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101. Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome

Author

Chen, Yin-Huai, primary, Grigelioniene, Giedre, additional, Newton, Phillip T., additional, Gullander, Jacob, additional, Elfving, Maria, additional, Hammarsjö, Anna, additional, Batkovskyte, Dominyka, additional, Alsaif, Hessa S., additional, Kurdi, Wesam I.Y., additional, Abdulwahab, Firdous, additional, Shanmugasundaram, Veerabahu, additional, Devey, Luke, additional, Bacrot, Séverine, additional, Brodszki, Jana, additional, Huber, Celine, additional, Hamel, Ben, additional, Gisselsson, David, additional, Papadogiannakis, Nikos, additional, Jedrycha, Katarina, additional, Gürtl-Lackner, Barbara, additional, Chagin, Andrei S., additional, Nishimura, Gen, additional, Aschenbrenner, Dominik, additional, Alkuraya, Fowzan S., additional, Laurence, Arian, additional, Cormier-Daire, Valérie, additional, and Uhlig, Holm H., additional

Published
2020
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104. Treatment resilience of cancer through clonal evolution

Author

Karlsson, Jenny, Yasui, Hiroaki, Andersson, Natalie, Valind, Anders, Bakker, Bjorn, Mengelbier, Linda Holmquist, Foijer, Floris, Gisselsson, David, Stem Cell Aging Leukemia and Lymphoma (SALL), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)

Published
2019

116. The Iroquois homeobox proteins IRX3 and IRX5 have distinct roles in Wilms tumour development and human nephrogenesis

Author

Holmquist Mengelbier, Linda, primary, Lindell-Munther, Simon, additional, Yasui, Hiroaki, additional, Jansson, Caroline, additional, Esfandyari, Javanshir, additional, Karlsson, Jenny, additional, Lau, Kimberly, additional, Hui, Chi-chung, additional, Bexell, Daniel, additional, Hopyan, Sevan, additional, and Gisselsson, David, additional

Published
2018
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119. A case of Cornelia de Lange syndrome from Sudan

Author

Elagib Atif, Nilsson Therese, Gisselsson David, Ellaithi Mona, Fadl-Elmula Imad, and Abdelgadir Mashair

Subjects
Pediatrics, RJ1-570
Abstract

Abstract Background Brachmann de Lange syndrome (BDLS) is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. Case presentation Here we present for the first time a case of BDLS from Sudan, a 7-month-old female infant, who was referred as a case of malnutrition. The patient was from a Sudanese western tribe. Clinical investigation showed that the child was a classical case of BDLS, but with some additional clinical findings not previously reported including crowded ribs and tied tongue. Conclusion Reporting BDLS cases of different ethnic backgrounds could add nuances to the phenotypic description of the syndrome and be helpful in diagnosis.

Published
2007
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121. Euploidy in somatic cells from R6/2 transgenic Huntington's disease mice

Author

Stewénius Ylva, Petersén Åsa, Björkqvist Maria, and Gisselsson David

Subjects
Cytology, QH573-671
Abstract

Abstract Background Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a CAG repeat expansion in the HD gene. The huntingtin protein expressed from HD has an unknown function but is suggested to interact with proteins involved in the cell division machinery. The R6/2 transgenic mouse is the most widely used model to study HD. In R6/2 fibroblast cultures, a reduced mitotic index and high frequencies of multiple centrosomes and aneuploid cells have recently been reported. Aneuploidy is normally a feature closely connected to neoplastic disease. To further explore this unexpected aspect of HD, we studied cultures derived from 6- and 12-week-old R6/2 fibroblasts, skeletal muscle cells, and liver cells. Results Cytogenetic analyses revealed a high frequency of polyploid cells in cultures from both R6/2 and wild-type mice with the greatest proportions of polyploid cells in cultures derived from skeletal muscle cells of both genotypes. The presence of polyploid cells in skeletal muscle in vivo was confirmed by fluorescence in situ hybridisation with centromeric probes. Enlarged and supernumerary centrosomes were found in cultures from both R6/2 and wild-type mice. However, no aneuploid cells could be found in any of the tissues. Conclusion We conclude that polyploid cells are found in fibroblast and skeletal muscle cultures derived from both R6/2 and wild-type littermate mice and that aneuploidy is unlikely to be a hallmark of HD.

Published
2005
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123. Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma

Author

Braekeveldt, Noémie, primary, von Stedingk, Kristoffer, additional, Fransson, Susanne, additional, Martinez-Monleon, Angela, additional, Lindgren, David, additional, Axelson, Håkan, additional, Levander, Fredrik, additional, Willforss, Jakob, additional, Hansson, Karin, additional, Øra, Ingrid, additional, Backman, Torbjörn, additional, Börjesson, Anna, additional, Beckman, Siv, additional, Esfandyari, Javanshir, additional, Berbegall, Ana P., additional, Noguera, Rosa, additional, Karlsson, Jenny, additional, Koster, Jan, additional, Martinsson, Tommy, additional, Gisselsson, David, additional, Påhlman, Sven, additional, and Bexell, Daniel, additional

Published
2018
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126. Mosaicism in health and disease — clones picking up speed

Author

Forsberg, Lars A., Gisselsson, David, Dumanski, Jan P., Forsberg, Lars A., Gisselsson, David, and Dumanski, Jan P.

Abstract

Post-zygotic variation refers to genetic changes that arise in the soma of an individual and that are not usually inherited by the next generation. Although there is a paucity of research on such variation, emerging studies show that it is common: individuals are complex mosaics of genetically distinct cells, to such an extent that no two somatic cells are likely to have the exact same genome. Although most types of mutation can be involved in post-zygotic variation, structural genetic variants are likely to leave the largest genomic footprint. Somatic variation has diverse physiological roles and pathological consequences, particularly when acquired variants influence the clonal trajectories of the affected cells. Post-zygotic variation is an important confounder in medical genetic testing and a promising avenue for research: future studies could involve analyses of sorted and single cells from multiple tissue types to fully explore its potential.

Published
2017
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127. Abstracts from the 3rd Conference on Aneuploidy and Cancer: Clinical and Experimental Aspects

Author

Biological Sciences, Fralin Life Sciences Institute, Cornish-Bowden, Athel, Rasnick, David, Heng, Henry H., Horne, Steven, Abdallah, Batoul, Liu, Guo, Ye, Christine J., Bloomfield, Mathew, Vincent, Mark D., Aldaz, C. M., Karlsson, Jenny, Valind, Anders, Jansson, Caroline, Gisselsson, David, Graves, Jennifer A. M., Stepanenko, Aleksei A., Andreieva, Svitlana V., Korets, Kateryna V., Mykytenko, Dmytro O., Huleyuk, Nataliya L., Baklaushev, Vladimir P., Kovaleva, Oksana A., Chekhonin, Vladimir P., Vassetzky, Yegor S., Avdieiev, Stanislav S., Bakker, Bjorn, Taudt, Aaron S., Belderbos, Mirjam E., Porubsky, David, Spierings, Diana C. J., de Jong, Tristan V., Halsema, Nancy, Kazemier, Hinke G., Hoekstra-Wakker, Karina, Bradley, Allan, de Bont, Eveline S. J. M., van den Berg, Anke, Guryev, Victor, Lansdorp, Peter M., Tatché, Maria C., Foijer, Floris, Liehr, Thomas, Baudoin, Nicolaas C., Nicholson, Joshua M., Soto, Kimberly, Quintanilla, Isabel, Camps, Jordi, Cimini, Daniela, Dürrbaum, M., Donnelly, N., Passerini, V., Kruse, C., Habermann, B., Storchová, Z., Mandrioli, Daniele, Belpoggi, Fiorella, Silbergeld, Ellen K., Perry, Melissa J., Skotheim, Rolf I., Løvf, Marthe, Johannessen, Bjarne, Hoff, Andreas M., Zhao, Sen, SveeStrømme, Jonas M., Sveen, Anita, Lothe, Ragnhild A., Hehlmann, R., Voskanyan, A., Fabarius, A., Böcking, Alfred, Biesterfeld, Stefan, Berynskyy, Leonid, Börgermann, Christof, Engers, Rainer, Dietz, Josef, Fritz, A., Sehgal, N., Vecerova, J., Stojkovicz, B., Ding, H., Page, N., Tye, C., Bhattacharya, S., Xu, J., Stein, G., Stein, J., Berezney, R., Gong, Xue, Grasedieck, Sarah, Swoboda, Julian, Rücker, Frank G., Bullinger, Lars, Pollack, Jonathan R., Roumelioti, Fani-Marlen, Chiourea, Maria, Raftopoulou, Christina, Gagos, Sarantis, Duesberg, Peter, Hwang, Sunyoung, Gustafsson, Hans T., O’Sullivan, Ciara, Acevedo-Colina, Aracelli, Huang, Xinhe, Klose, Christian, Schevchenko, Andrej, Dickson, Robert C., Cavaliere, Paola, Dephoure, Noah, Torres, Eduardo M., Stampfer, Martha R., Vrba, Lukas, LaBarge, Mark A., Futscher, Bernard, Garbe, James C., Trinh, Andrew L., Zhou, Yi-Hong, Digman, Michelle, Biological Sciences, Fralin Life Sciences Institute, Cornish-Bowden, Athel, Rasnick, David, Heng, Henry H., Horne, Steven, Abdallah, Batoul, Liu, Guo, Ye, Christine J., Bloomfield, Mathew, Vincent, Mark D., Aldaz, C. M., Karlsson, Jenny, Valind, Anders, Jansson, Caroline, Gisselsson, David, Graves, Jennifer A. M., Stepanenko, Aleksei A., Andreieva, Svitlana V., Korets, Kateryna V., Mykytenko, Dmytro O., Huleyuk, Nataliya L., Baklaushev, Vladimir P., Kovaleva, Oksana A., Chekhonin, Vladimir P., Vassetzky, Yegor S., Avdieiev, Stanislav S., Bakker, Bjorn, Taudt, Aaron S., Belderbos, Mirjam E., Porubsky, David, Spierings, Diana C. J., de Jong, Tristan V., Halsema, Nancy, Kazemier, Hinke G., Hoekstra-Wakker, Karina, Bradley, Allan, de Bont, Eveline S. J. M., van den Berg, Anke, Guryev, Victor, Lansdorp, Peter M., Tatché, Maria C., Foijer, Floris, Liehr, Thomas, Baudoin, Nicolaas C., Nicholson, Joshua M., Soto, Kimberly, Quintanilla, Isabel, Camps, Jordi, Cimini, Daniela, Dürrbaum, M., Donnelly, N., Passerini, V., Kruse, C., Habermann, B., Storchová, Z., Mandrioli, Daniele, Belpoggi, Fiorella, Silbergeld, Ellen K., Perry, Melissa J., Skotheim, Rolf I., Løvf, Marthe, Johannessen, Bjarne, Hoff, Andreas M., Zhao, Sen, SveeStrømme, Jonas M., Sveen, Anita, Lothe, Ragnhild A., Hehlmann, R., Voskanyan, A., Fabarius, A., Böcking, Alfred, Biesterfeld, Stefan, Berynskyy, Leonid, Börgermann, Christof, Engers, Rainer, Dietz, Josef, Fritz, A., Sehgal, N., Vecerova, J., Stojkovicz, B., Ding, H., Page, N., Tye, C., Bhattacharya, S., Xu, J., Stein, G., Stein, J., Berezney, R., Gong, Xue, Grasedieck, Sarah, Swoboda, Julian, Rücker, Frank G., Bullinger, Lars, Pollack, Jonathan R., Roumelioti, Fani-Marlen, Chiourea, Maria, Raftopoulou, Christina, Gagos, Sarantis, Duesberg, Peter, Hwang, Sunyoung, Gustafsson, Hans T., O’Sullivan, Ciara, Acevedo-Colina, Aracelli, Huang, Xinhe, Klose, Christian, Schevchenko, Andrej, Dickson, Robert C., Cavaliere, Paola, Dephoure, Noah, Torres, Eduardo M., Stampfer, Martha R., Vrba, Lukas, LaBarge, Mark A., Futscher, Bernard, Garbe, James C., Trinh, Andrew L., Zhou, Yi-Hong, and Digman, Michelle

Published
2017

128. Neuroblastoma patient-derived xenograft cells cultured in stem-cell promoting medium retain tumorigenic and metastatic capacities but differentiate in serum

Author

Persson, Camilla U., primary, von Stedingk, Kristoffer, additional, Bexell, Daniel, additional, Merselius, My, additional, Braekeveldt, Noémie, additional, Gisselsson, David, additional, Arsenian-Henriksson, Marie, additional, Påhlman, Sven, additional, and Wigerup, Caroline, additional

Published
2017
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133. The Iroquois homeobox proteins IRX3 and IRX5 have distinct roles in Wilms tumour development and human nephrogenesis.

Author

Holmquist Mengelbier, Linda, Lindell‐Munther, Simon, Yasui, Hiroaki, Jansson, Caroline, Esfandyari, Javanshir, Karlsson, Jenny, Lau, Kimberly, Hui, Chi‐chung, Bexell, Daniel, Hopyan, Sevan, and Gisselsson, David

Abstract

Wilms tumour is a paediatric malignancy with features of halted kidney development. Here, we demonstrate that the Iroquois homeobox genes IRX3 and IRX5 are essential for mammalian nephrogenesis and govern the differentiation of Wilms tumour. Knock‐out Irx3−/Irx5− mice showed a strongly reduced embryonic nephron formation. In human foetal kidney and Wilms tumour, IRX5 expression was already activated in early proliferative blastema, whereas IRX3 protein levels peaked at tubular differentiation. Accordingly, an orthotopic xenograft mouse model of Wilms tumour showed that IRX3−/− cells formed bulky renal tumours dominated by immature mesenchyme and active canonical WNT/β‐catenin‐signalling. In contrast, IRX5−/− cells displayed activation of Hippo and non‐canonical WNT‐signalling and generated small tumours with abundant tubulogenesis. Our findings suggest that promotion of IRX3 signalling or inhibition of IRX5 signalling could be a route towards differentiation therapy for Wilms tumour, in which WNT5A is a candidate molecule for enforced tubular maturation. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Published
2019
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134. Genetic Heterogeneity in Rhabdomyosarcoma Revealed by SNP Array Analysis

Author

Walther, Charles, Mayrhofer, Markus, Nilsson, Jenny, Hofvander, Jakob, Jonson, Tord, Mandahl, Nils, Ora, Ingrid, Gisselsson, David, Mertens, Fredrik, Walther, Charles, Mayrhofer, Markus, Nilsson, Jenny, Hofvander, Jakob, Jonson, Tord, Mandahl, Nils, Ora, Ingrid, Gisselsson, David, and Mertens, Fredrik

Abstract

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Alveolar (ARMS) and embryonal (ERMS) histologies predominate, but rare cases are classified as spindle cell/sclerosing (SRMS). For treatment stratification, RMS is further subclassified as fusion-positive (FP-RMS) or fusion-negative (FN-RMS), depending on whether a gene fusion involving PAX3 or PAX7 is present or not. We investigated 19 cases of pediatric RMS using high resolution single-nucleotide polymorphism (SNP) array. FP-ARMS displayed, on average, more structural rearrangements than ERMS; the single FN-ARMS had a genomic profile similar to ERMS. Apart from previously known amplification (e.g., MYCN, CDK4, and MIR17HG) and deletion (e.g., NF1, CDKN2A, and CDKN2B) targets, amplification of ERBB2 and homozygous loss of ASCC3 or ODZ3 were seen. Combining SNP array with cytogenetic data revealed that most cases were polyploid, with at least one case having started as a near-haploid tumor. Further bioinformatic analysis of the SNP array data disclosed genetic heterogeneity, in the form of subclonal chromosomal imbalances, in five tumors. The outcome was worse for patients with FP-ARMS than ERMS or FN-ARMS (6/8 vs. 1/9 dead of disease), and the only children with ERMS showing intratumor diversity or with MYOD1 mutation-positive SRMS also died of disease. High resolution SNP array can be useful in evaluating genomic imbalances in pediatric RMS.

Published
2016
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135. Limitations of Chromosome Classification by Multicolor Karyotyping

Author

Lee, Charles, Gisselsson, David, Jin, Charlotte, Nordgren, Ann, Ferguson, David O., Blennow, Elisabeth, Fletcher, Jonathan A., and Morton, Cynthia C.

Subjects
Cytogenetics -- Research, Chromosomes -- Research, Fluorspar -- Research, Biological sciences
Published
2001

137. Gain of 1q As a Prognostic Biomarker in Wilms Tumors (WTs) Treated With Preoperative Chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 Trial: A SIOP Renal Tumours Biology Consortium Study

Author

Chagtai, Tasnim, primary, Zill, Christina, additional, Dainese, Linda, additional, Wegert, Jenny, additional, Savola, Suvi, additional, Popov, Sergey, additional, Mifsud, William, additional, Vujanić, Gordan, additional, Sebire, Neil, additional, Le Bouc, Yves, additional, Ambros, Peter F., additional, Kager, Leo, additional, O'Sullivan, Maureen J., additional, Blaise, Annick, additional, Bergeron, Christophe, additional, Mengelbier, Linda Holmquist, additional, Gisselsson, David, additional, Kool, Marcel, additional, Tytgat, Godelieve A.M., additional, van den Heuvel-Eibrink, Marry M., additional, Graf, Norbert, additional, van Tinteren, Harm, additional, Coulomb, Aurore, additional, Gessler, Manfred, additional, Williams, Richard Dafydd, additional, and Pritchard-Jones, Kathy, additional

Published
2016
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140. Abstract A02: Neuroblastoma patient-derived orthotopic xenografts: Clinically relevant models for drug testing

Author

Braekeveldt, Noémie, primary, Wigerup, Caroline, additional, Gisselsson, David, additional, Mohlin, Sofie, additional, Merselius, My, additional, Beckman, Siv, additional, Tadeo, Irene, additional, Berbegall, Anna P., additional, Öra, Ingrid, additional, Navarro, Samuel, additional, Noguera, Rosa, additional, Påhlman, Sven, additional, and Bexell, Daniel, additional

Published
2016
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143. Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer

Author

Mengelbier, Linda Holmquist, Karlsson, Jenny, Lindgren, David, Valind, Anders, Lilljebjorn, Henrik, Jansson, Caroline, Bexell, Daniel, Braekeveldt, Noemie, Ameur, Adam, Jonson, Tord, Kultima, Hanna Göransson, Isaksson, Anders, Asmundsson, Jurate, Versteeg, Rogier, Rissler, Marianne, Fioretos, Thoas, Sandstedt, Bengt, Borjesson, Anna, Backman, Torbjorn, Pal, Niklas, Ora, Ingrid, Mayrhofer, Markus, Gisselsson, David, Mengelbier, Linda Holmquist, Karlsson, Jenny, Lindgren, David, Valind, Anders, Lilljebjorn, Henrik, Jansson, Caroline, Bexell, Daniel, Braekeveldt, Noemie, Ameur, Adam, Jonson, Tord, Kultima, Hanna Göransson, Isaksson, Anders, Asmundsson, Jurate, Versteeg, Rogier, Rissler, Marianne, Fioretos, Thoas, Sandstedt, Bengt, Borjesson, Anna, Backman, Torbjorn, Pal, Niklas, Ora, Ingrid, Mayrhofer, Markus, and Gisselsson, David

Abstract

Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral diversity in a set of chemotherapy-treated childhood tumours. By analysis of multiple tumour samples from seven patients we demonstrate intratumoral diversity in all patients analysed after chemotherapy, typically presenting as multiple clones within a single millimetre-sized tumour sample (microdiversity). We show that microdiversity often acts as the foundation for further genome evolution in metastases. In addition, we find that microdiversity predicts poor cancer-specific survival (60%; P = 0.009), independent of other risk factors, in a cohort of 44 patients with chemotherapy-treated childhood kidney cancer. Survival was 100% for patients lacking microdiversity. Thus, intratumoral genetic diversity is common in childhood cancers after chemotherapy and may be an important factor behind treatment failure.

Published
2015
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144. Abstract A1-59: Multiple mechanisms of MYCN dysregulation in Wilms tumor

Author

Williams, Richard D., primary, Chagtai, Tasnim, additional, Alcaide-German, Marisa, additional, Apps, John, additional, Wegert, Jenny, additional, Popov, Sergey, additional, Vujanic, Gordan, additional, Tinteren, Harm van, additional, Heuvel-Eibrink, Marry M. van den, additional, Kool, Marcel, additional, Gisselsson, David, additional, Graf, Norbert, additional, Gessler, Manfred, additional, and Pritchard-Jones, Kathy, additional

Published
2015
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145. Abstract A1-67: Prognostic significance of copy number aberrations in Wilms tumor

Author

Chagtai, Tasnim, primary, Zill, Christina, additional, Dainese, Linda, additional, Wegert, Jenny, additional, Maschietto, Mariana, additional, Vujanic, Gordan, additional, Sebire, Neil, additional, Leuschner, Ivo, additional, Ambros, Peter, additional, O'Sullivan, Maureen, additional, Bergeron, Christophe, additional, Gisselsson, David, additional, Kool, Marcel, additional, Heuvel-Eibrink, Marry van den, additional, Graf, Norbert, additional, Tinteren, Harm van, additional, Coulomb, Aurore, additional, Gessler, Manfred, additional, Williams, Richard, additional, and Pritchard-Jones, Kathy, additional

Published
2015
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150. Multiple mechanisms of MYCN dysregulation in Wilms tumour

Author

Williams, Richard D., primary, Chagtai, Tasnim, additional, Alcaide-German, Marisa, additional, Apps, John, additional, Wegert, Jenny, additional, Popov, Sergey, additional, Vujanic, Gordan, additional, van Tinteren, Harm, additional, van den Heuvel-Eibrink, Marry M., additional, Kool, Marcel, additional, de Kraker, Jan, additional, Gisselsson, David, additional, Graf, Norbert, additional, Gessler, Manfred, additional, and Pritchard-Jones, Kathy, additional

Published
2015
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