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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 | 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 | ||
Permanent link to this record | |||||
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 | 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 | ||
Permanent link to this record | |||||
Author | De Backer, J.; Maric, D.; Zuhra, K.; Bogaerts, A.; Szabo, C.; Vanden Berghe, W.; Hoogewijs, D. | ||||
Title | Cytoglobin Silencing Promotes Melanoma Malignancy but Sensitizes for Ferroptosis and Pyroptosis Therapy Response | Type ![]() |
A1 Journal article | ||
Year | 2022 | Publication | Antioxidants | Abbreviated Journal | Antioxidants |
Volume | 11 | Issue | 8 | Pages | 1548 |
Keywords | A1 Journal article; Pharmacology. Therapy; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Proteinscience, proteomics and epigenetic signaling (PPES) | ||||
Abstract | Despite recent advances in melanoma treatment, there are still patients that either do not respond or develop resistance. This unresponsiveness and/or acquired resistance to therapy could be explained by the fact that some melanoma cells reside in a dedifferentiated state. Interestingly, this dedifferentiated state is associated with greater sensitivity to ferroptosis, a lipid peroxidation-reliant, iron-dependent form of cell death. Cytoglobin (CYGB) is an iron hexacoordinated globin that is highly enriched in melanocytes and frequently downregulated during melanomagenesis. In this study, we investigated the potential effect of CYGB on the cellular sensitivity towards (1S, 3R)-RAS-selective lethal small molecule (RSL3)-mediated ferroptosis in the G361 melanoma cells with abundant endogenous expression. Our findings show that an increased basal ROS level and higher degree of lipid peroxidation upon RSL3 treatment contribute to the increased sensitivity of CYGB knockdown G361 cells to ferroptosis. Furthermore, transcriptome analysis demonstrates the enrichment of multiple cancer malignancy pathways upon CYGB knockdown, supporting a tumor-suppressive role for CYGB. Remarkably, CYGB knockdown also triggers activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and subsequent induction of pyroptosis target genes. Altogether, we show that silencing of CYGB expression modulates cancer therapy sensitivity via regulation of ferroptosis and pyroptosis cell death signaling pathways. | ||||
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Corporate Author | Thesis | ||||
Publisher | Place of Publication | Editor | |||
Language | Wos | 000846411000001 | Publication Date | 2022-08-10 | |
Series Editor | Series Title | Abbreviated Series Title | |||
Series Volume | Series Issue | Edition | |||
ISSN | 2076-3921 | ISBN | Additional Links | UA library record; WoS full record; WoS citing articles | |
Impact Factor | 7 | Times cited | Open Access | OpenAccess | |
Notes | Approved | Most recent IF: 7 | |||
Call Number | PLASMANT @ plasmant @c:irua:190686 | Serial | 7102 | ||
Permanent link to this record | |||||
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 | 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 | ||
Permanent link to this record | |||||
Author | Vingerhoets, R.; Spiller, M.; De Backer, J.; Adriaens, A.; Vlaeminck, S.E.; Meers, E. | ||||
Title | Detailed nitrogen and phosphorus flow analysis, nutrient use efficiency and circularity in the agri-food system of a livestock-intensive region | Type ![]() |
A1 Journal article | ||
Year | 2023 | Publication | Journal of cleaner production | Abbreviated Journal | |
Volume | 410 | Issue | Pages | 137278-13 | |
Keywords | A1 Journal article; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL) | ||||
Abstract | The agri-food value chain is a major cause of nitrogen (N) and phosphorus (P) emissions and associated environmental and health impacts. The EU's farm-to-fork strategy (F2F) demands an agri-food value chain approach to reduce nutrient emissions by 50% and fertilizer use by 20%. Substance flow analysis (SFA) is a method that can be applied to study complex systems such as the agri-food chain. A review of 60 SFA studies shows that they often lack detail by not sufficiently distinguishing between nodes, products and types of emissions. The present study aims to assess the added value of detail in SFAs and to illustrate that valuable indicators can be derived from detailed assessments. This aim will be attained by presenting a highly-detailed SFA for the livestock-intensive region of Flanders, Belgium. The SFA distinguishes 40 nodes and 1827 flows that are classified into eight different categories (e.g. by-products, point source emissions) following life cycle methods. Eight novel indicators were calculated, including indicators that assess the N and P recovery potential. Flanders has a low overall nutrient use efficiency (11% N, 18% P). About 55% of the N and 56% of the P embedded in recoverable streams are reused providing 35% and 37% of the total N and P input. Optimized nutrient recycling could replace 45% of N and 48% of P of the external nutrient input, exceeding the target set by the F2F strategy. Detailed accounting for N and P flows and nodes leads to the identification of more recoverable streams and larger N and P flows. More detailed flow accounting is a prerequisite for the quantification of technological intervention options. Future research should focus on including concentration and quality as a parameter in SFAs. | ||||
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Corporate Author | Thesis | ||||
Publisher | Place of Publication | Editor | |||
Language | Wos | 000991013600001 | Publication Date | 2023-04-21 | |
Series Editor | Series Title | Abbreviated Series Title | |||
Series Volume | Series Issue | Edition | |||
ISSN | 0959-6526 | ISBN | Additional Links | UA library record; WoS full record; WoS citing articles | |
Impact Factor | 11.1 | Times cited | Open Access | OpenAccess | |
Notes | Approved | Most recent IF: 11.1; 2023 IF: 5.715 | |||
Call Number | UA @ admin @ c:irua:196227 | Serial | 7770 | ||
Permanent link to this record |