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Author Lin, A.; Razzokov, J.; Verswyvel, H.; Privat-Maldonado, A.; De Backer, J.; Yusupov, M.; Cardenas De La Hoz, E.; Ponsaerts, P.; Smits, E.; Bogaerts, A.
Title Oxidation of Innate Immune Checkpoint CD47 on Cancer Cells with Non-Thermal Plasma Type A1 Journal article
Year 2021 Publication Cancers Abbreviated Journal Cancers
Volume 13 Issue 3 Pages 579
Keywords A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Laboratory for Experimental Hematology (LEH); Center for Oncological Research (CORE)
Abstract Non-thermal plasma (NTP) therapy has been emerging as a promising cancer treatment strategy, and recently, its ability to locally induce immunogenic cancer cell death is being unraveled. We hypothesized that the chemical species produced by NTP reduce immunosuppressive surface proteins and checkpoints that are overexpressed on cancerous cells. Here, 3D in vitro tumor models, an in vivo mouse model, and molecular dynamics simulations are used to investigate the effect of NTP on CD47, a key innate immune checkpoint. CD47 is immediately modulated after NTP treatment and simulations reveal the potential oxidized salt-bridges responsible for conformational changes. Umbrella sampling simulations of CD47 with its receptor, signal-regulatory protein alpha (SIRPα), demonstrate that the induced-conformational changes reduce its binding affinity. Taken together, this work provides new insight into fundamental, chemical NTP-cancer cell interaction mechanisms and a previously overlooked advantage of present NTP cancer therapy: reducing immunosuppressive signals on the surface of cancer cells.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000614960600001 Publication Date 2021-02-02
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2072-6694 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor Times cited Open Access OpenAccess
Notes We thank Erik Fransen (University of Antwerp; Antwerp, Belgium) for his help and guidance on the statistical analysis. Approved Most recent IF: NA
Call Number PLASMANT @ plasmant @c:irua:176455 Serial 6709
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Author Kaushik, N.K.; Bekeschus, S.; Tanaka, H.; Lin, A.; Choi, E.H.
Title Plasma medicine technologies Type Editorial
Year 2021 Publication Applied Sciences-Basel Abbreviated Journal Appl Sci-Basel
Volume 11 Issue 10 Pages 4584-4
Keywords Editorial; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Abstract This Special Issue, entitled “Plasma Medicine Technologies”, covers the latest remarkable developments in the field of plasma bioscience and medicine. Plasma medicine is an interdisciplinary field that combines the principles of plasma physics, material science, bioscience, and medicine, towards the development of therapeutic strategies. A study on plasma medicine has yielded the development of new treatment opportunities in medical and dental sciences. An important aspect of this issue is the presentation of research underlying new therapeutic methods that are useful in medicine, dentistry, sterilization, and, in the current scenario, that challenge perspectives in biomedical sciences. This issue is focused on basic research on the characterization of the bioplasma sources applicable to living cells, especially to the human body, and fundamental research on the mutual interactions between bioplasma and organic–inorganic liquids, and bio or nanomaterials.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000662527200001 Publication Date 2021-05-18
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2076-3417 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 1.679 Times cited Open Access OpenAccess
Notes Approved Most recent IF: 1.679
Call Number UA @ admin @ c:irua:178139 Serial 6771
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Author Van Loenhout, J.; Freire Boullosa, L.; Quatannens, D.; De Waele, J.; Merlin, C.; Lambrechts, H.; Lau, H.W.; Hermans, C.; Lin, A.; Lardon, F.; Peeters, M.; Bogaerts, A.; Smits, E.; Deben, C.
Title Auranofin and Cold Atmospheric Plasma Synergize to Trigger Distinct Cell Death Mechanisms and Immunogenic Responses in Glioblastoma Type A1 Journal Article;oxidative stress
Year 2021 Publication Cells Abbreviated Journal Cells
Volume 10 Issue 11 Pages 2936
Keywords A1 Journal Article;oxidative stress; auranofin; cold atmospheric plasma; glioblastoma; cancer cell death; Plasma, laser ablation and surface modeling Antwerp (PLASMANT) ;
Abstract Targeting the redox balance of malignant cells via the delivery of high oxidative stress unlocks a potential therapeutic strategy against glioblastoma (GBM). We investigated a novel reactive oxygen species (ROS)-inducing combination treatment strategy, by increasing exogenous ROS via cold atmospheric plasma and inhibiting the endogenous protective antioxidant system via auranofin (AF), a thioredoxin reductase 1 (TrxR) inhibitor. The sequential combination treatment of AF and cold atmospheric plasma-treated PBS (pPBS), or AF and direct plasma application, resulted in a synergistic response in 2D and 3D GBM cell cultures, respectively. Differences in the baseline protein levels related to the antioxidant systems explained the cell-line-dependent sensitivity towards the combination treatment. The highest decrease of TrxR activity and GSH levels was observed after combination treatment of AF and pPBS when compared to AF and pPBS monotherapies. This combination also led to the highest accumulation of intracellular ROS. We confirmed a ROS-mediated response to the combination of AF and pPBS, which was able to induce distinct cell death mechanisms. On the one hand, an increase in caspase-3/7 activity, with an increase in the proportion of annexin V positive cells, indicates the induction of apoptosis in the GBM cells. On the other hand, lipid peroxidation and inhibition of cell death through an iron chelator suggest the involvement of ferroptosis in the GBM cell lines. Both cell death mechanisms induced by the combination of AF and pPBS resulted in a significant increase in danger signals (ecto-calreticulin, ATP and HMGB1) and dendritic cell maturation, indicating a potential increase in immunogenicity, although the phagocytotic capacity of dendritic cells was inhibited by AF. In vivo, sequential combination treatment of AF and cold atmospheric plasma both reduced tumor growth kinetics and prolonged survival in GBM-bearing mice. Thus, our study provides a novel therapeutic strategy for GBM to enhance the efficacy of oxidative stress-inducing therapy through a combination of AF and cold atmospheric plasma.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000807134000001 Publication Date 2021-10-28
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2073-4409 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor Times cited Open Access OpenAccess
Notes Olivia Hendrickx Research Fund, 21OCL06 ; University of Antwerp, FFB160231 ; The authors would express their gratitude to Hans de Reu for technical assistance with flow cytometry. Approved Most recent IF: NA
Call Number PLASMANT @ plasmant @c:irua:182915 Serial 6826
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Author Lin, A.; Biscop, E.; Gorbanev, Y.; Smits, E.; Bogaerts, A.
Title Toward defining plasma treatment dose : the role of plasma treatment energy of pulsed‐dielectric barrier discharge in dictating in vitro biological responses Type A1 Journal article
Year 2022 Publication Plasma Processes And Polymers Abbreviated Journal Plasma Process Polym
Volume 19 Issue 3 Pages e2100151
Keywords A1 Journal article; Pharmacology. Therapy; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Abstract The energy dependence of a pulsed-dielectric barrier discharge (DBD) plasma treatment on chemical species production and biological responses was investigated. We hypothesized that the total plasma energy delivered during treatment encompasses the influence of major application parameters. A microsecond-pulsed DBD system was used to treat three different cancer cell lines and cell viability was analyzed. The energy per pulse was measured and the total plasma treatment energy was controlled by adjusting the pulse frequency, treatment time, and application distance. Our data suggest that the delivered plasma energy plays a predominant role in stimulating a biological response in vitro. This study aids in developing steps toward defining a plasma treatment unit and treatment dose for biomedical and clinical research.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000711907800001 Publication Date 2021-10-28
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1612-8850 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 3.5 Times cited Open Access OpenAccess
Notes Approved Most recent IF: 3.5
Call Number UA @ admin @ c:irua:182916 Serial 7219
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Author Privat-Maldonado, A.; Verloy, R.; Cardenas Delahoz, E.; Lin, A.; Vanlanduit, S.; Smits, E.; Bogaerts, A.
Title Cold Atmospheric Plasma Does Not Affect Stellate Cells Phenotype in Pancreatic Cancer Tissue in Ovo Type A1 Journal article
Year 2022 Publication International Journal Of Molecular Sciences Abbreviated Journal Int J Mol Sci
Volume 23 Issue 4 Pages 1954
Keywords A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a challenging neoplastic disease, mainly due to the development of resistance to radio- and chemotherapy. Cold atmospheric plasma (CAP) is an alternative technology that can eliminate cancer cells through oxidative damage, as shown in vitro, in ovo, and in vivo. However, how CAP affects the pancreatic stellate cells (PSCs), key players in the invasion and metastasis of PDAC, is poorly understood. This study aims to determine the effect of an anti-PDAC CAP treatment on PSCs tissue developed in ovo using mono- and co-cultures of RLT-PSC (PSCs) and Mia PaCa-2 cells (PDAC). We measured tissue reduction upon CAP treatment and mRNA expression of PSC activation markers and extracellular matrix (ECM) remodelling factors via qRT-PCR. Protein expression of selected markers was confirmed via immunohistochemistry. CAP inhibited growth in Mia PaCa-2 and co-cultured tissue, but its effectiveness was reduced in the latter, which correlates with reduced ki67 levels. CAP did not alter the mRNA expression of PSC activation and ECM remodelling markers. No changes in MMP2 and MMP9 expression were observed in RLT-PSCs, but small changes were observed in Mia PaCa-2 cells. Our findings support the ability of CAP to eliminate PDAC cells, without altering the PSCs.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000763630900001 Publication Date 2022-02-10
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1422-0067 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 5.6 Times cited Open Access OpenAccess
Notes The authors would like to thank Hanne Verswyvel for her support with sample collection from the in ovo model and Peter Ponsaerts for providing the facilities for the microscopy studies. Approved Most recent IF: 5.6
Call Number PLASMANT @ plasmant @c:irua:187155 Serial 7049
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Author Lin, A.; De Backer, J.; Quatannens, D.; Cuypers, B.; Verswyvel, H.; De La Hoz, E.C.; Ribbens, B.; Siozopoulou, V.; Van Audenaerde, J.; Marcq, E.; Lardon, F.; Laukens, K.; Vanlanduit, S.; Smits, E.; Bogaerts, A.
Title The effect of local non‐thermal plasma therapy on the<scp>cancer‐immunity</scp>cycle in a melanoma mouse model Type University Hospital Antwerp
Year 2022 Publication Bioengineering & Translational Medicine Abbreviated Journal Bioengineering & Transla Med
Volume Issue Pages
Keywords University Hospital Antwerp; A1 Journal article; Pharmacology. Therapy; Engineering sciences. Technology; ADReM Data Lab (ADReM); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE); Proteinscience, proteomics and epigenetic signaling (PPES)
Abstract Melanoma remains a deadly cancer despite significant advances in immune checkpoint blockade and targeted therapies. The incidence of melanoma is also growing worldwide, which highlights the need for novel treatment options and strategic combination of therapies. Here, we investigate non-thermal plasma (NTP), an ionized gas, as a promising, therapeutic option. In a melanoma mouse model, direct treatment of tumors with NTP results in reduced tumor burden and prolonged survival. Physical characterization of NTP treatment in situ reveals the deposited NTP energy and temperature associated with therapy response, and whole transcriptome analysis of the tumor identified several modulated pathways. NTP treatment also enhances the cancer-immunity cycle, as immune cells in both the tumor and tumor-draining lymph nodes appear more stimulated to perform their anti-cancer functions. Thus, our data suggest that local NTP therapy stimulates systemic, anti-cancer immunity. We discuss, in detail, how these fundamental insights will help direct the translation of NTP technology into the clinic and inform rational combination strategies to address the challenges in melanoma therapy.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000784103500001 Publication Date 2022-04-21
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2380-6761 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor Times cited Open Access OpenAccess
Notes Vlaamse regering, 1S67621N 1S76421N G044420N 12S9221N 12S9218N ; The authors would like to thank and acknowledge Christophe Hermans, Ho Wa Lau, and Hilde Lambrechts for their help with sectioning and preparing the IHC slides. The authors would also like to thank Dani Banner for designing the ergonomic NTP applicator handle and Hasan Baysal for 3D printing the pieces used in this experiment. We would also like to thank several patrons, as part of this research was funded by donations from different donors, including Dedert Schilde vzw, Mr Willy Floren, and the Vereycken family. Some of the resources and services used in this work were provided by the VSC (Flemish Supercomputer Center) The data that support the findings of this study are available from the Flemish Government. The FWO fellowships and grants that funded this work also include: 12S9218N (Abraham Lin), 12S9221N (Abraham Lin), G044420N (Abraham Lin, Annemie Bogaert, and Steve Vanlanduit), 1S76421N (Delphine Quatannens), and 1S67621N (Hanne Verswyvel). Figure 7 was created with BioRender.com. Approved Most recent IF: NA
Call Number PLASMANT @ plasmant @c:irua:187909 Serial 7056
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Author De Backer, J.; Lin, A.; Berghe, W.V.; Bogaerts, A.; Hoogewijs, D.
Title Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response Type A1 Journal article
Year 2022 Publication Redox Biology Abbreviated Journal Redox Biol
Volume 55 Issue Pages 102399
Keywords A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Proteinscience, proteomics and epigenetic signaling (PPES)
Abstract Melanoma arises from pigment-producing cells called melanocytes located in the basal layers of the epidermis of the skin. Cytoglobin (CYGB) is a ubiquitously expressed hexacoordinated globin that is highly enriched in me­lanocytes and frequently downregulated during melanomagenesis. Previously, we showed that non-thermal plasma (NTP)-produced reactive oxygen and nitrogen species (RONS) lead to the formation of an intra­ molecular disulfide bridge that would allow CYGB to function as a redox-sensitive protein. Here, we investigate the cytotoxic effect of indirect NTP treatment in two melanoma cell lines with divergent endogenous CYGB expression levels, and we explore the role of CYGB in determining treatment outcome. Our findings are consistent with previous studies supporting that NTP cytotoxicity is mediated through the production of RONS and leads to apoptotic cell death in melanoma cells. Furthermore, we show that NTP-treated solutions elicit an antioxidant response through the activation of nuclear factor erythroid 2–related factor 2 (NRF2). The knock­ down and overexpression of CYGB respectively sensitizes and protects melanoma cells from RONS-induced apoptotic cell death. The presence of CYGB enhances heme-oxygenase 1 (HO-1) and NRF2 protein expression levels, whereas the absence impairs their expression. Moreover, analysis of the CYGB-dependent transcriptome demonstrates the tumor suppressor long non-coding RNA maternally expressed 3 (MEG3) as a hitherto unde­ scribed link between CYGB and NRF2. Thus, the presence of CYGB, at least in melanoma cells, seems to play a central role in determining the therapeutic outcome of RONS-inducing anticancer therapies, like NTP-treated solutions, possessing both tumor-suppressive and oncogenic features. Hence, CYGB expression could be of in­ terest either as a biomarker or as a candidate for future targeted therapies in melanoma.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000844595100002 Publication Date 0000-00-00
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2213-2317 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 11.4 Times cited Open Access OpenAccess
Notes This work was funded in part by the Research Foundation – Flanders (FWO) and the Flemish Government. The FWO fellowships and grants that funded this work include: 12S9221 N (Abraham Lin) and G044420 N (Abraham Lin and Annemie Bogaerts). Joey De Backer acknowledges a visiting fellowship from the University of Fribourg. David Hoogewijs acknowledges support by the Swiss National Science Foundation (grants 31003A173000 and 310030207460). Approved Most recent IF: 11.4
Call Number PLASMANT @ plasmant @c:irua:190635 Serial 7101
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Author Oliveira, M.C.; Verswyvel, H.; Smits, E.; Cordeiro, R.M.; Bogaerts, A.; Lin, A.
Title The pro- and anti-tumoral properties of gap junctions in cancer and their role in therapeutic strategies Type A1 Journal article
Year 2022 Publication Redox Biology Abbreviated Journal Redox Biol
Volume 57 Issue Pages 102503
Keywords A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Abstract Gap junctions (GJs), essential structures for cell-cell communication, are made of two hemichannels (commonly called connexons), one on each adjacent cell. Found in almost all cells, GJs play a pivotal role in many physi­ological and cellular processes, and have even been linked to the progression of diseases, such as cancer. Modulation of GJs is under investigation as a therapeutic strategy to kill tumor cells. Furthermore, GJs have also been studied for their key role in activating anti-cancer immunity and propagating radiation- and oxidative stress-induced cell death to neighboring cells, a process known as the bystander effect. While, gap junction (GJ)based therapeutic strategies are being developed, one major challenge has been the paradoxical role of GJs in both tumor progression and suppression, based on GJ composition, cancer factors, and tumoral context. Therefore, understanding the mechanisms of action, regulation, and the dual characteristics of GJs in cancer is critical for developing effective therapeutics. In this review, we provide an overview of the current under­ standing of GJs structure, function, and paradoxical pro- and anti-tumoral role in cancer. We also discuss the treatment strategies to target these GJs properties for anti-cancer responses, via modulation of GJ function.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000871090800004 Publication Date 0000-00-00
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2213-2317 ISBN Additional Links (up) UA library record; WoS full record
Impact Factor 11.4 Times cited Open Access OpenAccess
Notes We thank Coordination of Superior Level Staff Improvement (CAPES, Brazil) for the scholarship granted, and the Turing HPC infrastructure at the CalcUA core facility of the University of Antwerp, a division of the Flemish Supercomputer Center VSC, funded by the Hercules Founda­tion, the Flemish Government (department EWI) and the University of Antwerp, for providing the computational resources needed for running the simulations. This work was also funded in part by the funded by the Research Foundation – Flanders (FWO) and the Flemish Government. The FWO fellowships and grants that funded this work include: 12S9221N (Abraham Lin), G044420N (Abraham Lin and Annemie Bogaerts), and 1S67621N (Hanne Verswyvel). Figs. 1, 4 and 5 were created in BioRender.com. Approved Most recent IF: 11.4
Call Number PLASMANT @ plasmant @c:irua:191362 Serial 7112
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Author Deben, C.; Cardenas De La Hoz, E.; Le Compte, M.; Van Schil, P.; Hendriks, J.M.H.; Lauwers, P.; Yogeswaran, S.K.; Lardon, F.; Pauwels, P.; van Laere, S.; Bogaerts, A.; Smits, E.; Vanlanduit, S.; Lin, A.
Title OrBITS : label-free and time-lapse monitoring of patient derived organoids for advanced drug screening Type A1 Journal article
Year 2022 Publication Cellular Oncology (2211-3428) Abbreviated Journal Cell Oncol
Volume Issue Pages 1-16
Keywords A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Center for Oncological Research (CORE)
Abstract Background Patient-derived organoids are invaluable for fundamental and translational cancer research and holds great promise for personalized medicine. However, the shortage of available analysis methods, which are often single-time point, severely impede the potential and routine use of organoids for basic research, clinical practise, and pharmaceutical and industrial applications. Methods Here, we developed a high-throughput compatible and automated live-cell image analysis software that allows for kinetic monitoring of organoids, named Organoid Brightfield Identification-based Therapy Screening (OrBITS), by combining computer vision with a convolutional network machine learning approach. The OrBITS deep learning analysis approach was validated against current standard assays for kinetic imaging and automated analysis of organoids. A drug screen of standard-of-care lung and pancreatic cancer treatments was also performed with the OrBITS platform and compared to the gold standard, CellTiter-Glo 3D assay. Finally, the optimal parameters and drug response metrics were identified to improve patient stratification. Results OrBITS allowed for the detection and tracking of organoids in routine extracellular matrix domes, advanced Gri3D (R)-96 well plates, and high-throughput 384-well microplates, solely based on brightfield imaging. The obtained organoid Count, Mean Area, and Total Area had a strong correlation with the nuclear staining, Hoechst, following pairwise comparison over a broad range of sizes. By incorporating a fluorescent cell death marker, infra-well normalization for organoid death could be achieved, which was tested with a 10-point titration of cisplatin and validated against the current gold standard ATP-assay, CellTiter-Glo 3D. Using this approach with OrBITS, screening of chemotherapeutics and targeted therapies revealed further insight into the mechanistic action of the drugs, a feature not achievable with the CellTiter-Glo 3D assay. Finally, we advise the use of the growth rate-based normalised drug response metric to improve accuracy and consistency of organoid drug response quantification. Conclusion Our findings validate that OrBITS, as a scalable, automated live-cell image analysis software, would facilitate the use of patient-derived organoids for drug development and therapy screening. The developed wet-lab workflow and software also has broad application potential, from providing a launching point for further brightfield-based assay development to be used for fundamental research, to guiding clinical decisions for personalized medicine.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000898426100001 Publication Date 2022-12-12
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2211-3428; 2211-3436 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 6.6 Times cited Open Access OpenAccess
Notes Approved Most recent IF: 6.6
Call Number UA @ admin @ c:irua:192698 Serial 7272
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Author Živanić, M.; Espona‐Noguera, A.; Lin, A.; Canal, C.
Title Current State of Cold Atmospheric Plasma and Cancer‐Immunity Cycle: Therapeutic Relevance and Overcoming Clinical Limitations Using Hydrogels Type A1 Journal article
Year 2023 Publication Advanced Science Abbreviated Journal Adv Sci
Volume Issue Pages 2205803
Keywords A1 Journal article; Engineering sciences. Technology; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Abstract Cold atmospheric plasma (CAP) is a partially ionized gas that gains attention

as a well-tolerated cancer treatment that can enhance anti-tumor immune

responses, which are important for durable therapeutic effects. This review

offers a comprehensive and critical summary on the current understanding of

mechanisms in which CAP can assist anti-tumor immunity: induction of

immunogenic cell death, oxidative post-translational modifications of the

tumor and its microenvironment, epigenetic regulation of aberrant gene

expression, and enhancement of immune cell functions. This should provide

a rationale for the effective and meaningful clinical implementation of CAP. As

discussed here, despite its potential, CAP faces different clinical limitations

associated with the current CAP treatment modalities: direct exposure of

cancerous cells to plasma, and indirect treatment through injection of

plasma-treated liquids in the tumor. To this end, a novel modality is proposed:

plasma-treated hydrogels (PTHs) that can not only help overcome some of the

clinical limitations but also offer a convenient platform for combining CAP

with existing drugs to improve therapeutic responses and contribute to the

clinical translation of CAP. Finally, by integrating expertise in biomaterials and

plasma medicine, practical considerations and prospective for the

development of PTHs are offered.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000918224200001 Publication Date 2023-01-20
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2198-3844 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 15.1 Times cited Open Access OpenAccess
Notes European Research Council, 714793 ; Fonds Wetenschappelijk Onderzoek, 12S9221N G044420N ; Ministerio de Economía y Competitividad, PID2019‐103892RB‐I00/AEI/10.13039/501100011033 ; Approved Most recent IF: 15.1; 2023 IF: 9.034
Call Number PLASMANT @ plasmant @c:irua:193166 Serial 7238
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Author Lin, A.; Sahun, M.; Biscop, E.; Verswyvel, H.; De Waele, J.; De Backer, J.; Theys, C.; Cuypers, B.; Laukens, K.; Berghe, W.V.; Smits, E.; Bogaerts, A.
Title Acquired non-thermal plasma resistance mediates a shift towards aerobic glycolysis and ferroptotic cell death in melanoma Type A1 Journal article
Year 2023 Publication Drug resistance updates Abbreviated Journal
Volume 67 Issue Pages 100914
Keywords A1 Journal article; Pharmacology. Therapy; ADReM Data Lab (ADReM); Center for Oncological Research (CORE); Proteinscience, proteomics and epigenetic signaling (PPES); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Abstract To gain insights into the underlying mechanisms of NTP therapy sensitivity and resistance, using the firstever

NTP-resistant cell line derived from sensitive melanoma cells (A375).

Methods: Melanoma cells were exposed to NTP and re-cultured for 12 consecutive weeks before evaluation

against the parental control cells. Whole transcriptome sequencing analysis was performed to identify differentially

expressed genes and enriched molecular pathways. Glucose uptake, extracellular lactate, media acidification,

and mitochondrial respiration was analyzed to determine metabolic changes. Cell death inhibitors were

used to assess the NTP-induced cell death mechanisms, and apoptosis and ferroptosis was further validated via

Annexin V, Caspase 3/7, and lipid peroxidation analysis.

Results: Cells continuously exposed to NTP became 10 times more resistant to NTP compared to the parental cell

line of the same passage, based on their half-maximal inhibitory concentration (IC50). Sequencing and metabolic

analysis indicated that NTP-resistant cells had a preference towards aerobic glycolysis, while cell death analysis

revealed that NTP-resistant cells exhibited less apoptosis but were more vulnerable to lipid peroxidation and

ferroptosis.

Conclusions: A preference towards aerobic glycolysis and ferroptotic cell death are key physiological changes in

NTP-resistance cells, which opens new avenues for further, in-depth research into other cancer types.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000925156500001 Publication Date 2022-12-29
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1368-7646 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 24.3 Times cited Open Access OpenAccess
Notes The authors would like to thank Dr. Christophe Deben and Ms. Hannah Zaryouh (Center for Oncological Research, University of Antwerp) for the use and their help with the D300e Digital Dispenser and Spark® Cyto, as well as Ms. Rapha¨elle Corremans (Laboratory Pathophysiology, University of Antwerp) for the use of their lactate meter. The authors would also like to acknowledge the help from Ms. Tias Verhezen and Mr. Cyrus Akbari, who was involved at the start of the project but could not continue due to the COVID-19 pandemic. The authors also acknowledge the resources and services provided by the VSC (Flemish Supercomputer Center). This work was funded in part by the Research Foundation – Flanders (FWO) and the Flemish Government. The FWO fellowships and grants that funded this work also include: 12S9221N (Abraham Lin), G044420N (Abraham Lin, Annemie Bogaerts), and 1S67621N (Hanne Verswyvel). We would also like to thank several patrons, as part of this research was funded by donations from different donors, including Dedert Schilde vzw, Mr. Willy Floren, and the Vereycken family. We would also like to acknowledge the support from the European Cooperation in Science & Technology (COST) Action on Therapeutical applications of Cold Plasmas (CA20114; PlasTHER). Approved Most recent IF: 24.3; 2023 IF: 10.906
Call Number PLASMANT @ plasmant @c:irua:193167 Serial 7240
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Author Le Compte, M.; Cardenas De La Hoz, E.; Peeters, S.; Smits, E.; Lardon, F.; Roeyen, G.; Vanlanduit, S.; Prenen, H.; Peeters, M.; Lin, A.; Deben, C.
Title Multiparametric tumor organoid drug screening using widefield live-cell imaging for bulk and single-organoid analysis Type A1 Journal article
Year 2022 Publication Jove-Journal Of Visualized Experiments Abbreviated Journal Jove-J Vis Exp
Volume Issue 190 Pages 1-18
Keywords A1 Journal article; Engineering sciences. Technology; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Center for Oncological Research (CORE)
Abstract Patient-derived tumor organoids (PDTOs) hold great promise for preclinical and translational research and predicting the patient therapy response from ex vivo drug screenings. However, current adenosine triphosphate (ATP)-based drug screening assays do not capture the complexity of a drug response (cytostatic or cytotoxic) and intratumor heterogeneity that has been shown to be retained in PDTOs due to a bulk readout. Live-cell imaging is a powerful tool to overcome this issue and visualize drug responses more in-depth. However, image analysis software is often not adapted to the three-dimensionality of PDTOs, requires fluorescent viability dyes, or is not compatible with a 384-well microplate format. This paper describes a semi-automated methodology to seed, treat, and image PDTOs in a high-throughput, 384-well format using conventional, widefield, live-cell imaging systems. In addition, we developed viability marker-free image analysis software to quantify growth rate-based drug response metrics that improve reproducibility and correct growth rate variations between different PDTO lines. Using the normalized drug response metric, which scores drug response based on the growth rate normalized to a positive and negative control condition, and a fluorescent cell death dye, cytotoxic and cytostatic drug responses can be easily distinguished, profoundly improving the classification of responders and non-responders. In addition, drug-response heterogeneity can by quantified from single-organoid drug response analysis to identify potential, resistant clones. Ultimately, this method aims to improve the prediction of clinical therapy response by capturing a multiparametric drug response signature, which includes kinetic growth arrest and cell death quantification. ,
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000928020400010 Publication Date 2022-12-24
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1940-087x ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 1.2 Times cited Open Access OpenAccess
Notes Approved Most recent IF: 1.2
Call Number UA @ admin @ c:irua:193168 Serial 7271
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Author Sahun, M.; Privat-Maldonado, A.; Lin, A.; De Roeck, N.; Van de Heyden, L.; Hillen, M.; Michiels, J.; Steenackers, G.; Smits, E.; Ariën, K.K.; Jorens, P.G.; Delputte, P.; Bogaerts, A.
Title Inactivation of SARS-CoV-2 and other enveloped and non-enveloped viruses with non-thermal plasma for hospital disinfection Type A1 Journal article
Year 2023 Publication ACS Sustainable Chemistry and Engineering Abbreviated Journal
Volume Issue Pages 1-10
Keywords A1 Journal article; Engineering sciences. Technology; Center for Oncological Research (CORE); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Abstract As recently highlighted by the SARS-CoV-2 pandemic, viruses have become an increasing burden for health, global economy, and environment. The control of transmission by contact with contaminated materials represents a major challenge, particularly in hospital environments. However, the current disinfection methods in hospital settings suffer from numerous drawbacks. As a result, several medical supplies that cannot be properly disinfected are not reused, leading to severe shortages and increasing amounts of waste, thus prompting the search for alternative solutions. In this work, we report that non-thermal plasma (NTP) can effectively inactivate SARS-CoV-2 from non-porous and porous materials commonly found in healthcare facilities. We demonstrated that 5 min treatment with a dielectric barrier discharge NTP can inactivate 100% of SARS-CoV-2 (Wuhan and Omicron strains) from plastic material. Using porcine respiratory coronavirus (surrogate for SARS-CoV-2) and coxsackievirus B3 (highly resistant non-enveloped virus), we tested the NTP virucidal activity on hospital materials and obtained complete inactivation after 5 and 10 min, respectively. We hypothesize that the produced reactive species and local acidification contribute to the overall virucidal effect of NTP. Our results demonstrate the potential of dielectric barrier discharge NTPs for the rapid, efficient, and low-cost disinfection of healthcare materials.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000964269500001 Publication Date 2023-03-23
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2168-0485 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 8.4 Times cited Open Access OpenAccess
Notes Approved Most recent IF: 8.4; 2023 IF: 5.951
Call Number UA @ admin @ c:irua:194897 Serial 7269
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Author Verswyvel, H.; Deben, C.; Wouters, A.; Lardon, F.; Bogaerts, A.; Smits, E.; Lin, A.
Title Phototoxicity and cell passage affect intracellular reactive oxygen species levels and sensitivity towards non-thermal plasma treatment in fluorescently-labeled cancer cells Type A1 Journal article
Year 2023 Publication Journal of physics: D: applied physics Abbreviated Journal
Volume 56 Issue 29 Pages 294001
Keywords A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Abstract Live-cell imaging with fluorescence microscopy is a powerful tool, especially in cancer research, widely-used for capturing dynamic cellular processes over time. However, light-induced toxicity (phototoxicity) can be incurred from this method, via disruption of intracellular redox balance and an overload of reactive oxygen species (ROS). This can introduce confounding effects in an experiment, especially in the context of evaluating and screening novel therapies. Here, we aimed to unravel whether phototoxicity can impact cellular homeostasis and response to non-thermal plasma (NTP), a therapeutic strategy which specifically targets the intracellular redox balance. We demonstrate that cells incorporated with a fluorescent reporter for live-cell imaging have increased sensitivity to NTP, when exposed to ambient light or fluorescence excitation, likely through altered proliferation rates and baseline intracellular ROS levels. These changes became even more pronounced the longer the cells stayed in culture. Therefore, our results have important implications for research implementing this analysis technique and are particularly important for designing experiments and evaluating redox-based therapies like NTP.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000978180500001 Publication Date 2023-07-20
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-3727 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 3.4 Times cited Open Access OpenAccess
Notes This work was partially funded by the Research Foundation— Flanders (FWO) and supported by the following Grants: 1S67621N (H V), 12S9221N (A L), and G044420N (A B and A L). We would also like to thank several patrons, as part of this research was funded by donations from different donors, including Dedert Schilde vzw, Mr Willy Floren, and the Vereycken family. Approved Most recent IF: 3.4; 2023 IF: 2.588
Call Number PLASMANT @ plasmant @c:irua:196441 Serial 7381
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Author Lin, A.; Gromov, M.; Nikiforov, A.; Smits, E.; Bogaerts, A.
Title Characterization of Non-Thermal Dielectric Barrier Discharges for Plasma Medicine: From Plastic Well Plates to Skin Surfaces Type A1 Journal Article
Year 2023 Publication Plasma Chemistry and Plasma Processing Abbreviated Journal Plasma Chem Plasma Process
Volume 43 Issue 6 Pages 1587-1612
Keywords A1 Journal Article; Non-thermal plasma · Plasma medicine · Dielectric barrier discharge · Plasma diagnostics · Plasma surface interaction · In situ plasma monitoring; Plasma, laser ablation and surface modeling Antwerp (PLASMANT) ;
Abstract technologies have been expanding, and one of the most exciting and rapidly growing

applications is in biology and medicine. Most biomedical studies with DBD plasma systems are performed in vitro, which include cells grown on the surface of plastic well plates, or in vivo, which include animal research models (e.g. mice, pigs). Since many DBD systems use the biological target as the secondary electrode for direct plasma generation and treatment, they are sensitive to the surface properties of the target, and thus can be altered based on the in vitro or in vivo system used. This could consequently affect biological response from plasma treatment. Therefore, in this study, we investigated the DBD plasma behavior both in vitro (i.e. 96-well flat bottom plates, 96-well U-bottom plates, and 24-well flat bottom plates), and in vivo (i.e. mouse skin). Intensified charge coupled device (ICCD) imaging was performed and the plasma discharges were visually distinguishable between the different systems. The geometry of the wells did not affect DBD plasma generation for low application distances (≤ 2 mm), but differentially affected plasma uniformity on the bottom of the well at greater distances. Since DBD plasma treatment in vitro is rarely performed in dry wells for plasma medicine experiments, the effect of well wetness was also investigated. In all in vitro cases, the uniformity of the DBD plasma was affected when comparing wet versus dry wells, with the plasma in the wide-bottom wells appearing the most similar to plasma generated on mouse skin. Interestingly, based on quantification of ICCD images, the DBD plasma intensity per surface area demonstrated an exponential one-phase decay with increasing application distance, regardless of the in vitro or in vivo system. This trend is similar to that of the energy per pulse of plasma, which is used to determine the total plasma treatment energy for biological systems. Optical emission spectroscopy performed on the plasma revealed similar trends in radical species generation between the plastic well plates and mouse skin. Therefore, taken together, DBD plasma intensity per surface area may be a valuable parameter to be used as a simple method for in situ monitoring during biological treatment and active plasma treatment control, which can be applied for in vitro and in vivo systems.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 001072607700001 Publication Date 2023-09-27
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0272-4324 ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 3.6 Times cited Open Access Not_Open_Access
Notes This work was partially funded by the Research Foundation—Flanders (FWO) and supported by the following Grants: 12S9221N (A. L.), G044420N (A. L. and A. B.), and G033020N (A.B.). We would also like to thank several patrons, as part of this research was funded by donations from different donors, including Dedert Schilde vzw, Mr Willy Floren, and the Vereycken family. We would also like to acknowledge the support from the European Cooperation in Science & Technology (COST) Action on “Therapeutical applications of Cold Plasmas” (CA20114; PlasTHER). Approved Most recent IF: 3.6; 2023 IF: 2.355
Call Number PLASMANT @ plasmant @c:irua:200285 Serial 8970
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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 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 (up) 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 Živanić, M.; Espona‐Noguera, A.; Verswyvel, H.; Smits, E.; Bogaerts, A.; Lin, A.; Canal, C.
Title Injectable Plasma‐Treated Alginate Hydrogel for Oxidative Stress Delivery to Induce Immunogenic Cell Death in Osteosarcoma Type A1 Journal article
Year 2023 Publication Advanced functional materials Abbreviated Journal Adv Funct Materials
Volume Issue Pages
Keywords A1 Journal article; Engineering sciences. Technology; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Abstract Cold atmospheric plasma (CAP) is a source of cell‐damaging oxidant molecules that may be used as low‐cost cancer treatment with minimal side effects. Liquids treated with cold plasma and enriched with oxidants are a modality for non‐invasive treatment of internal tumors with cold plasma via injection. However, liquids are easily diluted with body fluids which impedes high and localized delivery of oxidants to the target. As an alternative, plasma‐treated hydrogels (PTH) emerge as vehicles for the precise delivery of oxidants. This study reports an optimal protocol for the preparation of injectable alginate PTH that ensures the preservation of plasma‐generated oxidants. The generation, storage, and release of oxidants from the PTH are assessed. The efficacy of the alginate PTH in cancer treatment is demonstrated in the context of cancer cell cytotoxicity and immunogenicity–release of danger signals and phagocytosis by immature dendritic cells, up to now unexplored for PTH. These are shown in osteosarcoma, a hard‐to‐treat cancer. The study aims to consolidate PTH as a novel cold plasma treatment modality for non‐invasive or postoperative tumor treatment. The results offer a rationale for further exploration of alginate‐based PTHs as a versatile platform in biomedical engineering.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 001129424500001 Publication Date 2023-12-21
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1616-301X ISBN Additional Links (up) UA library record; WoS full record
Impact Factor 19 Times cited Open Access
Notes Fonds Wetenschappelijk Onderzoek, 1S67621N ; European Cooperation in Science and Technology, COST Action CA20114 ; Agència de Gestió d'Ajuts Universitaris i de Recerca, SGR2022‐1368 ; Agencia Estatal de Investigación, PID2019‐ 103892RB‐I00/AEI/10.13039/501100011033 ; Instituto de Salud Carlos III, IHRC22/00003 ; Approved Most recent IF: 19; 2023 IF: 12.124
Call Number PLASMANT @ plasmant @c:irua:202030 Serial 8979
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Author Zaryouh, H.; Verswyvel, H.; Bauwens, M.; Van Haesendonck, G.; Deben, C.; Lin, A.; De Waele, J.; Vermorken, J.B.; Koljenovic, S.; Bogaerts, A.; Lardon, F.; Smits, E.; Wouters, A.
Title De belofte van hoofdhalskankerorganoïden in kankeronderzoek : een blik op de toekomst Type A2 Journal article
Year 2023 Publication Onco-hemato : multidisciplinair tijdschrift voor oncologie Abbreviated Journal
Volume 17 Issue 7 Pages 54-58
Keywords A2 Journal article; Center for Oncological Research (CORE); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Abstract Hoofd-halskanker vormt een aanzienlijke uitdaging met bijna 900.000 nieuwe diagnoses per jaar, waarbij de jaarlijkse incidentie blijft stijgen. Vaak wordt de diagnose pas in een laat stadium gesteld, wat complexe behandelingen noodzakelijk maakt. Terugval van patiënten is helaas een veelvoorkomend probleem. De gemiddelde overlevingsduur is beperkt tot enkele maanden. Daarom is er een dringende behoefte om nieuwe, veelbelovende behandelingen te ontwikkelen voor patiënten met hoofd-halskanker. Voor het bereiken van deze vooruitgang spelen innovatieve studiemodellen een cruciale rol. Het ontwikkelen van deze nieuwe behandelingen start met laboratoriumonderzoek, waarbij traditionele tweedimensionale celculturen hun beperkingen hebben. Daarom verschuiven onderzoekers hun aandacht meer en meer naar geavanceerdere driedimensionale modellen, met hoofd-halskankerorganoïden als beloftevol nieuw model. Dit model behoudt immers zowel het genetische profiel als de morfologische kenmerken van de originele tumor van de hoofd-halskankerpatiënt. Hoofdhalskankerorganoïden bieden daarom de mogelijkheid om innovatieve behandelingen te testen en kunnen mogelijk zelfs de respons van een patiënt op bepaalde therapieën voorspellen. Hoewel tumororganoïden als ‘patiënt-in-het-lab’ veelbelovend zijn, zijn er uitdagingen te overwinnen, zoals de ontwikkelingstijd en de toepasbaarheid bij alle tumortypes, evenals het ontbreken van immuuncellen en andere micro-omgevingscomponenten. Er is daarom een grote behoefte aan gestandaardiseerde protocollen voor de ontwikkeling van organoïden en verkorting van de ontwikkelingstijd. Concluderend bieden driedimensionale hoofd-halskankerorganoïden een veelbelovend perspectief voor de toekomst van kankerbehandelingen. Ze hebben het potentieel om bij te dragen aan de ontwikkeling van gepersonaliseerde behandelingen en zo de overlevingskansen van kankerpatiënten te verbeteren. Het is echter belangrijk om hun voorspellend vermogen en toepassingsmogelijkheden verder te onderzoeken, voordat ze op grote schaal worden geïmplementeerd.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos Publication Date
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2030-2738 ISBN Additional Links (up) UA library record
Impact Factor Times cited Open Access
Notes Approved Most recent IF: NA
Call Number UA @ admin @ c:irua:202271 Serial 9004
Permanent link to this record
 

 
Author Deben, C.; Freire Boullosa, L.; Rodrigues Fortes, F.; Cardenas De La Hoz, E.; Le Compte, M.; Seghers, S.; Peeters, M.; Vanlanduit, S.; Lin, A.; Dijkstra, K.K.; Van Schil, P.; Hendriks, J.M.H.; Prenen, H.; Roeyen, G.; Lardon, F.; Smits, E.
Title Auranofin repurposing for lung and pancreatic cancer : low CA12 expression as a marker of sensitivity in patient-derived organoids, with potentiated efficacy by AKT inhibition Type A1 Journal article
Year 2024 Publication Journal of Experimental and Clinical Cancer Research Abbreviated Journal
Volume 43 Issue 1 Pages 88-15
Keywords A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Center for Oncological Research (CORE)
Abstract Background This study explores the repurposing of Auranofin (AF), an anti-rheumatic drug, for treating non-small cell lung cancer (NSCLC) adenocarcinoma and pancreatic ductal adenocarcinoma (PDAC). Drug repurposing in oncology offers a cost-effective and time-efficient approach to developing new cancer therapies. Our research focuses on evaluating AF's selective cytotoxicity against cancer cells, identifying RNAseq-based biomarkers to predict AF response, and finding the most effective co-therapeutic agents for combination with AF. Methods Our investigation employed a comprehensive drug screening of AF in combination with eleven anticancer agents in cancerous PDAC and NSCLC patient-derived organoids (n = 7), and non-cancerous pulmonary organoids (n = 2). Additionally, we conducted RNA sequencing to identify potential biomarkers for AF sensitivity and experimented with various drug combinations to optimize AF's therapeutic efficacy. Results The results revealed that AF demonstrates a preferential cytotoxic effect on NSCLC and PDAC cancer cells at clinically relevant concentrations below 1 µM, sparing normal epithelial cells. We identified Carbonic Anhydrase 12 (CA12) as a significant RNAseq-based biomarker, closely associated with the NF-κB survival signaling pathway, which is crucial in cancer cell response to oxidative stress. Our findings suggest that cancer cells with low CA12 expression are more susceptible to AF treatment. Furthermore, the combination of AF with the AKT inhibitor MK2206 was found to be particularly effective, exhibiting potent and selective cytotoxic synergy, especially in tumor organoid models classified as intermediate responders to AF, without adverse effects on healthy organoids. Conclusion Our research offers valuable insights into the use of AF for treating NSCLC and PDAC. It highlights AF's cancer cell selectivity, establishes CA12 as a predictive biomarker for AF sensitivity, and underscores the enhanced efficacy of AF when combined with MK2206 and other therapeutics. These findings pave the way for further exploration of AF in cancer treatment, particularly in identifying patient populations most likely to benefit from its use and in optimizing combination therapies for improved patient outcomes.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 001190581500001 Publication Date 2024-03-22
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1756-9966 ISBN Additional Links (up) UA library record; WoS full record
Impact Factor Times cited Open Access
Notes Approved Most recent IF: NA
Call Number UA @ admin @ c:irua:204924 Serial 9136
Permanent link to this record
 

 
Author Chernaya, V.V.; Tsirlin, A.A.; Shpanchenko, R.V.; Antipov, E.V.; Gippius, A.A.; Morozova, E.N.; Dyakov, V.; Hadermann, J.; Kaul, E.E.; Geibel, C.
Title Crystal structure and properties of the new vanadyl(IV)phosphates Na2MVO(PO4)2 M=Ca and Sr Type A1 Journal article
Year 2004 Publication Journal of solid state chemistry Abbreviated Journal J Solid State Chem
Volume 177 Issue Pages 2875-2880
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract
Address
Corporate Author Thesis
Publisher Place of Publication London Editor
Language Wos 000223145500033 Publication Date 2004-08-04
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-4596; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 2.299 Times cited 6 Open Access
Notes Approved Most recent IF: 2.299; 2004 IF: 1.815
Call Number UA @ lucian @ c:irua:47317 Serial 565
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Author Tsirlin, A.A.; Chernaya, V.V.; Shpanchenko, R.V.; Antipov, E.V.; Hadermann, J.
Title Crystal structure and properties of the new complex vanadium oxide K2SrV3O9 Type A1 Journal article
Year 2005 Publication Materials research bulletin Abbreviated Journal Mater Res Bull
Volume 40 Issue 5 Pages 800-809
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract
Address
Corporate Author Thesis
Publisher Place of Publication New York, N.Y. Editor
Language Wos 000229376500010 Publication Date 2005-03-01
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0025-5408; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 2.446 Times cited 9 Open Access
Notes Approved Most recent IF: 2.446; 2005 IF: 1.380
Call Number UA @ lucian @ c:irua:52373 Serial 564
Permanent link to this record
 

 
Author Lebedev, O.I.; Van Tendeloo, G.; Attfield, J.P.; McLaughlin, A.C.
Title Defect structure of ferromagnetic superconducting RuSr2GdCu2O8 Type A1 Journal article
Year 2006 Publication Physical review : B : condensed matter and materials physics Abbreviated Journal Phys Rev B
Volume 73 Issue 22 Pages
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract The structure and defect structure of superconducting ferromagnetic bulk RuSr2GdCu2O8 has been investigated using high-resolution transmission electron microscopy and high-resolution scanning transmission microscopy. Two distinct, but closely related structures, due to ordering of rotated RuO6 octahedra and due to Cu substitution in the Ru-O layer, have been revealed. The structure of Ru1-xSr2GdCu2+xO8-delta can be described as a periodic alteration along the c axis of CuO4 planes and RuO6 octahedra. The unit-cell parameters of this phase are root 2a(p) x root 2a(p) x 2c. The possible influence of this phase and defect structure on the sensitivity of the superconductivity and magnetic properties is discussed. Local defects such as 90 S domain boundaries, (130) antiphase boundaries, and the associated dislocations are analyzed.
Address
Corporate Author Thesis
Publisher Place of Publication Lancaster, Pa Editor
Language Wos 000238696300115 Publication Date 2006-06-26
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1098-0121;1550-235X; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 3.836 Times cited 11 Open Access
Notes Iap V-I Approved Most recent IF: 3.836; 2006 IF: 3.107
Call Number UA @ lucian @ c:irua:59707 Serial 619
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Author Tsirlin, A.A.; Shpanchenko, R.V.; Antipov, E.V.; Bougerol, C.; Hadermann, J.; Van Tendeloo, G.; Schnelle, W.; Rosner, H.
Title Spin ladder compound Pb0.55Cd0.45V2O5: synthesis and investigation Type A1 Journal article
Year 2007 Publication Physical review : B : condensed matter and materials physics Abbreviated Journal Phys Rev B
Volume 76 Issue 10 Pages 104429,1-7
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract
Address
Corporate Author Thesis
Publisher Place of Publication Lancaster, Pa Editor
Language Wos 000249786300074 Publication Date 2007-09-25
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1098-0121;1550-235X; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 3.836 Times cited 1 Open Access
Notes Approved Most recent IF: 3.836; 2007 IF: 3.172
Call Number UA @ lucian @ c:irua:65594 Serial 3091
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Author d' Hondt, H.; Hadermann, J.; Abakumov, A.M.; Kalyuzhnaya, A.S.; Rozova, M.G.; Tsirlin, A.A.; Tan, H.; Verbeeck, J.; Antipov, E.V.; Van Tendeloo, G.
Title Synthesis, crystal structure and magnetic properties of the Sr2Al0.78Mn1.22O5.2 anion-deficient layered perovskite Type A1 Journal article
Year 2009 Publication Journal of solid state chemistry Abbreviated Journal J Solid State Chem
Volume 182 Issue 2 Pages 356-363
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract A new layered perovskite Sr2Al0.78Mn1.22O5.2 has been synthesized by solid state reaction in a sealed evacuated silica tube. The crystal structure has been determined using electron diffraction, high-resolution electron microscopy, and high-angle annular dark field imaging and refined from X-ray powder diffraction data (space group P4/mmm, a=3.89023(5) Å, c=7.8034(1) Å, RI=0.023, RP=0.015). The structure is characterized by an alternation of MnO2 and (Al0.78Mn0.22)O1.2 layers. Oxygen atoms and vacancies, as well as the Al and Mn atoms in the (Al0.78Mn0.22)O1.2 layers are disordered. The local atomic arrangement in these layers is suggested to consist of short fragments of brownmillerite-type tetrahedral chains of corner-sharing AlO4 tetrahedra interrupted by MnO6 octahedra, at which the chain fragments rotate over 90°. This results in an averaged tetragonal symmetry. This is confirmed by the valence state of Mn measured by EELS. The relationship between the Sr2Al0.78Mn1.22O5.2 tetragonal perovskite and the parent Sr2Al1.07Mn0.93O5 brownmillerite is discussed. Magnetic susceptibility measurements indicate spin glass behavior of Sr2Al0.78Mn1.22O5.2. The lack of long-range magnetic ordering contrasts with Mn-containing brownmillerites and is likely caused by the frustration of interlayer interactions due to presence of the Mn atoms in the (Al0.78Mn0.22)O1.2 layers.
Address
Corporate Author Thesis
Publisher Place of Publication London Editor
Language Wos 000263124700022 Publication Date 2008-11-14
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-4596; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 2.299 Times cited 12 Open Access
Notes Iap Vi Approved Most recent IF: 2.299; 2009 IF: 2.340
Call Number UA @ lucian @ c:irua:72943 Serial 3450
Permanent link to this record
 

 
Author Shpanchenko, R.V.; Tsirlin, A.A.; Kondakova, E.S.; Antipov, E.V.; Bougerol, C.; Hadermann, J.; Van Tendeloo, G.; Sakurai, H.; Takayama-Muromachi, E.
Title New germanates RCrGeO5 (R=NdEr, Y): synthesis, structure, and properties Type A1 Journal article
Year 2008 Publication Journal of solid state chemistry Abbreviated Journal J Solid State Chem
Volume 181 Issue 9 Pages 2433-2441
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract The new complex germanates RCrGeO5 (R=NdEr, Y) have been synthesized and investigated by means of X-ray powder diffraction, electron microscopy, magnetic susceptibility and specific heat measurements. All the compounds are isostructural and crystallize in the orthorhombic symmetry, space group Pbam, and Z=4. The crystal structure of RCrGeO5, as refined using X-ray powder diffraction data, includes infinite chains built by edge-sharing Cr+3O6 octahedra with two alternating Cr−Cr distances. The chains are combined into a three-dimensional framework by Ge2O8 groups consisting of two edge-linked square pyramids oriented in opposite directions. The resulting framework contains pentagonal channels where rare-earth elements are located. Thus, RCrGeO5 germanates present new examples of RMn2O5-type compounds and show ordering of Cr+3 and Ge+4 cations. Electron diffraction as well as high-resolution electron microscopy confirm the structure solution. Magnetic susceptibility data for R=Nd, Sm, and Eu are qualitatively consistent with the presence of isolated 3d (antiferromagnetically coupled Cr+3 cations) and 4f (R+3) spin subsystems in the RCrGeO5 compounds. NdCrGeO5 undergoes long-range magnetic ordering at 2.6 K, while SmCrGeO5 and EuCrGeO5 do not show any phase transitions down to 2 K.
Address
Corporate Author Thesis
Publisher Place of Publication London Editor
Language Wos 000259415800047 Publication Date 2008-06-06
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-4596; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 2.299 Times cited 6 Open Access
Notes Approved Most recent IF: 2.299; 2008 IF: 1.910
Call Number UA @ lucian @ c:irua:72948 Serial 2314
Permanent link to this record
 

 
Author Shpanchenko, R.V.; Tsirlin, A.A.; Hadermann, J.; Antipov, E.V.
Title Synthesis and crystal structure of new titanyl phosphate Sr2TiO(PO4)2 Type A1 Journal article
Year 2008 Publication Russian chemical bulletin Abbreviated Journal Russ Chem B+
Volume 57 Issue 3 Pages 552-556
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract New strontium titanyl phosphate Sr2TiO(PO4)2 (1) was synthesized and characterized by X-ray powder diffraction, electron diffraction, high-resolution electron microscopy, and band structure calculations. Titanyl phosphate 1 is isostructural with vanadyl phosphate Sr2VO(PO4)2 and has a layered structure. The titanium atoms are shifted from the centers of the TiO6 octahedra and form short (1.74 Å) titanyl bonds. The structure of 1 is an unusual example of the disordered orientation of the chains formed by TiO6 octahedra in complex titanium phosphates.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000263566900015 Publication Date 2009-03-06
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1066-5285;1573-9171; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 0.529 Times cited 2 Open Access
Notes Approved Most recent IF: 0.529; 2008 IF: 0.469
Call Number UA @ lucian @ c:irua:73712 Serial 3423
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Author Abakumov, A.M.; Hadermann, J.; Tsirlin, A.A.; Tan, H.; Verbeeck, J.; Zhang, H.; Dikarev, E.V.; Shpanchenko, R.V.; Antipov, E.V.
Title Original close-packed structure and magnetic properties of the Pb4Mn9O20 manganite Type A1 Journal article
Year 2009 Publication Journal of solid state chemistry Abbreviated Journal J Solid State Chem
Volume 182 Issue 8 Pages 2231-2238
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract The crystal structure of the Pb4Mn9O20 compound (previously known as Pb0.43MnO2.18) was solved from powder X-ray diffraction, electron diffraction, and high resolution electron microscopy data (S.G. Pnma, a=13.8888(2) Å, b=11.2665(2) Å, c=9.9867(1) Å, RI=0.016, RP=0.047). The structure is based on a 6H (cch)2 close packing of pure oxygen h-type (O16) layers alternating with mixed c-type (Pb4O12) layers. The Mn atoms occupy octahedral interstices formed by the oxygen atoms of the close-packed layers. The MnO6 octahedra share edges within the layers, whereas the octahedra in neighboring layers are linked through corner sharing. The relationship with the closely related Pb3Mn7O15 structure is discussed. Magnetization measurements reveal a peculiar magnetic behavior with a phase transition at 52 K, a small net magnetization below the transition temperature, and a tendency towards spin freezing.
Address
Corporate Author Thesis
Publisher Place of Publication London Editor
Language Wos 000269066400035 Publication Date 2009-06-12
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-4596; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 2.299 Times cited 5 Open Access
Notes The authors are grateful to Christoph Geibel for the help in magnetization measurements. A.Ts. acknowledges MPI CKS for hospitality and financial support during the stay. E.D. thanks the National Science Foundation (CHE-0718900) for financial support. This work was supported by the Russian Foundation of Basic Research (RFBR Grants 07-03-00664-a, 06-03-90168-a and 07-03-00890-a). The authors acknowledge financial support from the European Union under the Framework 6 program under a contract for an Integrated Infrastructure Initiative. Reference 026019 ESTEEM. Approved Most recent IF: 2.299; 2009 IF: 2.340
Call Number UA @ lucian @ c:irua:78935UA @ admin @ c:irua:78935 Serial 2529
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Author Tsirlin, A.A.; Nath, R.; Abakumov, A.M.; Shpanchenko, R.V.; Geibel, C.; Rosner, H.
Title Frustrated square lattice with spatial anisotropy: crystal structure and magnetic properties of PbZnVO(PO4)2 Type A1 Journal article
Year 2010 Publication Physical review : B : condensed matter and materials physics Abbreviated Journal Phys Rev B
Volume 81 Issue 17 Pages 174424,1-174424,13
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract Crystal structure and magnetic properties of the layered vanadium phosphate PbZnVO(PO4)2 are studied using x-ray powder diffraction, magnetization and specific-heat measurements, as well as band-structure calculations. The compound resembles AA′VO(PO4)2 vanadium phosphates and fits to the extended frustrated square-lattice model with the couplings J1, J1′ between nearest neighbors and J2, J2′ between next-nearest neighbors. The temperature dependence of the magnetization yields estimates of averaged nearest-neighbor and next-nearest-neighbor couplings, J̅ 1≃−5.2 K and J̅ 2≃10.0 K, respectively. The effective frustration ratio α=J̅ 2/J̅ 1 amounts to −1.9 and suggests columnar antiferromagnetic ordering in PbZnVO(PO4)2. Specific-heat data support the estimates of J̅ 1 and J̅ 2 and indicate a likely magnetic ordering transition at 3.9 K. However, the averaged couplings underestimate the saturation field, thus pointing to the spatial anisotropy of the nearest-neighbor interactions. Band-structure calculations confirm the identification of ferromagnetic J1, J1′ and antiferromagnetic J2, J2′ in PbZnVO(PO4)2 and yield (J1′−J1)≃1.1 K in excellent agreement with the experimental value of 1.1 K, deduced from the difference between the expected and experimentally measured saturation fields. Based on the comparison of layered vanadium phosphates with different metal cations, we show that a moderate spatial anisotropy of the frustrated square lattice has minor influence on the thermodynamic properties of the model. We discuss relevant geometrical parameters, controlling the exchange interactions in these compounds and propose a strategy for further design of strongly frustrated square-lattice materials.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000278141600082 Publication Date 2010-05-25
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1098-0121;1550-235X; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 3.836 Times cited 27 Open Access
Notes Approved Most recent IF: 3.836; 2010 IF: 3.774
Call Number UA @ lucian @ c:irua:83384 Serial 1294
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Author Tsirlin, A.A.; Abakumov, A.M.; Van Tendeloo, G.; Rosner, H.
Title Interplay of atomic displacement in the quantum magnet (CuCI)LaNb2O7 Type A1 Journal article
Year 2010 Publication Physical review : B : condensed matter and materials physics Abbreviated Journal Phys Rev B
Volume 82 Issue 5 Pages 054107,1-054107,12
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract We report on the crystal structure of the quantum magnet CuClLaNb2O7 that was controversially described with respect to its structural organization and magnetic behavior. Using high-resolution synchrotron powder x-ray diffraction, electron diffraction, transmission electron microscopy, and band-structure calculations, we solve the room-temperature structure of this compound -CuClLaNb2O7 and find two high-temperature polymorphs. The -CuClLaNb2O7 phase, stable above 640 K, is tetragonal with asub=3.889 Å, csub =11.738 Å, and the space group P4/mmm. In the -CuClLaNb2O7 structure, the Cu and Cl atoms are randomly displaced from the special positions along the 100 directions. The phase asub2asubcsub, space group Pbmm and the phase 2asub2asubcsub, space group Pbam are stable between 640 K and 500 K and below 500 K, respectively. The structural changes at 500 and 640 K are identified as order-disorder phase transitions. The displacement of the Cl atoms is frozen upon the → transformation while a cooperative tilting of the NbO6 octahedra in the phase further eliminates the disorder of the Cu atoms. The low-temperature -CuClLaNb2O7 structure thus combines the two types of the atomic displacements that interfere due to the bonding between the Cu atoms and the apical oxygens of the NbO6 octahedra. The precise structural information resolves the controversy between the previous computation-based models and provides the long-sought input for understanding CuClLaNb2O7 and related compounds with unusual magnetic properties.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Wos 000280849400001 Publication Date 2010-08-12
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1098-0121;1550-235X; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 3.836 Times cited 13 Open Access
Notes Approved Most recent IF: 3.836; 2010 IF: 3.774
Call Number UA @ lucian @ c:irua:83991 Serial 1706
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Author Hadermann, J.; Abakumov, A.M.; Tsirlin, A.A.; Filonenko, V.P.; Gonnissen, J.; Tan, H.; Verbeeck, J.; Gemmi, M.; Antipov, E.V.; Rosner, H.
Title Direct space structure solution from precession electron diffraction data: resolving heavy and light scatterers in Pb13Mn9O25 Type A1 Journal article
Year 2010 Publication Ultramicroscopy Abbreviated Journal Ultramicroscopy
Volume 110 Issue 7 Pages 881-890
Keywords A1 Journal article; Electron microscopy for materials research (EMAT)
Abstract The crystal structure of a novel compound Pb13Mn9O25 has been determined through a direct space structure solution with a Monte-Carlo-based global optimization using precession electron diffraction data (a=14.177(3) Å, c=3.9320(7) Å, SG P4/m, RF=0.239) and compositional information obtained from energy dispersive X-ray analysis and electron energy loss spectroscopy. This allowed to obtain a reliable structural model even despite the simultaneous presence of both heavy (Pb) and light (O) scattering elements and to validate the accuracy of the electron diffraction-based structure refinement. This provides an important benchmark for further studies of complex structural problems with electron diffraction techniques. Pb13Mn9O25 has an anion- and cation-deficient perovskite-based structure with the A-positions filled by the Pb atoms and 9/13 of the B positions filled by the Mn atoms in an ordered manner. MnO6 octahedra and MnO5 tetragonal pyramids form a network by sharing common corners. Tunnels are formed in the network due to an ordered arrangement of vacancies at the B-sublattice. These tunnels provide sufficient space for localization of the lone 6s2 electron pairs of the Pb2+ cations, suggested as the driving force for the structural difference between Pb13Mn9O25 and the manganites of alkali-earth elements with similar compositions.
Address
Corporate Author Thesis
Publisher Place of Publication Amsterdam Editor
Language Wos 000280050900023 Publication Date 2010-04-01
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0304-3991; ISBN Additional Links (up) UA library record; WoS full record; WoS citing articles
Impact Factor 2.843 Times cited 24 Open Access
Notes Fwo; Bof; Esteem Approved Most recent IF: 2.843; 2010 IF: 2.063
Call Number UA @ lucian @ c:irua:84085UA @ admin @ c:irua:84085 Serial 721
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