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Freund, E.; Spadola, C.; Schmidt, A.; Privat-Maldonado, A.; Bogaerts, A.; von Woedtke, T.; Weltmann, K.-D.; Heidecke, C.-D.; Partecke, L.-I.; Käding, A.; Bekeschus, S. |
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Title |
Risk Evaluation of EMT and Inflammation in Metastatic Pancreatic Cancer Cells Following Plasma Treatment |
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A1 Journal article |
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Year  |
2020 |
Publication |
Frontiers in physics |
Abbreviated Journal |
Front. Phys. |
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Volume |
8 |
Issue |
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Pages |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
The requirements for new technologies to serve as anticancer agents go far beyond their toxicity potential. Novel applications also need to be safe on a molecular and patient level. In a broader sense, this also relates to cancer metastasis and inflammation. In a previous study, the toxicity of an atmospheric pressure argon plasma jet in four human pancreatic cancer cell lines was confirmed and plasma treatment did not promote metastasis in vitro and in ovo. Here, these results are extended by additional types of analysis and new models to validate and define on a molecular level the changes related to metastatic processes in pancreatic cancer cells following plasma treatment in vitro and in ovo. In solid tumors that were grown on the chorion-allantois membrane of fertilized chicken eggs (TUM-CAM), plasma treatment induced modest to profound apoptosis in the tissues. This, however, was not associated with a change in the expression levels of adhesion molecules, as shown using immunofluorescence of ultrathin tissue sections. Culturing of the cells detached from these solid tumors for 6d revealed a similar or smaller total growth area and expression of ZEB1, a transcription factor associated with cancer metastasis, in the plasma-treated pancreatic cancer tissues. Analysis of in vitro and in ovo supernatants of 13 different cytokines and chemokines revealed cell line-specific effects of the plasma treatment but a noticeable increase of, e.g., growth-promoting interleukin 10 was not observed. Moreover, markers of epithelial-to-mesenchymal transition (EMT), a metastasis-promoting cellular program, were investigated. Plasma-treated pancreatic cancer cells did not present an EMT-profile. Finally, a realistic 3D tumor spheroid co-culture model with pancreatic stellate cells was employed, and the invasive properties in a gel-like cellular matrix were investigated. Tumor outgrowth and spread was similar or decreased in the plasma conditions. Altogether, these results provide valuable insights into the effect of plasma treatment on metastasis-related properties of cancer cells and did not suggest EMT-promoting effects of this novel cancer therapy. |
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Wos |
000581086900001 |
Publication Date |
2020-10-09 |
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Edition |
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ISSN |
2296-424X |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
3.1 |
Times cited |
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Open Access |
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Notes |
We thankfully acknowledge the technical support by Felix Niessner and Antje Janetzko. We also thank Jonas Van Audenaerde and Evelien Smits for generating the transduced cell lines used in this study. |
Approved |
Most recent IF: 3.1; 2020 IF: NA |
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Call Number |
PLASMANT @ plasmant @c:irua:172448 |
Serial |
6425 |
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Author |
Privat-Maldonado, A.; Schmidt, A.; Lin, A.; Weltmann, K.-D.; Wende, K.; Bogaerts, A.; Bekeschus, S. |
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Title |
ROS from Physical Plasmas: Redox Chemistry for Biomedical Therapy |
Type |
A1 Journal article |
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Year |
2019 |
Publication |
Oxidative medicine and cellular longevity |
Abbreviated Journal |
Oxid Med Cell Longev |
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Volume |
2019 |
Issue |
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Pages |
1-29 |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
Physical plasmas generate unique mixes of reactive oxygen and nitrogen species (RONS or ROS). Only a bit more than a decade ago, these plasmas, operating at body temperature, started to be considered for medical therapy with considerably little mechanistic redox chemistry or biomedical research existing on that topic at that time. Today, a vast body of evidence is available on physical plasma-derived ROS, from their spatiotemporal resolution in the plasma gas phase to sophisticated chemical and biochemical analysis of these species once dissolved in liquids. Data from<italic>in silico</italic>analysis dissected potential reaction pathways of plasma-derived reactive species with biological membranes, and<italic>in vitro</italic>and<italic>in vivo</italic>experiments in cell and animal disease models identified molecular mechanisms and potential therapeutic benefits of physical plasmas. In 2013, the first medical plasma systems entered the European market as class IIa devices and have proven to be a valuable resource in dermatology, especially for supporting the healing of chronic wounds. The first results in cancer patients treated with plasma are promising, too. Due to the many potentials of this blooming new field ahead, there is a need to highlight the main concepts distilled from plasma research in chemistry and biology that serve as a mechanistic link between plasma physics (how and which plasma-derived ROS are produced) and therapy (what is the medical benefit). This inevitably puts cellular membranes in focus, as these are the natural interphase between ROS produced by plasmas and translation of their chemical reactivity into distinct biological responses. |
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000493001000003 |
Publication Date |
2019-10-08 |
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ISSN |
1942-0900 |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
4.593 |
Times cited |
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Open Access |
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Notes |
KW and SB acknowledge funding by the German Federal Ministry of Education and Research (grant numbers 03Z22DN11 and 03Z22DN12). The work of SB is further supported by the European Social Fund (grant number ESF/14-BM-A55-0006). APM and AB acknowledge funding by the Methusalem Project. AL acknowledges funding from the Research Foundation Flanders (grant number 12S9218N). APM thanks Yury Gorbanev for his assistance with the preparation of this review. |
Approved |
Most recent IF: 4.593 |
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Call Number |
PLASMANT @ plasmant @c:irua:163476 |
Serial |
5373 |
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Author |
Bekeschus, S.; Freund, E.; Spadola, C.; Privat-Maldonado, A.; Hackbarth, C.; Bogaerts, A.; Schmidt, A.; Wende, K.; Weltmann, K.-D.; von Woedtke, T.; Heidecke, C.-D.; Partecke, L.-I.; Käding, A. |
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Title |
Risk Assessment of kINPen Plasma Treatment of Four Human Pancreatic Cancer Cell Lines with Respect to Metastasis |
Type |
A1 Journal article |
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Year |
2019 |
Publication |
Cancers |
Abbreviated Journal |
Cancers |
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Volume |
11 |
Issue |
9 |
Pages |
1237 |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
Cold physical plasma has limited tumor growth in many preclinical models and is, therefore, suggested as a putative therapeutic option against cancer. Yet, studies investigating the cells’ metastatic behavior following plasma treatment are scarce, although being of prime importance to evaluate the safety of this technology. Therefore, we investigated four human pancreatic cancer cell lines for their metastatic behavior in vitro and in chicken embryos (in ovo). Pancreatic cancer was chosen as it is particularly metastatic to the peritoneum and systemically, which is most predictive for outcome. In vitro, treatment with the kINPen plasma jet reduced pancreatic cancer cell activity and viability, along with unchanged or decreased motility. Additionally, the expression of adhesion markers relevant for metastasis was down-regulated, except for increased CD49d. Analysis of 3D tumor spheroid outgrowth showed a lack of plasma-spurred metastatic behavior. Finally, analysis of tumor tissue grown on chicken embryos validated the absence of an increase of metabolically active cells physically or chemically detached with plasma treatment. We conclude that plasma treatment is a safe and promising therapeutic option and that it does not promote metastatic behavior in pancreatic cancer cells in vitro and in ovo. |
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Wos |
000489719000022 |
Publication Date |
2019-08-23 |
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Edition |
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ISSN |
2072-6694 |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
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Times cited |
4 |
Open Access |
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Notes |
The authors acknowledge that this work was supported by grants funded by the German Federal Ministry of Education and Research (BMBF), grant number 03Z22DN11. We want to thank the Research Foundation – Flanders (FWO) for providing funding to APM under the “long stay abroad” scheme (grant code V415618N). APM and AB acknowledge financial support from the Methusalem project. Technical support by Felix Niessner and Antje Janetzko is gratefully acknowledged. |
Approved |
Most recent IF: NA |
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Call Number |
PLASMANT @ plasmant @c:irua:162106 |
Serial |
5357 |
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