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1.
Gastrointest Endosc ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583543

RESUMO

BACKGROUND AND AIMS: Endobiliary radiofrequency ablation (RFA) is an emerging endoscopic palliative adjunctive therapy used for the local treatment of unresectable malignant biliary obstruction (MBO). However, irregular ablation ranges caused by insufficient electrode-to-bile duct contact pose a significant obstacle. The aim was to investigate the feasibility of a self-expandable stent (SES)-based electrode with a customized RFA generator in the porcine liver and common bile duct (CBD). METHODS: A SES-RFA system with polarity-switching was developed to perform endobiliary RFA. The ablation ranges of 20 ablation protocols were evaluated to validate the feasibility of the newly developed RFA system in the porcine liver. Nine of the 20 ablation protocols were selected for evaluation in the porcine CBD with cholangiography, endoscopy, and histological and immunohistochemical analysis. RESULTS: The SES-RFA system with polarity-switching was successfully constructed and demonstrated high accuracy and reproducibility. The ablation area was clearly identified between the two SESs. The ablation ranges and degree of mucosal damage including TUNEL- and HSP70-positive depositions increased proportionally with ablation protocols in the porcine liver and CBD (all P < .05). Ablation length and depth linearly increased with ablation protocols from 8.74 ± 0.25 to 31.25 ± 0.67 mm and 1.61 ± 0.09 to 11.94 ± 0.44 mm, respectively. CONCLUSIONS: The SES-RFA system with polarity-switching between electrodes provided an even circumferential area of ablation and enhanced ablation depth between the electrodes. This novel endobiliary RFA system is a promising modality for local ablation in patients with unresectable MBO.

2.
Sci Rep ; 14(1): 9902, 2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688960

RESUMO

Irreversible electroporation (IRE) is a non-thermal ablation technique for local tumor treatment known to be influenced by pulse duration and voltage settings, affecting its efficacy. This study aims to investigate the effects of bipolar IRE with different pulse durations in a prostate cancer mouse model. The therapeutic effectiveness was assessed with in vitro cell experiments, in vivo tumor volume changes with magnetic resonance imaging, and gross and histological analysis in a mouse model. The tumor volume continuously decreased over time in all IRE-treated groups. The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300 µs) were significantly increased compared to the short pulse duration-treated groups (100 µs) (all p < 0.001). The bipolar IRE with a relatively long pulse duration at the same voltage significantly increased IRE-induced cell death in a prostate cancer mouse model.


Assuntos
Modelos Animais de Doenças , Eletroporação , Neoplasias da Próstata , Animais , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Camundongos , Eletroporação/métodos , Linhagem Celular Tumoral , Humanos , Imageamento por Ressonância Magnética , Carga Tumoral , Apoptose
3.
Bioact Mater ; 37: 172-190, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38549771

RESUMO

Biliary strictures are characterized by the narrowing of the bile duct lumen, usually caused by surgical biliary injury, cancer, inflammation, and scarring from gallstones. Endoscopic stent placement is a well-established method for the management of biliary strictures. However, maintaining optimal mechanical properties of stents and designing surfaces that can prevent stent-induced tissue hyperplasia and biofilm formation are challenges in the fabrication of biodegradable biliary stents (BBSs) for customized treatment. This study proposes a novel approach to fabricating functionalized polymer BBSs with nanoengineered surfaces using 3D printing. The 3D printed stents, fabricated from bioactive silica poly(ε-carprolactone) (PCL) via a sol-gel method, exhibited tunable mechanical properties suitable for supporting the bile duct while ensuring biocompatibility. Furthermore, a nanoengineered surface layer was successfully created on a sirolimus (SRL)-coated functionalized PCL (fPCL) stent using Zn ion sputtering-based plasma immersion ion implantation (S-PIII) treatment to enhance the performance of the stent. The nanoengineered surface of the SRL-coated fPCL stent effectively reduced bacterial responses and remarkably inhibited fibroblast proliferation and initial burst release of SRL in vitro systems. The physicochemical properties and biological behaviors, including in vitro biocompatibility and in vivo therapeutic efficacy in the rabbit bile duct, of the Zn-SRL@fPCL stent demonstrated its potential as a versatile platform for clinical applications in bile duct tissue engineering.

4.
Neuroradiology ; 66(5): 825-834, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38438630

RESUMO

PURPOSE: The elastase-induced aneurysm (EIA) model in rabbits has been proposed for translational research; however, the adjustment of aneurysm neck size remains challenging. In this study, the technical feasibility and safety of balloon neck-plasty to create a wide-necked aneurysm in rabbit EIA model were investigated. METHODS: Male New Zealand White rabbits (N = 15) were randomly assigned to three groups: group A, EIA creation without neck-plasty; group B, neck-plasty immediately after EIA creation; group C, neck-plasty 4 weeks after EIA creation. The diameter of balloon used for neck-plasty was determined 1 mm larger than origin carotid artery diameter. All rabbits were euthanized 4 weeks after their final surgery. Aneurysm neck, height, dome-to-neck (D/N) ratio, and histologic parameters were compared among the groups. RESULTS: Aneurysm creation was technically successful in 14 out of 15 rabbits (93.3%), with one rabbit experiencing mortality due to an adverse anesthetic event during the surgery. Saccular and wide-necked aneurysms were successfully created in all rabbits. Aneurysm neck was significantly greater in groups B and C compared to group A (all P < .05). D/N ratio was significantly lower in groups B and C compared to group A (all P < .05). Additionally, tunica media thickness, vessel area, and luminal area were significantly greater in groups B and C compared to group A (all P < .05). These variables were found to be significantly greater in group B compared to group C (all P < .05). CONCLUSION: The creation of a wide-necked aneurysm using balloon neck-plasty after elastase induction in rabbits has been determined to be technically feasible and safe.


Assuntos
Aneurisma Intracraniano , Masculino , Coelhos , Animais , Aneurisma Intracraniano/patologia , Elastase Pancreática/efeitos adversos , Modelos Animais de Doenças , Artéria Carótida Primitiva
6.
ACS Biomater Sci Eng ; 10(3): 1869-1879, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38291563

RESUMO

Localized photodynamic therapy (PDT) uses a polymeric-photosensitizer (PS)-embedded, covered self-expandable metallic stent (SEMS). PDT is minimally invasive and a noteworthy potential alternative for treating esophageal strictures, where surgery is not a viable option. However, preclinical evidence is insufficient, and optimized irradiation energy dose ranges for localized PDT are unclear. Herein, we validated the irradiation energy doses of the SEMS (embedded in a PS using chlorin e6 [Ce6] and covered in silicone) and PDT-induced tissue changes in a rat esophagus. Cytotoxicity and phototoxicity in the Ce6-embedded SEMS piece with laser irradiation were significantly higher than that of the silicone-covered SEMS with or without laser and the Ce6-embedded silicone-covered SEMS without laser groups (all p < 0.001). Moreover, surface morphology, atomic changes, and homogeneous coverage of the Ce6-embedded silicone-covered membrane were confirmed. The ablation range of the porcine liver was proportionally increased with the irradiation dose (all p < 0.001). The ablation region was identified at different irradiation energy doses of 50, 100, 200, and 400 J/cm2. The in vivo study in the rat esophagus comprised a control group and 100, 200, and 400 J/cm2 energy-dose groups. Finally, histology and immunohistochemistry (TUNEL and Ki67) confirmed that the optimized Ce6-embedded silicone-covered SEMS with selected irradiation energy doses (200 and 400 J/cm2) effectively damaged the esophageal tissue without ductal perforation. The polymeric PS-embedded silicone-covered SEMS can be easily placed via a minimally invasive approach and represents a promising new approach for the palliative treatment of malignant esophageal strictures.


Assuntos
Clorofilídeos , Estenose Esofágica , Fotoquimioterapia , Porfirinas , Stents Metálicos Autoexpansíveis , Humanos , Ratos , Suínos , Animais , Estenose Esofágica/tratamento farmacológico , Estenose Esofágica/cirurgia , Cuidados Paliativos , Silicones , Constrição Patológica/tratamento farmacológico , Porfirinas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/uso terapêutico
7.
BMC Gastroenterol ; 24(1): 14, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172745

RESUMO

PURPOSE: To explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients. MATERIALS AND METHODS: A consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided. RESULTS: All of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths. CONCLUSION: The technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.


Assuntos
Neoplasias Esofágicas , Gastrostomia , Humanos , Gastrostomia/métodos , Endoscopia , Fluoroscopia/métodos , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos
8.
J Pineal Res ; 76(1): e12921, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37846173

RESUMO

Evidence suggests that the neuroprotective effects of melatonin involve both receptor-dependent and -independent actions. However, little is known about the effects of melatonin receptor activation on the kainate (KA) neurotoxicity. This study examined the effects of repeated post-KA treatment with ramelteon, a selective agonist of melatonin receptors, on neuronal loss, cognitive impairment, and depression-like behaviors following KA-induced seizures. The expression of melatonin receptors decreased in neurons, whereas it was induced in astrocytes 3 and 7 days after seizures elicited by KA (0.12 µg/µL) in the hippocampus of mice. Ramelteon (3 or 10 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) mitigated KA-induced oxidative stress and impairment of glutathione homeostasis and promoted the nuclear translocation and DNA binding activity of Nrf2 in the hippocampus after KA treatment. Ramelteon and melatonin also attenuated microglial activation but did not significantly affect astroglial activation induced by KA, despite the astroglial induction of melatonin receptors after KA treatment. However, ramelteon attenuated KA-induced proinflammatory phenotypic changes in astrocytes. Considering the reciprocal regulation of astroglial and microglial activation, these results suggest ramelteon inhibits microglial activation by regulating astrocyte phenotypic changes. These effects were accompanied by the attenuation of the nuclear translocation and DNA binding activity of nuclear factor κB (NFκB) induced by KA. Consequently, ramelteon attenuated the KA-induced hippocampal neuronal loss, memory impairment, and depression-like behaviors; the effects were comparable to those of melatonin. These results suggest that ramelteon-mediated activation of melatonin receptors provides neuroprotection against KA-induced neurotoxicity in the mouse hippocampus by activating Nrf2 signaling to attenuate oxidative stress and restore glutathione homeostasis and by inhibiting NFκB signaling to attenuate neuroinflammatory changes.


Assuntos
Indenos , Melatonina , Camundongos , Animais , Melatonina/farmacologia , Melatonina/metabolismo , Receptores de Melatonina/metabolismo , Ácido Caínico/toxicidade , Ácido Caínico/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Hipocampo , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo , Glutationa/metabolismo , DNA
9.
Front Bioeng Biotechnol ; 11: 1244569, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744261

RESUMO

Background: In-stent restenosis caused by tissue hyperplasia and tumor growth through the wire meshes of an implanted self-expandable metallic stent (SEMS) remains an unresolved obstacle. This study aimed to investigate the safety and efficacy of SEMS-mediated radiofrequency ablation (RFA) for treating stent-induced tissue hyperplasia in a rat gastric outlet obstruction model. Methods: The ablation zone was investigated using extracted porcine liver according to the ablation time. The optimal RFA parameters were evaluated in the dissected rat gastric outlet. We allocated 40 male rats to four groups of 10 rats as follows: group A, SEMS placement only; group B, SEMS-mediated RFA at 4 weeks; group C, SEMS-mediated RFA at 4 weeks and housed until 8 weeks; and group D, SEMS-mediated RFA at 4 and 8 weeks. Endoscopy and fluoroscopy for in vivo imaging and histological and immunohistochemical analysis were performed to compare experimental groups. Results: Stent placement and SEMS-mediated RFA with an optimized RFA parameter were technically successful in all groups. Granulation tissue formation-related variables were significantly higher in group A than in groups B-D (all p < 0.05). Endoscopic and histological findings confirmed that the degrees of stent-induced tissue hyperplasia in group D were significantly lower than in groups B and C (all p < 0.05). Hsp70 and TUNEL expressions were significantly higher in groups B-D than in group A (all p < 0.001). Conclusion: The implanted SEMS-mediated RFA successfully managed stent-induced tissue hyperplasia, and repeated or periodic RFA seems to be more effective in treating in-stent restenosis in a rat gastric outlet obstruction model.

10.
ACS Appl Mater Interfaces ; 15(29): 34475-34487, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37452740

RESUMO

The application of irreversible electroporation (IRE) to endoluminal organs is being investigated; however, the current preclinical evidence and optimized electrodes are insufficient for clinical translation. Here, a novel self-expandable electrode (SE) made of chemically polished nickel-titanium (Ni-Ti) alloy wire for endoluminal IRE is developed in this study. Chemically polished heat-treated Ni-Ti alloy wires demonstrate increased electrical conductivity, reduced carbon and oxygen levels, and good mechanical and self-expanding properties. Bipolar IRE using chemically polished Ni-Ti wires successfully induces cancer cell death. IRE-treated potato tissue shows irreversibly and reversibly electroporated areas containing dead cells in an electrical strength-dependent manner. In vivo study using an optimized electric field strength demonstrates that endobiliary IRE using the SE evenly induces well-distributed mucosal injuries in the common bile duct (CBD) with the overexpression of the TUNEL, HSP70, and inflammatory cells without ductal perforation or stricture formation. This study demonstrates the basic concept of the endobiliary IRE procedure, which is technically feasible and safe in a porcine CBD as a novel therapeutic strategy for malignant biliary obstruction. The SE is a promising electrical energy delivery platform for effectively treating endoluminal organs.


Assuntos
Neoplasias , Titânio , Suínos , Animais , Titânio/química , Níquel/química , Eletroporação/métodos , Eletrodos , Ligas
11.
Food Chem Toxicol ; 178: 113869, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37308051

RESUMO

Although the anticonvulsant effects of ginsenosides are recognized, little is known about their effects on the convulsive behaviors induced by the activation of L-type Ca2+ channels. Here, we investigated whether ginsenoside Re (GRe) modulates excitotoxicity induced by the L-type Ca2+ channel activator Bay k-8644. GRe significantly attenuated Bay k-8644-induced convulsive behaviors and hippocampal oxidative stress in mice. GRe-mediated antioxidant potential was more pronounced in the mitochondrial fraction than cytosolic fraction. As L-type Ca2+ channels are thought to be targets of protein kinase C (PKC), we investigated the role of PKC under excitotoxic conditions. GRe attenuated Bay k-8644-induced mitochondrial dysfunction, PKCδ activation, and neuronal loss. The PKCδ inhibition and neuroprotection mediated by GRe were comparable to those by the ROS inhibitor N-acetylcysteine, the mitochondrial protectant cyclosporin A, the microglial inhibitor minocycline, or the PKCδ inhibitor rottlerin. Consistently, the GRe-mediated PKCδ inhibition and neuroprotection were counteracted by the mitochondrial toxin 3-nitropropionic acid or the PKC activator bryostatin-1. GRe treatment did not have additional effects on PKCδ gene knockout-mediated neuroprotection, suggesting that PKCδ is a molecular target of GRe. Collectively, our results suggest that GRe-mediated anticonvulsive/neuroprotective effects require the attenuation of mitochondrial dysfunction and altered redox status and inactivation of PKCδ.


Assuntos
Ginsenosídeos , Metanfetamina , Animais , Camundongos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Baías , Ginsenosídeos/farmacologia , Ginsenosídeos/metabolismo , Hipocampo , Metanfetamina/toxicidade , Camundongos Knockout , Mitocôndrias , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/prevenção & controle , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)
12.
Vet Sci ; 10(6)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37368781

RESUMO

Although many studies have been conducted on the use of median and transverse incisions in various surgeries in the field of human medicine, related studies in veterinary medicine are lacking. This study aimed to present treatment options for dogs requiring cholecystectomy by reporting the pros and cons of 121 cholecystectomies performed via transverse incision at our hospital over 10 years. In most included cases, nonelective cholecystectomy was performed in an unstable emergency situation. The perioperative mortality rate was 23.14%, which was not significantly different from that of cholecystectomy performed via the conventional midline approach. However, the overall operation time (46.24 ± 6.13 min; range 35-65 min) was shortened by securing an adequate surgical field of view. The transverse incision approach facilitates fast and accurate surgery without increasing the fatality rate in small-breed dogs, in whom securing an adequate surgical field of view is difficult. Thus, transverse incision should be actively considered in dogs undergoing cholecystectomy due to emergency conditions, such as bile leakage or biliary tract obstruction, since prolonged anesthesia can be burdensome. This study may improve cholecystectomy outcomes in small-breed dogs with difficult-to-secure surgical fields.

13.
Biomater Sci ; 11(13): 4652-4663, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37218418

RESUMO

Clostridium novyi-NT (C. novyi-NT) is an anaerobic bacterium that can be used for targeted cancer therapy because it germinates selectively in the hypoxic regions of tumor tissues. However, systemic administration of C. novyi-NT spores cannot effectively treat tumors because of the limited intratumoral delivery of active spores. In this study, we demonstrated that multifunctional porous microspheres (MPMs) containing C. novyi-NT spores have the potential for image-guided local tumor therapy. The MPMs can be repositioned under an external magnetic field, enabling precise tumor targeting and retention. Polylactic acid-based MPMs were prepared using the oil-in-water emulsion technique and then coated with a cationic polyethyleneimine polymer prior to loading with negatively charged C. novyi-NT spores. The C. novyi-NT spores delivered by MPMs were released and germinated in a simulated tumor microenvironment, effectively secreting proteins cytotoxic to tumor cells. In addition, the germinated C. novyi-NT induced immunogenic death of the tumor cells and M1 polarization of macrophages. These results indicate that MPMs encapsulated with C. novyi-NT spores have great potential for image-guided cancer immunotherapy.


Assuntos
Neoplasias , Esporos Bacterianos , Humanos , Microesferas , Composição de Bases , Porosidade , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Neoplasias/patologia , Imunoterapia , Microambiente Tumoral
14.
Biomaterials ; 299: 122159, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37209542

RESUMO

An intragastric satiety-inducing device (ISD) located in the stomach induce satiety and fullness in the absence of food by continuously pressing on the distal esophagus and cardia of the stomach. To improve the therapeutic function of ISD, Chlorin e6 (Ce6) was embedded in a disk portion of ISD, generating reactive oxygen species and stimulating endocrine cells under the laser irradiation. Since Ce6 has remarkable light efficiency but poor solubility in various solvents, it is essential to use a polymeric photosensitizer and optimize a suitable coating solution composition. Methoxy polyethylene glycol-Ce6 was uniformly coated and the spontaneous release amount of the Ce6 from the device could be reduced, which induced photo-responsive cell death and reduced ghrelin levels in vitro. In mini pigs operated single therapy (PDT or ISD) or combination therapy (Photoreactive ISD), there were differences in body weight (control: 28% vs. Photoreactive ISD: 4%, P < 0.001), ghrelin (control: 4% vs. Photoreactive ISD: 35%, P < 0.001), and leptin levels (control: 8% vs. Photoreactive PDT: 35%, P < 0.001) at 4 weeks.


Assuntos
Fotoquimioterapia , Porfirinas , Suínos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Grelina , Linhagem Celular Tumoral , Porco Miniatura , Polímeros , Redução de Peso , Porfirinas/uso terapêutico
15.
Surgery ; 173(4): 1008-1014, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36577598

RESUMO

BACKGROUND: The relatively low aqueous solubility of EW-7197 that was administered orally may have affected the desired concentration in the systemic circulation for treating peritoneal adhesion. This experimental study aimed to compare the efficacy of different routes of administering EW-7197 (2-fluoro-N-[(5-[6-methylpyridin-2-yl]-4-[(1,2,4)triazolo(1,5-a)pyridin-6-yl]-1H-imidazol-2-yl)methyl]aniline) and EW-7197·hydrobromide (HBr), with improved aqueous solubility, for inhibiting peritoneal adhesion in a rat model. METHODS: After peritoneal adhesion induction, 30 male Sprague-Dawley rats were randomly divided into 5 groups with 6 rats in each: group A, sham control; group B, orally administered 25 mg/kg of EW-7197·HBr for 7 days; group C, locally administered 25 mg/kg of EW-7197·HBr; group D, orally administered 20 mg/kg of EW-7197 for 7 days; and group E, locally administered 20 mg/kg of EW-7197. Gross examination, histologic staining (hematoxylin and eosin and Masson's trichrome), and immunohistochemical analyses (Ki-67 and α-smooth muscle actin marker [α-SMA]) were performed to evaluate the efficacy of both drugs. RESULTS: All procedures were technically successful. All treatment groups, except for group C, showed significantly reduced incidence, quality, tenacity, fibrosis, and collagen deposition scores and lowered expressions of Ki-67- and α-SMA-positive cells compared with group A. When comparing between groups, all scores were significantly lower in group B than in group C (all P < .001), whereas no significant difference was noted in any of the scores between groups D and E and groups B and E (all P > .05). CONCLUSION: Orally administering EW-7197·HBr and both orally and locally administering EW-7197 significantly prevented peritoneal adhesion formation, and orally administering EW-7197·HBr was the most effective overall.


Assuntos
Compostos de Anilina , Doenças Peritoneais , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Antígeno Ki-67 , Fibrose , Compostos de Anilina/farmacologia
16.
Sci Rep ; 12(1): 22336, 2022 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-36572706

RESUMO

As a non-thermal ablation method, irreversible electroporation (IRE) has been widely investigated in the treatment of prostate cancer. However, no consensus has been achieved on the optimal parameters of IRE for prostate cancer. Since high voltage is known to carry risks of muscle contraction and patient discomfort, it is crucial to identify the minimum but effective and safer applied voltage to inhibit tumor growth. In this study, the effect of different applied voltages of IRE on prostate cancer was evaluated in BALB/c nude mice. Mathematical simulation and measurement of the actual ablation area revealed a larger ablation area at a higher voltage. In in vivo experiment, except for the three different voltages applied, all groups received identical electrical conditions: pulse number, 180 (20 groups × 9 pulses/group); pulse width, 100 µs; pulse interval, 2 ms; distance between the electrodes, 5 mm; and electrode exposure length, 15 mm. Whilst the tumor volume initially decreased in the 500 V (1000 V/cm) and 700 V (1400 V/cm) groups and subsequently increased, only a transient increase followed by a continuous decrease until the sacrifice was observed in the 900 V (1800 V/cm) group. This result demonstrated a lasting effect of a higher applied voltage on tumor growth inhibition. The histological, immunohistochemical, and western blot findings all confirmed IRE-induced apoptosis in the treatment groups. Taken together, 900 V seemed to be the minimum applied voltage required to reduce tumor growth, though subsequent studies are anticipated to further narrow the voltage intervals and lower the minimum voltage required for tumor inhibition.


Assuntos
Eletroporação , Neoplasias da Próstata , Humanos , Masculino , Animais , Camundongos , Camundongos Nus , Eletroporação/métodos , Neoplasias da Próstata/terapia , Modelos Animais de Doenças , Simulação por Computador
17.
Sci Rep ; 12(1): 19135, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352051

RESUMO

Endoluminal radiofrequency (RF) ablation has been widely used as a safe and effective treatment for Barrett's esophagus. However, inadequate RF ablation may occur due to insufficient contact between the electrode and target tissues. Herein, a stent-based monopolar RF electrode (SE) was developed to evenly deliver RF energy to the inner wall of the rat esophagus. The optimal RF parameters were evaluated in the exposed rat esophagus. The temperature in the rat esophagus reached 70 â„ƒ in 89 s at 30 W, 59 s at 40 W, and 34 s at 50 W. The technical feasibility and efficacy of RF ablation using SE were evaluated based on changes in histological transformation and immunohistochemical parameters of tissues compared at immediately, 1 and 2 weeks after the procedure. The degrees of inflammatory cell infiltration, fibrotic changes, TUNEL, and HSP70 in the RF-ablated rat esophagus were significantly higher than compared with sham control (all p < 0.05). TUNEL-positive deposition gradually decreased, but HSP 70-positive deposition maintained a similar level for 2 weeks. The stent-based RF ablation was technically feasible and effective in evenly inducing thermal damages to the rat esophagus. The RF ablation system using the SE may represent a promising treatment for endoluminal malignancies.


Assuntos
Esôfago de Barrett , Ablação por Cateter , Ablação por Radiofrequência , Ratos , Humanos , Esôfago de Barrett/patologia , Ablação por Cateter/métodos , Eletrodos , Stents
18.
Cancers (Basel) ; 14(20)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36291771

RESUMO

Conventional irreversible electroporation (IRE) with low-frequency pulsed electric field (LF-PEF) is used to induce cell death; however, it has several disadvantages including a long procedure time and severe muscle contraction due to high-voltage electric field. This study investigates a novel IRE protocol with high-frequency pulsed electric field (HF-PEF) of 500 Hz repetition to ablate the prostate tissue in beagles for treatment of prostate cancer. A finite element analysis was performed to validate optimal electrical field strength for the procedure. In total, 12 beagles received HF-PEF of 500 Hz and were sacrificed at 4 h, 4 days, and 28 days (3 each). The remaining three beagles underwent sham procedure. The outcomes of HF-PEF were assessed by histological responses. HF-PEF successfully decellularized the prostate tissues 4 h after the treatment. The prostate glands, duct, and urethra were well preserved after IRE with HF-PEF. The ablated prostatic tissues were gradually regenerated and appeared similar to the original tissues 28 d after IRE with HF-PEF. Moreover, electrocardiography and hematology demonstrated that IRE with HF-PEF did not seriously affect the cardiac tissue. HF-PEF was effective and safe in the beagle prostate and effectively induced the ablation and gradually recovered with cellular regeneration.

19.
Biomaterials ; 289: 121762, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36058029

RESUMO

Cancer immunotherapy is a next-generation treatment strategy; however, its side effects limit its clinical translation. Here, a novel combination of a multi-functional nano-adjuvant (M-NA) prepared with an iron oxide/gold core and a cationic polymer shell via multilayer synthesis with CpG oligodeoxynucleotide (CpG-ODN) electrostatically complexed on its surface, and irreversible electroporation (IRE) technique was developed for effective image-guided in situ cancer vaccination. The M-NA can be retained long-term in the dense tumoral extracellular matrix after intratumoral injection and internalized by antigen-presenting cells (APCs). The IRE can induce immunogenic cell death. Indeed, in a mouse tumor model, the M-NA showed longer tumor retention time than free CpG-ODN. Compared with other treatments, the combined treatment significantly inhibited tumor growth with 100% survival rate for ∼60 days. The therapy induced the activation of cytotoxic lymphocytes and the maturation of APCs in vivo. This treatment could be effective in image-guided local cancer immunotherapy.


Assuntos
Neoplasias , Oligodesoxirribonucleotídeos , Adjuvantes Imunológicos , Animais , Eletroporação/métodos , Ouro , Camundongos , Neoplasias/terapia , Polímeros , Vacinação
20.
Membranes (Basel) ; 12(7)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35877896

RESUMO

In recent years, reactive ammonia (NH3) has emerged as a major source of indoor air pollution. In this study, Al2O3-based hollow fiber membranes functionalized with nitrogen-doped titanium dioxide were produced and successfully applied for efficient heterogeneous photocatalytic NH3 gas degradation. Al2O3 hollow fiber membranes were prepared using the phase inversion process. A dip-coating technique was used to deposit titanium dioxide (TiO2) and nitrogen-doped titanium dioxide (N-TiO2) thin films on well-cleaned Al2O3-based hollow fiber membranes. All heterogeneous photocatalytic degradation tests of NH3 gas were performed with both UV and visible light irradiation at room temperature. The nitrogen doping effects on the NH3 heterogeneous photocatalytic degradation capacity of TiO2 were investigated, and the effect of the number of membranes (30, 36, 42, and 48 membranes) of the prototype lab-scale photocatalytic membrane reactor, with a modular design, on the performances in different light conditions was also elucidated. Moreover, under ultraviolet and visible light, the initial concentration of gaseous NH3 was reduced to zero after only fifteen minutes in a prototype lab-scale stage with a photocatalytic membrane reactor based on an N-TiO2 photocatalyst. The number of Al2O3-based hollow fiber membranes functionalized with N-TiO2 photocatalysts increases the capacity for NH3 heterogeneous photocatalytic degradation.

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