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Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model

SIMPLE SUMMARY: Ultrasound waves can be applied for diagnostic and therapeutic purposes. Focused ultrasound is approved for tissue ablation, e.g., in the treatment of uterine fibroids or essential tremors. Besides the non-invasive image-guided surgical intervention at temperatures above 55 °C, FUS i...

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Autores principales: Landgraf, Lisa, Kozlowski, Adam, Zhang, Xinrui, Fournelle, Marc, Becker, Franz-Josef, Tretbar, Steffen, Melzer, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099905/
https://www.ncbi.nlm.nih.gov/pubmed/35563823
http://dx.doi.org/10.3390/cells11091518
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author Landgraf, Lisa
Kozlowski, Adam
Zhang, Xinrui
Fournelle, Marc
Becker, Franz-Josef
Tretbar, Steffen
Melzer, Andreas
author_facet Landgraf, Lisa
Kozlowski, Adam
Zhang, Xinrui
Fournelle, Marc
Becker, Franz-Josef
Tretbar, Steffen
Melzer, Andreas
author_sort Landgraf, Lisa
collection PubMed
description SIMPLE SUMMARY: Ultrasound waves can be applied for diagnostic and therapeutic purposes. Focused ultrasound is approved for tissue ablation, e.g., in the treatment of uterine fibroids or essential tremors. Besides the non-invasive image-guided surgical intervention at temperatures above 55 °C, FUS is investigated in other fields like blood-brain barrier opening, hyperthermia, and neuromodulation. FUS offers potential as an adjuvant therapy in cancer treatment. Therefore, analysis of FUS effects on cancer cells is necessary. We performed studies on two human cancer cell line spheroids using a newly developed high-throughput in vitro FUS applicator with 32 individual transducers. This study aimed to perform basic experiments with a new in vitro FUS device on a 3D tumour model to acquire insight into the effects of FUS at the cellular level. These experiments may contribute to a better understanding and predictions of cancer treatment efficacy. ABSTRACT: Focused ultrasound (FUS) is a non-invasive technique producing a variety of biological effects by either thermal or mechanical mechanisms of ultrasound interaction with the targeted tissue. FUS could bring benefits, e.g., tumour sensitisation, immune stimulation, and targeted drug delivery, but investigation of FUS effects at the cellular level is still missing. New techniques are commonly tested in vitro on two-dimensional (2D) monolayer cancer cell culture models. The 3D tumour model—spheroid—is mainly utilised to mimic solid tumours from an architectural standpoint. It is a promising method to simulate the characteristics of tumours in vitro and their various responses to therapeutic alternatives. This study aimed to evaluate the effects of FUS on human prostate and glioblastoma cancer tumour spheroids in vitro. The experimental follow-up enclosed the measurements of spheroid integrity and growth kinetics, DNA damage, and cellular metabolic activity by measuring intracellular ATP content in the spheroids. Our results showed that pulsed FUS treatment induced molecular effects in 3D tumour models. With the disruption of the spheroid integrity, we observed an increase in DNA double-strand breaks, leading to damage in the cancer cells depending on the cancer cell type.
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spelling pubmed-90999052022-05-14 Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model Landgraf, Lisa Kozlowski, Adam Zhang, Xinrui Fournelle, Marc Becker, Franz-Josef Tretbar, Steffen Melzer, Andreas Cells Article SIMPLE SUMMARY: Ultrasound waves can be applied for diagnostic and therapeutic purposes. Focused ultrasound is approved for tissue ablation, e.g., in the treatment of uterine fibroids or essential tremors. Besides the non-invasive image-guided surgical intervention at temperatures above 55 °C, FUS is investigated in other fields like blood-brain barrier opening, hyperthermia, and neuromodulation. FUS offers potential as an adjuvant therapy in cancer treatment. Therefore, analysis of FUS effects on cancer cells is necessary. We performed studies on two human cancer cell line spheroids using a newly developed high-throughput in vitro FUS applicator with 32 individual transducers. This study aimed to perform basic experiments with a new in vitro FUS device on a 3D tumour model to acquire insight into the effects of FUS at the cellular level. These experiments may contribute to a better understanding and predictions of cancer treatment efficacy. ABSTRACT: Focused ultrasound (FUS) is a non-invasive technique producing a variety of biological effects by either thermal or mechanical mechanisms of ultrasound interaction with the targeted tissue. FUS could bring benefits, e.g., tumour sensitisation, immune stimulation, and targeted drug delivery, but investigation of FUS effects at the cellular level is still missing. New techniques are commonly tested in vitro on two-dimensional (2D) monolayer cancer cell culture models. The 3D tumour model—spheroid—is mainly utilised to mimic solid tumours from an architectural standpoint. It is a promising method to simulate the characteristics of tumours in vitro and their various responses to therapeutic alternatives. This study aimed to evaluate the effects of FUS on human prostate and glioblastoma cancer tumour spheroids in vitro. The experimental follow-up enclosed the measurements of spheroid integrity and growth kinetics, DNA damage, and cellular metabolic activity by measuring intracellular ATP content in the spheroids. Our results showed that pulsed FUS treatment induced molecular effects in 3D tumour models. With the disruption of the spheroid integrity, we observed an increase in DNA double-strand breaks, leading to damage in the cancer cells depending on the cancer cell type. MDPI 2022-04-30 /pmc/articles/PMC9099905/ /pubmed/35563823 http://dx.doi.org/10.3390/cells11091518 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Landgraf, Lisa
Kozlowski, Adam
Zhang, Xinrui
Fournelle, Marc
Becker, Franz-Josef
Tretbar, Steffen
Melzer, Andreas
Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model
title Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model
title_full Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model
title_fullStr Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model
title_full_unstemmed Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model
title_short Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model
title_sort focused ultrasound treatment of a spheroid in vitro tumour model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099905/
https://www.ncbi.nlm.nih.gov/pubmed/35563823
http://dx.doi.org/10.3390/cells11091518
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