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51. An antibody drug engineered for prevention of malaria in global populations

Author

Emerling, Daniel, primary, Williams, Katherine, additional, Guerrero, Steve, additional, Flores-Garcia, Yevel, additional, Andrews, Kayla, additional, Kim, Dongkyoon, additional, Williamson, Kevin, additional, Siska, Christine, additional, Smidt, Pauline, additional, Jepson, Sofia, additional, Liu, Hong, additional, Li, Kan, additional, Dennison, S, additional, Mathis-Torres, Shamika, additional, Chen, Xiaomu, additional, Wille-Reece, Ulrike, additional, MacGill, Randall, additional, Walker, Michael, additional, Jongert, Erik, additional, King, C, additional, Ockenhouse, Christian, additional, Glanville, Jacob, additional, Moon, James, additional, Regules, Jason, additional, Tan, Yann Chong, additional, Cavet, Guy, additional, Lippow, Shaun, additional, Robinson, William, additional, Dutta, Sheetij, additional, Tomaras, Georgia, additional, Zavala, Fidel, additional, and Ketchem, Randal, additional

Published
2023
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52. Supplementary Table S1 from Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes

Author

Hu, Xiaolan, primary, Stern, Howard M., primary, Ge, Lin, primary, O'Brien, Carol, primary, Haydu, Lauren, primary, Honchell, Cynthia D., primary, Haverty, Peter M., primary, Peters, Brock A., primary, Wu, Thomas D., primary, Amler, Lukas C., primary, Chant, John, primary, Stokoe, David, primary, Lackner, Mark R., primary, and Cavet, Guy, primary

Published
2023
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54. Supplementary Data from Oncogenic Activating Mutations Are Associated with Local Copy Gain

Author

Modrek, Barmak, primary, Ge, Lin, primary, Pandita, Ajay, primary, Lin, Eva, primary, Mohan, Sankar, primary, Yue, Peng, primary, Guerrero, Steve, primary, Lin, William M., primary, Pham, Thinh, primary, Modrusan, Zora, primary, Seshagiri, Somasekar, primary, Stern, Howard M., primary, Waring, Paul, primary, Garraway, Levi A., primary, Chant, John, primary, Stokoe, David, primary, and Cavet, Guy, primary

Published
2023
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55. Supplementary Figures S1-S4 from Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes

Author

Hu, Xiaolan, primary, Stern, Howard M., primary, Ge, Lin, primary, O'Brien, Carol, primary, Haydu, Lauren, primary, Honchell, Cynthia D., primary, Haverty, Peter M., primary, Peters, Brock A., primary, Wu, Thomas D., primary, Amler, Lukas C., primary, Chant, John, primary, Stokoe, David, primary, Lackner, Mark R., primary, and Cavet, Guy, primary

Published
2023
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56. SUSTENTABILIDADE NAS UNIVERSIDADES: INTERESSES, CRÍTICAS E PREOCUPAÇÕES DA COMUNIDADE ACADÊMICA SOBRE ATITUDES SUSTENTÁVEIS ALICERÇADO AO UI GREENMETRIC

Author

Cavet, Guilherme Rodrigues, Lago, Sandra Mara Stocker, Johann, Jerry Adriani, and Bertolini, Geysler Rogis Flor

Subjects
RSU, Ranking GM, Universidades Sustentáveis, Comunidade Acadêmica
Abstract

Um dos modos de medir o quanto uma universidade é sustentável, é por meio do UI GreenMetric (GM) Ranking, que realiza uma análise dos três pilares da sustentabilidade, por meio de seis categorias avaliadas: infraestrutura e meio ambiente; energia; resíduos; água; transporte; e educação. Neste estudo se objetiva analisar as preocupações e interesses da comunidade acadêmica, fundamentado pelo GM Ranking, sobre as práticas sustentáveis do Campus. Foram realizadas análises sobre quatro variáveis: gênero, vínculo com a instituição, acadêmicos que cursam ou não disciplinas sobre sustentabilidade e faixa etária, os resultados indicam que não houve diferenças significativas entre diferenças de sexo e de vínculos com a universidade, porém acadêmicos que cursam disciplinas sobre sustentabilidade tem mais interesse sobre o tema, e os mais jovens, além do interesse, se mostram mais preocupados com o assunto. Conclui-se que há uma demanda por cursos, treinamentos e disciplinas curriculares sobre sustentabilidade por parte da comunidade acadêmica, e que os mais jovens são mais críticos e preocupados com as atitudes sustentáveis do campus.

Published
2023

57. An antibody drug engineered for prevention of malaria in global populations

Author

Katherine Williams, Steve Guerrero, Yevel Flores-Garcia, Kayla Andrews, Dongkyoon Kim, Kevin Williamson, Christine Siska, Pauline Smidt, Sofia Jepson, Hong Liu, Kan Li, S Dennison, Shamika Mathis-Torres, Xiaomu Chen, Ulrike Wille-Reece, Randall MacGill, Michael Walker, Erik Jongert, C King, Christian Ockenhouse, Jacob Glanville, James Moon, Jason Regules, Yann Chong Tan, Guy Cavet, Shaun Lippow, William Robinson, Sheetij Dutta, Georgia Tomaras, Fidel Zavala, Randal Ketchem, and Daniel Emerling

Abstract

Over 80% of malaria-attributable deaths are in children under five. However, the only malaria vaccine recommended by the World Health Organization (WHO) for paediatric use, Mosquirix™, has limited efficacy. Complementary strategies, like monoclonal antibodies (mAbs), will be required to eradicate malaria. To discover new anti-malaria mAbs, we evaluated >28,000 antibody sequences from circulating B cells obtained from 45 Mosquirix™ vaccinees and selected 369 for testing. Many antibodies bound the circumsporozoite protein (CSP), a main surface protein on malaria and the malaria antigen in Mosquirix™, and several were exceptionally protective in mouse models of malaria. Through this work, we identified surprising correlations that suggest certain CSP sequences in Mosquirix™ may induce immunodominant antibody responses that dilute protective immunity. Further, we selected the antibodies most protective in preclinical mouse models and engineered them for improved manufacturability and developability to meet WHO guidelines. An optimised clinical candidate, MAM01, suitable for paediatric populations living in low-to-middle-income countries, was selected for clinical development.

Published
2023
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60. Supplementary Figures S1-S4 from Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes

Author

Guy Cavet, Mark R. Lackner, David Stokoe, John Chant, Lukas C. Amler, Thomas D. Wu, Brock A. Peters, Peter M. Haverty, Cynthia D. Honchell, Lauren Haydu, Carol O'Brien, Lin Ge, Howard M. Stern, and Xiaolan Hu

Abstract

Supplementary Figures S1-S4 from Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes

Published
2023
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61. Data from Oncogenic Activating Mutations Are Associated with Local Copy Gain

Author

Guy Cavet, David Stokoe, John Chant, Levi A. Garraway, Paul Waring, Howard M. Stern, Somasekar Seshagiri, Zora Modrusan, Thinh Pham, William M. Lin, Steve Guerrero, Peng Yue, Sankar Mohan, Eva Lin, Ajay Pandita, Lin Ge, and Barmak Modrek

Abstract

Although activating mutations and gains in copy number are key mechanisms for oncogene activation, the relationship between the two is not well understood. In this study, we focused on KRAS copy gains and mutations in non–small cell lung cancer. We found that KRAS copy gains occur more frequently in tumors with KRAS activating mutations and are associated with large increases in KRAS expression. These copy gains tend to be more focal in tumors with activating mutations than in those with wild-type KRAS. Fluorescence in situ hybridization analysis revealed that some tumors have homogeneous low-level gains of the KRAS locus, whereas others have high-level amplification of KRAS, often in only a fraction of tumor cells. Associations between activating mutation and copy gains were also observed for other oncogenes (EGFR in non–small cell lung cancer, BRAF and NRAS in melanoma). Activating mutations were associated with copy gains only at the mutated oncogene locus but not other oncogene loci. However, KRAS activating mutations in colorectal cancer were not associated with copy gains. Future work is warranted to clarify the relationship among the different mechanisms of oncogene activation. (Mol Cancer Res 2009;7(8):1244–52)

Published
2023
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65. Commentary on this Article from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Author

Mark R. Lackner, Lukas C. Amler, Xiaolan Hu, Guy Cavet, Elizabeth Luis, Gail D. Lewis Phillips, Leanne Berry, Fiona Zhong, Ling-Yuh Huw, Heidi Savage, Carol O'Brien, and Jiping Zha

Abstract

Commentary on this Article from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Published
2023
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66. Data from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Author

Mark R. Lackner, Lukas C. Amler, Xiaolan Hu, Guy Cavet, Elizabeth Luis, Gail D. Lewis Phillips, Leanne Berry, Fiona Zhong, Ling-Yuh Huw, Heidi Savage, Carol O'Brien, and Jiping Zha

Abstract

The insulin-like growth factor-I receptor (IGF-IR) pathway is required for the maintenance of the transformed phenotype in neoplastic cells and hence has been the subject of intensive drug discovery efforts. A key aspect of successful clinical development of targeted therapies directed against IGF-IR will be identification of responsive patient populations. Toward that end, we have endeavored to identify predictive biomarkers of response to an anti-IGF-IR-targeting monoclonal antibody in preclinical models of breast and colorectal cancer. We find that levels of the IGF-IR itself may have predictive value in these tumor types and identify other gene expression predictors of in vitro response. Studies in breast cancer models suggest that IGF-IR expression is both correlated and functionally linked with estrogen receptor signaling and provide a basis for both patient stratification and rational combination therapy with antiestrogen-targeting agents. In addition, we find that levels of other components of the signaling pathway such as the adaptor proteins IRS1 and IRS2, as well as the ligand IGF-II, have predictive value and report on the development of a pathway-focused panel of diagnostic biomarkers that could be used to test these hypotheses during clinical development of IGF-IR-targeting therapies. [Mol Cancer Ther 2009;8(8):2110–21]

Published
2023
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67. Supplementary Figures 1-7 from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Author

Mark R. Lackner, Lukas C. Amler, Xiaolan Hu, Guy Cavet, Elizabeth Luis, Gail D. Lewis Phillips, Leanne Berry, Fiona Zhong, Ling-Yuh Huw, Heidi Savage, Carol O'Brien, and Jiping Zha

Abstract

Supplementary Figures 1-7 from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Published
2023
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68. Data from In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

Author

Mark R. Lackner, Lori S. Friedman, Marcia Belvin, Lukas Amler, Lesley Murray, Leanne Berry, Wei Zhou, Tom Truong, Elizabeth Punnoose, Heidi Savage, Tom Januario, Kenneth Jung, Steve Guerrero, Guy Cavet, Zachary Boyd, Carol O'Brien, and Klaus P. Hoeflich

Abstract

Purpose: The pathways underlying basal-like breast cancer are poorly understood, and as yet, there is no approved targeted therapy for this disease. We investigated the role of mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) inhibitors as targeted therapies for basal-like breast cancer.Experimental Design: We used pharmacogenomic analysis of a large panel of breast cancer cell lines with detailed accompanying molecular information to identify molecular predictors of response to a potent and selective inhibitor of MEK and also to define molecular mechanisms underlying combined MEK and PI3K targeting in basal-like breast cancer. Hypotheses were confirmed by testing in multiple tumor xenograft models.Results: We found that basal-like breast cancer models have an activated RAS-like transcriptional program and show greater sensitivity to a selective inhibitor of MEK compared with models representative of other breast cancer subtypes. We also showed that loss of PTEN is a negative predictor of response to MEK inhibition, that treatment with a selective MEK inhibitor caused up-regulation of PI3K pathway signaling, and that dual blockade of both PI3K and MEK/extracellular signal–regulated kinase signaling synergized to potently impair the growth of basal-like breast cancer models in vitro and in vivo.Conclusions: Our studies suggest that single-agent MEK inhibition is a promising therapeutic modality for basal-like breast cancers with intact PTEN, and also provide a basis for rational combination of MEK and PI3K inhibitors in basal-like cancers with both intact and deleted PTEN.

Published
2023
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69. Supplementary Data from In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

Author

Mark R. Lackner, Lori S. Friedman, Marcia Belvin, Lukas Amler, Lesley Murray, Leanne Berry, Wei Zhou, Tom Truong, Elizabeth Punnoose, Heidi Savage, Tom Januario, Kenneth Jung, Steve Guerrero, Guy Cavet, Zachary Boyd, Carol O'Brien, and Klaus P. Hoeflich

Abstract

Supplementary Data from In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

Published
2023
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73. Data from Functional Genomics Identifies ABCC3 as a Mediator of Taxane Resistance in HER2-Amplified Breast Cancer

Author

Mark R. Lackner, Lukas C. Amler, Zora Modrusan, Celina Sanchez Rivers, Karen Toy, Sankar Mohan, Lauren Haydu, Xiaolan Hu, Ajay Pandita, Guy Cavet, and Carol O'Brien

Abstract

Breast cancer is a heterogeneous disease with distinct molecular subtypes characterized by differential response to targeted and chemotherapeutic agents. Enhanced understanding of the genetic alterations characteristic of different subtypes is needed to pave the way for more personalized administration of therapeutic agents. We have taken a functional genomics approach using a well-characterized panel of breast cancer cell lines to identify putative biomarkers of resistance to antimitotic agents such as paclitaxel and monomethyl-auristatin-E (MMAE). In vitro studies revealed a striking difference in sensitivity to these agents between cell lines from different subtypes, with basal-like cell lines being significantly more sensitive to both agents than luminal or HER2-amplified cell lines. Genome-wide association studies using copy number data from Affymetrix single nucleotide polymorphism arrays identified amplification of the chromosome 17q21 region as being highly associated with resistance to both paclitaxel and MMAE. An unbiased approach consisting of RNA interference and high content analysis was used to show that amplification and concomitant overexpression of the gene encoding the ABCC3 drug transporter is responsible for conferring in vitro resistance to paclitaxel and MMAE. We also show that amplification of ABCC3 is present in primary breast tumors and that it occurs predominantly in HER2-amplified and luminal tumors, and we report on development of a specific fluorescence in situ hybridization assay that may have utility as a predictive biomarker of taxane resistance in breast cancer. [Cancer Res 2008;68(13):5380–9]

Published
2023
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75. Supplementary Figure Legends 1-5 from Functional Genomics Identifies ABCC3 as a Mediator of Taxane Resistance in HER2-Amplified Breast Cancer

Author

Mark R. Lackner, Lukas C. Amler, Zora Modrusan, Celina Sanchez Rivers, Karen Toy, Sankar Mohan, Lauren Haydu, Xiaolan Hu, Ajay Pandita, Guy Cavet, and Carol O'Brien

Abstract

Supplementary Figure Legends 1-5 from Functional Genomics Identifies ABCC3 as a Mediator of Taxane Resistance in HER2-Amplified Breast Cancer

Published
2023
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80. How a European network of FAIR-enabling Trustworthy Data Repositories can align to the vision of EOSC

Author

Anglada, Lluís, Antos, David, Burgi, Pierre-Yves, Cavet, Cécile, Celjak, Draženko, Dillo, Ingrid, Dubois, Olesea, Fernandes, Rui, Lamers, Didi, L'Hours, Hervé, Venkataraman, Shanmugasundaram, Viljoen, Matthew, Wyns, Roxanne, L'Hours, Hervé, and Wyns, Roxanne

Subjects
EOSC, HorizonEU, EOSC Association, Advancing OpenScience in Europe, Long term data preservation, EOSC Association Long Term Data Preservation Task Force, OpenScience, Trustworthy Digital Repositories, FAIR, Response paper
Abstract

This paper is a response from the EOSC Association Long Term Data Preservation Task Force to the working paper “Toward a European network of FAIR-enabling Trustworthy Digital Repositories”. In this response the EOSC LTDP Task Force addresses the proposals in the paper and elaborates on how the suggested functions can contribute to realising the EOSC.

Published
2023
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81. EOSC Preservation: Overview Discussion Paper

Author

Andreu, Toni, Anglada, Lluís, Antos, David, Bähr, Thomas, Brzeźniak, Maciej, Burgi, Pierre-Yves, Cavet, Cécile, Celjak, Draženko, Crépé-Renaudin, Sabine, De Loof, Chris, Dillo, Ingrid, Dubois, Olesea, Fernandes, Rui, Forsström, Pirjo-Leena, Ganis, Gerardo, Gibney, Eileen, Holl, András, L'Hours, Hervé, Lamers, Didi, Lammert, Andrea, Lloret Iglesias, Lara, Maggi, Marcello, Majdanski, Mariusz, Nief, Jean-Yves, Novacek, Jiri, Piroi, Florina, Presser, Karl, Saenen, Bregt, Shankar, Sangeetha, Smareglia, Riccardo, Stockhause, Martina, Stokes, Paul, Tenhunen, Ville, Venkataraman, Shanmugasundaram, Viljoen, Matthew, Wali, Mojib, Wyns, Roxanne, Hervé L'Hours, and Roxanne Wyns

Subjects
EOSC, HorizonEU, EOSC Association, Advancing OpenScience in Europe, EOSC Association Long Term Data Preservation Task force, Long term data preservation, OpenScience, Trustworthy Digital Repositories, FAIR, Overview Discussion Paper
Abstract

TheLong-Term Data Preservation Task Force(LTDP TF) of the EOSC Association has since its establishment worked on mapping the status and further clarification of the meaning of long-term preservation within the EOSC. This work has resulted in anoverview and discussion paperto presents the context, activities and ongoing issues surrounding the EOSC Association Long Term Data Preservation Task Force. The paper describes our approach on preservation in the context of EOSC concerning outcomes, systems, and actions with attention to the vision, roles, finance, and networks needed to deliver preservation for FAIR digital objects in the EOSC. This document is intended to collect community feedback on our approach as well as future recommendations to be considered. We kindly ask the community for feedback on our approach as well as future recommendations to be considered through a short survey: https://ec.europa.eu/eusurvey/runner/TFLTDPsurvey2023

Published
2023
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82. CCR Translation for the Article from In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

Author

Hoeflich, Klaus P., primary, O'Brien, Carol, primary, Boyd, Zachary, primary, Cavet, Guy, primary, Guerrero, Steve, primary, Jung, Kenneth, primary, Januario, Tom, primary, Savage, Heidi, primary, Punnoose, Elizabeth, primary, Truong, Tom, primary, Zhou, Wei, primary, Berry, Leanne, primary, Murray, Lesley, primary, Amler, Lukas, primary, Belvin, Marcia, primary, Friedman, Lori S., primary, and Lackner, Mark R., primary

Published
2023
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83. Supplementary Data from In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

Author

Hoeflich, Klaus P., primary, O'Brien, Carol, primary, Boyd, Zachary, primary, Cavet, Guy, primary, Guerrero, Steve, primary, Jung, Kenneth, primary, Januario, Tom, primary, Savage, Heidi, primary, Punnoose, Elizabeth, primary, Truong, Tom, primary, Zhou, Wei, primary, Berry, Leanne, primary, Murray, Lesley, primary, Amler, Lukas, primary, Belvin, Marcia, primary, Friedman, Lori S., primary, and Lackner, Mark R., primary

Published
2023
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84. Commentary on this Article from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Author

Zha, Jiping, primary, O'Brien, Carol, primary, Savage, Heidi, primary, Huw, Ling-Yuh, primary, Zhong, Fiona, primary, Berry, Leanne, primary, Lewis Phillips, Gail D., primary, Luis, Elizabeth, primary, Cavet, Guy, primary, Hu, Xiaolan, primary, Amler, Lukas C., primary, and Lackner, Mark R., primary

Published
2023
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85. Supplementary Figures 1-7 from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Author

Zha, Jiping, primary, O'Brien, Carol, primary, Savage, Heidi, primary, Huw, Ling-Yuh, primary, Zhong, Fiona, primary, Berry, Leanne, primary, Lewis Phillips, Gail D., primary, Luis, Elizabeth, primary, Cavet, Guy, primary, Hu, Xiaolan, primary, Amler, Lukas C., primary, and Lackner, Mark R., primary

Published
2023
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86. Supplementary Table 1 from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Author

Zha, Jiping, primary, O'Brien, Carol, primary, Savage, Heidi, primary, Huw, Ling-Yuh, primary, Zhong, Fiona, primary, Berry, Leanne, primary, Lewis Phillips, Gail D., primary, Luis, Elizabeth, primary, Cavet, Guy, primary, Hu, Xiaolan, primary, Amler, Lukas C., primary, and Lackner, Mark R., primary

Published
2023
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100. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial

Author

van Rhee, Frits, Wong, Raymond S, Munshi, Nikhil, Rossi, Jean-Francois, Ke, Xiao-Yan, Fosså, Alexander, Simpson, David, Capra, Marcelo, Liu, Ting, Hsieh, Ruey Kuen, Goh, Yeow Tee, Zhu, Jun, Cho, Seok-Goo, Ren, Hanyun, Cavet, James, Bandekar, Rajesh, Rothman, Margaret, Puchalski, Thomas A, Reddy, Manjula, van de Velde, Helgi, Vermeulen, Jessica, and Casper, Corey

Published
2014
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