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1.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36769173

RESUMO

In the human environment, the increasing exposure to radiofrequency (RF) radiation, especially that emitted by wireless devices, could be absorbed in the body. Recently, mobile and emerging wireless technologies (UMTS, DECT, LTE, and Wi-Fi) have been using higher frequencies than 2G GSM systems (900/1800 MHz), which means that most of the circulating RF currents are absorbed into the skin and the superficial soft tissue. The harmful genotoxic, cytotoxic, and mutagenic effects of solar ultraviolet (UV) radiation on the skin are well-known. This study aimed at investigating whether 2422 MHz (Wi-Fi) RF exposure combined with UV radiation in different sequences has any effect on the inflammation process in the skin. In vitro experiments examined the inflammation process by cytokines (IL-1α, IL-6, IL-8) and MMP-1 enzyme secretion in a 3D full-thickness human skin model. In the first study, UV exposure was immediately followed by RF exposure to measure the potential additive effects, while in the second study, the possible protective phenomenon (i.e., adaptive response) was investigated when adaptive RF exposure was challenged by UV radiation. Our results suggest that 2422 MHz Wi-Fi exposure slightly, not significantly increased cytokine concentrations of the prior UV exposure. We could not detect the adaptive response phenomenon.


Assuntos
Inflamação , Ondas de Rádio , Humanos , Ondas de Rádio/efeitos adversos , Raios Ultravioleta/efeitos adversos , Pele , Citocinas
2.
Bioelectromagnetics ; 41(4): 308-317, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32043629

RESUMO

The expected imminent widespread use of electromobility in transport systems draws attention to the possible effects of human exposure to magnetic fields generated inside electric vehicles and during their recharge. The current trend is to increase the capacity of the battery inside the vehicles to extend the available driving range and to increase the power of recharging columns to reduce the time required for a full recharge. This leads to higher currents and potentially stronger magnetic fields. The Interoperability Center of the Joint Research Center started an experimental activity focused on the assessment of low-frequency magnetic fields emitted by five fast-charging devices available on the market in recharge and standby conditions. The aim of this study was to contribute to the development of a standard measurement procedure for the assessment of magnetic fields emitted by direct current charging columns. The spectrum and amplitudes of the magnetic field, as well as exposure indices according to guidelines for the general public and occupational exposure, were recorded by means of a magnetic field probe analyzer. The worst-case scenario for instantaneous physical direct and indirect effects was identified. Measurements within the frequency range of 25 Hz-2 kHz revealed localized magnetic flux density peaks above 100 µT at the 50 Hz frequency in three out of five chargers, registered in close proximity during the recharge. Beyond this distance, exposure indices were recorded showing values below 50% of reference levels. Bioelectromagnetics. 2020;41:308-317 © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.


Assuntos
Fontes de Energia Elétrica/efeitos adversos , Campos Eletromagnéticos , Automóveis
3.
Int J Hyperthermia ; 33(1): 101-109, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27439333

RESUMO

PURPOSE: The aim of this study was to develop a predictive model of the shrinkage of liver tissues in microwave ablation. METHODS: Thirty-seven cuboid specimens of ex vivo bovine liver of size ranging from 2 cm to 8 cm were heated exploiting different techniques: 1) using a microwave oven (2.45 GHz) operated at 420 W, 500 W and 700 W for 8 to 20 min, achieving complete carbonisation of the specimens, 2) using a radiofrequency ablation apparatus (450 kHz) operated at 70 W for a time ranging from 6 to 7.5 min obtaining white coagulation of the specimens, and 3) using a microwave (2.45 GHz) ablation apparatus operated at 60 W for 10 min. Measurements of specimen dimensions, carbonised and coagulated regions were performed using a ruler with an accuracy of 1 mm. Based on the results of the first two experiments a predictive model for the contraction of liver tissue from microwave ablation was constructed and compared to the result of the third experiment. RESULTS: For carbonised tissue, a linear contraction of 31 ± 6% was obtained independently of the heating source, power and operation time. Radiofrequency experiments determined that the average percentage linear contraction of white coagulated tissue was 12 ± 5%. The average accuracy of our model was determined to be 3 mm (5%). CONCLUSIONS: The proposed model allows the prediction of the shrinkage of liver tissues upon microwave ablation given the extension of the carbonised and coagulated zones. This may be useful in helping to predict whether sufficient tissue volume is ablated in clinical practice.


Assuntos
Técnicas de Ablação , Hipertermia Induzida , Fígado/cirurgia , Micro-Ondas , Modelos Biológicos , Animais , Bovinos
4.
Bioelectromagnetics ; 37(4): 201-11, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26992028

RESUMO

This study investigates effects of gradient magnetic fields (GMFs) emitted by magnetic resonance imaging (MRI) devices on hematopoietic stem cells. Field measurements were performed to assess exposure to GMFs of staff working at 1.5 T and 3 T MRI units. Then an exposure system reproducing measured signals was realized to expose in vitro CD34+ cells to GMFs (1.5 T-protocol and 3 T-protocol). CD34+ cells were obtained by Fluorescence Activated Cell Sorting from six blood donors and three MRI-exposed workers. Blood donor CD34+ cells were exposed in vitro for 72 h to 1.5 T or 3 T-protocol and to sham procedure. Cells were then cultured and evaluated in colony forming unit (CFU)-assay up to 4 weeks after exposure. Results showed that in vitro GMF exposure did not affect cell proliferation but instead induced expansion of erythroid and monocytes progenitors soon after exposure and for the subsequent 3 weeks. No decrease of other clonogenic cell output (i.e., CFU-granulocyte/erythroid/macrophage/megakaryocyte and CFU-granulocyte/macrophage) was noticed, nor exposed CD34+ cells underwent the premature exhaustion of their clonogenic potential compared to sham-exposed controls. On the other hand, pilot experiments showed that CD34+ cells exposed in vivo to GMFs (i.e., samples from MRI workers) behaved in culture similarly to sham-exposed CD34+ cells, suggesting that other cells and/or microenvironment factors might prevent GMF effects on hematopoietic stem cells in vivo. Accordingly, GMFs did not affect the clonogenic potential of umbilical cord blood CD34+ cells exposed in vitro together with the whole mononuclear cell fraction.


Assuntos
Ensaio de Unidades Formadoras de Colônias , Células-Tronco Hematopoéticas/citologia , Campos Magnéticos/efeitos adversos , Espectroscopia de Ressonância Magnética/instrumentação , Adulto , Antígenos CD34/metabolismo , Células Eritroides/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/citologia
5.
Int J Hyperthermia ; 31(1): 48-57, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25677838

RESUMO

PURPOSE: The aim of this study was to numerically and experimentally characterise the influence of tissues dimensions on the size and shape of microwave-induced ablation zones. MATERIALS AND METHODS: A 2.45 GHz interstitial antenna was introduced into ex vivo bovine liver samples, delivering 60 W for 10 min; then the dimensions of the coagulated area were measured. Ablations were performed both in large samples (termed unrestricted tissue) for characterising the tissue response, and in thin samples, whose dimensions in the plane perpendicular to the antenna were smaller than the short axis of the ablated area obtained in unrestricted samples. In the numerical study the electromagnetic field emitted from the antenna and the corresponding temperature increase were evaluated in both unrestricted and thin tissue samples. RESULTS: When the height of the tissue was smaller than the ablation diameter measured in unrestricted samples, a 7.5% increase in length of the ablated zone was experimentally observed. When both the height and width were lower than the diameter measured in unrestricted samples, an elongation of about 23.4% was experimentally obtained. The numerical study showed that the boundary conditions between the target tissue and the surrounding materials are critical. CONCLUSIONS: The ex vivo performances of microwave ablation devices are notably influenced by the shape and dimension of the tissues where the procedure takes place. Accordingly, dedicated interventional protocols should be developed for treatment planning on targets of different shape and size.


Assuntos
Ablação por Cateter , Fígado/anatomia & histologia , Fígado/cirurgia , Micro-Ondas , Animais , Bovinos , Modelos Teóricos , Tamanho do Órgão
6.
Int J Hyperthermia ; 30(2): 110-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24571174

RESUMO

PURPOSE: This work focuses on the characterisation of the ablated area induced by a microwave thermal ablation (MTA) procedure. An experimental methodology for establishing a straightforward correlation between the temperature gradient and the changes in the dielectric properties of the tissue is presented and discussed. MATERIALS AND METHODS: Temperature measurements were performed during an ablation procedure in ex vivo bovine liver, at different distances from the antenna, whereas measurements of complex permittivity were conducted in sagittal sections of the ablated samples. The measured temperatures and dielectric properties were then correlated to obtain the dependence of the dielectric properties' spatial variation on the temperature gradient. The obtained correlation has been validated through comparison with previously obtained experimental data. A weighted cubic polynomial function and a weighted sigmoid function have been tested for best-fit interpolation of the measured data. RESULTS: Temperatures in the range 23-105 °C were measured during the MTA procedure, while, after the end of the MTA trials, relative permittivities in the range 7-43 and electric conductivities in the range 0.3-1.8 S/m were measured according to the distance from the antenna's axis. The polynomial function showed better regression coefficients than the sigmoid one for both the relative permittivity (R(2 )= 0.9947 versus R(2 )= 0.9912, respectively) and the conductivity (R(2 )= 0.9919 versus R(2 )= 0.9866, respectively). However, the weighted cubic function showed an unrealistic behaviour for the relative permittivity at temperatures lower than 40 °C. CONCLUSIONS: According to the results obtained, information on the changes in the dielectric properties of the tissue under MTA treatment could be inferred from measured temperature data. Once validated by in vivo studies, the proposed methodology could be exploited to develop predictive tools for treatment planning.


Assuntos
Técnicas de Ablação , Fígado/efeitos da radiação , Micro-Ondas , Animais , Bovinos , Temperatura Alta , Fígado/cirurgia , Modelos Teóricos
7.
Int J Hyperthermia ; 30(7): 419-28, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25323026

RESUMO

PURPOSE: The aim of this study was to characterise changes in tissue volume during image-guided microwave ablation in order to arrive at a more precise determination of the true ablation zone. MATERIALS AND METHODS: The effect of power (20-80 W) and time (1-10 min) on microwave-induced tissue contraction was experimentally evaluated in various-sized cubes of ex vivo liver (10-40 mm ± 2 mm) and muscle (20 and 40 mm ± 2 mm) embedded in agar phantoms (N = 119). Post-ablation linear and volumetric dimensions of the tissue cubes were measured and compared with pre-ablation dimensions. Subsequently, the process of tissue contraction was investigated dynamically during the ablation procedure through real-time X-ray CT scanning. RESULTS: Overall, substantial shrinkage of 52-74% of initial tissue volume was noted. The shrinkage was non-uniform over time and space, with observed asymmetry favouring the radial (23-43 % range) over the longitudinal (21-29%) direction. Algorithmic relationships for the shrinkage as a function of time were demonstrated. Furthermore, the smallest cubes showed more substantial and faster contraction (28-40% after 1 min), with more considerable volumetric shrinkage (>10%) in muscle than in liver tissue. Additionally, CT imaging demonstrated initial expansion of the tissue volume, lasting in some cases up to 3 min during the microwave ablation procedure, prior to the contraction phenomenon. CONCLUSIONS: In addition to an asymmetric substantial shrinkage of the ablated tissue volume, an initial expansion phenomenon occurs during MW ablation. Thus, complex modifications of the tissue close to a radiating antenna will likely need to be taken into account for future methods of real-time ablation monitoring.


Assuntos
Fígado/efeitos da radiação , Micro-Ondas , Músculos/efeitos da radiação , Animais , Bovinos , Imagens de Fantasmas , Perus
8.
Bioelectromagnetics ; 35(4): 309-12, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24482311

RESUMO

Recently, the use of liposomes loaded with magnetic nanoparticles (magnetoliposomes, (MLs)) has been intensely growing as a new drug delivery system. With the use of alternating magnetic fields, it is possible to remotely control the delivery of a drug or any other macromolecule loaded inside the MLs. In this experiment, the release of a fluorescent dye from MLs is achieved through an alternating magnetic field of 20 kHz and amplitude below 100 A/m, and without a macroscopic temperature increase.


Assuntos
Lipossomos , Campos Magnéticos , Nanopartículas Metálicas/administração & dosagem , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Projetos Piloto , Temperatura
9.
Artigo em Inglês | MEDLINE | ID: mdl-39200630

RESUMO

In this systematic review, the potential role of in vivo RF-EMF exposure combined with the administration of well-known carcinogens in tumor promotion/progression is assessed. A total of 25 papers were included in the review. Each paper was assessed for Risk of Bias and for the attribution of the quality category. A meta-analysis was conducted on 18 studies, analyzing data for nine different organs/tumors to assess the potential increased risk for the onset of tumors as well as the effects on survival. A descriptive review was performed for the remaining seven eligible papers. In most cases, the results of the meta-analysis did not reveal a statistically significant difference in tumor onset between the sham and co-exposed samples. There was a numerically small increase in the risk of malignant tumors observed in the kidney and liver, as well as benign lung tumors. The level of evidence for health effects indicated "inadequate" evidence for an association between in vivo co-exposure to RF-EMF and known carcinogens and the onset of malignant or benign tumors in most of the analyzed tissues. Nevertheless, the limited number of eligible papers/studies for most of the analyzed tissues suggests that these results cannot be considered definitively conclusive.


Assuntos
Campos Eletromagnéticos , Ondas de Rádio , Humanos , Ondas de Rádio/efeitos adversos , Campos Eletromagnéticos/efeitos adversos , Animais , Carcinogênese/efeitos da radiação , Carcinógenos/toxicidade , Neoplasias/etiologia
10.
Front Oncol ; 14: 1307516, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884089

RESUMO

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.

11.
Bioelectromagnetics ; 34(3): 211-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23060274

RESUMO

In occupational environments, an increasing number of electromagnetic sources emitting complex magnetic field waveforms in the range of intermediate frequencies is present, requiring an accurate exposure risk assessment with both in vitro and in vivo experiments. In this article, an in vitro exposure system able to generate complex magnetic flux density B-fields, reproducing signals from actual intermediate frequency sources such as magnetic resonance imaging (MRI) scanners, for instance, is developed and validated. The system consists of a magnetic field generation system and an exposure apparatus realized with a couple of square coils. A wide homogeneity (99.9%) volume of 210 × 210 × 110 mm(3) was obtained within the coils, with the possibility of simultaneous exposure of a large number of standard Petri dishes. The system is able to process any numerical input sequence through a filtering technique aimed at compensating the coils' impedance effect. The B-field, measured in proximity to a 1.5 T MRI bore during a typical examination, was excellently reproduced (cross-correlation index of 0.99). Thus, it confirms the ability of the proposed setup to accurately simulate complex waveforms in the intermediate frequency band. Suitable field levels were also attained. Moreover, a dosimetry index based on the weighted-peak method was evaluated considering the induced E-field on a Petri dish exposed to the reproduced complex B-field. The weighted-peak index was equal to 0.028 for the induced E-field, indicating an exposure level compliant with the basic restrictions of the International Commission on Non-Ionizing Radiation Protection. Bioelectromagnetics 34:211-219, 2013. © 2012 Wiley Periodicals, Inc.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/efeitos adversos , Radiometria/métodos , Fenômenos Eletromagnéticos , Humanos , Imageamento por Ressonância Magnética , Doses de Radiação
12.
Artigo em Inglês | MEDLINE | ID: mdl-36767440

RESUMO

The increasing exposure of the human population to radiofrequency electromagnetic fields has increased concern about its possible health effects. The aim of this systematic review is to provide an update of the state of the research on this topic, through a quantitative analysis, to assess the increased risk of tumor incidence in laboratory animals (rodents) without limitations of species, strain, sex or genotype. The review was conducted according to the PRISMA guideline and individual studies were assessed by referring to the OHAT Risk of Bias Rating Tool for Human and Animal Studies. A total of 27 studies were considered eligible for the evaluation of tumor incidence; a meta-analysis was carried out on 23 studies to assess the possible increased risk of both malignant and benign tumors onset at the systemic level or in different organs/tissues. A significant association between exposure to RF and the increased/decreased risk of cancer does not result from the meta-analysis in most of considered tissues. A significant increased/decreased risk can be numerically observed only in heart, CNS/brain, and intestine for malignant tumors. Nevertheless, the assessment of the body of evidence attributes low or inadequate evidence for an association between RF exposure and the onset of neoplasm in all tissues.


Assuntos
Campos Eletromagnéticos , Neoplasias , Animais , Humanos , Campos Eletromagnéticos/efeitos adversos , Ondas de Rádio/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/etiologia , Encéfalo , Incidência
13.
Bioelectromagnetics ; 33(8): 652-61, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22556007

RESUMO

Wireless local area networks are an increasing alternative to wired data networks in workplaces, homes, and public areas. Concerns about possible health effects of this type of signal, especially when exposure occurs early in life, have been raised. We examined the effects of prenatal (in utero) exposure to wireless fidelity (WiFi) signal-associated electromagnetic fields (2450 MHz center-frequency band) on T cell development and function. Pregnant mice were exposed whole body to a specific absorption rate of 4 W/kg, 2 h per day, starting 5 days after mating and ending 1 day before the expected delivery. Sham-exposed and cage control groups were used as controls. No effects on cell count, phenotype, and proliferation of thymocytes were observed. Also, spleen cell count, CD4/CD8 cell frequencies, T cell proliferation, and cytokine production were not affected by the exposure. These findings were consistently observed in the male and female offspring at early (5 weeks of age) and late (26 weeks of age) time points. Nevertheless, the expected differences associated with aging and/or gender were confirmed. In conclusion, our results do not support the hypothesis that the exposure to WiFi signals during prenatal life results in detrimental effects on the immune T cell compartment.


Assuntos
Feto/imunologia , Feto/efeitos da radiação , Ondas de Rádio/efeitos adversos , Timócitos/citologia , Timócitos/efeitos da radiação , Tecnologia sem Fio , Animais , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Citocinas/biossíntese , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Gravidez , Timócitos/imunologia , Timócitos/metabolismo , Timo/citologia , Timo/efeitos da radiação
14.
Syst Rev ; 11(1): 29, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35172887

RESUMO

BACKGROUND: An Italian project aims to review the scientific literature on the possible carcinogenicity of radiofrequency (100 kHz-300 GHz) electromagnetic field (RF-EMF) exposure. The ENEA team has to carry out a systematic review of the in vivo studies on this topic. OBJECTIVES: Development of a protocol for a systematic review (meta-analysis included) to investigate the potential carcinogenic risk following RF-EMF in vivo exposure to doses above or within legal limits. The aims of this review are (1) to provide a descriptive and, if possible, a quantitative summary of the results of the examined RF-EMF in vivo studies, together with an assessment of the consistency of observations and of the causes of heterogeneity, and (2) to assess the weight of evidence to support or refute the hypothesis of carcinogenic effects caused by RF-EMF exposure and to draw conclusions about the potential for carcinogenicity of RF-EMF exposure. METHODS: We will search for relevant studies in electronic academic databases and in the reference list of selected papers and reviews on the topic, including the descriptive reviews on RF-EMF carcinogenic effect carried out by international panels of experts since 2011. The following elements of the PECO question were defined: experimental studies on rodents of both sexes, all ages and species, all genetic backgrounds (Population) exposed to RF-EMF alone, or in combination with other physical or chemical agents (Exposure); only studies reporting outcome data in exposed and sham control groups (Comparison); and all types of cancer with all tumor-related outcome measures (Outcome) will be included. Only peer-reviewed articles written in English will be considered without limit in the publication date. Eligibility criteria were defined for papers to be included. A risk of bias assessment will be performed using a tool specifically developed for animal studies. A meta-analysis will be performed, if feasible, for all outcome measures; for subgroup analysis, a minimum of 3 studies per subgroup will be required. If meta-analysis will not be possible, a narrative synthesis of the results will be reported. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020191105 HIGHLIGHTS: An Italian collaborative research agreement aims to review the scientific literature on the possible carcinogenicity of RF-EMF (100 kHz - 300 GHz). The ENEA team will systematically review and, if possible, meta-analyse estimates the effects of in vivo exposure to RF-EMF exposure on cancer. The ENEA group is a multidisciplinary team of researchers with a consolidated experience both in carcinogenicity experiments and radiofrequency dosimetric assessment. The proposed protocol uses the NTP OHAT Approach for Systematic Review as an organizing framework. The proposed protocol aims to lead to the first systematic review providing a strength of evidence assessment on this topic.


Assuntos
Campos Eletromagnéticos , Neoplasias , Animais , Campos Eletromagnéticos/efeitos adversos , Feminino , Masculino , Metanálise como Assunto , Avaliação de Resultados em Cuidados de Saúde , Ondas de Rádio/efeitos adversos , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
15.
Int J Radiat Oncol Biol Phys ; 109(5): 1495-1507, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33509660

RESUMO

PURPOSE: Cancer stem cells constitute an endless reserve for the maintenance and progression of tumors, and they could be the reason for conventional therapy failure. New therapeutic strategies are necessary to specifically target them. In this context, microsecond pulsed electric fields have been selected to expose D283Med cells, a human medulloblastoma cell line resulted to be rich in cancer stem cells, and normal human astrocytes. METHODS: We analyzed in vitro different endpoints at different times after microsecond pulsed electric field exposure, such as permeabilization, reactive oxygen species generation, cell viability/proliferation, cell cycle, and clonogenicity, as well as the expression of different genes involved in cell cycle, apoptosis, and senescence. Furthermore, the response of D283Med cells exposed to microsecond pulsed electric fields was validated in vivo in a heterotopic mouse xenograft model. RESULTS: Our in vitro results showed that a specific pulse protocol (ie, 0.3 MV/m, 40 µs, 5 pulses) was able to induce irreversible membrane permeabilization and apoptosis exclusively in medulloblastoma cancer stem cells. In the surviving cells, reactive oxygen species generation was observed, together with a transitory G2/M cell-cycle arrest with a senescence-associated phenotype via the upregulation of GADD45A. In vivo results, after pulsed electric field exposure, demonstrated a significant tumor volume reduction with no eradication of tumor mass. In conjunction, we verified the efficacy of electric pulse pre-exposure followed by ionizing irradiation in vivo to enable complete inhibition of tumor growth. CONCLUSIONS: Our data reveal novel therapeutic options for the targeting of medulloblastoma cancer stem cells, indicating nonionizing pulsed electric field pre-exposure as an effective means to overcome the radioresistance of cancer stem cells.


Assuntos
Neoplasias Cerebelares/terapia , Eletroporação/métodos , Meduloblastoma/terapia , Células-Tronco Neoplásicas/fisiologia , Animais , Apoptose/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Proliferação de Células , Sobrevivência Celular , Senescência Celular/genética , Neoplasias Cerebelares/patologia , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Genes cdc , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/genética , Meduloblastoma/patologia , Camundongos , Camundongos Nus , Tolerância a Radiação , Espécies Reativas de Oxigênio/metabolismo , Carga Tumoral , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Mol Neurobiol ; 58(4): 1634-1649, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33230715

RESUMO

We here characterize the response to the extremely low-frequency (ELF) magnetic field (MF, 50 Hz, 1 mT) of SH-SY5Y human neuroblastoma cells, cultured in a three-dimensional (3D) Alvetex® scaffold compared to conventional two-dimensional (2D) monolayers. We proved that the growing phenotype of proliferating SH-SY5Y cells is not affected by the culturing conditions, as morphology, cell cycle distribution, proliferation/differentiation gene expression of 3D-cultures overlap what reported in 2D plates. In response to 72-h exposure to 50-Hz MF, we demonstrated that no proliferation change and apoptosis activation occur in both 2D and 3D cultures. Consistently, no modulation of Ki67, MYCN, CCDN1, and Nestin, of invasiveness and neo-angiogenesis-controlling genes (HIF-1α, VEGF, and PDGF) and of microRNA epigenetic signature (miR-21-5p, miR-222-3p and miR-133b) is driven by ELF exposure. Conversely, intracellular glutathione content and SOD1 expression are exclusively impaired in 3D-culture cells in response to the MF, whereas no change of such redox modulators is observed in SH-SY5Y cells if grown on 2D monolayers. Moreover, ELF-MF synergizes with the differentiating agents to stimulate neuroblastoma differentiation into a dopaminergic (DA) phenotype in the 3D-scaffold culture only, as growth arrest and induction of p21, TH, DAT, and GAP43 are reported in ELF-exposed SH-SY5Y cells exclusively if grown on 3D scaffolds. As overall, our findings prove that 3D culture is a more reliable experimental model for studying SH-SY5Y response to ELF-MF if compared to 2D conventional monolayer, and put the bases for promoting 3D systems in future studies addressing the interaction between electromagnetic fields and biological systems.


Assuntos
Técnicas de Cultura de Células , Campos Magnéticos , Neuroblastoma/patologia , Apoptose , Biomarcadores/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Neurônios Dopaminérgicos/patologia , Glutationa/deficiência , Glutationa/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Fisiológica , Neuroblastoma/genética , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
17.
Bioelectromagnetics ; 30(5): 385-92, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19242955

RESUMO

UMTS communication devices are becoming common in everyday use. This could raise public concern about their possible detrimental effects on human health. The aim of this study, in the framework of the EMF nEAR Project, was to evaluate possible influence of UMTS electromagnetic fields (EMF) exposure on cochlear outer hair cells' (OHCs) functionality in laboratory animals. Forty-eight male Sprague-Dawley rats were locally exposed (right ear) or sham-exposed to a controlled UMTS EMF, frequency of 1946 MHz, at SAR level of 10 W/kg, 2 h a day, 5 days a week, for 4 weeks. A group of 12 rats treated with kanamycin (KM) was also included as positive control. Rats were tested by recording Distortion Product Otaoacoustic Emissions (DPOAEs), a non-invasive test capable of assessing the status of the OHCs in the inner ear. DPOAEs were performed before, during (one or three times a week) and after (1-week) exposure to the EMF. The analysis of the data shows that no statistically significant differences were found between the audiological signals recorded from the different experimental groups. The ototoxic effect of KM has been confirmed.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Células Ciliadas Auditivas Externas/citologia , Células Ciliadas Auditivas Externas/efeitos da radiação , Telecomunicações , Animais , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Canamicina/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley
18.
Bioelectromagnetics ; 30(7): 564-72, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19479910

RESUMO

In this work we tested viability, proliferation, and vulnerability of neural cells, after continuous radiofrequency (RF) electromagnetic fields exposure (global system for mobile telecommunications (GSM) modulated 900 MHz signal at a specific absorption rate (SAR) of 1 W/kg and maximum duration 144 h) generated by transverse electromagnetic cells. We used two cellular systems, SN56 cholinergic for example, SN56 cholinergic cell line and rat primary cortical neurons, and well-known neurotoxic challenges, such as glutamate, 25-35AA beta-amyloid, and hydrogen peroxide. Exposure to RF did not change viability/proliferation rate of the SN56 cholinergic cells or viability of cortical neurons. Co-exposure to RF exacerbated neurotoxic effect of hydrogen peroxide in SN56, but not in primary cortical neurons, whereas no cooperative effects of RF with glutamate and 25-35AA beta-amyloid were found. These data suggest that only under particular circumstances exposure to GSM modulated, 900 MHz signal act as a co-stressor for oxidative damage of neural cells.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Exposição Ambiental , Ácido Glutâmico/metabolismo , Micro-Ondas , Doenças Neurodegenerativas/fisiopatologia , Neurônios/efeitos da radiação , Animais , Células Cultivadas , Ratos
19.
Diagnostics (Basel) ; 8(4)2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30563280

RESUMO

Thermal ablation treatments are gaining a lot of attention in the clinics thanks to their reduced invasiveness and their capability of treating non-surgical patients. The effectiveness of these treatments and their impact in the hospital's routine would significantly increase if paired with a monitoring technique able to control the evolution of the treated area in real-time. This is particularly relevant in microwave thermal ablation, wherein the capability of treating larger tumors in a shorter time needs proper monitoring. Current diagnostic imaging techniques do not provide effective solutions to this issue for a number of reasons, including economical sustainability and safety. Hence, the development of alternative modalities is of interest. Microwave tomography, which aims at imaging the electromagnetic properties of a target under test, has been recently proposed for this scope, given the significant temperature-dependent changes of the dielectric properties of human tissues induced by thermal ablation. In this paper, the outcomes of the first ex vivo experimental study, performed to assess the expected potentialities of microwave tomography, are presented. The paper describes the validation study dealing with the imaging of the changes occurring in thermal ablation treatments. The experimental test was carried out on two ex vivo bovine liver samples and the reported results show the capability of microwave tomography of imaging the transition between ablated and untreated tissue. Moreover, the discussion section provides some guidelines to follow in order to improve the achievable performances.

20.
Mol Neurobiol ; 55(7): 5698-5714, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29039021

RESUMO

The exposure to extremely low-frequency magnetic fields (ELF-MFs) has been associated to increased risk of neurodegenerative diseases, although the underlying molecular mechanisms are still undefined. Since epigenetic modulation has been recently encountered among the key events leading to neuronal degeneration, we here aimed at assessing if the control of gene expression mediated by miRNAs, namely miRs-34, has any roles in driving neuronal cell response to 50-Hz (1 mT) magnetic field in vitro. We demonstrate that ELF-MFs drive an early reduction of the expression level of miR-34b and miR-34c in SH-SY5Y human neuroblastoma cells, as well as in mouse primary cortical neurons, by affecting the transcription of the common pri-miR-34. This modulation is not p53 dependent, but attributable to the hyper-methylation of the CpG island mapping within the miR-34b/c promoter. Incubation with N-acetyl-l-cysteine or glutathione ethyl-ester fails to restore miR-34b/c expression, suggesting that miRs-34 are not responsive to ELF-MF-induced oxidative stress. By contrast, we show that miRs-34 control reactive oxygen species production and affect mitochondrial oxidative stress triggered by ELF-MFs, likely by modulating mitochondria-related miR-34 targets identified by in silico analysis. We finally demonstrate that ELF-MFs alter the expression of the α-synuclein, which is specifically stimulated upon ELF-MFs exposure via both direct miR-34 targeting and oxidative stress. Altogether, our data highlight the potential of the ELF-MFs to tune redox homeostasis and epigenetic control of gene expression in vitro and shed light on the possible mechanism(s) producing detrimental effects and predisposing neurons to degeneration.


Assuntos
Epigênese Genética , Campos Magnéticos , MicroRNAs/genética , Neurônios/metabolismo , Animais , Sequência de Bases , Linhagem Celular Tumoral , Córtex Cerebral/citologia , Metilação de DNA/genética , Humanos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Modelos Biológicos , Oxirredução , Estresse Oxidativo/genética , Regiões Promotoras Genéticas/genética , Transcrição Gênica , Proteína Supressora de Tumor p53/metabolismo , alfa-Sinucleína/metabolismo
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