| Records |
| 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. |
| 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 |
Type |
A1 Journal article |
Year  |
2024 |
Publication |
Journal of Experimental and Clinical Cancer Research |
Abbreviated Journal |
|
| Volume |
43 |
Issue |
1 |
Pages |
88-15 |
| 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) |
| 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. |
| Address |
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| Corporate Author |
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Thesis |
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| Publisher |
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Place of Publication |
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Editor |
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| Language |
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Wos |
001190581500001 |
Publication Date |
2024-03-22 |
| Series Editor |
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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 |
1756-9966 |
ISBN |
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Additional Links |
UA library record; WoS full record |
| 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 |
| Call Number |
UA @ admin @ c:irua:204924 |
Serial |
9136 |
| Permanent link to this record |
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| Author |
Deben, C.; Cardenas De La Hoz, E.; Le Compte, M.; Van Schil, P.; Hendriks, J.M.H.; Lauwers, P.; Yogeswaran, S.K.; Lardon, F.; Pauwels, P.; van Laere, S.; Bogaerts, A.; Smits, E.; Vanlanduit, S.; Lin, A. |
| Title |
OrBITS : label-free and time-lapse monitoring of patient derived organoids for advanced drug screening |
Type |
A1 Journal article |
| Year |
2022 |
Publication |
Cellular Oncology (2211-3428) |
Abbreviated Journal |
Cell Oncol |
| Volume |
|
Issue |
|
Pages |
1-16 |
| 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) |
| 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. |
| Address |
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| Corporate Author |
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Thesis |
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| Publisher |
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Place of Publication |
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Editor |
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| Language |
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Wos |
000898426100001 |
Publication Date |
2022-12-12 |
| Series Editor |
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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 |
2211-3428; 2211-3436 |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
| Impact Factor |
6.6 |
Times cited |
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Open Access |
OpenAccess |
| Notes |
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Approved |
Most recent IF: 6.6 |
| Call Number |
UA @ admin @ c:irua:192698 |
Serial |
7272 |
| Permanent link to this record |
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| |
| Author |
Van Holsbeke, C.S.; Leemans, G.; Vos, W.G.; de Backer, J.W.; Vinchurkar, S.C.; Geldof, M.; Verdonck, P.R.; Parizel, P.M.; van Schil, P.E.; de Backer, W.A. |
| Title |
Functional Respiratory Imaging as a tool to personalize respiratory treatment in subjects with unilateral diaphragmatic paralysis |
Type |
A1 Journal article |
| Year |
2013 |
Publication |
Respiratory care |
Abbreviated Journal |
Resp Care |
| Volume |
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Issue |
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Pages |
1-20 |
| Keywords |
A1 Journal article; Condensed Matter Theory (CMT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP) |
| Abstract |
In two subjects with a unilateral diaphragmatic paralysis and complaints of dyspnea, a completely different treatment approach was chosen despite similar anatomical and physiological abnormalities. These decisions were supported by the results generated by Functional Respiratory Imaging (FRI). FRI was able to generate functional information with respect to lobar ventilation and local drug deposition. In one subject, it was found that some lobes were poorly ventilated and drug deposition simulation showed that some regions were undertreated. This subject underwent a diaphragm plication to restore the ventilation. In the other subject, it was found that all lobes were still ventilated. A conservative approach with regular follow-up was chosen to wait for spontaneous recovery of the diaphragmatic function. Both subjects improved subjectively and objectively. These cases demonstrate how novel medical imaging techniques such as FRI can be used to personalize respiratory treatment in subjects with unilateral diaphragmatic paralysis. |
| Address |
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| Corporate Author |
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Thesis |
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| Publisher |
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Place of Publication |
Dallas, Tex. |
Editor |
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| Language |
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Wos |
000349200100024 |
Publication Date |
2013-12-11 |
| Series Editor |
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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 |
0020-1324;1943-3654; |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
| Impact Factor |
1.733 |
Times cited |
5 |
Open Access |
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| Notes |
; ; |
Approved |
Most recent IF: 1.733; 2013 IF: 1.840 |
| Call Number |
UA @ lucian @ c:irua:112982 |
Serial |
1303 |
| Permanent link to this record |
