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“Development and validation of optical detection methods to screen photocatalytic materials for soot oxidation”. Smits M, Tytgat T, Hauchecorne B, Lenaerts S, (2012)
Keywords: P3 Proceeding; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL)
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“Injectable Plasma‐Treated Alginate Hydrogel for Oxidative Stress Delivery to Induce Immunogenic Cell Death in Osteosarcoma”. Živanić, M, Espona‐Noguera A, Verswyvel H, Smits E, Bogaerts A, Lin A, Canal C, Advanced functional materials (2023). http://doi.org/10.1002/adfm.202312005
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.
Keywords: A1 Journal article; Engineering sciences. Technology; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Impact Factor: 19
DOI: 10.1002/adfm.202312005
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Lin A, De Backer J, Quatannens D, Cuypers B, Verswyvel H, De La Hoz EC, Ribbens B, Siozopoulou V, Van Audenaerde J, Marcq E, Lardon F, Laukens K, Vanlanduit S, Smits E, Bogaerts A (2022) The effect of local non‐thermal plasma therapy on the<scp>cancer‐immunity</scp>cycle in a melanoma mouse model
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.
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)
DOI: 10.1002/btm2.10314
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“Enrichment procedures for water analysis by X-ray energy spectrometry”. Van Grieken R, Bresseleers K, Smits J, Vanderborght B, Vanderstappen M, (1976)
Keywords: P3 Proceeding; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation)
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“Unlocking Novel Anticancer Strategies: Bioactive Hydrogels for Local Delivery of Plasma‐Derived Oxidants in an In Ovo Cancer Model”. Espona‐Noguera A, Živanić, M, Smits E, Bogaerts A, Privat‐Maldonado A, Canal C, Macromolecular Bioscience (2024). http://doi.org/10.1002/mabi.202400213
Abstract: Cold atmospheric plasma (CAP) is a tool with the ability to generate reactive oxygen and nitrogen species (RONS), which can induce therapeutic effects like disinfection, wound healing, and cancer treatment. In the plasma oncology field, CAP‐treated hydrogels (PTHs) are being explored for the local administration of CAP‐derived RONS as a novel anticancer approach. PTHs have shown anticancer effects in vitro, however, they have not yet been studied in more relevant cancer models. In this context, the present study explores for the first time the therapeutic potential of PTHs using an advanced in ovo cancer model. PTHs composed of alginate (Alg), gelatin (Gel), Alg/Gel combination, or Alg/hyaluronic acid (HA) combination are investigated. All embryos survived the PTHs treatment, suggesting that the in ovo model could become a time‐ and cost‐effective tool for developing hydrogel‐based anticancer approaches. Results revealed a notable reduction in CD44+ cell population and their proliferative state for the CAP‐treated Alg‐HA condition. Moreover, the CAP‐treated Alg‐HA formulation alters the extracellular matrix composition, which may help combat drug‐resistance. In conclusion, the present study validates the utility of in ovo cancer model for PTHs exploration and highlights the promising potential of Alg‐based PTHs containing HA and CAP‐derived RONS for cancer treatment.
Keywords: A1 Journal Article; Plasma, laser ablation and surface modeling Antwerp (PLASMANT) ;
Impact Factor: 4.6
DOI: 10.1002/mabi.202400213
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“Critical Evaluation of the Interaction of Reactive Oxygen and Nitrogen Species with Blood to Inform the Clinical Translation of Nonthermal Plasma Therapy”. Lin A, Biscop E, Breen C, Butler SJ, Smits E, Bogaerts A, Jakovljevic V, Oxidative Medicine And Cellular Longevity 2020, 1 (2020). http://doi.org/10.1155/2020/9750206
Abstract: Non-thermal plasma (NTP), an ionized gas generated at ambient pressure and temperature, has been an emerging technology for medical applications. Through controlled delivery of reactive oxygen and nitrogen species (ROS/RNS), NTP can elicit hormetic cellular responses, thus stimulating broad therapeutic effects. To enable clinical translation of the promising preclinical research into NTP therapy, a deeper understanding of NTP interactions with clinical substrates is profoundly needed. Since NTP-generated ROS/RNS will inevitably interact with blood in several clinical contexts, understanding their stability in this system is crucial. In this study, two medically relevant NTP delivery modalities were used to assess the stability of NTP-generated ROS/RNS in three aqueous solutions with increasing organic complexities: phosphate-buffered saline (PBS), blood plasma (BP), and processed whole blood. NTP-generated RNS collectively (NO2−, ONOO−), H2O2, and ONOO− exclusively were analyzed over time. We demonstrated that NTP-generated RNS and H2O2 were stable in PBS but scavenged by different components of the blood. While RNS remained stable in BP after initial scavenging effects, it was completely reduced in processed whole blood. On the other hand, H2O2 was completely scavenged in both liquids over time. Our previously developed luminescent probe europium(III) was used for precision measurement of ONOO− concentration. NTP-generated ONOO− was detected in all three liquids for up to at least 30 seconds, thus highlighting its therapeutic potential. Based on our results, we discussed the necessary considerations to choose the most optimal NTP modality for delivery of ROS/RNS to and via blood in the clinical context.
Keywords: A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Impact Factor: 4.593
DOI: 10.1155/2020/9750206
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“Inactivation of SARS-CoV-2 and other enveloped and non-enveloped viruses with non-thermal plasma for hospital disinfection”. Sahun M, Privat-Maldonado A, Lin A, De Roeck N, Van de Heyden L, Hillen M, Michiels J, Steenackers G, Smits E, Ariën KK, Jorens PG, Delputte P, Bogaerts A, ACS Sustainable Chemistry and Engineering , 1 (2023). http://doi.org/10.1021/ACSSUSCHEMENG.2C07622
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.
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)
Impact Factor: 8.4
DOI: 10.1021/ACSSUSCHEMENG.2C07622
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“Multiparametric tumor organoid drug screening using widefield live-cell imaging for bulk and single-organoid analysis”. 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, Jove-Journal Of Visualized Experiments , 1 (2022). http://doi.org/10.3791/64434
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. ,
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)
Impact Factor: 1.2
DOI: 10.3791/64434
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“OrBITS : label-free and time-lapse monitoring of patient derived organoids for advanced drug screening”. Deben C, Cardenas De La Hoz E, Le Compte M, Van Schil P, Hendriks JMH, Lauwers P, Yogeswaran SK, Lardon F, Pauwels P, van Laere S, Bogaerts A, Smits E, Vanlanduit S, Lin A, Cellular Oncology (2211-3428) , 1 (2022). http://doi.org/10.1007/S13402-022-00750-0
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.
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)
Impact Factor: 6.6
DOI: 10.1007/S13402-022-00750-0
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“Enrichment of trace anions from water with 2,2'-diaminodiethylamine cellulose filters”. Smits J, Van Grieken R, Analytica chimica acta 123, 9 (1981). http://doi.org/10.1016/S0003-2670(01)83152-4
Abstract: Cellulose filters with immobilized 2,2'-diaminodiethylamine (DEN) functional groups are studied for trace anion preconcentration from aqueous solution, with subsequent x-ray fluorescence measurements. For most oxoanions with a central metal atom, nearly quantitative collection can be achieved by 10-cm2 DEN filters under the following optimized conditions: pH 36, filtration rate up to 0.5 ml cm-2 min-1, and sample volume up to 100 ml cm-2. The collection yield is independent of the trace oxoanion concentration up to at least 1.5 μmol cm-2. Although the DEN filter exhibits some selectivity towards oxoanions with a central metal atom, ionic strength affects the results; the collection efficiency is strongly depressed with salt (e.g. NaCl) concentrations above 0.01 M. The applicability of the DEN filter in anion collection is therefore limited to dilute solutions.
Keywords: A1 Journal article; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation)
DOI: 10.1016/S0003-2670(01)83152-4
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“De belofte van hoofdhalskankerorganoïden in kankeronderzoek : een blik op de toekomst”. Zaryouh H, Verswyvel H, Bauwens M, Van Haesendonck G, Deben C, Lin A, De Waele J, Vermorken JB, Koljenovic S, Bogaerts A, Lardon F, Smits E, Wouters A, Onco-hemato : multidisciplinair tijdschrift voor oncologie 17, 54 (2023)
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.
Keywords: A2 Journal article; Center for Oncological Research (CORE); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
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“Chelating 2,2′-diaminodiethylamine cellulose filters and X-ray fluorescence for preconcentration and trace analysis of natural waters”. Smits J, Van Grieken R, International journal of environmental analytical chemistry 9, 81 (1981). http://doi.org/10.1080/03067318108071902
Abstract: The 2,2′-diaminodiethylamine (DEN) functional group can be expected to have ideal properties for the chelation of transition metals and their collection from aqueous solutions, independent of the alkali and alkaline earth ions concentration. Introducing DEN into cellulose filters allows straightforward preconcentration of trace cations by a simple filtration step, and the DEN-filter constitutes a suitable target for X-ray fluorescence (XRF) analysis. The linearity between the XRF-response on the loaded DEN-filter and the trace cation concentration in the solution appears excellent, up to a total filter capacity of ca. 3 μeq.cm−2. The detection limits are around 0.5 μg. l−1 in most practical cases. Accuracy and precision are around 10%. The applicability of the proposed procedure is illustrated on a comparative basis by XRF-analysis of drinking water and surface water, after preconcentration by DEN-filtration and by alternative procedures.
Keywords: A1 Journal article; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation)
DOI: 10.1080/03067318108071902
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“Exhaust composition of a small diesel engine”. Smits M, Vanpachtenbeke F, Hauchecorne B, van Langenhove H, Demeestere K, Lenaerts S, Communications in agricultural and applied biological sciences 77, 85 (2012)
Keywords: A2 Journal article; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL)
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“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”. 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 KK, Van Schil P, Hendriks JMH, Prenen H, Roeyen G, Lardon F, Smits E, Journal of Experimental and Clinical Cancer Research 43, 88 (2024). http://doi.org/10.1186/S13046-024-03012-Z
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.
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)
DOI: 10.1186/S13046-024-03012-Z
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“Optimization of a simple spotting procedure for x-ray fluorescence analysis of waters”. Smits J, Van Grieken R, Analytica chimica acta 88, 97 (1977). http://doi.org/10.1016/S0003-2670(01)96053-2
Abstract: Several sample preparation methods for waters for energy-dispersive x.r.f. were examined, as well as the influence of sample size on the analytical characteristics. The most satisfactory simple, rapid method proved to be spotting of 1.5 ml of water sample on a Whatman-41 cellulose filter paper provided with a wax ring of 29-mm diameter and evaporating the water with an unheated air stream from underneath. Sensitivities are below 100 p.p.b. for most elements and often below 50 p.p.b. when the optimal secondary fluorescer is used. Accuracy and precision are usually in the 1520 % range. The method is applicable to many dilute aqueous solutions as is illustrated by analysis of industrial water samples and ashed biological material.
Keywords: A1 Journal article; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation)
DOI: 10.1016/S0003-2670(01)96053-2
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“Synthesis of a chelating cellulose filter with 2,2-diaminodiethylamine functional groups”. Smits J, Van Grieken R, Zeitschrift für angewandte Makromolekare Chemie 72, 105 (1978)
Keywords: A3 Journal article; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation)
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“Photocatalytic degradation of ethylene : an FTIR in situ study under atmospheric conditions”. Hauchecorne B, Tytgat T, Verbruggen SW, Hauchecorne D, Terrens D, Smits M, Vinken K, Lenaerts S, Applied catalysis : B : environmental 105, 111 (2011). http://doi.org/10.1016/J.APCATB.2011.03.041
Abstract: In this paper, the reaction mechanism of the photocatalytic oxidation of ethylene is elucidated by means of an in-house developed FTIR in situ reactor. This reactor allowed us to look at the catalytic surface at the moment the reactions actually occur. This new approach gave some exciting new insights in how ethylene is photocatalytically oxidised. It was found that there is a change in dipole moment of the ethylene molecule when it is brought in the neighbourhood of the catalyst. From this finding, a hypothesis was formulated on how the CC-bond from ethylene will break. It was found that the aforementioned interaction between the catalyst and the molecule, allows the excited electrons from the UV irradiated catalyst to occupy the lowest unoccupied molecular orbital (LUMO) of the ethylene molecule through a process known as backdonation. Following this hypothesis, it was found that the degradation occurs through the formation of two intermediates: formaldehyde and formic acid, for which formaldehyde is bound in two different ways (coordinatively and as bidentate). Finally CO2 and H2O are found as end products, resulting in the complete mineralisation of the pollutant.
Keywords: A1 Journal article; Engineering sciences. Technology; Molecular Spectroscopy (MolSpec); Sustainable Energy, Air and Water Technology (DuEL)
Impact Factor: 9.446
Times cited: 29
DOI: 10.1016/J.APCATB.2011.03.041
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“Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer”. 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, npj Precision Oncology 7, 128 (2023). http://doi.org/10.1038/S41698-023-00480-Y
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.
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)
DOI: 10.1038/S41698-023-00480-Y
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“Concept and validation of a fully automated photocatalytic test setup”. Tytgat T, Hauchecorne B, Smits M, Verbruggen S, Lenaerts S, Journal of laboratory automation 17, 134 (2012). http://doi.org/10.1177/2211068211424554
Abstract: Photocatalytic activity can be studied by several methods, each with its own strengths and weaknesses. To study photocatalytic activity in an easy, user-friendly, and realistic way, a completely new setup has been built. The setup is modularly constructed around Fourier transform infrared spectroscopy (FTIR) spectroscopy at the heart of it, resulting in great versatility. Complementary software has been written for automatic control of the setup and for processing the generated data. Two pollutants, oil and n-octane, are tested to validate the performance of the setup. These validation experiments confirm the usefulness and added value of the setup in general and of the FTIR detection methodology as well. It becomes clear that a system of online measurements with good repeatability, accuracy, and user-friendliness has been created.
Keywords: A1 Journal article; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL)
Impact Factor: 2.85
Times cited: 15
DOI: 10.1177/2211068211424554
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“Diatom silica-titania materials for photocatalytic air purification”. Van Eynde E, Tytgat T, Smits M, Verbruggen S, Hauchecorne B, Blust R, Lenaerts S, Communications in agricultural and applied biological sciences 1, 141 (2013)
Keywords: A2 Journal article; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL)
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Smits M (2013) Photocatalytic degradation of diesel soot : from application to reaction mechanism. 160 p
Keywords: Doctoral thesis; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL)
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“Physical plasma-derived oxidants sensitize pancreatic cancer cells to ferroptotic cell death”. Kumar N, Perez-Novo C, Shaw P, Logie E, Privat-Maldonado A, Dewilde S, Smits E, Berghe WV, Bogaerts A, Free Radical Biology And Medicine 166, 187 (2021). http://doi.org/10.1016/j.freeradbiomed.2021.02.026
Abstract: Despite modern therapeutic advances, the survival prospects of pancreatic cancer patients remain poor, due to chemoresistance and dysregulated oncogenic kinase signaling networks. We applied a novel kinome activitymapping approach using biological peptide targets as phospho-sensors to identify vulnerable kinase dependencies for therapy sensitization by physical plasma. Ser/Thr-kinome specific activity changes were mapped upon induction of ferroptotic cell death in pancreatic tumor cells exposed to reactive oxygen and nitrogen species of plasma-treated water (PTW). This revealed a broad kinome activity response involving the CAMK, the AGC and CMGC family of kinases. This systems-level kinome network response supports stress adaptive switches between chemoresistant anti-oxidant responses of Kelch-like ECH-associated protein 1 (KEAP1)/Heme Oxygenase 1 (HMOX1) and ferroptotic cell death sensitization upon suppression of Nuclear factor (erythroid derived 2)-like 2 (NRF2) and Glutathione peroxidase 4 (GPX4). This is further supported by ex vivo experiments in the chicken chorioallantoic membrane assay, showing decreased GPX4 and Glutathione (GSH) expression as well as increased lipid peroxidation, along with suppressed BxPC-3 tumor growth in response to PTW. Taken all together, we demonstrate that plasma treated water-derived oxidants sensitize pancreatic cancer cells to ferroptotic cell death by targeting a NRF2-HMOX1-GPX4 specific kinase signaling network.
Keywords: A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Impact Factor: 5.606
DOI: 10.1016/j.freeradbiomed.2021.02.026
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“Comparison of preconcentration procedures for trace metals in natural waters”. Smits J, Nelissen J, Van Grieken R, Analytica chimica acta 111, 215 (1979). http://doi.org/10.1016/S0003-2670(01)93264-7
Abstract: The relative merits of eight procedures for preconcentrations of trace metal ions from natural water samples and synthetic solutions are evaluated. Spikes (100 μg l−1 ) of Mn, Co, Zn, Eu, Cs and Ba and the corresponding radioactive tracers were added to batches of drinking water, estuarine water, sea water, ground water, twice-distilled water and ahumic material solution. After equilibration for 25 months, the following techniques were applied: passage through columns of Dowex Al chelating resin and ofsilylated silica gel, filtration through laminate membrane filters and chelating diethylenetriamine cellulose filters, precipitation with sodium diethyldithiocarbamate and l-(2-pyridylazo)-2-naphthol, extraction with ammonium pyrrolidinedithiocarbamate, and chelation by 8-quinolinol (oxine) followed by adsorption on activated carbon. The quantitative characteristics of these techniques and the influence of the water matrix effects are discussed, as well as the applicability for x-ray fluorescence analysis.
Keywords: A1 Journal article; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation)
DOI: 10.1016/S0003-2670(01)93264-7
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“Effect of process parameters on the photocatalytic soot degradation on self-cleaning cementitious materials”. Smits M, Huygh D, Craeye B, Lenaerts S, Catalysis today 230, 250 (2014). http://doi.org/10.1016/J.CATTOD.2013.10.001
Abstract: Soot deposition has the negative ability to devalue the aesthetic appearance of buildings. Titanium dioxide applied on the building material is one way to counteract this problem as it provides air-purifying and self-cleaning properties due to its photocatalytic activity. In literature, photocatalytic soot oxidation was described, but until now, little information was available about the influence of process parameters on the photocatalytic degradation efficiency. The influence of three process parameters was tested in this study, namely TiO2 concentration, soot concentration and water-to-cement ratio (WIC-ratio) of the mortar substrates. The results revealed 50 mu gTiO(2) cm(-2) is better to use on the cementitious materials than 250 mu gTiO(2) cm(-2). The soot concentrations occurring in real-world situations will not inhibit the photocatalyst to be activated by light. Furthermore, the photonic efficiency increases slightly for lower WIC-ratios. This can be of interest for structural building applications, since a lower WIC-ratio results in a lower porosity of the samples and consequently in an increase in mortar strength. (C) 2013 Elsevier B.V. All rights reserved.
Keywords: A1 Journal article; Sustainable Energy, Air and Water Technology (DuEL); Energy and Materials in Infrastructure and Buildings (EMIB)
Impact Factor: 4.636
Times cited: 14
DOI: 10.1016/J.CATTOD.2013.10.001
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“Correlations between molecular and operational parameters in continuous lab-scale anaerobic reactors”. Carballa M, Smits M, Etchebehere C, Boon N, Verstraete W, Applied microbiology and biotechnology 89, 303 (2011). http://doi.org/10.1007/S00253-010-2858-Y
Abstract: In this study, the microbial community characteristics in continuous lab-scale anaerobic reactors were correlated to reactor functionality using the microbial resource management (MRM) approach. Two molecular techniques, denaturing gradient gel electrophoresis (DGGE) and terminal-restriction fragment length polymorphism (T-RFLP), were applied to analyze the bacterial and archaeal communities, and the results obtained have been compared. Clustering analyses showed a similar discrimination of samples with DGGE and T-RFLP data, with a clear separation between the meso- and thermophilic communities. Both techniques indicate that bacterial and mesophilic communities were richer and more even than archaeal and thermophilic communities, respectively. Remarkably, the community composition was highly dynamic for both Bacteria and Archaea, with a rate of change between 30% and 75% per 18 days, also in stable performing periods. A hypothesis to explain the latter in the context of the converging metabolism in anaerobic processes is proposed. Finally, a more even and diverse bacterial community was found to be statistically representative for a well-functioning reactor as evidenced by a low Ripley index and high biogas production.
Keywords: A1 Journal article; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL)
DOI: 10.1007/S00253-010-2858-Y
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“The benefit of glass bead supports for efficient gas phase photocatalysis : case study of a commercial and a synthesised photocatalyst”. Verbruggen SW, Ribbens S, Tytgat T, Hauchecorne B, Smits M, Meynen V, Cool P, Martens JA, Lenaerts S, Chemical engineering journal 174, 318 (2011). http://doi.org/10.1016/J.CEJ.2011.09.038
Abstract: In the field of photocatalytic air purification, the immobilisation of catalyst particles on support surfaces without loss of photon efficiency is an important challenge. Therefore, an immobilisation method involving a one-step suspension coating of pre-synthesised photocatalysts on glass beads was applied. The various benefits are exemplified in the gas phase photodegradation of ethylene. Coating of glass beads is easy, fast, cheap and offers a more efficient alternative to bulk catalyst pellets. Furthermore, this coating procedure allows to use porous, pre-synthesised catalysts to their full potential, as the surface area and morphology of the initial powder is barely altered after coating, in strong contrast to pelletising. With this technique it became possible to study the gas phase photocatalytic activity of commercial titanium dioxide, trititanate nanotubes and mixed phase anatase/trititanate nanotubes in a packed bed reactor towards the degradation of ethylene without changing the catalyst properties. Coating of glass beads with the photocatalyst revealed the superior activity of the as-prepared nanotubes, compared to TiO2 Aerolyst® 7710 in gaseous phase.
Keywords: A1 Journal article; Engineering sciences. Technology; Laboratory of adsorption and catalysis (LADCA); Sustainable Energy, Air and Water Technology (DuEL)
Impact Factor: 6.216
Times cited: 39
DOI: 10.1016/J.CEJ.2011.09.038
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“Reduction of Human Glioblastoma Spheroids Using Cold Atmospheric Plasma: The Combined Effect of Short- and Long-Lived Reactive Species”. Privat-Maldonado A, Gorbanev Y, Dewilde S, Smits E, Bogaerts A, Cancers 10, 394 (2018). http://doi.org/10.3390/cancers10110394
Abstract: Cold atmospheric plasma (CAP) is a promising technology against multiple types of cancer. However, the current findings on the effect of CAP on two-dimensional glioblastoma cultures do not consider the role of the tumour microenvironment. The aim of this study was to determine the ability of CAP to reduce and control glioblastoma spheroid tumours in vitro . Three-dimensional glioblastoma spheroid tumours (U87-Red, U251-Red) were consecutively treated directly and indirectly with a CAP using dry He, He + 5% H 2 O or He + 20% H 2 O. The cytotoxicity and spheroid shrinkage were monitored using live imaging. The reactive oxygen and nitrogen species produced in phosphate buffered saline (PBS) were measured by electron paramagnetic resonance (EPR) and colourimetry. Cell migration was also assessed. Our results demonstrate that consecutive CAP treatments (He + 20% H 2 O) substantially shrank U87-Red spheroids and to a lesser degree, U251-Red spheroids. The cytotoxic effect was due to the short- and long-lived species delivered by CAP: they inhibited spheroid growth, reduced cell migration and decreased proliferation in CAP-treated spheroids. Direct treatments were more effective than indirect treatments, suggesting the importance of CAP-generated, short-lived species for the growth inhibition and cell cytotoxicity of solid glioblastoma tumours. We concluded that CAP treatment can effectively reduce glioblastoma tumour size and restrict cell migration, thus demonstrating the potential of CAP therapies for glioblastoma.
Keywords: A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
DOI: 10.3390/cancers10110394
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“Photocatalytic degradation of soot deposition : self-cleaning effect on titanium dioxide coated cementitious materials”. Smits M, Chan C kit, Tytgat T, Craeye B, Costarramone N, Lacombe S, Lenaerts S, Chemical engineering journal 222, 411 (2013). http://doi.org/10.1016/J.CEJ.2013.02.089
Abstract: Diesel soot emissions deteriorate the appearance of architectural building materials by soot fouling. This soot deposition devalue the aesthetic value of the building. A solution to counteract this problem is applying titanium dioxide on building materials. TiO2 can provide air-purifying and self-cleaning properties due to its photocatalytic activity. In literature, photocatalytic soot oxidation is observed on glass or silicon substrates. However, degradation of soot by photocatalysis was not yet investigated on cementitious samples (mortar, concrete) although it is one of the most frequently used building materials. In this study, photocatalytic soot oxidation by means of TiO2 coated cementitious samples is addressed. The soot removal capacity of four types of TiO2 layers, coated on mortar samples, is evaluated by means of two detection methods. The first method is based on colorimetric measurements, while the second method uses digital image processing to calculate the area of soot coverage. The experimental data revealed that cementitious materials coated with commercially available TiO2 exhibited self-cleaning properties as it was found that all coated samples were able to remove soot. The P25 coating gave the best soot degradation performance, while the Eoxolit product showed the slowest soot degradation rate. In addition, gas chromatography measurements in a closed chamber experiment with P25 confirmed that complete mineralization of about 60% of the soot was obtained within 24 hours since CO2 was the sole observed oxidation product. Due to its realistic approach, this study proves that photocatalytic soot removal on TiO2 coated cementitious surfaces is possible in practice, which is an important step towards the practical application of self-cleaning building materials.
Keywords: A1 Journal article; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL)
Impact Factor: 6.216
Times cited: 43
DOI: 10.1016/J.CEJ.2013.02.089
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“Characterization of regulated cancer cell death pathways induced by the different modalities of non-thermal plasma treatment”. Biscop E, Baroen J, De Backer J, Vanden Berghe W, Smits E, Bogaerts A, Lin A, Cell Death Discovery 10, 416 (2024). http://doi.org/10.1038/s41420-024-02178-x
Abstract: Non-thermal plasma (NTP) has shown promising anti-cancer effects, but there is still limited knowledge about the underlying cell death mechanisms induced by NTP and inherent differences between NTP treatment modalities. This study aimed to investigate four major regulated cell death (RCD) pathways, namely apoptosis, pyroptosis, necroptosis, and ferroptosis, in melanoma cancer cells following NTP treatment, and to provide an overview of molecular mechanistic differences between direct and indirect NTP treatment modalities. To discriminate which cell death pathways were triggered after treatment, specific inhibitors of apoptosis, pyroptosis, necroptosis, and ferroptosis were evaluated. RCD-specific molecular pathways were further investigated to validate the findings with inhibitors. Both direct and indirect NTP treatment increased caspase 3/7 and annexin V expression, indicative of apoptosis, as well as lipid peroxidation, characteristic of ferroptosis. Pyroptosis, on the other hand, was only induced by direct NTP treatment, evidenced by increased caspase 1 activity, whereas necroptosis was stimulated in a cell line-dependent manner. These findings highlight the molecular differences and implications of direct and indirect NTP treatment for cancer therapy. Altogether, activation of multiple cell death pathways offers advantages in minimizing treatment resistance and enhancing therapeutic efficacy, particularly in a combination setting. Understanding the mechanisms underlying NTP-induced RCD will enable the development of strategic combination therapies targeting multiple pathways to achieve cancer lethality.
Keywords: A1 Journal Article; Plasma, laser ablation and surface modeling Antwerp (PLASMANT) ;
DOI: 10.1038/s41420-024-02178-x
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“Photocatalytic process optimisation for ethylene oxidation”. Tytgat T, Hauchecorne B, Abakumov AM, Smits M, Verbruggen SW, Lenaerts S, Chemical engineering journal 209, 494 (2012). http://doi.org/10.1016/j.cej.2012.08.032
Abstract: When studying photocatalysis it is important to consider, beside the chemical approach, the engineering part related to process optimisation. To achieve this a fixed bed photocatalytic set-up consisting of different catalyst placings, in order to vary catalyst distribution, is studied. The use of a fixed quantity of catalyst placed packed or randomly distributed in the reactor, results in an almost double degradation for the distributed catalyst. Applying this knowledge leads to an improved performance with limited use of catalyst. A reactor only half filled with catalyst leads to higher degradation performance compared to a completely filled reactor. Taking into account this simple process optimisation by better distributing the catalyst a more sustainable photocatalytic air purification process is achieved. (C) 2012 Elsevier B.V. All rights reserved.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT); Sustainable Energy, Air and Water Technology (DuEL)
Impact Factor: 6.216
Times cited: 12
DOI: 10.1016/j.cej.2012.08.032
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