On the Effects of 30.5 GHz Sinusoidal Wave Exposure on Glioblastoma Organoids

Overview

Journal Front Oncol

Specialty Oncology

Date 2024 Jun 17

PMID 38884089

Authors

Elena Rampazzo

Luca Persano

Nissar Karim

George Hodgking

Rosanna Pinto

Arianna Casciati

Mirella Tanori

Alessandro Zambotti

Silvia Bresolin

Alice Cani

Alessandro Pannicelli

Ilan W Davies

Cristopher Hancock

Cristiano Palego

Giampietro Viola

Mariateresa Mancuso

Caterina Merla

Affiliations

Soon will be listed here.

Abstract

Introduction: Glioblastoma (grade IV) is the most aggressive primary brain tumor in adults, representing one of the biggest therapeutic challenges due to its highly aggressive nature. In this study, we investigated the impact of millimeter waves on tridimensional glioblastoma organoids derived directly from patient tumors. Our goal was to explore novel therapeutic possibilities in the fight against this challenging disease.

Methods: The exposure setup was meticulously developed in-house, and we employed a comprehensive dosimetry approach, combining numerical and experimental methods. Biological endpoints included a global transcriptional profiling analysis to highlight possible deregulated pathways, analysis of cell morphological changes, and cell phenotypic characterization which are all important players in the control of glioblastoma progression.

Results And Discussion: Our results revealed a significant effect of continuous millimeter waves at 30.5 GHz on cell proliferation and apoptosis, although without affecting the differentiation status of glioblastoma cells composing the organoids. Excitingly, when applying a power level of 0.1 W (Root Mean Square), we discovered a remarkable (statistically significant) therapeutic effect when combined with the chemotherapeutic agent Temozolomide, leading to increased glioblastoma cell death. These findings present a promising interventional window for treating glioblastoma cells, harnessing the potential therapeutic benefits of 30.5 GHz CW exposure. Temperature increase during treatments was carefully monitored and simulated with a good agreement, demonstrating a negligible involvement of the temperature elevation for the observed effects. By exploring this innovative approach, we pave the way for improved future treatments of glioblastoma that has remained exceptionally challenging until now.

References

Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M . Long-term survival with glioblastoma multiforme. Brain. 2007; 130(Pt 10):2596-606. DOI: 10.1093/brain/awm204. View

Hubert C, Rivera M, Spangler L, Wu Q, Mack S, Prager B . A Three-Dimensional Organoid Culture System Derived from Human Glioblastomas Recapitulates the Hypoxic Gradients and Cancer Stem Cell Heterogeneity of Tumors Found In Vivo. Cancer Res. 2016; 76(8):2465-77. PMC: 4873351. DOI: 10.1158/0008-5472.CAN-15-2402. View

Jenkins E, Finch A, Gerigk M, Triantis I, Watts C, Malliaras G . Electrotherapies for Glioblastoma. Adv Sci (Weinh). 2021; 8(18):e2100978. PMC: 8456216. DOI: 10.1002/advs.202100978. View

Tanori M, Casciati A, Zambotti A, Pinto R, Gianlorenzi I, Pannicelli A . Microsecond Pulsed Electric Fields: An Effective Way to Selectively Target and Radiosensitize Medulloblastoma Cancer Stem Cells. Int J Radiat Oncol Biol Phys. 2021; 109(5):1495-1507. DOI: 10.1016/j.ijrobp.2020.11.047. View

Lancaster M, Knoblich J . Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc. 2014; 9(10):2329-40. PMC: 4160653. DOI: 10.1038/nprot.2014.158. View

Kaina B, Beltzig L, Strik H . Temozolomide - Just a Radiosensitizer?. Front Oncol. 2022; 12:912821. PMC: 9246413. DOI: 10.3389/fonc.2022.912821. View

Pistollato F, Abbadi S, Rampazzo E, Persano L, Della Puppa A, Frasson C . Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma. Stem Cells. 2010; 28(5):851-62. DOI: 10.1002/stem.415. View

Paffi A, Liberti M, Apollonio F, Sheppard A, Balzano Q . In vitro exposure: Linear and non-linear thermodynamic events in Petri dishes. Bioelectromagnetics. 2015; 36(7):527-37. DOI: 10.1002/bem.21923. View

Eisenbarth D, Wang Y . Glioblastoma heterogeneity at single cell resolution. Oncogene. 2023; 42(27):2155-2165. PMC: 10913075. DOI: 10.1038/s41388-023-02738-y. View

10.

Woehrer A, Bauchet L, Barnholtz-Sloan J . Glioblastoma survival: has it improved? Evidence from population-based studies. Curr Opin Neurol. 2014; 27(6):666-74. DOI: 10.1097/WCO.0000000000000144. View

11.

. Guidelines for Limiting Exposure to Electromagnetic Fields (100 kHz to 300 GHz). Health Phys. 2020; 118(5):483-524. DOI: 10.1097/HP.0000000000001210. View

12.

Facciorusso A, Abd El Aziz M, Tartaglia N, Ramai D, Mohan B, Cotsoglou C . Microwave Ablation Versus Radiofrequency Ablation for Treatment of Hepatocellular Carcinoma: A Meta-Analysis of Randomized Controlled Trials. Cancers (Basel). 2020; 12(12). PMC: 7766963. DOI: 10.3390/cancers12123796. View

13.

Zhadobov M, Alekseev S, Le Drean Y, Sauleau R, Fesenko E . Millimeter waves as a source of selective heating of skin. Bioelectromagnetics. 2015; 36(6):464-75. DOI: 10.1002/bem.21929. View

14.

Casciati A, Tanori M, Gianlorenzi I, Rampazzo E, Persano L, Viola G . Effects of Ultra-Short Pulsed Electric Field Exposure on Glioblastoma Cells. Int J Mol Sci. 2022; 23(6). PMC: 8950115. DOI: 10.3390/ijms23063001. View

15.

Rampazzo E, Manfreda L, Bresolin S, Cani A, Mariotto E, Bortolozzi R . Histone Deacetylase Inhibitors Impair Glioblastoma Cell Motility and Proliferation. Cancers (Basel). 2022; 14(8). PMC: 9027190. DOI: 10.3390/cancers14081897. View

16.

Stupp R, Mason W, van den Bent M, Weller M, Fisher B, Taphoorn M . Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10):987-96. DOI: 10.1056/NEJMoa043330. View

17.

Merla C, Liberti M, Marracino P, Muscat A, Azan A, Apollonio F . A wide-band bio-chip for real-time optical detection of bioelectromagnetic interactions with cells. Sci Rep. 2018; 8(1):5044. PMC: 5864909. DOI: 10.1038/s41598-018-23301-w. View

18.

Hancock C, Chaudhry S, Wall P, Goodman A . Proof of concept percutaneous treatment system to enable fast and finely controlled ablation of biological tissue. Med Biol Eng Comput. 2007; 45(6):531-40. DOI: 10.1007/s11517-007-0184-z. View

19.

Le Pogam P, Le Page Y, Habauzit D, Doue M, Zhadobov M, Sauleau R . Untargeted metabolomics unveil alterations of biomembranes permeability in human HaCaT keratinocytes upon 60 GHz millimeter-wave exposure. Sci Rep. 2019; 9(1):9343. PMC: 6597695. DOI: 10.1038/s41598-019-45662-6. View

20.

Sugiyama J, Tokunaga Y, Hishida M, Tanaka M, Takeuchi K, Satoh D . Nonthermal acceleration of protein hydration by sub-terahertz irradiation. Nat Commun. 2023; 14(1):2825. PMC: 10203368. DOI: 10.1038/s41467-023-38462-0. View