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Author Le Compte, M.; Cardenas De La Hoz, E.; Peeters, S.; Rodrigues Fortes, F.; Hermans, C.; Domen, A.; Smits, E.; Lardon, F.; Vandamme, T.; Lin, A.; Vanlanduit, S.; Roeyen, G.; van Laere, S.; Prenen, H.; Peeters, M.; Deben, C.
Title Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer Type A1 Journal article
Year 2023 Publication npj Precision Oncology Abbreviated Journal
Volume 7 Issue 1 Pages 128-14
Keywords (down) A1 Journal article; Center for Oncological Research (CORE); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)
Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, characterized by a treatment-resistant and invasive nature. In line with these inherent aggressive characteristics, only a subset of patients shows a clinical response to the standard of care therapies, thereby highlighting the need for a more personalized treatment approach. In this study, we comprehensively unraveled the intra-patient response heterogeneity and intrinsic aggressive nature of PDAC on bulk and single-organoid resolution. We leveraged a fully characterized PDAC organoid panel ( N  = 8) and matched our artificial intelligence-driven, live-cell organoid image analysis with retrospective clinical patient response. In line with the clinical outcomes, we identified patient-specific sensitivities to the standard of care therapies (gemcitabine-paclitaxel and FOLFIRINOX) using a growth rate-based and normalized drug response metric. Moreover, the single-organoid analysis was able to detect resistant as well as invasive PDAC organoid clones, which was orchestrates on a patient, therapy, drug, concentration and time-specific level. Furthermore, our in vitro organoid analysis indicated a correlation with the matched patient progression-free survival (PFS) compared to the current, conventional drug response readouts. This work not only provides valuable insights on the response complexity in PDAC, but it also highlights the potential applications (extendable to other tumor types) and clinical translatability of our approach in drug discovery and the emerging era of personalized medicine.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 001118015800001 Publication Date 2023-12-08
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2397-768x ISBN Additional Links UA library record; WoS full record; WoS citing articles
Impact Factor Times cited Open Access
Notes Approved Most recent IF: NA
Call Number UA @ admin @ c:irua:201455 Serial 9091
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Author van der Linden, V.; Bultinck, E.; de Ruytter, J.; Schalm, O.; Janssens, K.; Devos, W.; Tiri, W.
Title Compositional analysis of 17-18th century archaeological glass fragments, excavated in Mechelen, Belgium: comparison with data from neighboring cities in the Low Countries Type A1 Journal article
Year 2005 Publication Nuclear instruments and methods in physics research: B: beam interactions with materials and atoms Abbreviated Journal Nucl Instrum Meth B
Volume 239 Issue 1/2 Pages 100-106
Keywords (down) A1 Journal article; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Abstract
Address
Corporate Author Thesis
Publisher Place of Publication Amsterdam Editor
Language Wos 000233514700013 Publication Date 2005-08-19
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0168-583X; ISBN Additional Links UA library record; WoS full record; WoS citing articles
Impact Factor 1.109 Times cited 15 Open Access
Notes Approved Most recent IF: 1.109; 2005 IF: 1.181
Call Number UA @ lucian @ c:irua:56068 Serial 444
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Author Tambuyzer, B.R.; Bergwerf, I.; de Vocht, N.; Reekmans, K.; Daans, J.; Jorens, P.G.; Goossens, H.; Ysebaert, D.K.; Chatterjee, S.; Van Marck, E.; Berneman, Z.N.; Ponsaerts, P.
Title Allogeneic stromal cell implantation in brain tissue leads to robust microglial activation Type A1 Journal article
Year 2009 Publication Immunology and cell biology Abbreviated Journal Immunol Cell Biol
Volume Issue Pages
Keywords (down) A1 Journal article; Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP); Bio-Imaging lab; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Abstract Although adult and embryonic stem cell-based therapy for central nervous system (CNS) injury is being developed worldwide, less attention is given to the immunological aspects of allogeneic cell implantation in the CNS. The latter is of major importance because, from a practical point of view, future stem cell-based therapy for CNS injury will likely be performed using well-characterised allogeneic stem cell populations. In this study, we aimed to further describe the immunological mechanism leading to rejection of allogeneic bone marrow-derived stromal cells (BM-SC) after implantation in murine CNS. For this, we first investigated the impact of autologous and allogeneic BM-SC on microglia activation in vitro. Although the results indicate that both autologous and allogeneic BM-SC do not activate microglia themselves in vitro, they also do not inhibit activation of microglia after exogenous stimuli in vitro. Next, we investigated the impact of allogeneic BM-SC on microglia activation in vivo. In contrast to the in vitro observations, microglia become highly activated in vivo after implantation of allogeneic BM-SC in the CNS of immune-competent mice. Moreover, our results suggest that microglia, rather than T-cells, are the major contributors to allograft rejection in the CNS.
Address
Corporate Author Thesis
Publisher Place of Publication Adelaide Editor
Language Wos 000266208800003 Publication Date 2009-03-17
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0818-9641 ISBN Additional Links UA library record; WoS full record; WoS citing articles
Impact Factor 4.557 Times cited 31 Open Access
Notes Approved Most recent IF: 4.557; 2009 IF: 4.200
Call Number UA @ lucian @ c:irua:74903 Serial 4515
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Author Bergwerf, I.; de Vocht, N.; Tambuyzer, B.; Verschueren, J.; Reekmans, K.; Daans, J.; Ibrahimi, A.; Van Tendeloo, V.; Chatterjee, S.; Goossens, H.; Jorens, P.G.; Baekelandt, V.; Ysebaert, D.; Van Marck, E.; Berneman, Z.N.; Van Der Linden, A.; Ponsaerts, P.
Title Reporter gene-expressing bone marrow-derived stromal cells are immune-tolerated following implantation in the central nervous system of syngeneic immunocompetent mice Type A1 Journal article
Year 2009 Publication BMC biotechnology Abbreviated Journal Bmc Biotechnol
Volume Issue Pages
Keywords (down) A1 Journal article; Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP); Bio-Imaging lab; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Abstract Background Cell transplantation is likely to become an important therapeutic tool for the treatment of various traumatic and ischemic injuries to the central nervous system (CNS). However, in many pre-clinical cell therapy studies, reporter gene-assisted imaging of cellular implants in the CNS and potential reporter gene and/or cell-based immunogenicity, still remain challenging research topics. Results In this study, we performed cell implantation experiments in the CNS of immunocompetent mice using autologous (syngeneic) luciferase-expressing bone marrow-derived stromal cells (BMSC-Luc) cultured from ROSA26-L-S-L-Luciferase transgenic mice, and BMSC-Luc genetically modified using a lentivirus encoding the enhanced green fluorescence protein (eGFP) and the puromycin resistance gene (Pac) (BMSC-Luc/eGFP/Pac). Both reporter gene-modified BMSC populations displayed high engraftment capacity in the CNS of immunocompetent mice, despite potential immunogenicity of introduced reporter proteins, as demonstrated by real-time bioluminescence imaging (BLI) and histological analysis at different time-points post-implantation. In contrast, both BMSC-Luc and BMSC-Luc/eGFP/Pac did not survive upon intramuscular cell implantation, as demonstrated by real-time BLI at different time-points post-implantation. In addition, ELISPOT analysis demonstrated the induction of IFN-ã-producing CD8+ T-cells upon intramuscular cell implantation, but not upon intracerebral cell implantation, indicating that BMSC-Luc and BMSC-Luc/eGFP/Pac are immune-tolerated in the CNS. However, in our experimental transplantation model, results also indicated that reporter gene-specific immune-reactive T-cell responses were not the main contributors to the immunological rejection of BMSC-Luc or BMSC-Luc/eGFP/Pac upon intramuscular cell implantation. Conclusion We here demonstrate that reporter gene-modified BMSC derived from ROSA26-L-S-L-Luciferase transgenic mice are immune-tolerated upon implantation in the CNS of syngeneic immunocompetent mice, providing a research model for studying survival and localisation of autologous BMSC implants in the CNS by real-time BLI and/or histological analysis in the absence of immunosuppressive therapy.
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Corporate Author Thesis
Publisher Place of Publication London Editor
Language Wos 000262698500001 Publication Date 2009-01-07
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1472-6750 ISBN Additional Links UA library record; WoS full record; WoS citing articles
Impact Factor 2.415 Times cited 33 Open Access
Notes Approved Most recent IF: 2.415; 2009 IF: 2.723
Call Number UA @ lucian @ c:irua:72911 Serial 4527
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Author Logie, E.; Chirumamilla, C.S.; Perez-Novo, C.; Shaw, P.; Declerck, K.; Palagani, A.; Rangarajan, S.; Cuypers, B.; De Neuter, N.; Mobashar Hussain Urf Turabe, F.; Kumar Verma, N.; Bogaerts, A.; Laukens, K.; Offner, F.; Van Vlierberghe, P.; Van Ostade, X.; Berghe, W.V.
Title Covalent Cysteine Targeting of Bruton’s Tyrosine Kinase (BTK) Family by Withaferin-A Reduces Survival of Glucocorticoid-Resistant Multiple Myeloma MM1 Cells Type A1 Journal article
Year 2021 Publication Cancers Abbreviated Journal Cancers
Volume 13 Issue 7 Pages 1618
Keywords (down) A1 Journal article; ADReM Data Lab (ADReM); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Abstract Multiple myeloma (MM) is a hematological malignancy characterized by plasma cells’ uncontrolled growth. The major barrier in treating MM is the occurrence of primary and acquired therapy resistance to anticancer drugs. Often, this therapy resistance is associated with constitutive hyperactivation of tyrosine kinase signaling. Novel covalent kinase inhibitors, such as the clinically approved BTK inhibitor ibrutinib (IBR) and the preclinical phytochemical withaferin A (WA), have, therefore, gained pharmaceutical interest. Remarkably, WA is more effective than IBR in killing BTK-overexpressing glucocorticoid (GC)-resistant MM1R cells. To further characterize the kinase inhibitor profiles of WA and IBR in GC-resistant MM cells, we applied phosphopeptidome- and transcriptome-specific tyrosine kinome profiling. In contrast to IBR, WA was found to reverse BTK overexpression in GC-resistant MM1R cells. Furthermore, WA-induced cell death involves covalent cysteine targeting of Hinge-6 domain type tyrosine kinases of the kinase cysteinome classification, including inhibition of the hyperactivated BTK. Covalent interaction between WA and BTK could further be confirmed by biotin-based affinity purification and confocal microscopy. Similarly, molecular modeling suggests WA preferably targets conserved cysteines in the Hinge-6 region of the kinase cysteinome classification, favoring inhibition of multiple B-cell receptors (BCR) family kinases. Altogether, we show that WA’s promiscuous inhibition of multiple BTK family tyrosine kinases represents a highly effective strategy to overcome GC-therapy resistance in MM.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000638328000001 Publication Date 2021-03-31
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2072-6694 ISBN Additional Links UA library record; WoS full record; WoS citing articles
Impact Factor Times cited Open Access OpenAccess
Notes The authors thank Eva Lion, Head of Tumor Immunology Group of the Laboratory of Experimental Hematology (University of Antwerp), for kindly providing GC‐resistant U266 cells. Approved Most recent IF: NA
Call Number PLASMANT @ plasmant @c:irua:177781 Serial 6751
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Author Zhang, Q.-Z.; Bogaerts, A.
Title Plasma streamer propagation in structured catalysts Type A1 Journal Article
Year 2018 Publication Plasma Sources Science & Technology Abbreviated Journal Plasma Sources Sci T
Volume 27 Issue 10 Pages 105013
Keywords (down) A1 Journal Article; plasma catalysis, streamer propagation, 3D structures, PIC/MCC; Plasma, laser ablation and surface modeling Antwerp (PLASMANT) ;
Abstract Plasma catalysis is gaining increasing interest for various environmental applications. Catalytic

material can be inserted in different shapes in the plasma, e.g., as pellets, (coated) beads, but also

as honeycomb monolith and 3DFD structures, also called ‘structured catalysts’, which have high

mass and heat transfer properties. In this work, we examine the streamer discharge propagation

and the interaction between plasma and catalysts, inside the channels of such structured catalysts,

by means of a two-dimensional particle-in-cell/Monte Carlo collision model. Our results reveal

that plasma streamers behave differently in various structured catalysts. In case of a honeycomb

structure, the streamers are limited to only one channel, with low or high plasma density when

the channels are parallel or perpendicular to the electrodes, respectively. In contrast, in case of a

3DFD structure, the streamers can distribute to different channels, causing discharge

enhancement due to surface charging on the dielectric walls of the structured catalyst, and

especially giving rise to a broader plasma distribution. The latter should be beneficial for plasma

catalysis applications, as it allows a larger catalyst surface area to be exposed to the plasma.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000448131900002 Publication Date 2018-10-22
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1361-6595 ISBN Additional Links UA library record; WoS full record; WoS citing articles
Impact Factor 3.302 Times cited 3 Open Access Not_Open_Access
Notes We acknowledge financial support from the European Marie Skłodowska-Curie Individual Fellowship within H2020 (Grant Agreement 702604). This work was carried out in part using the Turing HPC infrastructure at the CalcUA core facility of the Universiteit Antwerpen, a division of the Flemish Supercomputer Center VSC, funded by the Hercules Foundation, the Flemish Government (department EWI) and the University of Antwerp. Approved Most recent IF: 3.302
Call Number PLASMANT @ plasmant @c:irua:155510 Serial 5068
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