The effect of modulated electro-hyperthermia on temperature and blood flow in human cervical carcinoma

Lee, Sun Young; Kim, Jong-Hun; Han, Young Jin; Cho, Dong‐Hyu

doi:10.1080/02656736.2018.1423709

Cited by 51 publications

(55 citation statements)

References 26 publications

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“…Radiation therapy (RT) induces counter-effective hypoxia, which activates hypoxia-inducible factor-1a (HIF-1a) and its target genes, e.g., vascular endothelial growth factor (VEGF) [ 87 ]. On the contrary, loco-regional hyperthermia, including mEHT, can increase tumor perfusion and oxygenation, which promote the efficiency of RT-induced DNA breaks and inhibition of DNA repair mechanisms [ 88 , 89 ]. The mEHT treatment (41 °C for 30 min) immediately followed by 15 Gy (60Co) RT resulted in the most reduced growth of FSaII mouse fibrosarcoma allografts in C3H mice compared to mEHT or RT alone, or when these were combined in the opposite order [ 39 , 88 , 89 ].…”

Section: Combination With Radiotherapymentioning

confidence: 99%

“…On the contrary, loco-regional hyperthermia, including mEHT, can increase tumor perfusion and oxygenation, which promote the efficiency of RT-induced DNA breaks and inhibition of DNA repair mechanisms [ 88 , 89 ]. The mEHT treatment (41 °C for 30 min) immediately followed by 15 Gy (60Co) RT resulted in the most reduced growth of FSaII mouse fibrosarcoma allografts in C3H mice compared to mEHT or RT alone, or when these were combined in the opposite order [ 39 , 88 , 89 ]. Hypoxic areas labelled with pimonidazole were reduced so those of Hif-1a, CaIX (carboanhydrase IX), and Vegf levels, while blood perfusion assessed with Hoechst 33,342 as well as the apoptosis were increased more than with any other tested options.…”

Section: Combination With Radiotherapymentioning

confidence: 99%

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Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

Krenács

Meggyesházi

Forika

et al. 2020

IJMS

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The benefits of high-fever range hyperthermia have been utilized in medicine from the Ancient Greek culture to the present day. Amplitude-modulated electro-hyperthermia, induced by a 13.56 MHz radiofrequency current (mEHT, or Oncothermia), has been an emerging means of delivering loco-regional clinical hyperthermia as a complementary of radiation-, chemo-, and molecular targeted oncotherapy. This unique treatment exploits the metabolic shift in cancer, resulting in elevated oxidative glycolysis (Warburg effect), ion concentration, and electric conductivity. These promote the enrichment of electric fields and induce heat (controlled at 42 °C), as well as ion fluxes and disequilibrium through tumor cell membrane channels. By now, accumulating preclinical studies using in vitro and in vivo models of different cancer types have revealed details of the mechanism and molecular background of the oncoreductive effects of mEHT monotherapy. These include the induction of DNA double-strand breaks, irreversible heath and cell stress, and programmed cells death; the upregulation of molecular chaperones and damage (DAMP) signaling, which may contribute to a secondary immunogenic tumor cell death. In combination therapies, mEHT proved to be a good chemosensitizer through increasing drug uptake and tumor reductive effects, as well as a good radiosensitizer by downregulating hypoxia-related target genes. Recently, immune stimulation or intratumoral antigen-presenting dendritic cell injection have been able to extend the impact of local mEHT into a systemic “abscopal” effect. The complex network of pathways emerging from the published mEHT experiments has not been overviewed and arranged yet into a framework to reveal links between the pieces of the “puzzle”. In this paper, we review the mEHT-related damage mechanisms published in tumor models, which may allow some geno-/phenotype treatment efficiency correlations to be exploited both in further research and for more rational clinical treatment planning when mEHT is involved in combination therapies.

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Section: Combination With Radiotherapymentioning

confidence: 99%

Section: Combination With Radiotherapymentioning

confidence: 99%

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

Krenács

Meggyesházi

Forika

et al. 2020

IJMS

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“…The safety and heating efficacy of mEHT in cervical cancer patients has been demonstrated (18)(19)(20). Minnaar et al (19) reported on local disease control in an ongoing randomized controlled trial investigating the effects of the addition of mEHT to chemoradiotherapy (CRT) protocols for the treatment of LACC.…”

Section: Introductionmentioning

confidence: 99%

Potentiation of the Abscopal Effect by Modulated Electro-Hyperthermia in Locally Advanced Cervical Cancer Patients

et al. 2020

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“…All appropriate vital sign monitoring during and after treatment was conducted as per standard practice. With this technique, intratumoral temperature measurement is typically not performed because the temperature elevation measured by a conventional thermocouple is usually <2 • C (28). Adverse events were assessed throughout each treatment, which included heat sensitivity, skin burning, pain, and gastric discomfort.…”

Section: Hyperthermia (Meht)mentioning

confidence: 99%

Putative Abscopal Effect in Three Patients Treated by Combined Radiotherapy and Modulated Electrohyperthermia

Shin

Mehta²,

Yang

et al. 2020

Front. Oncol.

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True abscopal responses from radiation therapy are extremely rare; the combination of immune checkpoint inhibitors with radiation therapy has led to more reports of the abscopal effect, but even in this setting, the genuine magnitude remains unknown and is still considered generally uncommon. We report the occurrence of what appears to be putative, durable abscopal tumor responses with associated auto-immune systemic reactions resulting from the combination of local radiotherapy (RT) and modulated electrohyperthermia (mEHT). Materials and Methods: Data from advanced cancer patients treated palliatively with RT and mEHT between January and December 2017 were collected as part of a post-marketing safety monitoring program of mEHT therapy. We specified a minimum RT dose of 30 Gy and at least four mEHT treatments for reporting toxicities, which was the primary aim of the larger study. Results: Thirty-three patients treated with RT and mEHT, both applied to the same lesion, were included. The median RT dose was 45.5 Gy in 20 fractions (fxs) and the median number of mEHT treatments was 12 (range, 4-20). Most patients had subsequent systemic therapy after one course of RT and mEHT. Three patients (9.1%) developed autoimmune toxicities. Case number 1 received RT and mEHT only; case number 2 had two cycles of concurrent low dose chemotherapy during RT; and case number 3 received concurrent immune checkpoint inhibitors. None of the three patients received any further systemic treatment due to obvious treatment-related autoimmune reactions which occurred rapidly after RT; one had autoimmune hepatitis, one had dermatitis herpetiformis and the third developed severe myasthenia gravis. Interestingly, what we surmise to be long-lasting abscopal responses outside the irradiated area, were noted in all three patients. Conclusion: RT combined with mEHT could putatively result in enhancing immune responsiveness. These preliminary observational findings lead to the generation of a hypothesis that this combination induces both an in-situ, tumor-specific immune reaction Chi et al. RT-mEHT Unleashed Autoimmune-Mediated Abscopal Effect and an anti-self-autoimmune reaction, in at least a small proportion of patients, and of those who experience the auto-immune response, tumor response is a concomitant finding. Mechanisms underlying this phenomenon need to be investigated further.

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The effect of modulated electro-hyperthermia on temperature and blood flow in human cervical carcinoma

Cited by 51 publications

References 26 publications

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

Potentiation of the Abscopal Effect by Modulated Electro-Hyperthermia in Locally Advanced Cervical Cancer Patients

Putative Abscopal Effect in Three Patients Treated by Combined Radiotherapy and Modulated Electrohyperthermia

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