Protocol for live-cell imaging during Tumor Treating Fields treatment with Inovitro Live

Slangen, Paul; Porat, Yaara; Mertz, Marjolijn; Broek, Bram van den; Jalink, Kees; Gooijer, Mark C. de; Tellingen, Olaf van; Borst, Gerben R.

doi:10.1016/j.xpro.2022.101246

Cited by 4 publications

(3 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several laboratory systems have been developed by Novocure Ltd. to facilitate studies of the effects of TTFields on cultured cells. In our studies, we used the Novocure inovitro™ live system, which allows one to monitor the effects of TTFields on cells in vitro in real time using live-cell imaging [ 42 ]. This system has been used in several past in vitro studies on the effects of TTFields on cancer cells (e.g., Refs.…”

Section: Methodsmentioning

confidence: 99%

Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging

Staelens

Lazzari

et al. 2022

Cells

View full text Add to dashboard Cite

The effects of electric fields (EFs) on various cell types have been thoroughly studied, and exhibit a well-known regulatory effect on cell processes, implicating their usage in several medical applications. While the specific effect exerted on cells is highly parameter-dependent, the majority of past research has focused primarily on low-frequency alternating fields (<1 kHz) and high-frequency fields (in the order of MHz). However, in recent years, low-intensity (1–3 V/cm) alternating EFs with intermediate frequencies (100–500 kHz) have been of topical interest as clinical treatments for cancerous tumours through their disruption of cell division and the mitotic spindle, which can lead to cell death. These aptly named tumour-treating fields (TTFields) have been approved by the FDA as a treatment modality for several cancers, such as malignant pleural mesothelioma and glioblastoma multiforme, demonstrating remarkable efficacy and a high safety profile. In this work, we report the results of in vitro experiments with HeLa and MCF-10A cells exposed to TTFields for 18 h, imaged in real time using live-cell imaging. Both studied cell lines were exposed to 100 kHz TTFields with a 1-1 duty cycle, which resulted in significant mitotic and cytokinetic arrest. In the experiments with HeLa cells, the effects of the TTFields’ frequency (100 kHz vs. 200 kHz) and duty cycle (1-1 vs. 1-0) were also investigated. Notably, the anti-mitotic effect was stronger in the HeLa cells treated with 100 kHz TTFields. Additionally, it was found that single and two-directional TTFields (oriented orthogonally) exhibit a similar inhibitory effect on HeLa cell division. These results provide real-time evidence of the profound ability of TTFields to hinder the process of cell division by significantly delaying both the mitosis and cytokinesis phases of the cell cycle.

show abstract

Section: Methodsmentioning

confidence: 99%

Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging

Staelens

Lazzari

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Thereby, the temperature of the culture dish is continuously measured and the field strength increased until the dish temperature is equilibrated at 37 • C. Different temperatures in incubator and culture dish, however, causes a lower water vapor pressure in the incubator than in the dish, resulting in continuous evaporation from the culture medium. with iso-osmotic cell culture medium, the inovitro TM system in our opinion cannot distinguish between hyperosmotic stress- (Burg et al, 2007;Zhou et al, 2016) and TTFields-mediated cellular effects and hence, the conclusions drawn from the data are limited (discussed also in Slangen et al, 2022). Unfortunately, the majority of the TTFields in vitro data were obtained with the inovitro TM system and published without mentioning the system-inherent weakness of the experimental setup (e.g., Voloshin et al, 2016, Chang et al, 2018Voloshin et al, 2020b;Chen D. et al, 2022).…”

Section: Tumor Treating Fields (Ttfields) a Superweapon Against Gliob...mentioning

confidence: 99%

Ion channels as molecular targets of glioblastoma electrotherapy

Abed

Ganser

Eckert

et al. 2023

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Therapies with weak, non-ionizing electromagnetic fields comprise FDA-approved treatments such as Tumor Treating Fields (TTFields) that are used for adjuvant therapy of glioblastoma. In vitro data and animal models suggest a variety of biological TTFields effects. In particular, effects ranging from direct tumoricidal, radio- or chemotherapy-sensitizing, metastatic spread-inhibiting, up to immunostimulation have been described. Diverse underlying molecular mechanisms, such as dielectrophoresis of cellular compounds during cytokinesis, disturbing the formation of the spindle apparatus during mitosis, and perforating the plasma membrane have been proposed. Little attention, however, has been paid to molecular structures that are predestinated to percept electromagnetic fields—the voltage sensors of voltage-gated ion channels. The present review article briefly summarizes the mode of action of voltage sensing by ion channels. Moreover, it introduces into the perception of ultra-weak electric fields by specific organs of fishes with voltage-gated ion channels as key functional units therein. Finally, this article provides an overview of the published data on modulation of ion channel function by diverse external electromagnetic field protocols. Combined, these data strongly point to a function of voltage-gated ion channels as transducers between electricity and biology and, hence, to voltage-gated ion channels as primary targets of electrotherapy.

show abstract

“…necroptosis and ferroptosis). A recent work by Slangen et al. (2022) , which provides a protocol for live cell imaging during TTFields exposure, could provide a means to understand the temporal dynamics of TTFields initiation and its downstream effects.…”

Section: Future Directionsmentioning

confidence: 99%

Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields])

Shams

2022

Journal of Molecular Cell Biology

View full text Add to dashboard Cite

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Although the pre-clinical and clinical data are promising, the mechanisms of TTFields are not fully elucidated. Many investigations are underway to better understand how and why TTFields is able to selectively kill cancer cells and impede their proliferation. The purpose of this review is to summarize and discuss the reported mechanisms of action of TTFields from pre-clinical studies (both in vitro and in vivo). An improved understanding of how TTFields works will guide strategies focused on the timing and combination of TTFields with other therapies, to further improve survival outcomes in patients with solid organ cancers.

show abstract

Protocol for live-cell imaging during Tumor Treating Fields treatment with Inovitro Live

Cited by 4 publications

References 3 publications

Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging

Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging

Ion channels as molecular targets of glioblastoma electrotherapy

Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields])

Contact Info

Product

Resources

About