Evaluation of a tumor electric field treatment system in a rat model of glioma

Wu, Hao; Wang, Chenxi; Liu, Jialin; Zhou, Dajun; Chen, Dikang; Liu, Zhixiong; Wu, Anhua; Yang, Lin; Chang, Jiusheng; Luo, Chengke; Cheng, Wen; Shen, Shuai; Bai, Yun-juan; Mu, Xuetao; Li, Chong; Wang, Zhifei; Chen, Ling

doi:10.1111/cns.13441

Cited by 20 publications

(26 citation statements)

References 32 publications

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“…Permanent neural implants have been clinically available for multiple neurological disorders for years (50) .Simultaneously, an FDA-approved device for glioblastoma now exists (worn on the scalp, powered by a backpack battery, and applies tumor-treating fields) (8) . This is despite its mild benefit on survival in patients (8) and in rats (5.8 ± 2.7 wks median and 10% total survival) (55) . To induce hypothermia, heat must be transported out of the tissue.…”

Section: Discussionmentioning

confidence: 99%

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Cytostatic hypothermia and its impact on glioblastoma and survival

Enam

Kilic

Huang

et al. 2021

Preprint

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Novel therapeutic approaches are needed for patients with recurrent glioblastoma (GBM) who otherwise have limited options. Hypothermia has been used to cryo-ablate tumor locally, but this is ineffective against infiltrative cells as it damages healthy tissue too. Alternatively, here we developed and deployed local ′cytostatic′ hypothermia to stunt GBM growth. We first investigated three grades of hypothermia in vitro and identified a cytostatic window of 20-25°C. We also determined that 18 h/d of cytostatic hypothermia can be sufficient to prevent growth. Cytostatic hypothermia resulted in cell cycle arrest, reduced metabolite production and consumption, and reduced inflammatory cytokine synthesis. We designed a device to deliver local cytostatic hypothermia in vivo in two rodent models of GBM: utilizing the rat F98 and the human U-87 MG lines. Local hypothermia more than doubled the median survival of F98 bearing rats from 3.9 weeks to 9.7 weeks. Two rats survived through 12 weeks. No loss of U-87 MG bearing rats was observed during their study period of 9 weeks. Additionally, we demonstrated that cytostatic hypothermia is synergistic with chemotherapy in vitro. Interestingly, we also demonstrate that CAR T immunotherapy can function with cytostatic hypothermia. Unlike modern targeted therapeutics, cytostatic hypothermia affects multiple cellular processes simultaneously. Thus, irrespective of the host species (e.g., rodent vs. human), it could slow tumor progression and the evolution of resistance. Our studies show that this approach enhances progression-free survival without chemical interventions. However, it may also provide time and opportunities to use standard concomitant, adjuvant, and novel cytotoxic treatments. For these reasons, local cytostatic hypothermia could be a critical addition to the limited options patients with GBM have.

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Section: Discussionmentioning

confidence: 99%

“…Immunotherapy: Briefly, using a previously described protocol (55) , CAR T cells were generated by harvesting splenocytes from mice, and transducing them with a retrovirus that induces CAR T expression specifically targeting EGFRvIII on CT2A tumor cells. CAR T cells were stored in liquid nitrogen 4 days post-transduction.…”

Section: Methodsmentioning

confidence: 99%

Cytostatic hypothermia and its impact on glioblastoma and survival

Enam

Kilic

Huang

et al. 2021

Preprint

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“…Furthermore, combined with radiotherapy [ 20 – 25 ], chemotherapy [ 22 , 26 – 38 ], and other treatments, TTFields obtains better therapeutic effects. As a non-invasive physical therapy, TTFields has mild adverse reactions, mostly grade 1–2 cutaneous adverse reactions such as mild to moderate rash under the electrodes [ 3 , 6 ], erythema, dermatitis, pruritus [ 2 , 4 , 9 , 10 , 14 , 15 , 19 , 39 , 40 ], erosions [ 24 , 41 , 42 ], with no or minimal grade 3 skin adverse events [ 2 , 10 , 14 ]. Reassuringly, these symptoms improve with steroid treatment, electrode replacement, or temporary cessation of TTFields [ 2 , 9 , 10 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…In vitro and in vivo studies have shown that TTFields increase cell death through P53-dependent [ 57 ], reactive oxygen species elevation [ 30 ], caspase-dependent/independent pathways, and O 6 -methylguanine-DNA methyltransferase (MGMT)-independent pathways [ 20 , 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

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The schemes, mechanisms and molecular pathway changes of Tumor Treating Fields (TTFields) alone or in combination with radiotherapy and chemotherapy

et al. 2022

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Tumor Treating Fields (TTFields) is a physical therapy that uses moderate frequency (100–300 kHz) and low-intensity (1–3 V/cm) alternating electric fields to inhibit tumors. Currently, the Food and Drug Administration approves TTFields for treating recurrent or newly diagnosed glioblastoma (GBM) and malignant pleural mesothelioma (MPM). The classical mechanism of TTFields is mitotic inhibition by hindering the formation of tubulin and spindle. In addition, TTFields inhibits cell proliferation, invasion, migration and induces cell death, such as apoptosis, autophagy, pyroptosis, and cell cycle arrest. Meanwhile, it regulates immune function and changes the permeability of the nuclear membrane, cell membrane, and blood-brain barrier. Based on the current researches on TTFields in various tumors, this review comprehensively summarizes the in-vitro effects, changes in pathways and molecules corresponding to relevant parameters of TTFields (frequency, intensity, and duration). In addition, radiotherapy and chemotherapy are common tumor treatments. Thus, we also pay attention to the sequence and dose when TTFields combined with radiotherapy or chemotherapy. TTFields has inhibitory effects in a variety of tumors. The study of TTFields mechanism is conducive to subsequent research. How to combine common tumor therapy such as radiotherapy and chemotherapy to obtain the maximum benefit is also a problem that’s worthy of our attention.

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Millifluidic Nanogenerator Lab‐on‐a‐Chip Device for Blood Electrical Conductivity Monitoring at Low Frequency

Luo,

Lu,

Jang

et al. 2024

Advanced Materials

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The electrical conductivity of blood is a crucial physiological parameter with diverse applications in medical diagnostics. Here, we introduce a novel approach utilizing a portable millifluidic nanogenerator lab‐on‐a‐chip device for measuring blood conductivity at low frequencies. The proposed device employs blood as a conductive substance within its built‐in triboelectric nanogenerator system. Voltage generated by this blood‐based nanogenerator device is analyzed to determine the electrical conductivity of the blood sample. The self‐powering functionality of the device eliminates the need for complex embedded electronics and external electrodes. Experimental results using simulated body fluid and human blood plasma demonstrate the device's efficacy in detecting variations in conductivity related to changes in electrolyte concentrations. Furthermore, we use artificial intelligence models to analyze the generated voltage patterns and to estimate the blood electrical conductivity. The models exhibit high accuracy in predicting conductivity based solely on the device‐generated voltage. The 3D‐printed, disposable design of the device enhances portability and usability, providing a point‐of‐care solution for rapid blood conductivity assessment. A comparative analysis with traditional conductivity measurement methods highlights the advantages of the proposed device in terms of simplicity, portability, and adaptability for various applications beyond blood analysis. Finally, we underscore the importance of overcoming the challenge of measuring blood conductivity at frequencies below 100 Hz using the proposed device for the exploration of fundamental biological processes and the advancement of medical treatments reliant on electrical fields.This article is protected by copyright. All rights reserved

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Evaluation of a tumor electric field treatment system in a rat model of glioma

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 20 publications

References 32 publications

Cytostatic hypothermia and its impact on glioblastoma and survival

Cytostatic hypothermia and its impact on glioblastoma and survival

The schemes, mechanisms and molecular pathway changes of Tumor Treating Fields (TTFields) alone or in combination with radiotherapy and chemotherapy

Millifluidic Nanogenerator Lab‐on‐a‐Chip Device for Blood Electrical Conductivity Monitoring at Low Frequency

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