The aim of this study was to develop a statistical model for cell death by irreversible electroporation (IRE) and to show that the statistic model is more accurate than the electric field threshold ...model in the literature using cervical cancer cells in vitro.
HeLa cell line was cultured and treated with different IRE protocols in order to obtain data for modeling the statistical relationship between the cell death and pulse-setting parameters. In total, 340 in vitro experiments were performed with a commercial IRE pulse system, including a pulse generator and an electric cuvette. Trypan blue staining technique was used to evaluate cell death after 4 hours of incubation following IRE treatment. Peleg-Fermi model was used in the study to build the statistical relationship using the cell viability data obtained from the in vitro experiments. A finite element model of IRE for the electric field distribution was also built. Comparison of ablation zones between the statistical model and electric threshold model (drawn from the finite element model) was used to show the accuracy of the proposed statistical model in the description of the ablation zone and its applicability in different pulse-setting parameters.
The statistical models describing the relationships between HeLa cell death and pulse length and the number of pulses, respectively, were built. The values of the curve fitting parameters were obtained using the Peleg-Fermi model for the treatment of cervical cancer with IRE. The difference in the ablation zone between the statistical model and the electric threshold model was also illustrated to show the accuracy of the proposed statistical model in the representation of ablation zone in IRE.
This study concluded that: (1) the proposed statistical model accurately described the ablation zone of IRE with cervical cancer cells, and was more accurate compared with the electric field model; (2) the proposed statistical model was able to estimate the value of electric field threshold for the computer simulation of IRE in the treatment of cervical cancer; and (3) the proposed statistical model was able to express the change in ablation zone with the change in pulse-setting parameters.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Electroporation-based therapy (EBT), as a high-voltage-pulse technology has been prevalent with favorable clinical outcomes in the treatment of various solid tumors. This review paper aims to promote ...the clinical translation of EBT for brain tumors. First, we briefly introduced the mechanism of pore formation in a cell membrane activated by external electric fields using a single cell model. Then, we summarized and discussed the current in vitro and in vivo preclinical studies, in terms of (1) the safety and effectiveness of EBT for brain tumors in animal models, and (2) the blood-brain barrier (BBB) disruption induced by EBT. Two therapeutic effects could be achieved in EBT for brain tumors simultaneously, i.e., the tumor ablation induced by irreversible electroporation (IRE) and transient BBB disruption induced by reversible electroporation (RE). The BBB disruption could potentially improve the uptake of antitumor drugs thereby enhancing brain tumor treatment. The challenges that hinder the application of EBT in the treatment of human brain tumors are discussed in the review paper as well.
Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the ...transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion.
Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL), and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD).
Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers.
Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The multidisciplinary fields of tissue engineering and regenerative medicine have the potential to revolutionize the practise of medicine through the abilities to repair, regenerate, or replace ...tissues and organs with functional engineered constructs. To this end, tissue engineering combines scaffolding materials with cells and biologically active molecules into constructs with the appropriate structures and properties for tissue/organ regeneration, where scaffolding materials and biomolecules are the keys to mimic the native extracellular matrix (ECM). For this, one emerging way is to decellularize the native ECM into the materials suitable for, directly or in combination with other materials, creating functional constructs. Over the past decade, decellularized ECM (or dECM) has greatly facilitated the advance of tissue engineering and regenerative medicine, while being challenged in many ways. This article reviews the recent development of dECM for tissue engineering and regenerative medicine, with a focus on the preparation of dECM along with its influence on cell culture, the modification of dECM for use as a scaffolding material, and the novel techniques and emerging trends in processing dECM into functional constructs. We highlight the success of dECM and constructs in the
,
, and clinical applications and further identify the key issues and challenges involved, along with a discussion of future research directions.
In the present study, we used a computational and experimental study in a 3D liver tumor model (LTM) to explore the tumor ablation enhancement of irreversible electroporation (IRE) by pre-heating ...with radiofrequency ablation (RFA) and elucidate the mechanism whereby this enhancement occurs. Three ablation protocols, including IRE alone, RFA45 → IRE (with the pre-heating temperature of 45 °C), and RFA60 → IRE (with the pre-heating temperature of 60 °C) were investigated. Both the thermal conductivity and electrical conductivity of the 3D LTM were characterized with the change in the pre-heating temperature. The results showed, compared to IRE alone, a significant increase in the tumor ablation volume (19.59
±
0.61 vs. 15.29 ± 0.61 mm
3
,
p
= 0.002 and 22.87
±
0.35 vs. 15.29 ± 0.61 mm
3
,
p
< 0.001) was observed with both RFA45 → IRE and RFA60 → IRE, leading to a decrease in lethal electric filed strength (8 and 17%, correspondingly). The mechanism can be attributed to the change of cell microenvironment by pre-heating and/or a synergistic effect of RFA and IRE. The proposed enhancing method might contribute to the improvement of interventional oncology in the treatment of large tumors close to critical organs (e.g., large blood vessels and bile ducts).
Transbronchial microwave ablation (MWA) with flexible antennas has gradually become an attractive alternative to percutaneous MWA for lung cancer due to its characteristic of non-invasiveness. ...However, flexible antennas for the precision ablation of lung tumors that are adjacent to critical bronchial structures are still not available. In this study, a non-invasive flexible directional (FD) antenna for early stage central lung tumors surrounding the bronchia was proposed. A comprehensive numerical MWA model with the FD antenna was developed in a real human-sized left lung model. The structure of the antenna and the treatment protocol were optimized by a generic algorithm for the precision ablation of two cases of early stage central lung cancer (i.e. spherical-like and ellipsoidal tumors). The electromagnetic efficiency of the optimized antenna was also improved by implementing an optimizedπ-matching network for impedance matching. The results indicate that the electromagnetic energy of MWA can be restricted to a particular area for precision ablation of specific lung tumors using the FD antenna. This study contributes to the field of lung cancer management with MWA.
Highlights • We review the state-of-the-art of RFA specifically for tumours ⩾3 cm in diameter. • We review the tissue charring, one of the reasons for the so-called “3-cm” problem. • We discuss the ...state-of-the-art of mathematical modelling of RFA. • We propose the temperature control of target tissue in RFA for the “3-cm” problem.
Background:
Fear of reinjury and lack of confidence influence return-to-sport outcomes after anterior cruciate ligament (ACL) reconstruction. The physical, psychosocial, and functional recovery of ...patients reporting fear of reinjury or lack of confidence as their primary barrier to resuming sports participation is unknown.
Purpose:
To compare physical impairment, functional, and psychosocial measures between subgroups based on return-to-sport status and fear of reinjury/lack of confidence in the return-to-sport stage and to determine the association of physical impairment and psychosocial measures with function for each subgroup at 6 months and 1 year after surgery.
Study Design:
Case-control study; Level of evidence, 3.
Methods:
Physical impairment (quadriceps index QI, quadriceps strength/body weight QSBW, hamstring:quadriceps strength ratio HQ ratio, pain intensity), self-report of function (International Knee Documentation Committee IKDC), and psychosocial (Tampa Scale for Kinesiophobia–shortened form TSK-11) measures were collected at 6 months and 1 year after surgery in 73 patients with ACL reconstruction. At 1 year, subjects were divided into “return-to-sport” (YRTS) or “not return-to-sport” (NRTS) subgroups based on their self-reported return to preinjury sport status. Patients in the NRTS subgroup were subcategorized as NRTS-Fear/Confidence if fear of reinjury/lack of confidence was the primary reason for not returning to sports, and all others were categorized as NRTS-Other.
Results:
A total of 46 subjects were assigned to YRTS, 13 to NRTS-Other, and 14 to NRTS-Fear/Confidence. Compared with the YRTS subgroup, the NRTS-Fear/Confidence subgroup was older and had lower QSBW, lower IKDC score, and higher TSK-11 score at 6 months and 1 year; however, they had similar pain levels. In the NRTS-Fear/Confidence subgroup, the IKDC score was associated with QSBW and pain at 6 months and QSBW, QI, pain, and TSK-11 scores at 1 year.
Conclusion:
Elevated pain-related fear of movement/reinjury, quadriceps weakness, and reduced IKDC score distinguish patients who are unable to return to preinjury sports participation because of fear of reinjury/lack of confidence. Despite low average pain ratings, fear of pain may influence function in this subgroup. Assessment of fear of reinjury, quadriceps strength, and self-reported function at 6 months may help identify patients at risk for not returning to sports at 1 year and should be considered for inclusion in return-to-sport guidelines.
The lethal electric field (LEF) thresholds for three typical cerebral cells, including a malignant glioblastoma (GBM) cell line and two cell lines from the healthy blood-brain barrier (BBB), treated ...by irreversible electroporation (IRE) or high-frequency irreversible electroporation (H-FIRE) protocols were investigated in an in vitro three-dimensional (3D) cell model. A conventional IRE protocol (90 pulses, 1 Hz, and 100-μs pulse duration) and three novel H-FIRE protocols (1-3-1, 0.5-1-0.5, and 1-1-1) were used to treat the cerebral cells in both 3D single-cell and two-cell models. The electrical conductivity of the 3D cell model under different electric field strengths were characterized with the method of electrochemical impedance spectroscopy (EIS). Based on EIS, a numerical electrothermal model of electroporation was built for the determination of the LEF threshold with different protocols and temperature monitoring. Cell viability was assessed by fluorescence staining 6 h after the treatment. The results showed no thermal lethal effect on cells when these protocols were used. The LEF threshold for GBM cells was significantly lower than that of the healthy BBB cells. These results suggest the possibility of selective ablation of human cerebral GBM by IRE and H-FIRE treatments with no injury or reversible injury to healthy cells, and the potential use of IRE or H-FIRE for transient disruption of the BBB to allow chemotherapy to reach the tumor.
In this study, we combined electrochemical impedance spectroscopy (EIS) and artificial neural network (ANN) to predict the ablation zone of irreversible electroporation (IRE) in a heterogeneous plant ...model. The heterogeneous plant model was built by implanting an exotic material with a different electrical conductivity (copper or wood) into potato cubes. For each heterogeneous model, 55 IRE trials were performed with the pulse strength of 300-1300 V and the pulse number of 30, 60, or 90 (<inline-formula> <tex-math notation="LaTeX">100 \mu \text{s} </tex-math></inline-formula> in the pulsewidth and the frequency of 1 Hz) for different positions of exotic implants. The ANN for each model was trained, tested, and validated by a total of 165 experimental data with five inputs (pulse strength, pulse number, implant <inline-formula> <tex-math notation="LaTeX">x </tex-math></inline-formula>-/<inline-formula> <tex-math notation="LaTeX">y </tex-math></inline-formula>-axis values, and impedance variation parameter) and four outputs (ablation area, major axis length (MaAL), minor axis length (MiAL), and ablation boundary in the first quadrant). Both the experiment and simulation results showed that the two implants with different electrical conductivities could distort the electric field distribution in the plant model. This study concludes that the method combining ANN and EIS can be used to predict the ablation zone of heterogeneous IRE with acceptable accuracy (<inline-formula> <tex-math notation="LaTeX">> </tex-math></inline-formula>90%), which might bring a hint to the rapid monitoring of IRE in the treatment of tumors.
PDF
