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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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Place of Publication | Editor | |||
Language | Wos | 000784103500001 | Publication Date | 2022-04-21 | |
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Series Volume | Series Issue | Edition | |||
ISSN | 2380-6761 | ISBN | Additional Links | 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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Language | Wos | 000844595100002 | Publication Date | 0000-00-00 | |
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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 | ||
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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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Language | Wos | 000846411000001 | Publication Date | 2022-08-10 | |
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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 | ||
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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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Place of Publication | Editor | |||
Language | Wos | 000925156500001 | Publication Date | 2022-12-29 | |
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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 | ||
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Author | Parizel, P.M.; Corthouts, B.; Snoeckx, A.; de Backer, J.; de Backer, W. | ||||
Title | Klinische semiologie en radiologie | Type | H3 Book chapter | ||
Year | 2007 | Publication | Abbreviated Journal | ||
Volume | Issue | Pages | 133-146 | ||
Keywords | H3 Book chapter; Condensed Matter Theory (CMT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP) | ||||
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Acco | Place of Publication | Leuven | Editor | |
Language | Wos | Publication Date | 0000-00-00 | ||
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ISSN | ISBN | Additional Links | UA library record | ||
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Notes | Approved | Most recent IF: NA | |||
Call Number | UA @ lucian @ c:irua:63801 | Serial | 1765 | ||
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