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1. ‘Bear Hunt’ Sparks Change: Using Lesson Study to Integrate Spatial Thinking in Early Childhood Design Education

Author

Mishra, Rohit, Klapwijk, Remke M., Hartmanis, Juris, Founding Editor, van Leeuwen, Jan, Series Editor, Hutchison, David, Editorial Board Member, Kanade, Takeo, Editorial Board Member, Kittler, Josef, Editorial Board Member, Kleinberg, Jon M., Editorial Board Member, Kobsa, Alfred, Series Editor, Mattern, Friedemann, Editorial Board Member, Mitchell, John C., Editorial Board Member, Naor, Moni, Editorial Board Member, Nierstrasz, Oscar, Series Editor, Pandu Rangan, C., Editorial Board Member, Sudan, Madhu, Series Editor, Terzopoulos, Demetri, Editorial Board Member, Tygar, Doug, Editorial Board Member, Weikum, Gerhard, Series Editor, Vardi, Moshe Y, Series Editor, Goos, Gerhard, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Živković, Marija, editor, Buckley, Jeffrey, editor, Pagkratidou, Marianna, editor, and Duffy, Gavin, editor

Published
2024
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2. How Focus Creates Engagement in Primary Design and Technology Education: The Effect of Well-Defined Tasks and Joint Presentations on a Class of Nine to Twelve Years Old Pupils

Author

Looijenga, Annemarie, Klapwijk, Remke M., and de Vries, Marc J.

Abstract

During a Design and Technology class, engagement is both required to start creative hands-on work and a sign of pupil's creative thinking. To find ways to achieve engagement, we can look to the Montessori tradition. Due to the fact that learning is regarded as feeding insight through experimenting, tasks have to offer pupils the opportunity to gain knowledge about isolated details of the learning situation. This is realised by brief, simple and objective tasks combined with liberty to approach the hands-on work in one's own way. Applied to Design and Technology, we can define brief, simple and objective tasks with a focus on a technique as an isolated detail of the learning situation. Offering liberty during hands-on work enables creative thinking. The deployment of well-defined tasks with a focus on a technique is possible by dividing a complex assignment into a collection of brief tasks with single problems and working towards single objectives in the topic, making use of a single technique. Such a collection is a format that has the potential to enable ongoing engagement. This case-study researches the actual effect of a stepwise organised collection of tasks on the design performance of pupils of nine to twelve years old. The results show that the tasks turned out to be useful in initiating engagement. In combination with joint presentations, ongoing engagement was achieved resulting in well-considered designs and products. In addition, dialogue with disengaged pupils delivered solutions towards engagement. As a side-effect of dialogue the teacher-pupil relationships and the pupil-pupil relationships improved.

Published
2020

4. Constructing and storytelling: accommodating different play orientations in learning spatial thinking

Author

Leonie Sonneveld, Remke M. Klapwijk, and Pieter Jan Stappers

Subjects
spatial thinking, design and technology education, preschool, construction play, pretend play, storytelling, Education (General), L7-991
Abstract

Spatial ability is malleable and belongs in the preschool. For preschoolers, many analytical activities with one correct answer such as tangram have been developed. Less is known about employing open-ended design assignments to creatively practice spatial thinking. Little attention has been paid to the mutual qualitative differences between children when engaged in spatial thinking and insight in children’s motivation is lacking. As design and play have much in common, our first study investigated play orientations during free play of 49 Dutch preschoolers during free play in a low and a high SES school. Participative interviews and observations in the construction and home corners of two schools uncovered different play orientations– construction and pretend play - and either a focus on open-ended objects or on defined objects. In a subsequent study, the influence of these play and object orientations on how children design was investigated. This study with 13 children also used generative design research methods grounded in ethnographic research and therapeutic practices. Using an empathic, story-based, open-ended design challenge, results showed that play-orientations of children influence the length and nature of the design activities as well as the design outcomes. Children with a pretend-play orientation are longer engaged and talk more about the character involved. They usually built organic structures with a variety of objects, while construction-oriented children mainly built sturdy and geometrical structures and mainly used open-ended objects. In all play orientations, spatial thinking was practiced and children were spatially challenged. For example, in all orientations difficulties arose around getting the character in out the structure, however, as different structures were build, the nature of these difficulties were also different. Open-ended design activities that contain characters and problems children can empathize with are a valuable addition to the palette of activities to develop spatial thinking in early classrooms. Our study shows that design activities stimulate children to practice spatial thinking in a creative context and have the ability to engage children with a pretend-play orientation who are otherwise less engaged in construction. The play-orientations and object-orientations are informative for research and the development of spatial educational interventions aiming at a diversity of learners.

Published
2024
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5. Addressing the complexity of spatial teaching: a narrative review of barriers and enablers

Author

Ergi Bufasi, Ting Jun Lin, Ursa Benedicic, Marten Westerhof, Rohit Mishra, Dace Namsone, Inese Dudareva, Sheryl Sorby, Lena Gumaelius, Remke M. Klapwijk, Jeroen Spandaw, Brian Bowe, Colm O'Kane, Gavin Duffy, Marianna Pagkratidou, and Jeffrey Buckley

Subjects
spatial ability, barriers, enablers, primary school, mathematics education, science education, Education (General), L7-991
Abstract

Extensive research has established that spatial ability is a crucial factor for achieving success in Science, Technology, Engineering, and Mathematics (STEM). However, challenges that educators encounter while teaching spatial skills remain uncertain. The purpose of this study is to develop a research framework that examines the interrelationships, barriers, and enablers amongst various educational components, including schools, teachers, students, classrooms, and training programs, that are encountered when teaching for spatial ability development. A thorough examination of international research, in combination with a detailed review of the primary Science and Mathematics curricula in Ireland, Latvia, Sweden, and the Netherlands, is undertaken to acquire a more concentrated comprehension of the incorporation of spatial components in the curriculum. The review seeks to establish the fundamental factors that enable or hinder teachers in terms of curriculum, pedagogy, pedagogical content knowledge, and spatialized classroom practices.

Published
2024
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6. Towards Constructive Design Feedback Dialogues: Guiding Peer and Client Feedback to Stimulate Children's Creative Thinking

Author

Schut, Alice, van Mechelen, Maarten, Klapwijk, Remke M., Gielen, Mathieu, and de Vries, Marc J.

Abstract

Design feedback is an essential pedagogical tool that can help young novice designers navigate divergent and convergent paths while designing. However, design feedback is often met with resistance, which counteracts its potential to help novice designers evaluate their design and generate new solution directions. In this paper, we report on the construction and utilization of a design feedback intervention during a real-life design project with a group of primary school children (aged 8-12). The goal of the intervention was to stimulate young novice designers' creative thinking by guiding the design feedback dialogues with their peers and clients. The intervention was designed according to the following key principles: (1) guide towards a shared understanding of the design through low-level convergent feedback; (2) stimulate critical reflection and evaluation of the design to help identify and internalize possible shortcomings through high-level convergent feedback; and (3) provide a way to move forward by guiding new generative thoughts through high-level divergent feedback. Overall, the results show that the intervention can support young novice designers, their peers, and clients in engaging in constructive feedback dialogues, thereby stimulating their creative thinking. Our main contribution entails a detailed understanding of the successes and obstacles within the feedback dialogues, as guided by the intervention. Based on these results, we propose a set of refined design principles to inform feedback interventions. With this research we hope to give insight in the complexity of design feedback dialogues, while also inspiring design educators to actively try out these key principles.

Published
2022
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9. Addressing the complexity of spatial teaching: a narrative review of barriers and enablers

Author

Bufasi, Ergi, primary, Lin, Ting Jun, additional, Benedicic, Ursa, additional, Westerhof, Marten, additional, Mishra, Rohit, additional, Namsone, Dace, additional, Dudareva, Inese, additional, Sorby, Sheryl, additional, Gumaelius, Lena, additional, Klapwijk, Remke M., additional, Spandaw, Jeroen, additional, Bowe, Brian, additional, O'Kane, Colm, additional, Duffy, Gavin, additional, Pagkratidou, Marianna, additional, and Buckley, Jeffrey, additional

Published
2024
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10. Addressing the complexity of spatial teaching: a narrative review of barriers and enablers

Author

Bufasi, Ergi, Lin, Tingjun, Benedicic, Ursa, Westerhof, Marten, Mishra, Rohit, Namsone, Dace, Dudareva, Inese, Sorby, Sheryl, Gumaelius, Lena, Klapwijk, Remke M., Spandaw, Jeroen, Bowe, Brian, O'Kane, Colm, Duffy, Gavin, Pagkratidou, Marianna, Buckley, Jeffrey, Bufasi, Ergi, Lin, Tingjun, Benedicic, Ursa, Westerhof, Marten, Mishra, Rohit, Namsone, Dace, Dudareva, Inese, Sorby, Sheryl, Gumaelius, Lena, Klapwijk, Remke M., Spandaw, Jeroen, Bowe, Brian, O'Kane, Colm, Duffy, Gavin, Pagkratidou, Marianna, and Buckley, Jeffrey

Abstract

Extensive research has established that spatial ability is a crucial factor for achieving success in Science, Technology, Engineering, and Mathematics (STEM). However, challenges that educators encounter while teaching spatial skills remain uncertain. The purpose of this study is to develop a research framework that examines the interrelationships, barriers, and enablers amongst various educational components, including schools, teachers, students, classrooms, and training programs, that are encountered when teaching for spatial ability development. A thorough examination of international research, in combination with a detailed review of the primary Science and Mathematics curricula in Ireland, Latvia, Sweden, and the Netherlands, is undertaken to acquire a more concentrated comprehension of the incorporation of spatial components in the curriculum. The review seeks to establish the fundamental factors that enable or hinder teachers in terms of curriculum, pedagogy, pedagogical content knowledge, and spatialized classroom practices., QC 20240429

Published
2024
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11. EAG2 potassium channel with evolutionarily conserved function as a brain tumor target

Author

Huang, X, He, Y, Dubuc, AM, Hashizume, R, Zhang, W, Reimand, J, Yang, H, Wang, TA, Stehbens, SJ, Younger, S, Barshow, S, Zhu, S, Cooper, MK, Peacock, J, Ramaswamy, V, Garzia, L, Wu, X, Remke, M, Forester, CM, Kim, CC, Weiss, WA, James, CD, Shuman, MA, Bader, GD, Mueller, S, Taylor, MD, Jan, YN, and Jan, LY

Subjects
Neurosciences, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Over 20% of the drugs for treating human diseases target ion channels, but no cancer drug approved by the US Food and Drug Administration (FDA) is intended to target an ion channel. We found that the EAG2 (Ether-a-go-go 2) potassium channel has an evolutionarily conserved function for promoting brain tumor growth and metastasis, delineate downstream pathways, and uncover a mechanism for different potassium channels to functionally cooperate and regulate mitotic cell volume and tumor progression. EAG2 potassium channel was enriched at the trailing edge of migrating medulloblastoma (MB) cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identified the FDA-approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings illustrate the potential of targeting ion channels in cancer treatment.

Published
2015

12. WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

Author

Liau, Linda, Weiss, William, Zhukova, N, Ramaswamy, V, Remke, M, Martin, DC, Castelo-Branco, P, Zhang, CH, Fraser, M, Tse, K, Poon, R, and Shih, DJH

Abstract

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP

Published
2014

13. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy

Author

Mack, SC, Witt, H, Piro, RM, Gu, L, Zuyderduyn, S, Stütz, AM, Wang, X, Gallo, M, Garzia, L, Zayne, K, Zhang, X, Ramaswamy, V, Jäger, N, Jones, DTW, Sill, M, Pugh, TJ, Ryzhova, M, Wani, KM, Shih, DJH, Head, R, Remke, M, Bailey, SD, Zichner, T, Faria, CC, Barszczyk, M, Stark, S, Seker-Cin, H, Hutter, S, Johann, P, Bender, S, Hovestadt, V, Tzaridis, T, Dubuc, AM, Northcott, PA, Peacock, J, Bertrand, KC, Agnihotri, S, Cavalli, FMG, Clarke, I, Nethery-Brokx, K, Creasy, CL, Verma, SK, Koster, J, Wu, X, Yao, Y, Milde, T, Sin-Chan, P, Zuccaro, J, Lau, L, Pereira, S, Castelo-Branco, P, Hirst, M, Marra, MA, Roberts, SS, Fults, D, Massimi, L, Cho, YJ, Van Meter, T, Grajkowska, W, Lach, B, Kulozik, AE, von Deimling, A, Witt, O, Scherer, SW, Fan, X, Muraszko, KM, Kool, M, Pomeroy, SL, Gupta, N, Phillips, J, Huang, A, Tabori, U, Hawkins, C, Malkin, D, Kongkham, PN, Weiss, WA, Jabado, N, Rutka, JT, Bouffet, E, Korbel, JO, Lupien, M, Aldape, KD, Bader, GD, Eils, R, Lichter, P, Dirks, PB, Pfister, SM, Korshunov, A, and Taylor, MD

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Pediatric, Human Genome, Rare Diseases, Animals, Brain Neoplasms, CpG Islands, DNA Methylation, Embryonic Stem Cells, Ependymoma, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Regulation, Neoplastic, Gene Silencing, Histones, Humans, Infant, Mice, Mice, Inbred NOD, Mice, SCID, Mutation, Phenotype, Polycomb Repressive Complex 2, Prognosis, Rhombencephalon, Xenograft Model Antitumor Assays, General Science & Technology
Abstract

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Published
2014

14. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Author

Liau, Linda, Weiss, William, Remke, M, Ramaswamy, V, Peacock, J, Shih, DJH, Koelsche, C, Northcott, PA, Hill, N, Cavalli, FMG, Kool, M, and Wang, X

Abstract

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not

Published
2013

15. Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity

Author

Perry, Arie, Korshunov, A, Sturm, D, Ryzhova, M, Hovestadt, V, Gessi, M, Jones, DTW, Remke, M, Northcott, P, and Picard, D

Abstract

Three histological variants are known within the family of embryonal rosette-forming neuroepithelial brain tumors. These include embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). In th

Published
2013

16. Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN

Author

Fuchs, S., Danßmann, C., Klironomos, F., Winkler, A., Fallmann, J., Kruetzfeldt, L.M., Szymansky, A., Naderi, J., Bernhart, S.H., Grunewald, L., Helmsauer, K., Rodriguez-Fos, E., Kirchner, M., Mertins, P., Astrahantseff, K., Suenkel, C., Toedling, J., Meggetto, F., Remke, M., Stadler, P.F., Hundsdoerfer, P., Deubzer, H.E., Künkele, A., Lang, P., Fuchs, J., Henssen, A.G., Eggert, A., Rajewsky, N., Hertwig, F., and Schulte, J.H.

Subjects
Cancer Research, Cardiovascular and Metabolic Diseases, Technology Platforms
Abstract

Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis.

Published
2023

22. Persister state-directed transitioning and vulnerability in melanoma

Author

Chauvistre, H., Shannan, B., Daignault-Mill, S. M., Ju, R. J., Picard, D., Egetemaier, S., Váraljai, R., Gibhardt, C. S., Keminer, O., Horn, S., Remke, M., Paschen, Annette, Becker, Jürgen C., Helfrich, Iris, Gul, S., Herlyn, M., Bogeski, I., Rodríguez-López, J. N., Haass, N. K., Schadendorf, Dirk, and Rösch, Alexander

Subjects
Medizin
Abstract

Poster-Abstract

Published
2022

23. C.5 Musashi-1 is a master regulator of aberrant translation in MYC-amplified Group 3 medulloblastoma

Author

Kameda-Smith, MM, primary, Zhu, H, additional, Luo, E, additional, Venugopal, C, additional, Brown, K, additional, Yee, BA, additional, Xing, S, additional, Tan, F, additional, Bakhshinyan, D, additional, Adile, AA, additional, Subapanditha, M, additional, Picard, D, additional, Moffat, J, additional, Fleming, A, additional, Hope, K, additional, Provias, J, additional, Remke, M, additional, Lu, Y, additional, Reimand, J, additional, Wechsler-Reya, R, additional, Yeo, G, additional, and Singh, SK, additional

Published
2021
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24. Design Feedback that Stimulates Children’s Creative Thinking: A Feedback Intervention

Author

Schut, Alice, Van Mechelen, Maarten, Klapwijk, Remke M., Gielen, Mathieu, and de Vries, Marc J.

Subjects
Maker education, #CCTD, Design fixation, Creativity research, Design feedback, Creative thinking, Design Research, CCTD, Divergent thinking, K-12 education, Convergent thinking, Participatory design
Abstract

Designing is an inherently creative process in which divergent (generative) and convergent (evaluative) thinking drive the creation and development of a design. Nevertheless, navigating these creative thinking processes is not an easy endeavour, especially for young novice designers. In Design & Technology education, design feedback is often seen as an essential pedagogical tool to help guide novice designers' divergent and convergent paths while designing. Although design feedback can help the creative design process greatly, this does not happen by default. This paper reports on the construction and utilization of a design feedback intervention during a real-life design project with two groups of primary school children (aged 7-12). The goal of the intervention was to stimulate the young novice designers' creative thinking by guiding the design feedback dialogues with their peers and clients. It guides convergent and divergent design feedback to minimize the resistance towards the feedback and creates openness for new processes of reflection, evaluation, and generation. Our main contribution entails a detailed understanding of the successes and obstacles within the feedback dialogues, as guided by the new feedback intervention, and possible future improvements. Overall, the results show that the intervention can support young novice designers, their peers, and clients in engaging in constructive feedback dialogues, thereby stimulating their creative thinking.

Published
2021

25. Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

Author

Durno, C, Ercan, AB, Bianchi, V, Edwards, M, Aronson, M, Galati, M, Atenafu, EG, Abebe-Campino, G, Al-Battashi, A, Alharbi, M, Azad, VF, Baris, HN, Basel, D, Bedgood, R, Bendel, A, Ben-Shachar, S, Blumenthal, DT, Blundell, M, Bornhorst, M, Bronsema, A, Cairney, E, Rhode, S, Caspi, S, Chamdin, A, Chiaravalli, S, Constantini, S, Crooks, B, Das, A, Dvir, R, Farah, R, Foulkes, WD, Frenkel, Z, Gallinger, B, Gardner, S, Gass, D, Ghalibafian, M, Gilpin, C, Goldberg, Y, Goudie, C, Hamid, SA, Hampel, H, Hansford, JR, Harlos, C, Hijiya, N, Hsu, S, Kamihara, J, Kebudi, R, Knipstein, J, Koschmann, C, Kratz, C, Larouche, V, Lassaletta, A, Lindhorst, S, Ling, SC, Link, MP, De Mola, RL, Luiten, R, Lurye, M, Maciaszek, JL, MagimairajanIssai, V, Maher, OM, Massimino, M, McGee, RB, Mushtaq, N, Mason, G, Newmark, M, Nicholas, G, Nichols, KE, Nicolaides, T, Opocher, E, Osborn, M, Oshrine, B, Pearlman, R, Pettee, D, Rapp, J, Rashid, M, Reddy, A, Reichman, L, Remke, M, Robbins, G, Roy, S, Sabel, M, Samuel, D, Scheers, I, Schneider, KW, Sen, S, Stearns, D, Sumerauer, D, Swallow, C, Taylor, L, Thomas, G, Toledano, H, Tomboc, P, Van Damme, A, Winer, I, Yalon, M, Yen, LY, Zapotocky, M, Zelcer, S, Ziegler, DS, Zimmermann, S, Hawkins, C, Malkin, D, Bouffet, E, Villani, A, Tabori, U, Durno, C, Ercan, AB, Bianchi, V, Edwards, M, Aronson, M, Galati, M, Atenafu, EG, Abebe-Campino, G, Al-Battashi, A, Alharbi, M, Azad, VF, Baris, HN, Basel, D, Bedgood, R, Bendel, A, Ben-Shachar, S, Blumenthal, DT, Blundell, M, Bornhorst, M, Bronsema, A, Cairney, E, Rhode, S, Caspi, S, Chamdin, A, Chiaravalli, S, Constantini, S, Crooks, B, Das, A, Dvir, R, Farah, R, Foulkes, WD, Frenkel, Z, Gallinger, B, Gardner, S, Gass, D, Ghalibafian, M, Gilpin, C, Goldberg, Y, Goudie, C, Hamid, SA, Hampel, H, Hansford, JR, Harlos, C, Hijiya, N, Hsu, S, Kamihara, J, Kebudi, R, Knipstein, J, Koschmann, C, Kratz, C, Larouche, V, Lassaletta, A, Lindhorst, S, Ling, SC, Link, MP, De Mola, RL, Luiten, R, Lurye, M, Maciaszek, JL, MagimairajanIssai, V, Maher, OM, Massimino, M, McGee, RB, Mushtaq, N, Mason, G, Newmark, M, Nicholas, G, Nichols, KE, Nicolaides, T, Opocher, E, Osborn, M, Oshrine, B, Pearlman, R, Pettee, D, Rapp, J, Rashid, M, Reddy, A, Reichman, L, Remke, M, Robbins, G, Roy, S, Sabel, M, Samuel, D, Scheers, I, Schneider, KW, Sen, S, Stearns, D, Sumerauer, D, Swallow, C, Taylor, L, Thomas, G, Toledano, H, Tomboc, P, Van Damme, A, Winer, I, Yalon, M, Yen, LY, Zapotocky, M, Zelcer, S, Ziegler, DS, Zimmermann, S, Hawkins, C, Malkin, D, Bouffet, E, Villani, A, and Tabori, U

Abstract

PURPOSE: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Published
2021

28. Maker Education Meets Technology Education : Reflections on Good Practices

Author

Remke M. Klapwijk, Jianjun Gu, Qiuyue Yang, Marc J. de Vries, Remke M. Klapwijk, Jianjun Gu, Qiuyue Yang, and Marc J. de Vries

Subjects
Maker movement in education, Technology--Study and teaching
Abstract

In this book two fields meet, Technology Education with its long history, and Maker Education, a relative new shoot in the educational field. Both focus on learning through making and both value agency and motivation of learners. The purpose of this book is to understand and analyze the kind of informal and formal educational activities that take place under the umbrella of the Maker Movement and then relate this to the field of Technology Education to uncover what researchers, innovators and teachers in this field can learn from the principles, ideas and practices that are central to the Maker Movement and vice versa. The book contains two types of chapters. The first type is case study chapters that span from Mexico, China, Korea, Denmark, the Netherlands to Kenya and from primary to tertiary level, showing a variety of good practices in maker education including both formal and informal contexts. In the subsequent thematic chapters, dedicated authors have used the case studies to reflect on themes such as curriculum reform, social learning, materiality, spatial thinking, informal versus formal learning as well as the sustainability of learning and relate what is happening in Maker Education with Technology Education to imagine possible futures for Maker Education.

Published
2023

38. 18 Peroxiredoxin1 is a therapeutic target in group-3 medulloblastoma

Author

Sajesh, BV., primary, Ngoc, OH., additional, Omar, R., additional, Fediuk, H., additional, Li, L., additional, Alrushaid, S., additional, Wang, W., additional, Pu, J., additional, Sun, HD., additional, Siahaan, T., additional, Werbowetski-Ogilvie, T., additional, Wölfl, M., additional, Remke, M., additional, Ramaswamy, V., additional, Taylor, M., additional, Eberhart, C., additional, Symons, M., additional, Ruggieri, R., additional, Miller, DW, additional, and Vanan, MI, additional

Published
2018
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39. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Author

Thompson, EM, Hielscher, T, Bouffet, E, Remke, M, Luu, B, Gururangan, S, McLendon, RE, Bigner, DD, Lipp, ES, Perreault, S, Cho, YJ, Grant, G, Kim, SK, Lee, JY, Rao, AAN, Giannini, C, Li, KKW, Ng, HK, Yao, Y, Kumabe, T, Tominaga, T, Grajkowska, WA, Perek-Polnik, M, Low, DCY, Seow, WT, Chang, KTE, Mora, J, Pollack, IF, Hamilton, RL, Leary, S, Moore, AS, Ingram, WJ, Hallahan, AR, Jouvet, A, Fèvre-Montange, M, Vasiljevic, A, Faure-Conter, C, Shofuda, T, Kagawa, N, Hashimoto, N, Jabado, N, Weil, AG, Gayden, T, Wataya, T, Shalaby, T, Grotzer, M, Zitterbart, K, Sterba, J, Kren, L, Hortobágyi, T, Klekner, A, László, B, Pócza, T, Hauser, P, Schüller, U, Jung, S, Jang, WY, French, PJ, Kros, JM, van Veelen, MLC, Massimi, L, Leonard, JR, Rubin, JB, Vibhakar, R, Chambless, LB, Cooper, MK, Thompson, RC, Faria, CC, Carvalho, A, Nunes, S, Pimentel, J, Fan, X, Muraszko, KM, López-Aguilar, E, Lyden, D, Garzia, L, Shih, DJH, Kijima, N, Schneider, C, Adamski, J, Northcott, PA, Kool, M, Jones, DTW, Chan, JA, Nikolic, A, Garre, ML, Van Meir, EG, Osuka, S, Olson, JJ, Jahangiri, A, and Castro, BA

Subjects
Adult, Male, Canada, Brain Neoplasms, Infant, Prognosis, Magnetic Resonance Imaging, Combined Modality Therapy, Disease-Free Survival, Child, Preschool, Disease Progression, Humans, Female, Child, Medulloblastoma, Retrospective Studies
Abstract

© 2016 Elsevier Ltd Background Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07–1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87–1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71–1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75–1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67–1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22–3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00–4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93–2·99, p=0·084). Interpretation The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection. Funding Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

Published
2016
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41. CBF1 is clinically prognostic and serves as a target to block cellular invasion and chemoresistance of EMT-like glioblastoma cells

Author

Maciaczyk, D, primary, Picard, D, additional, Zhao, L, additional, Koch, K, additional, Herrera-Rios, D, additional, Li, G, additional, Marquardt, V, additional, Pauck, D, additional, Hoerbelt, T, additional, Zhang, W, additional, Ouwens, D M, additional, Remke, M, additional, Jiang, T, additional, Steiger, H J, additional, Maciaczyk, J, additional, and Kahlert, U D, additional

Published
2017
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42. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Author

Sturm, D., Orr, B.A., Toprak, U.H., Hovestadt, V., Jones, D.T., Capper, D., Sill, M., Buchhalter, I., Northcott, P.A., Leis, I., Ryzhova, M., Koelsche, C., Pfaff, E., Allen, S.J., Balasubramanian, G., Worst, B.C., Pajtler, K.W., Brabetz, S., Johann, P.D., Sahm, F., Reimand, J., Mackay, A., Carvalho, D.M., Remke, M., Phillips, J.J., Perry, A., Cowdrey, C., Drissi, R., Fouladi, M., Giangaspero, F., Lastowska, M., Grajkowska, W., Scheurlen, W., Pietsch, T., Hagel, C., Gojo, J., Lotsch, D., Berger, W., Slavc, I., Haberler, C., Jouvet, A., Holm, S., Hofer, S., Prinz, M., Keohane, C., Fried, I., Mawrin, C., Scheie, D., Mobley, B.C., Schniederjan, M.J., Santi, M., Buccoliero, A.M., Dahiya, S., Kramm, C.M., Bueren, A.O. von, Hoff, K. von, Rutkowski, S., Herold-Mende, C., Fruhwald, M.C., Milde, T., Hasselblatt, M., Wesseling, P., Rossler, J., Schuller, U., Ebinger, M., Schittenhelm, J., Frank, S., Grobholz, R., Vajtai, I., Hans, V., Schneppenheim, R., Zitterbart, K., Collins, V.P., Aronica, E., Varlet, P., Puget, S., Dufour, C., Grill, J., Figarella-Branger, D., Wolter, M., Schuhmann, M.U., Shalaby, T., Grotzer, M., Meter, T. van, Monoranu, C.M., Felsberg, J., Reifenberger, G., Snuderl, M., Forrester, L.A., Koster, J., Versteeg, R., Volckmann, R., Sluis, P. van, Wolf, S., Mikkelsen, T., Gajjar, A., Aldape, K., Moore, A.S., Taylor, M.D., Jones, C., et al., Sturm, D., Orr, B.A., Toprak, U.H., Hovestadt, V., Jones, D.T., Capper, D., Sill, M., Buchhalter, I., Northcott, P.A., Leis, I., Ryzhova, M., Koelsche, C., Pfaff, E., Allen, S.J., Balasubramanian, G., Worst, B.C., Pajtler, K.W., Brabetz, S., Johann, P.D., Sahm, F., Reimand, J., Mackay, A., Carvalho, D.M., Remke, M., Phillips, J.J., Perry, A., Cowdrey, C., Drissi, R., Fouladi, M., Giangaspero, F., Lastowska, M., Grajkowska, W., Scheurlen, W., Pietsch, T., Hagel, C., Gojo, J., Lotsch, D., Berger, W., Slavc, I., Haberler, C., Jouvet, A., Holm, S., Hofer, S., Prinz, M., Keohane, C., Fried, I., Mawrin, C., Scheie, D., Mobley, B.C., Schniederjan, M.J., Santi, M., Buccoliero, A.M., Dahiya, S., Kramm, C.M., Bueren, A.O. von, Hoff, K. von, Rutkowski, S., Herold-Mende, C., Fruhwald, M.C., Milde, T., Hasselblatt, M., Wesseling, P., Rossler, J., Schuller, U., Ebinger, M., Schittenhelm, J., Frank, S., Grobholz, R., Vajtai, I., Hans, V., Schneppenheim, R., Zitterbart, K., Collins, V.P., Aronica, E., Varlet, P., Puget, S., Dufour, C., Grill, J., Figarella-Branger, D., Wolter, M., Schuhmann, M.U., Shalaby, T., Grotzer, M., Meter, T. van, Monoranu, C.M., Felsberg, J., Reifenberger, G., Snuderl, M., Forrester, L.A., Koster, J., Versteeg, R., Volckmann, R., Sluis, P. van, Wolf, S., Mikkelsen, T., Gajjar, A., Aldape, K., Moore, A.S., Taylor, M.D., Jones, C., and et al.

Abstract

Item does not contain fulltext, Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

Published
2016

43. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: A retrospective integrated clinical and molecular analysis

Author

Thompson, E.M. (Eric M.), Hielscher, T. (Thomas), Bouffet, E. (Eric), Remke, M. (Marc), Luu, P. (Phan), Gururangan, S. (Sridharan), McLendon, R.E. (Roger E.), Bigner, D.D. (Darell), Lipp, E.S. (Eric S.), Perreault, S. (Sebastien), Cho, Y.-J. (Yoon-Jae), Grant, G. (Gerald), Kim, S.-K. (Seung-Ki), Lee, J.Y. (Ji Yeoun), Rao, A.A.N. (Amulya A. Nageswara), Giannini, C. (Caterina), Li, K.K.W. (Kay Ka Wai), Ng, H.-K. (Ho-Keung), Yao, Y. (Yu), Kumabe, T. (Toshihiro), Tominaga, T. (Teiji), Grajkowska, W.A. (Wieslawa), Perek-Polnik, M. (Marta), Low, D.C.Y. (David C.Y.), Seow, W.T. (Wan Tew), Chang, K.T.E. (Kenneth T.E.), Mora, J. (Jaume), Pollack, A. (Aaron), Hamilton, R.L. (Ronald L.), Leary, S. (Sarah), Moore, A.S. (Andrew S.), Ingram, W.J. (Wendy J.), Hallahan, A.R. (Andrew R.), Jouvet, A. (Anne), Fèvre-Montange, M. (Michelle), Vasiljevic, A. (Alexandre), Faure-Conter, C. (Cecile), Shofuda, T. (Tomoko), Kagawa, N. (Naoki), Hashimoto, N. (Naoya), Jabado, N. (Nada), Weil, A.G. (Alexander G.), Gayden, T. (Tenzin), Wataya, T. (Takafumi), Shalaby, T. (Tarek), Grotzer, M. (Michael), Zitterbart, K. (Karel), Sterba, J., Kren, L. (Leos), Hortobágyi, T. (Tibor), Klekner, A. (Almos), Bognár, L. (László), Pócza, T. (Tímea), Hauser, P. (Peter), Schüller, U. (Ulrich), Jung, S. (Shin), Jang, W.-Y. (Woo-Youl), French, P.J. (Pim), Kros, J.M. (Johan), Veelen-Vincent, M.L.C. (Marie-Lise) van, Massimi, L. (Luca), Leonard, J.R. (Jeffrey), Rubin, J.B. (Joshua), Vibhakar, R. (Rajeev), Chambless, L.B. (Lola B.), Cooper, M.K. (Michael), Thompson, R.C. (Reid), Faria, R. (Rui), Carvalho, A. (Alice), Nunes, S. (Sofia), Pimentel, J., Fan, X. (Xing), Muraszko, K.M. (Karin), López-Aguilar, E. (Enrique), Lyden, D. (David), Garzia, L. (Livia), Shih, D.J.H. (David J.), Kijima, N. (Noriyuki), Schneider, C. (Christian), Adamski, J. (Jennifer), Northcott, P.A. (Paul A.), Kool, M. (Marcel), Jones, D. (David), Chan, J.A. (Jennifer A.), Nikolic, A. (Ana), Garre, M.L. (Maria Luisa), Van Meir, E.G. (Erwin G.), Osuka, S. (Satoru), Olson, J.J. (Jeffrey J.), Jahangiri, A. (Arman), Castro, B.A. (Brandyn A.), Gupta, N. (Nalin), Weiss, W.A. (William A.), Moxon-Emre, I. (Iska), Mabbott, D.J. (Donald J.), Lassaletta, A. (Alvaro), Hawkins, C.E. (Cynthia), Tabori, U. (Uri), Drake, J. (James), Kulkarni, A. (Abhaya), Dirks, M. (Maaike), Rutka, J.T. (James), Korshunov, A. (Andrey), Pfister, S.M. (Stefan), Packer, R.J. (Roger J.), Ramaswamy, E.A., Taylor, M.D. (Michael), Thompson, E.M. (Eric M.), Hielscher, T. (Thomas), Bouffet, E. (Eric), Remke, M. (Marc), Luu, P. (Phan), Gururangan, S. (Sridharan), McLendon, R.E. (Roger E.), Bigner, D.D. (Darell), Lipp, E.S. (Eric S.), Perreault, S. (Sebastien), Cho, Y.-J. (Yoon-Jae), Grant, G. (Gerald), Kim, S.-K. (Seung-Ki), Lee, J.Y. (Ji Yeoun), Rao, A.A.N. (Amulya A. Nageswara), Giannini, C. (Caterina), Li, K.K.W. (Kay Ka Wai), Ng, H.-K. (Ho-Keung), Yao, Y. (Yu), Kumabe, T. (Toshihiro), Tominaga, T. (Teiji), Grajkowska, W.A. (Wieslawa), Perek-Polnik, M. (Marta), Low, D.C.Y. (David C.Y.), Seow, W.T. (Wan Tew), Chang, K.T.E. (Kenneth T.E.), Mora, J. (Jaume), Pollack, A. (Aaron), Hamilton, R.L. (Ronald L.), Leary, S. (Sarah), Moore, A.S. (Andrew S.), Ingram, W.J. (Wendy J.), Hallahan, A.R. (Andrew R.), Jouvet, A. (Anne), Fèvre-Montange, M. (Michelle), Vasiljevic, A. (Alexandre), Faure-Conter, C. (Cecile), Shofuda, T. (Tomoko), Kagawa, N. (Naoki), Hashimoto, N. (Naoya), Jabado, N. (Nada), Weil, A.G. (Alexander G.), Gayden, T. (Tenzin), Wataya, T. (Takafumi), Shalaby, T. (Tarek), Grotzer, M. (Michael), Zitterbart, K. (Karel), Sterba, J., Kren, L. (Leos), Hortobágyi, T. (Tibor), Klekner, A. (Almos), Bognár, L. (László), Pócza, T. (Tímea), Hauser, P. (Peter), Schüller, U. (Ulrich), Jung, S. (Shin), Jang, W.-Y. (Woo-Youl), French, P.J. (Pim), Kros, J.M. (Johan), Veelen-Vincent, M.L.C. (Marie-Lise) van, Massimi, L. (Luca), Leonard, J.R. (Jeffrey), Rubin, J.B. (Joshua), Vibhakar, R. (Rajeev), Chambless, L.B. (Lola B.), Cooper, M.K. (Michael), Thompson, R.C. (Reid), Faria, R. (Rui), Carvalho, A. (Alice), Nunes, S. (Sofia), Pimentel, J., Fan, X. (Xing), Muraszko, K.M. (Karin), López-Aguilar, E. (Enrique), Lyden, D. (David), Garzia, L. (Livia), Shih, D.J.H. (David J.), Kijima, N. (Noriyuki), Schneider, C. (Christian), Adamski, J. (Jennifer), Northcott, P.A. (Paul A.), Kool, M. (Marcel), Jones, D. (David), Chan, J.A. (Jennifer A.), Nikolic, A. (Ana), Garre, M.L. (Maria Luisa), Van Meir, E.G. (Erwin G.), Osuka, S. (Satoru), Olson, J.J. (Jeffrey J.), Jahangiri, A. (Arman), Castro, B.A. (Brandyn A.), Gupta, N. (Nalin), Weiss, W.A. (William A.), Moxon-Emre, I. (Iska), Mabbott, D.J. (Donald J.), Lassaletta, A. (Alvaro), Hawkins, C.E. (Cynthia), Tabori, U. (Uri), Drake, J. (James), Kulkarni, A. (Abhaya), Dirks, M. (Maaike), Rutka, J.T. (James), Korshunov, A. (Andrey), Pfister, S.M. (Stefan), Packer, R.J. (Roger J.), Ramaswamy, E.A., and Taylor, M.D. (Michael)

Abstract

Background: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm2 tumour remaining), or sub-total resection (≥1·5 cm2 tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings: We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox mod

Published
2016
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44. Targeting Primary Ciliogenesis in Atypical Teratoid/Rhabdoid Tumors

Author

Bluemel, L., Kerl, K., Picard, D., Malzkorn, B., Johann, P. D., Erkek, S., Fruehwald, M. C., Pfister, S. M., Kool, M., Liebau, M. C., Borkhardt, A., Reifenberger, G., Hasselblatt, M., Remke, M., Bluemel, L., Kerl, K., Picard, D., Malzkorn, B., Johann, P. D., Erkek, S., Fruehwald, M. C., Pfister, S. M., Kool, M., Liebau, M. C., Borkhardt, A., Reifenberger, G., Hasselblatt, M., and Remke, M.

Published
2016

45. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.

Author

Torchia, J, Golbourn, B, Feng, S, Ho, KC, Sin-Chan, P, Vasiljevic, A, Norman, JD, Guilhamon, P, Garzia, L, Agamez, NR, Lu, M, Chan, TS, Picard, D, de Antonellis, P, Khuong-Quang, D-A, Planello, AC, Zeller, C, Barsyte-Lovejoy, D, Lafay-Cousin, L, Letourneau, L, Bourgey, M, Yu, M, Gendoo, DMA, Dzamba, M, Barszczyk, M, Medina, T, Riemenschneider, AN, Morrissy, AS, Ra, Y-S, Ramaswamy, V, Remke, M, Dunham, CP, Yip, S, Ng, H-K, Lu, J-Q, Mehta, V, Albrecht, S, Pimentel, J, Chan, JA, Somers, GR, Faria, CC, Roque, L, Fouladi, M, Hoffman, LM, Moore, AS, Wang, Y, Choi, SA, Hansford, JR, Catchpoole, D, Birks, DK, Foreman, NK, Strother, D, Klekner, A, Bognár, L, Garami, M, Hauser, P, Hortobágyi, T, Wilson, B, Hukin, J, Carret, A-S, Van Meter, TE, Hwang, EI, Gajjar, A, Chiou, S-H, Nakamura, H, Toledano, H, Fried, I, Fults, D, Wataya, T, Fryer, C, Eisenstat, DD, Scheinemann, K, Fleming, AJ, Johnston, DL, Michaud, J, Zelcer, S, Hammond, R, Afzal, S, Ramsay, DA, Sirachainan, N, Hongeng, S, Larbcharoensub, N, Grundy, RG, Lulla, RR, Fangusaro, JR, Druker, H, Bartels, U, Grant, R, Malkin, D, McGlade, CJ, Nicolaides, T, Tihan, T, Phillips, J, Majewski, J, Montpetit, A, Bourque, G, Bader, GD, Reddy, AT, Gillespie, GY, Warmuth-Metz, M, Rutkowski, S, Tabori, U, Lupien, M, Brudno, M, Schüller, U, Pietsch, T, Judkins, AR, Hawkins, CE, Bouffet, E, Kim, S-K, Dirks, PB, Taylor, MD, Erdreich-Epstein, A, Arrowsmith, CH, De Carvalho, DD, Rutka, JT, Jabado, N, Huang, A, Torchia, J, Golbourn, B, Feng, S, Ho, KC, Sin-Chan, P, Vasiljevic, A, Norman, JD, Guilhamon, P, Garzia, L, Agamez, NR, Lu, M, Chan, TS, Picard, D, de Antonellis, P, Khuong-Quang, D-A, Planello, AC, Zeller, C, Barsyte-Lovejoy, D, Lafay-Cousin, L, Letourneau, L, Bourgey, M, Yu, M, Gendoo, DMA, Dzamba, M, Barszczyk, M, Medina, T, Riemenschneider, AN, Morrissy, AS, Ra, Y-S, Ramaswamy, V, Remke, M, Dunham, CP, Yip, S, Ng, H-K, Lu, J-Q, Mehta, V, Albrecht, S, Pimentel, J, Chan, JA, Somers, GR, Faria, CC, Roque, L, Fouladi, M, Hoffman, LM, Moore, AS, Wang, Y, Choi, SA, Hansford, JR, Catchpoole, D, Birks, DK, Foreman, NK, Strother, D, Klekner, A, Bognár, L, Garami, M, Hauser, P, Hortobágyi, T, Wilson, B, Hukin, J, Carret, A-S, Van Meter, TE, Hwang, EI, Gajjar, A, Chiou, S-H, Nakamura, H, Toledano, H, Fried, I, Fults, D, Wataya, T, Fryer, C, Eisenstat, DD, Scheinemann, K, Fleming, AJ, Johnston, DL, Michaud, J, Zelcer, S, Hammond, R, Afzal, S, Ramsay, DA, Sirachainan, N, Hongeng, S, Larbcharoensub, N, Grundy, RG, Lulla, RR, Fangusaro, JR, Druker, H, Bartels, U, Grant, R, Malkin, D, McGlade, CJ, Nicolaides, T, Tihan, T, Phillips, J, Majewski, J, Montpetit, A, Bourque, G, Bader, GD, Reddy, AT, Gillespie, GY, Warmuth-Metz, M, Rutkowski, S, Tabori, U, Lupien, M, Brudno, M, Schüller, U, Pietsch, T, Judkins, AR, Hawkins, CE, Bouffet, E, Kim, S-K, Dirks, PB, Taylor, MD, Erdreich-Epstein, A, Arrowsmith, CH, De Carvalho, DD, Rutka, JT, Jabado, N, and Huang, A

Abstract

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.

Published
2016

46. Procedures and tools for generating and selecting alternatives in LCA

Author

Remke M. Bras-Klapwijk

Subjects
Engineering, Scope (project management), Process (engineering), business.industry, Impact assessment, media_common.quotation_subject, Policy analysis, Toolbox, Risk analysis (engineering), Systems engineering, Quality (business), Product (category theory), business, Ecodesign, General Environmental Science, media_common
Abstract

Life Cycle Assessments (LCAs) frequently do not contribute to sustainable development because product alternatives with a truly low environmental burden are not included in the assessment. As a result, environmentally-friendly alternatives are not uncovered, although much effort has been put into collecting inventory data and making an impact assessment. Part of this problem is caused by the defensive use of LCAs. Companies eager to show that their product is not too bad for the environment prefer to compare their product with alternatives that are not very promising in an environmental sense. To (mis)use LCAs in this way is quite easy, because the LCA methodology and handbooks provide few guidelines and little advice on how to generate and select adequate alternatives. An analysis of the problems related to the alternatives is given using insights drawn from the field of policy analysis — a field in which methodological rules for the generation of alternatives in policy studies have been developed — ecodesign and the LCA discipline, and measures to reduce the problems are developed. Explicating the different steps in the determination of alternatives in the goal and scope formulation stage of an LCA process, and the development of a toolbox for this activity, would certainly improve the quality of the selection of alternatives. Furthermore, involving stakeholders and a group of experts in the generation and selection process will increase the variety and relevance of alternatives, and the social support for alternatives.

Published
2003
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47. Cytogenetic prognostication within medulloblastoma subgroups

Author

Shih, DJH, Northcott, PA, Remke, M, Korshunov, A, Ramaswamy, V, Kool, M, Luu, B, Yao, Y, Wang, X, Dubuc, AM, Garzia, L, Peacock, J, Mack, SC, Wu, X, Rolider, A, Morrissy, AS, Cavalli, FMG, Jones, DTW, Zitterbart, K, Faria, CC, Schüller, U, Kren, L, Kumabe, T, Tominaga, T, Ra, YS, Garami, M, Hauser, P, Chan, JA, Robinson, S, Bognár, L, Klekner, A, Saad, AG, Liau, LM, Albrecht, S, Fontebasso, A, Cinalli, G, De Antonellis, P, Zollo, M, Cooper, MK, Thompson, RC, Bailey, S, Lindsey, JC, Di Rocco, C, Massimi, L, Michiels, EMC, Scherer, SW, Phillips, JJ, Gupta, N, Fan, X, Muraszko, KM, Vibhakar, R, Eberhart, CG, Fouladi, M, Lach, B, Jung, S, Wechsler-Reya, RJ, Fèvre-Montange, M, Jouvet, A, Jabado, N, Pollack, IF, Weiss, WA, Lee, JY, Cho, BK, Kim, SK, Wang, KC, Leonard, JR, Rubin, JB, De Torres, C, Lavarino, C, Mora, J, Cho, YJ, Tabori, U, Olson, JM, Gajjar, A, Packer, RJ, Rutkowski, S, Pomeroy, SL, French, PJ, Kloosterhof, NK, Kros, JM, Van Meir, EG, Clifford, SC, Bourdeaut, F, Delattre, O, Doz, FF, Hawkins, CE, Malkin, D, and Grajkowska, WA

Subjects
Male, Adolescent, Kruppel-Like Transcription Factors, Zinc Finger Protein Gli2, Risk Assessment, Proto-Oncogene Proteins c-myc, Cytogenetics, Young Adult, Risk Factors, Predictive Value of Tests, Biomarkers, Tumor, Humans, Hedgehog Proteins, Oncology & Carcinogenesis, Child, In Situ Hybridization, Fluorescence, Proportional Hazards Models, Chromosomes, Human, Pair 14, Oncology And Carcinogenesis, Chromosomes, Human, Pair 11, Gene Expression Profiling, Nuclear Proteins, Reproducibility of Results, Infant, Prognosis, Gene Expression Regulation, Neoplastic, Wnt Proteins, Tissue Array Analysis, Child, Preschool, Female, Medulloblastoma
Abstract

Purpose: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. © 2014 by American Society of Clinical Oncology.

Published
2014
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50. Are life cycle assessments a threat to sound public policy making?

Author

Remke M. Bras-Klapwijk

Subjects
Public economics, Management science, media_common.quotation_subject, Public policy, Formal methods, Policy studies, Politics, Framing (social sciences), Perception, Economics, Normative, Life-cycle assessment, General Environmental Science, media_common
Abstract

This paper deals with the question of whether Life Cycle Assessments (LCAs), with their focus on objective and quantitative results, are the best way to support public policy processes. The public policy making process is characterized as a continuous discoursive struggle. Criteria are defined to distinguish between good and bad public policy discourses to judge the effects of LCA on the public policy process. Many policy scientists argue that methodologies that emphasize quantification and the use of formal methods are not beneficial for sound public policy making. An empirical report of the role LCAs played in public policy making processes on PVC and chlorine in the Netherlands is made to evaluate the contribution of LCAs to public policy making processes and to identify the main limitations of the current LCA methodologies and practices. It appears that political actors tend to use LCAs in a polarizing way. LCAs are easily misused due to their apparent objectivity, and the quantitative and black box nature of their results. LCAs contain an implicit, normative frame that does not match the environmentalists’ perception on the kind of evidence needed on toxic effects of organochlorines, which reduced the open nature of the Dutch PVC debate. It is recommended to develop a methodology for product evaluation that approaches the issue in a more open and emergent way to prevent “premature closure” of the analysis. It is expected that a focus on the development of balanced, rich arguments on facts and values in the study process will be more fruitful than the calculation of integral, quantitative indicators.

Published
1998
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