking HLAMP and demonstrating intermediate CIN-measurements formed a subgroup benefitting from carboplatin relative to docetaxel treatment within the TNT trial. This suggests a complex and paradoxical relationship between the extent of genomic instability in primary tumours and treatment response in the metastatic setting., Highlights • Patients with intermediate levels of allelic imbalanced CNAs show a better response rate to carboplatin in TNT. • The lack of amplifications on 1q, 8q and 10p is associated with a superior carboplatin response in TNT. • The relation between chromosomal instability in primary tumours and carboplatin response in advanced settings is non-linear.

Published
2021

27. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Author

Richard Gray, Rosie Bradley, Jeremy Braybrooke, Zulian Liu, Richard Peto, Lucy Davies, David Dodwell, Paul McGale, Hongchao Pan, Carolyn Taylor, William Barlow, Judith Bliss, Paolo Bruzzi, David Cameron, George Fountzilas, Sibylle Loibl, John Mackey, Miguel Martin, Lucia Del Mastro, Volker Möbus, Valentina Nekljudova, Sabino De Placido, Sandra Swain, Michael Untch, Kathleen I Pritchard, Jonas Bergh, Larry Norton, Clare Boddington, Julie Burrett, Mike Clarke, Christina Davies, Fran Duane, Vaughan Evans, Lucy Gettins, Jon Godwin, Robert Hills, Sam James, Hui Liu, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Simon Read, Yaochen Wang, Zhe Wang, Peter Fasching, Nadia Harbeck, Pascal Piedbois, Michael Gnant, Guenther Steger, Angelo Di Leo, Stella Dolci, Prue Francis, Denis Larsimont, Jean Marie Nogaret, Catherine Philippson, Martine Piccart, Sabine Linn, Petronella Peer, Vivianne Tjan-Heijnen, Sonja Vliek, Dennis Slamon, John Bartlett, Vivien H Bramwell, Bingshu Chen, Stephen Chia, Karen Gelmon, Paul Goss, Mark Levine, Wendy Parulekar, Joseph Pater, Eileen Rakovitch, Lois Shepherd, Dongsheng Tu, Tim Whelan, Don Berry, Gloria Broadwater, Constance Cirrincione, Hyman Muss, Raymond Weiss, Yi Shan, Yong Fu Shao, Xiang Wang, Binghe Xu, Dong-Bing Zhao, Harry Bartelink, Nina Bijker, Jan Bogaerts, Fatima Cardoso, Tanja Cufer, Jean-Pierre Julien, Philip Poortmans, Emiel Rutgers, Cornelis van de Velde, Eva Carrasco, Miguel Angel Segui, Jens Uwe Blohmer, Serban Costa, Bernd Gerber, Christian Jackisch, Gunter von Minckwitz, Mario Giuliano, Michele De Laurentiis, Christina Bamia, Georgia-Angeliki Koliou, Dimitris Mavroudis, Roger A'Hern, Paul Ellis, Lucy Kilburn, James Morden, John Yarnold, Mohammad Sadoon, Augustinus H Tulusan, Stewart Anderson, Gordon Bass, Joe Costantino, James Dignam, Bernard Fisher, Charles Geyer, Eleftherios P Mamounas, Soon Paik, Carol Redmond, D Lawrence Wickerham, Marco Venturini, Claudia Bighin, Simona Pastorino, Paolo Pronzato, Mario Roberto Sertoli, Theodorus Foukakis, Kathy Albain, Rodrigo Arriagada, Elizabeth Bergsten Nordström, Francesco Boccardo, Etienne Brain, Lisa Carey, Alan Coates, Robert Coleman, Candace Correa, Jack Cuzick, Nancy Davidson, Mitch Dowsett, Marianne Ewertz, John Forbes, Richard Gelber, Aron Goldhirsch, Pamela Goodwin, Daniel Hayes, Catherine Hill, James Ingle, Reshma Jagsi, Wolfgang Janni, Hirofumi Mukai, Yasuo Ohashi, Lori Pierce, Vinod Raina, Peter Ravdin, Daniel Rea, Meredith Regan, John Robertson, Joseph Sparano, Andrew Tutt, Giuseppe Viale, Nicholas Wilcken, Norman Wolmark, Wiliam Wood, Milvia Zambetti, Gray, R., Bradley, R., Braybrooke, J., Liu, Z., Peto, R., Davies, L., Dodwell, D., Mcgale, P., Pan, H., Taylor, C., Barlow, W., Bliss, J., Bruzzi, P., Cameron, D., Fountzilas, G., Loibl, S., Mackey, J., Martin, M., Del Mastro, L., Mobus, V., Nekljudova, V., De Placido, S., Swain, S., Untch, M., Pritchard, K. I., Bergh, J., Norton, L., Boddington, C., Burrett, J., Clarke, M., Davies, C., Duane, F., Evans, V., Gettins, L., Godwin, J., Hills, R., James, S., Liu, H., Mackinnon, E., Mannu, G., Mchugh, T., Morris, P., Read, S., Wang, Y., Wang, Z., Fasching, P., Harbeck, N., Piedbois, P., Gnant, M., Steger, G., Di Leo, A., Dolci, S., Francis, P., Larsimont, D., Nogaret, J. M., Philippson, C., Piccart, M., Linn, S., Peer, P., Tjan-Heijnen, V., Vliek, S., Slamon, D., Bartlett, J., Bramwell, V. H., Chen, B., Chia, S., Gelmon, K., Goss, P., Levine, M., Parulekar, W., Pater, J., Rakovitch, E., Shepherd, L., Tu, D., Whelan, T., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Weiss, R., Shan, Y., Shao, Y. F., Wang, X., Xu, B., Zhao, D. -B., Bartelink, H., Bijker, N., Bogaerts, J., Cardoso, F., Cufer, T., Julien, J. -P., Poortmans, P., Rutgers, E., van de Velde, C., Carrasco, E., Segui, M. A., Blohmer, J. U., Costa, S., Gerber, B., Jackisch, C., von Minckwitz, G., Giuliano, M., De Laurentiis, M., Bamia, C., Koliou, G. -A., Mavroudis, D., A'Hern, R., Ellis, P., Kilburn, L., Morden, J., Yarnold, J., Sadoon, M., Tulusan, A. H., Anderson, S., Bass, G., Costantino, J., Dignam, J., Fisher, B., Geyer, C., Mamounas, E. P., Paik, S., Redmond, C., Wickerham, D. L., Venturini, M., Bighin, C., Pastorino, S., Pronzato, P., Sertoli, M. R., Foukakis, T., Albain, K., Arriagada, R., Bergsten Nordstrom, E., Boccardo, F., Brain, E., Carey, L., Coates, A., Coleman, R., Correa, C., Cuzick, J., Davidson, N., Dowsett, M., Ewertz, M., Forbes, J., Gelber, R., Goldhirsch, A., Goodwin, P., Hayes, D., Hill, C., Ingle, J., Jagsi, R., Janni, W., Mukai, H., Ohashi, Y., Pierce, L., Raina, V., Ravdin, P., Rea, D., Regan, M., Robertson, J., Sparano, J., Tutt, A., Viale, G., Wilcken, N., Wolmark, N., Wood, W., and Zambetti, M.

Subjects
Oncology, treatment schedule, medicine.medical_specialty, Anthracycline, medicine.medical_treatment, novotvorbe dojk, Antineoplastic Agents, Breast Neoplasms, režim zdravljenja, Disease, randomized trials, 030204 cardiovascular system & hematology, chemotherapy, meta-analiza, klinični protokoli, Drug Administration Schedule, randomizirane raziskave, Antineoplastic Agent, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, Internal medicine, breast neoplasms, medicine, Humans, clinical protocols, terapija z zdravili, 030212 general & internal medicine, Early breast cancer, Chemotherapy, Taxane, business.industry, rak dojk, kemoterapija, General Medicine, medicine.disease, Dose intensity, udc:618.19-006, drug therapy, meta-analysis, Meta-analysis, Female, women, ženske, business, Breast Neoplasm
Abstract

Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.

Published
2019

28. Process Development and Manufacturing: GROWING A CELL THERAPY FACILITY TO SUPPORT SPONSORED CLINICAL TRIALS AND COMMERCIAL CELL THERAPY PRODUCTS

Author

McIntyre, C., primary, McLeod, M.G., additional, Tutt, T., additional, Petersen, A.G., additional, Lepori-Bui, N., additional, Patel, S., additional, Monterola, G., additional, Siddiqui, A., additional, Villar, K., additional, Tran, C., additional, Bainter, C., additional, Pham, T., additional, Diaz, N., additional, Lim, L., additional, Dibian, Z., additional, Wang, L., additional, and Meyer, E., additional

Published
2022
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29. Regulatory Affairs, Quality Systems, Policy, and Ethics: INVESTIGATING PARTICULATES IN CELLULAR THERAPY PRODUCTS

Author

Tutt, T., primary, Pham, T., additional, Brown, A., additional, Chinnasamy, H., additional, Feldman, S., additional, Egeler, E., additional, Patel, S., additional, Majzner, R., additional, Mackall, C., additional, Monje, M., additional, McLeod, M.G., additional, Lepori-Bui, N., additional, Villar, K., additional, Siddiqui, A., additional, Diaz, N., additional, Sukle, N., additional, McIntyre, C., additional, and Meyer, E., additional

Published
2022
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30. VP1-2022: Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer

Author

Tutt, A.N.J., primary, Garber, J., additional, Gelber, R.D., additional, Phillips, K-A., additional, Eisen, A., additional, Johannsson, O.T., additional, Rastogi, P., additional, Cui, K.Y., additional, Im, S-A., additional, Yerushalmi, R., additional, Brufsky, A.M., additional, Taboada, M., additional, Rossi, G., additional, Yothers, G., additional, Singer, C., additional, Fein, L.E., additional, Loman, N., additional, Cameron, D., additional, Campbell, C., additional, and Geyer, C.E., additional

Published
2022
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31. Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials

Author

Bradley, Rosie, primary, Braybrooke, Jeremy, additional, Gray, Richard, additional, Hills, Robert K, additional, Liu, Zulian, additional, Pan, Hongchao, additional, Peto, Richard, additional, Dodwell, David, additional, McGale, Paul, additional, Taylor, Carolyn, additional, Francis, Prudence A, additional, Gnant, Michael, additional, Perrone, Francesco, additional, Regan, Meredith M, additional, Berry, Richard, additional, Boddington, Clare, additional, Clarke, Mike, additional, Davies, Christina, additional, Davies, Lucy, additional, Duane, Fran, additional, Evans, Vaughan, additional, Gay, Jo, additional, Gettins, Lucy, additional, Godwin, Jon, additional, James, Sam, additional, Liu, Hui, additional, MacKinnon, Elizabeth, additional, Mannu, Gurdeep, additional, McHugh, Theresa, additional, Morris, Philip, additional, Read, Simon, additional, Straiton, Ewan, additional, Jakesz, Raimund, additional, Fesl, Christian, additional, Pagani, Olivia, additional, Gelber, Richard, additional, De Laurentiis, Michelino, additional, De Placido, Sabino, additional, Gallo, Ciro, additional, Albain, Kathy, additional, Anderson, Stewart, additional, Arriagada, Rodrigo, additional, Bartlett, John, additional, Bergsten-Nordström, Elizabeth, additional, Bliss, Judith, additional, Brain, Etienne, additional, Carey, Lisa, additional, Coleman, Robert, additional, Cuzick, Jack, additional, Davidson, Nancy, additional, Del Mastro, Lucia, additional, Di Leo, Angelo, additional, Dignam, James, additional, Dowsett, Mitch, additional, Ejlertsen, Bent, additional, Goetz, Matthew, additional, Goodwin, Pam, additional, Halpin-Murphy, Pat, additional, Hayes, Dan, additional, Hill, Catherine, additional, Jagsi, Reshma, additional, Janni, Wolfgang, additional, Loibl, Sibylle, additional, Mamounas, Eleftherios P, additional, Martín, Miguel, additional, Mukai, Hirofumi, additional, Nekljudova, Valentina, additional, Norton, Larry, additional, Ohashi, Yasuo, additional, Pierce, Lori, additional, Poortmans, Philip, additional, Pritchard, Kathleen I, additional, Raina, Vinod, additional, Rea, Daniel, additional, Robertson, John, additional, Rutgers, Emiel, additional, Spanic, Tanja, additional, Sparano, Joseph, additional, Steger, Guenther, additional, Tang, Gong, additional, Toi, Masakazu, additional, Tutt, Andrew, additional, Viale, Giuseppe, additional, Wang, Xiang, additional, Whelan, Tim, additional, Wilcken, Nicholas, additional, Wolmark, Norman, additional, Cameron, David, additional, Bergh, Jonas, additional, and Swain, Sandra M, additional

Published
2022
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32. A Cluster Randomized Trial of Systematic Targeted Universal Testing for Tuberculosis in Primary Care Clinics of South Africa (The TUTT Study)

Author

Neil A. Martinson, Bareng A.S. Nonyane, Leisha Patricia Genade, Rebecca H. Berhanu, Pren Naidoo, Zameer Brey, Anthony Kinghorn, Sipho Nyathi, Katherine Young, Harry Hausler, Lucy Connell, Keeren Lutchminarain, Khine Swe Swe-Han, Helena Vreede, Mohamed Said, Nina von Knorring, Lawrence H. Moulton, Limakatso Lebina, and TUTT Study Team

Published
2022

34. A Cluster Randomized Trial of Systematic Targeted Universal Testing for Tuberculosis in Primary Care Clinics of South Africa (The TUTT Study)

Author

Martinson, Neil A., primary, Nonyane, Bareng A.S., additional, Genade, Leisha Patricia, additional, Berhanu, Rebecca H., additional, Naidoo, Pren, additional, Brey, Zameer, additional, Kinghorn, Anthony, additional, Nyathi, Sipho, additional, Young, Katherine, additional, Hausler, Harry, additional, Connell, Lucy, additional, Lutchminarain, Keeren, additional, Swe-Han, Khine Swe, additional, Vreede, Helena, additional, Said, Mohamed, additional, von Knorring, Nina, additional, Moulton, Lawrence H., additional, Lebina, Limakatso, additional, and Team, TUTT Study, additional

Published
2022
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35. TGF-β1 potentiates Vγ9Vδ2 T cell adoptive immunotherapy of cancer

Author

Beatson, Richard E., primary, Parente-Pereira, Ana C., additional, Halim, Leena, additional, Cozzetto, Domenico, additional, Hull, Caroline, additional, Whilding, Lynsey M., additional, Martinez, Olivier, additional, Taylor, Chelsea A., additional, Obajdin, Jana, additional, Luu Hoang, Kim Ngan, additional, Draper, Benjamin, additional, Iqbal, Ayesha, additional, Hardiman, Tom, additional, Zabinski, Tomasz, additional, Man, Francis, additional, de Rosales, Rafael T.M., additional, Xie, Jinger, additional, Aswad, Fred, additional, Achkova, Daniela, additional, Joseph, Chung-Yang Ricardo, additional, Ciprut, Sara, additional, Adami, Antonella, additional, Roider, Helge G., additional, Hess-Stumpp, Holger, additional, Győrffy, Balázs, additional, Quist, Jelmar, additional, Grigoriadis, Anita, additional, Sommer, Anette, additional, Tutt, Andrew N.J., additional, Davies, David M., additional, and Maher, John, additional

Published
2021
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40. 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
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42. Impact of deep-ocean eddies and fronts on the shelf seas of a sub-Antarctic Archipelago: The Prince Edward Islands

Author

M.A. van den Berg, Isabelle J. Ansorge, G.C.O. Tutt, and Tarron Lamont

Subjects
0106 biological sciences, Polar front, geography, geography.geographical_feature_category, 010504 meteorology & atmospheric sciences, 010604 marine biology & hydrobiology, Front (oceanography), Geology, Aquatic Science, Oceanography, 01 natural sciences, Deep sea, Water column, Eddy, Anticyclone, Archipelago, Hydrography, 0105 earth and related environmental sciences
Abstract

Ecosystems within the Southern Ocean, such as the Prince Edward Islands (PEIs), fulfil a pivotal role in sustaining rich environments with large populations of top predators. Many of these have already undergone dramatic shifts in response to changes in climate, highlighting the crucial need to enhance our understanding of drivers of oceanographic variability in the region, as well as their impacts on biological communities. Daily averaged bottom temperatures and water-column current speeds from two moorings in the inter-island region, between April 2014 and April 2018, present the first continuous set of high temporal resolution in situ measurements at the PEIs. These data were investigated to determine the influence of passing deep-sea mesoscale eddies and fronts on hydrographic conditions on the inter-island shelf. Warming/cooling events of the order of 0.5–2 °C, sometimes lasting longer than 30 days at a time, concomitant with changes in current speed and direction were associated with advection of waters into the shelf region from passing anticyclonic/cyclonic eddies. Similarly, the impact of frontal movement was quantified by increased current speeds throughout the water column when the southern branch of the sub-Antarctic Front (S-SAF), or the northern branch of the Antarctic Polar Front was in close proximity to the islands. When the S-SAF was located north of the PEIs, bottom temperatures were overall lower due to the stronger influx of Antarctic surface and intermediate waters. In contrast, when the S-SAF was close to or south of the PEIs, bottom temperatures were elevated as a result of the occurrence of larger proportions of warmer, more saline surface and intermediate sub-Antarctic and even Subtropical waters. Notably, the predominance of westerly flow in the southern portion of inter-island region suggested the perpetual existence of a Taylor column which was at times enhanced by the juxtaposition of some eddies.

Published
2019

43. FcγRIIB controls antibody-mediated target cell depletion by ITIM-independent mechanisms

Author

Alexander P. Simpson, Ali Roghanian, Robert J. Oldham, H.T. Claude Chan, Christine A. Penfold, Hyung J. Kim, Tatyana Inzhelevskaya, C. Ian Mockridge, Kerry L. Cox, Yury D. Bogdanov, Sonya James, Alison L. Tutt, Daniel Rycroft, Peter Morley, Lekh N. Dahal, Ingrid Teige, Björn Frendeus, Stephen A. Beers, and Mark S. Cragg

Subjects
Mice, Receptors, IgG, Animals, Antibodies, Monoclonal, Humans, Immunotherapy, General Biochemistry, Genetics and Molecular Biology, Signal Transduction
Abstract

Many therapeutic antibodies deplete target cells and elicit immunotherapy by engaging activating Fc gamma receptors (FcγRs) on host effector cells. These antibodies are negatively regulated by the inhibitory FcγRIIB (CD32B). Dogma suggests inhibition is mediated through the FcγRIIB immunoreceptor tyrosine-based inhibition motif (ITIM), negatively regulating immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling from activating FcγR. To assess this, we generated experimental models expressing human (h)FcγRIIB on targets or effectors, lacking or retaining ITIM signaling capacity. We demonstrate that signaling through the hFcγRIIB ITIM is dispensable for impairing monoclonal antibody (mAb)-mediated depletion of normal and malignant murine target cells through three therapeutically relevant surface receptors (CD20, CD25, and OX40) affecting immunotherapy. We demonstrate that hFcγRIIB competition with activating FcγRs for antibody Fc, rather than ITIM signaling, is sufficient to impair activating FcγR engagement, inhibiting effector function and immunotherapy.

Published
2022

44. Adjuvant Breast Radiotherapy at an Academic Centre during the COVID-19 Pandemic: Reassuringly Safe

Author

Elinor J. Sawyer, C Goldsmith, G Azad, S. Ahmad, Angela Swampillai, Daniel J. Smith, V. Mullassery, J Timbres, A Mera, Andrew Tutt, N. Hanumanthappa, and F Castell

Subjects
Oncology, Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, Letter, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, MEDLINE, Breast radiotherapy, Breast Neoplasms, Internal medicine, Pandemic, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, business.industry, SARS-CoV-2, Dose fractionation, COVID-19, Middle Aged, Radiation therapy, Radiology Nuclear Medicine and imaging, Female, Radiotherapy, Adjuvant, Dose Fractionation, Radiation, business, Adjuvant
Published
2021
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45. Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials

Author

Bradley, Rosie, primary, Braybrooke, Jeremy, additional, Gray, Richard, additional, Hills, Robert, additional, Liu, Zulian, additional, Peto, Richard, additional, Davies, Lucy, additional, Dodwell, David, additional, McGale, Paul, additional, Pan, Hongchao, additional, Taylor, Carolyn, additional, Anderson, Stewart, additional, Gelber, Richard, additional, Gianni, Luca, additional, Jacot, William, additional, Joensuu, Heikki, additional, Moreno-Aspitia, Alvaro, additional, Piccart, Martine, additional, Press, Michael, additional, Romond, Edward, additional, Slamon, Dennis, additional, Suman, Vera, additional, Berry, Richard, additional, Boddington, Clare, additional, Clarke, Mike, additional, Davies, Christina, additional, Duane, Fran, additional, Evans, Vaughan, additional, Gay, Jo, additional, Gettins, Lucy, additional, Godwin, Jon, additional, James, Sam, additional, Liu, Hui, additional, MacKinnon, Elizabeth, additional, Mannu, Gurdeep, additional, McHugh, Theresa, additional, Morris, Philip, additional, Read, Simon, additional, Straiton, Ewan, additional, Wang, Yaochen, additional, Crown, John, additional, de Azambuja, Evandro, additional, Delaloge, Suzette, additional, Fung, Helena, additional, Geyer, Charles, additional, Spielmann, Marc, additional, Valagussa, Pinuccia, additional, Albain, Kathy, additional, Arriagada, Rodrigo, additional, Bartlett, John, additional, Bergsten-Nordström, Elizabeth, additional, Bliss, Judith, additional, Brain, Etienne, additional, Carey, Lisa, additional, Coleman, Robert, additional, Cuzick, Jack, additional, Davidson, Nancy, additional, Del Mastro, Lucia, additional, Di Leo, Angelo, additional, Dignam, James, additional, Dowsett, Mitch, additional, Ejlertsen, Bent, additional, Francis, Prue, additional, Gnant, Michael, additional, Goetz, Matthew, additional, Goodwin, Pam, additional, Halpin-Murphy, Pat, additional, Hayes, Dan, additional, Hill, Catherine, additional, Jagsi, Reshma, additional, Janni, Wolfgang, additional, Loibl, Sibylle, additional, Mamounas, Eleftherios P, additional, Martín, Miguel, additional, Mukai, Hirofumi, additional, Nekljudova, Valentina, additional, Norton, Larry, additional, Ohashi, Yasuo, additional, Pierce, Lori, additional, Poortmans, Philip, additional, Raina, Vinod, additional, Rea, Daniel, additional, Regan, Meredith, additional, Robertson, John, additional, Rutgers, Emiel, additional, Spanic, Tanja, additional, Sparano, Joseph, additional, Steger, Guenther, additional, Tang, Gong, additional, Toi, Masakazu, additional, Tutt, Andrew, additional, Viale, Giuseppe, additional, Wang, Xiang, additional, Whelan, Tim, additional, Wilcken, Nicholas, additional, Wolmark, Norman, additional, Cameron, David, additional, Bergh, Jonas, additional, Pritchard, Kathleen I, additional, and Swain, Sandra M, additional

Published
2021
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46. REX: X-ray experiment on the water recovery rocket

Author

Urban, Martin, primary, Nentvich, Ondřej, additional, Báča, Tomáš, additional, Veřtát, Ivo, additional, Maršíková, Veronika, additional, Doubravová, Daniela, additional, Dániel, Vladimír, additional, Inneman, Adolf, additional, Pína, Ladislav, additional, Sieger, Ladislav, additional, McEntaffer, Randall L., additional, Schultz, Ted B., additional, Miles, Drew M., additional, and Tutt, James H., additional

Published
2021
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47. TGF-β1 Potentiates Adoptive Immunotherapy of Hematological and Solid Tumors Using ex vivo Expanded γδ T-Cells

Author

Leena Halim, Antonella Adami, Balázs Győrffy, Lynsey M. Whilding, Benjamin Draper, Ana C. Parente-Pereira, Domenico Cozzetto, Chung-Yang Ricardo Joseph, Helge Roider, Chelsea A. Taylor, Jana Obajdin, Holger Hess-Stumpp, Jinger Xie, Ayesha Iqbal, Richard Beatson, Tomasz Zabinski, Fred Aswad, John Maher, Tom Hardiman, Jelmar Quist, Anette Sommer, Caroline M. Hull, Andrew Tutt, Daniela Achkova, Kim Ngan Luu Hoang, David M. Davies, Rafael Torres Martin de Rosales, Anita Grigoriadis, and Francis Man

Subjects
business.industry, medicine.medical_treatment, Myeloid leukemia, Cancer, medicine.disease, Cytokine, medicine.anatomical_structure, Cancer immunotherapy, Cancer cell, Cancer research, medicine, Cytarabine, Bone marrow, business, Ex vivo, medicine.drug
Abstract

Despite their role in cancer surveillance, adoptive immunotherapy using γδ T-cells has achieved limited efficacy. To enhance trafficking to bone marrow, circulating γδ T-cells were expanded in serum-free medium containing TGF-β1 and IL-2 (γδ[T2] cells).Unexpectedly, the yield and viability of γδ[T2] cells were also increased by TGF-β1,when compared to γδ[2] controls (IL-2 alone). γδ[T2] cells were less differentiated and yet displayed increased cytolytic activity, cytokine release and anti-tumor activity in several leukemic and solid tumor models. Efficacy was further enhanced by cancer cell sensitization using amino bisphosphonates or cytarabine, or by CAR re-programming. A number of contributory effects of TGF-β1 were identified, including prostaglandinE2 receptor downmodulation, upregulation of CD103 and enhanced IL-9 production by γδ[T2] cells. Biological relevance is supported by the identification of a favorable γδ[T2] signature in acute myeloid leukemia. Given their enhanced therapeutic activity and compatibility with allogeneic use, γδ[T2] cells warrant evaluation in cancer immunotherapy.

Published
2021

48. 3rd ESO–ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3)

Author

Cardoso, E, Costa, E, Senkus, E., Aapro, B, Andre, D., Barrios, B, Bergh, B, Bhattacharyya, B., Biganzoli, L., Cardoso, L., Carey, L., Corneliussen-James, E, Curigliano, E, Dieras, D, El Saghir, E, Eniu, E, Fallowfield, L., Fenech, E, Francis, D, Gelmon, B, Gennari, D, Harbeck, B, Hudis, B, Kaufman, B., Krop, B, Mayer, B, Meijer, D, Mertz, B, Ohno, B, Pagani, B, Papadopoulos, E., Peccatori, E, Penault-Llorca, L, Piccart, L, Pierga, D, Rugo, B, Shockney, L., Sledge, A, Swain, L, Thomssen, E, Tutt, L, Vorobiof, D., Xu, B., Norton, L., Winer, E., Cardoso, F., Costa, A., Aapro, M., Andre, F., Barrios, C., Bergh, J., Bhattacharyya, G., Cardoso, M.J., Corneliussen-James, D., Curigliano, G., Dieras, V., El Saghir, N., Eniu, A., Fenech, D., Francis, P., Gelmon, K., Gennari, A., Harbeck, N., Hudis, C., Krop, I., Mayer, M., Meijer, H., Mertz, S., Ohno, S., Pagani, O., Peccatori, F., Penault-Llorca, F., Piccart, M.J., Pierga, J.Y., Rugo, H., Sledge, G., Swain, S., Thomssen, C., Tutt, A., Jodrell Bank Centre for Astrophysics, University of Manchester [Manchester], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Division of Medical Oncology, and European Institute of Oncology [Milan] (ESMO)

Subjects
Male, 0301 basic medicine, Oncology, Palliative care, Receptor, ErbB-2, Consensus Development Conferences as Topic, medicine.medical_treatment, Triple Negative Breast Neoplasms, 0302 clinical medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, Palliative Care, General Medicine, Hematology, Corrigenda, Metastatic breast cancer, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, Observational Studies as Topic, Receptors, Estrogen, Geriatric oncology, 030220 oncology & carcinogenesis, Special Articles, Female, medicine.medical_specialty, Breast surgery, RC0280.B8, Antineoplastic Agents, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Male, RC0254, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Humans, Chirurgie, business.industry, Evidence-based medicine, medicine.disease, Cancérologie, Clinical trial, Editor's Choice, Oncology nursing, 030104 developmental biology, Family medicine, Surgery, business, Hématologie
Abstract

0, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017
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49. 1O Detection of homologous recombination repair deficiency (HRD) in treatment-naive early triple-negative breast cancer (TNBC) by RAD51 foci and comparison with DNA-based tests

Author

Serra Elizalde, V., primary, Llop-Guevara, A., additional, Pearson, A., additional, Cruz, C., additional, Castroviejo-Bermejo, M., additional, Chopra, N., additional, Tovey, H., additional, Toms, C., additional, Kriplani, D., additional, Gevensleben, H., additional, Roylance, R., additional, Chan, S., additional, Tutt, A., additional, Skene, A., additional, Evans, A., additional, Davies, H.R., additional, Bliss, J., additional, Nik-Zainal, S., additional, Balmaña, J., additional, and Turner, N., additional

Published
2021
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