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Author |
Fridman, A.; Lin, A.; Miller, V.; Bekeschus, S.; Wende, K.; Weltmann, K.-D. |
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Title |
The plasma treatment unit : an attempt to standardize cold plasma treatment for defined biological effects |
Type |
A1 Journal article |
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Year |
2018 |
Publication |
Plasma medicine |
Abbreviated Journal |
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Volume |
8 |
Issue |
2 |
Pages |
195-201 |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
Plasma bioscience and medicine are both rapidly growing fields. Their aim is to utilize cold physical plasmas for desired biological outcomes in medicine, biotechnology, agriculture, and general hygienic purposes. Great success has been achieved in many applications with individually designed plasma sources and plasma parameters. Although lab and application-specific tuning of plasmas is a great advantage of this technology, standardized units to define plasma treatments are required to facilitate comparison of the effects found by different researchers who do not use the same plasma sources. By drawing conclusions from over a century of plasma biomedical research, we propose that all researchers adopt the use of a standardized value, the plasma treatment unit (PTU), to describe the biological effects of different cold plasma sources and treatment regimens. It quantifies a key plasma effector in biological systems as an indicator and may provide the foundation for an analogous and clinically relevant unit in the future. |
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Publication Date |
2018-06-13 |
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Most recent IF: NA |
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Call Number |
UA @ lucian @ c:irua:155652 |
Serial |
5123 |
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Author |
Lin, A.G.; Xiang, B.; Merlino, D.J.; Baybutt, T.R.; Sahu, J.; Fridman, A.; Snook, A.E.; Miller, V. |
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Title |
Non-thermal plasma induces immunogenic cell death in vivo in murine CT26 colorectal tumors |
Type |
A1 Journal article |
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Year |
2018 |
Publication |
Oncoimmunology |
Abbreviated Journal |
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Volume |
7 |
Issue |
9 |
Pages |
e1484978 |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
Immunogenic cell death is characterized by the emission of danger signals that facilitate activation of an adaptive immune response against dead-cell antigens. In the case of cancer therapy, tumor cells undergoing immunogenic death promote cancer-specific immunity. Identification, characterization, and optimization of stimuli that induce immunogenic cancer cell death has tremendous potential to improve the outcomes of cancer therapy. In this study, we show that non-thermal, atmospheric pressure plasma can be operated to induce immunogenic cell death in an animal model of colorectal cancer. In vitro, plasma treatment of CT26 colorectal cancer cells induced the release of classic danger signals. Treated cells were used to create a whole-cell vaccine which elicited protective immunity in the CT26 tumor mouse model. Moreover, plasma treatment of subcutaneous tumors elicited emission of danger signals and recruitment of antigen presenting cells into tumors. An increase in T cell responses targeting the colorectal cancer-specific antigen guanylyl cyclase C (GUCY2C) were also observed. This study provides the first evidence that non-thermal plasma is a bone fide inducer of immunogenic cell death and highlights its potential for clinical translation for cancer immunotherapy. |
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Wos |
000443993100030 |
Publication Date |
2018-06-12 |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
2162-4011; 2162-402x |
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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 |
28 |
Open Access |
Not_Open_Access |
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Notes |
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Approved |
Most recent IF: NA |
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Call Number |
UA @ lucian @ c:irua:155651 |
Serial |
5119 |
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Author |
Demuynck, R.; Efimova, I.; Lin, A.; Declercq, H.; Krysko, D.V. |
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Title |
A 3D cell death assay to quantitatively determine ferroptosis in spheroids |
Type |
A1 Journal article |
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Year |
2020 |
Publication |
Cells |
Abbreviated Journal |
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Volume |
9 |
Issue |
3 |
Pages |
703-713 |
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Keywords |
A1 Journal article; Engineering sciences. Technology; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
The failure of drug efficacy in clinical trials remains a big issue in cancer research. This is largely due to the limitations of two-dimensional (2D) cell cultures, the most used tool in drug screening. Nowadays, three-dimensional (3D) cultures, including spheroids, are acknowledged to be a better model of the in vivo environment, but detailed cell death assays for 3D cultures (including those for ferroptosis) are scarce. In this work, we show that a new cell death analysis method, named 3D Cell Death Assay (3DELTA), can efficiently determine different cell death types including ferroptosis and quantitatively assess cell death in tumour spheroids. Our method uses Sytox dyes as a cell death marker and Triton X-100, which efficiently permeabilizes all cells in spheroids, was used to establish 100% cell death. After optimization of Sytox concentration, Triton X-100 concentration and timing, we showed that the 3DELTA method was able to detect signals from all cells without the need to disaggregate spheroids. Moreover, in this work we demonstrated that 2D experiments cannot be extrapolated to 3D cultures as 3D cultures are less sensitive to cell death induction. In conclusion, 3DELTA is a more cost-effective way to identify and measure cell death type in 3D cultures, including spheroids. |
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Wos |
000529337400180 |
Publication Date |
2020-03-13 |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
2073-4409 |
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 |
5 |
Open Access |
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Notes |
; Research in the D.V.K. group is supported by Fund for Scientific Research Flanders (1506218N, 1507118N, G051918N and G043219N) and Ghent University (Special Research Fund IOP 01/O3618). ; |
Approved |
Most recent IF: NA |
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Call Number |
UA @ admin @ c:irua:167215 |
Serial |
6446 |
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Author |
Truong, B.; Siegert, K.; Lin, A.; Miller, V.; Krebs, F.C. |
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Title |
Apical application of nanosecond-pulsed dielectric barrier discharge plasma causes the basolateral release of adenosine triphosphate as a damage-associated molecular pattern from polarized HaCaT cells |
Type |
A1 Journal article |
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Year |
2017 |
Publication |
Plasma medicine |
Abbreviated Journal |
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Volume |
7 |
Issue |
2 |
Pages |
117-131 |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
Promising biomedical uses for nonthermal plasma (NTP) in the fields of regenerative medicine, cancer therapy, and vaccine delivery involve the noninvasive application of uniform nonequilibrium plasma (including dielectric barrier discharge plasma) to living skin. Whereas most investigations have focused on achieving desired therapeutic outcomes, fewer studies have examined the mechanisms and pathways by which epithelial cells respond to NTP exposure. Using a transwell apical-basolateral-chambered system to culture the human keratinocyte HaCaT cell line, in vitro experiments were performed to demonstrate the effects of nanosecond-pulsed dielectric barrier discharge (nsDBD) plasma on polarized epithelial cell viability, monolayer permeability, intracellular oxidative stress, and the release of adenosine triphosphate (ATP). Application of nsDBD plasma at 60 Hz or below had minimal or no effect on HaCaT monolayer viability or permeability. nsDBD plasma exposure did, however, result in frequency-dependent reductions in intracellular glutathione (indicating direct induction of oxidative stress by nsDBD plasma) and increased extracellular ATP concentrations in the ba-solateral (subepithelial) media, which are indicators of cellular stress and an NTP-induced inflammatory response. These studies provide new insights into nsDBD plasma-induced inflammation and local innate immune responses initiated by polarized epithelial tissues. |
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Publication Date |
2017-02-24 |
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Additional Links |
UA library record |
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Impact Factor |
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Times cited |
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Open Access |
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Notes |
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Approved |
no |
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Call Number |
UA @ admin @ c:irua:155656 |
Serial |
7465 |
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Author |
Lin, A.; Truong, B.; Fridman, G.; Friedman, A.A.; Miller, V. |
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Title |
Immune cells enhance selectivity of nanosecond-pulsed DBD plasma against tumor cells |
Type |
A1 Journal article |
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Year |
2017 |
Publication |
Plasma medicine |
Abbreviated Journal |
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Volume |
7 |
Issue |
1 |
Pages |
85-96 |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
Cancer immunotherapy is a promising strategy that engages the patient's immune system to kill cancer cells selectively while sparing normal tissue. Treatment of macrophages with a nanosecond-pulsed dielectric barrier discharge directly enhanced their cytotoxic activity against tumor cells but not normal cells. These results underscore the clinical potential of plasma for cancer immunotherapy. |
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Publication Date |
2017-08-15 |
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Additional Links |
UA library record |
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Impact Factor |
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Times cited |
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Open Access |
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Notes |
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Approved |
no |
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Call Number |
UA @ admin @ c:irua:155657 |
Serial |
8058 |
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Author |
Lin, A.; Truong, B.; Patel, S.; Kaushik, N.; Choi, E.H.; Fridman, G.; Fridman, A.; Miller, V. |
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Title |
Nanosecond-pulsed DBD plasma-generated reactive oxygen species trigger immunogenic cell death in A549 lung carcinoma cells through intracellular oxidative stress |
Type |
A1 Journal article |
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Year |
2017 |
Publication |
International journal of molecular sciences |
Abbreviated Journal |
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Volume |
18 |
Issue |
5 |
Pages |
966 |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death. We assessed changes to the intracellular oxidative environment after plasma treatment and correlated it to emission of two danger signals: surface-exposed calreticulin and secreted adenosine triphosphate. Plasma-generated reactive oxygen and charged species were recognized as the major effectors of immunogenic cell death. Chemical attenuators of intracellular reactive oxygen species successfully abrogated oxidative stress following plasma treatment and modulated the emission of surface-exposed calreticulin. Secreted danger signals from cells undergoing immunogenic death enhanced the anti-tumor activity of macrophages. This study demonstrated that plasma triggers immunogenic cell death through oxidative stress pathways and highlights its potential development for cancer immunotherapy. |
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Wos |
000404113900073 |
Publication Date |
2017-05-03 |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
1422-0067; 1661-6596 |
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 |
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Open Access |
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Notes |
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Approved |
no |
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Call Number |
UA @ admin @ c:irua:155654 |
Serial |
8292 |
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Author |
Ranieri, P.; Shrivastav, R.; Wang, M.; Lin, A.; Fridman, G.; Fridman, A.A.; Han, L.-H.; Miller, V. |
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Title |
Nanosecond-pulsed dielectric barrier dischargeinduced antitumor effects propagate through depth of tissue via intracellular signaling |
Type |
A1 Journal article |
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Year |
2017 |
Publication |
Plasma medicine |
Abbreviated Journal |
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Volume |
7 |
Issue |
3 |
Pages |
283-297 |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
Studies using xenograft mouse models have shown that plasma applied to the skin overlying tumors results in tumor shrinkage. Plasma is considered a nonpenetrating treatment; however, these studies demonstrate plasma effects that occur beyond the postulated depth of physical penetration of plasma components. The present study examines the propagation of plasma effects through a tissue model using three-dimensional, cell-laden extracellular matrices (ECMs). These ECMs are used as barriers against direct plasma penetration. By placing them onto a monolayer of target cancer cells to create an in-vitro analog to in-vivo studies, we distinguished between cellular effects from direct plasma exposure and cellular effects due to cell-to-cell signaling stimulated by plasma. We show that nanosecond-pulsed dielectric barrier discharge plasma treatment applied atop an acellular barrier impedes the externalization of calreticulin (CRT) in the target cells. In contrast, when a barrier is populated with cells, CRT externalization is restored. Thus, we demonstrate that plasma components stimulate signaling among cells embedded in the barrier to transfer plasma effects to the target cells. |
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Publication Date |
2017-09-01 |
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Edition |
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Additional Links |
UA library record |
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Impact Factor |
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Times cited |
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Open Access |
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Notes |
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Approved |
no |
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Call Number |
UA @ admin @ c:irua:155658 |
Serial |
8293 |
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Author |
Friedman, P.C.; Miller, V.; Fridman, G.; Lin, A.; Fridman, A. |
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Title |
Successful treatment of actinic keratoses using nonthermal atmospheric pressure plasma : a case series |
Type |
L1 Letter to the editor |
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Year |
2017 |
Publication |
Journal of the American Academy of Dermatology |
Abbreviated Journal |
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Volume |
76 |
Issue |
2 |
Pages |
349-350 |
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Keywords |
L1 Letter to the editor; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Wos |
000396905000041 |
Publication Date |
2017-01-13 |
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Abbreviated Series Title |
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Series Volume |
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Edition |
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ISSN |
0190-9622 |
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 |
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Open Access |
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Notes |
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no |
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Call Number |
UA @ admin @ c:irua:155655 |
Serial |
8617 |
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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. |
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Title |
De belofte van hoofdhalskankerorganoïden in kankeronderzoek : een blik op de toekomst |
Type |
A2 Journal article |
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Year |
2023 |
Publication |
Onco-hemato : multidisciplinair tijdschrift voor oncologie |
Abbreviated Journal |
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Volume |
17 |
Issue |
7 |
Pages |
54-58 |
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Keywords |
A2 Journal article; Center for Oncological Research (CORE); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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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. |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
2030-2738 |
ISBN |
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Additional Links |
UA library record |
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Impact Factor |
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Times cited |
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Open Access |
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Notes |
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Approved |
Most recent IF: NA |
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Call Number |
UA @ admin @ c:irua:202271 |
Serial |
9004 |
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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. |
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Title |
Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer |
Type |
A1 Journal article |
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Year |
2023 |
Publication |
npj Precision Oncology |
Abbreviated Journal |
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Volume |
7 |
Issue |
1 |
Pages |
128-14 |
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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) |
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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. |
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Wos |
001118015800001 |
Publication Date |
2023-12-08 |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
2397-768x |
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 |
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Open Access |
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Notes |
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Approved |
Most recent IF: NA |
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Call Number |
UA @ admin @ c:irua:201455 |
Serial |
9091 |
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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. |
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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 |
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A1 Journal article |
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Year |
2024 |
Publication |
Journal of Experimental and Clinical Cancer Research |
Abbreviated Journal |
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Volume |
43 |
Issue |
1 |
Pages |
88-15 |
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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) |
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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. |
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Wos |
001190581500001 |
Publication Date |
2024-03-22 |
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ISSN |
1756-9966 |
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Additional Links |
UA library record; WoS full record |
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Open Access |
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Approved |
Most recent IF: NA |
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Call Number |
UA @ admin @ c:irua:204924 |
Serial |
9136 |
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