Abstract:Minimally invasive thermal ablation of tumours has become common since the advent of modern imaging. From the ablation of small, unresectable tumours to experimental therapies, percutaneous radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation have an increasing role in the treatment of solid neoplasms. This Opinion article examines the mechanisms of tumour cell death that are induced by the most common thermoablative techniques and discusses the rapidly developing areas of… Show more
“…Freeze-thaw cycles, applied here to group F, have been used extensively before to ablate tissues in human diseases (Erinjeri & Clark, 2010;Baust et al, 2014;Chu & Dupuy, 2014) including cyclocryodestruction in glaucoma (Benson & Nelson, 1990). It has also been used in research (Baust et al, 2014;Chan & Ooi, 2016;Liu et al, 2016) and in food production ("Fish and Fishery Products Hazards and Controls Guidance"; Gill, 2006;Craig, 2012).…”
Section: Discussionmentioning
confidence: 99%
“…It has also been used in research (Baust et al, 2014;Chan & Ooi, 2016;Liu et al, 2016) and in food production ("Fish and Fishery Products Hazards and Controls Guidance"; Gill, 2006;Craig, 2012). The mechanisms of cryoablation in medicine include direct cell injury, vascular injury, ischemia, apoptosis, and immunomodulation (Chu & Dupuy, 2014): cell injury during freezing causes dehydration from the so-called solution effect that causes the earlier freezing extracellular compartment to extract solutes, an osmotic gradient and cell shrinkage (Lovelock, 1953) that can be enhanced by ice crystal formation within the cell, damaging organelles and the cell membrane. During thawing, the intracellular compartment shifts to hypertonia, attracting fluid that causes the cell to burst.…”
Freeze-thaw decellularization of the trabecular meshwork in an ex vivo eye perfusion model
Materials and Methods:We obtained 24 porcine eyes from a local abattoir, dissected and mounted them in an anterior segment perfusion and pressure transduction system within two hours of sacrifice. After they stabilized for 72 hours, eight eyes each were assigned to freeze-thaw (F) ablation (-80°C×2), to 0.02% saponin (S) treatment, or the control group (C), respectively. The trabecular meshwork was transduced with an eGFP expressing feline immunodeficiency viral (FIV) vector and tracked via fluorescent microscopy to confirm ablation. Following treatment, the eyes were perfused with standard tissue culture medium for 180 hours. We assessed histological changes by hematoxylin and eosin staining. TM cell viability was evaluated with a calcein AM/propidium iodide (PI) assay. We measured IOP and modeled it with a linear mixed effects model using a B-spline function of time with 5 degrees of freedom.Results: F and S experienced a similar IOP reduction by 30% from baseline (P =0.64). IOP reduction of about 30% occurred in F within 24 hours and in S within 48 hours. Live visualization of eGFP demonstrated that F conferred a complete ablation of all TM cells and only a partial ablation in S. Histological analysis confirmed that no TM cells survived in F while the extracellular matrix remained. The viability assay showed very low PI and no calcein staining in F in contrast to numerous PI-labeled dead TM cells and calcein-labeled viable TM cells in S.
Conclusion:We developed a rapid TM ablation method that uses cyclic freezing that is free of biological or chemical agents and able to produce a decellularized TM scaffold with preserved TM extracellular matrix in an organotypic perfusion culture.
“…Freeze-thaw cycles, applied here to group F, have been used extensively before to ablate tissues in human diseases (Erinjeri & Clark, 2010;Baust et al, 2014;Chu & Dupuy, 2014) including cyclocryodestruction in glaucoma (Benson & Nelson, 1990). It has also been used in research (Baust et al, 2014;Chan & Ooi, 2016;Liu et al, 2016) and in food production ("Fish and Fishery Products Hazards and Controls Guidance"; Gill, 2006;Craig, 2012).…”
Section: Discussionmentioning
confidence: 99%
“…It has also been used in research (Baust et al, 2014;Chan & Ooi, 2016;Liu et al, 2016) and in food production ("Fish and Fishery Products Hazards and Controls Guidance"; Gill, 2006;Craig, 2012). The mechanisms of cryoablation in medicine include direct cell injury, vascular injury, ischemia, apoptosis, and immunomodulation (Chu & Dupuy, 2014): cell injury during freezing causes dehydration from the so-called solution effect that causes the earlier freezing extracellular compartment to extract solutes, an osmotic gradient and cell shrinkage (Lovelock, 1953) that can be enhanced by ice crystal formation within the cell, damaging organelles and the cell membrane. During thawing, the intracellular compartment shifts to hypertonia, attracting fluid that causes the cell to burst.…”
Freeze-thaw decellularization of the trabecular meshwork in an ex vivo eye perfusion model
Materials and Methods:We obtained 24 porcine eyes from a local abattoir, dissected and mounted them in an anterior segment perfusion and pressure transduction system within two hours of sacrifice. After they stabilized for 72 hours, eight eyes each were assigned to freeze-thaw (F) ablation (-80°C×2), to 0.02% saponin (S) treatment, or the control group (C), respectively. The trabecular meshwork was transduced with an eGFP expressing feline immunodeficiency viral (FIV) vector and tracked via fluorescent microscopy to confirm ablation. Following treatment, the eyes were perfused with standard tissue culture medium for 180 hours. We assessed histological changes by hematoxylin and eosin staining. TM cell viability was evaluated with a calcein AM/propidium iodide (PI) assay. We measured IOP and modeled it with a linear mixed effects model using a B-spline function of time with 5 degrees of freedom.Results: F and S experienced a similar IOP reduction by 30% from baseline (P =0.64). IOP reduction of about 30% occurred in F within 24 hours and in S within 48 hours. Live visualization of eGFP demonstrated that F conferred a complete ablation of all TM cells and only a partial ablation in S. Histological analysis confirmed that no TM cells survived in F while the extracellular matrix remained. The viability assay showed very low PI and no calcein staining in F in contrast to numerous PI-labeled dead TM cells and calcein-labeled viable TM cells in S.
Conclusion:We developed a rapid TM ablation method that uses cyclic freezing that is free of biological or chemical agents and able to produce a decellularized TM scaffold with preserved TM extracellular matrix in an organotypic perfusion culture.
“…Phototherapy, such as the well‐known photothermal therapy (PTT) and photodynamic therapy (PDT), is emerging as one of the most representative therapeutic modalities for the treatment of cancers due to its unique characteristics including noninvasiveness, high selectivity, and low systemic toxicity as compared to traditional chemotherapy and radiotherapy 1. PTT usually employs photothermal‐conversion agent (PTCA) to convert light into thermal energy for localized cancer hyperthermia under appropriate photoirradiation 2.…”
Phototherapy has emerged as a novel therapeutic modality for cancer treatment, but its low therapeutic efficacy severely hinders further extensive clinical translation and application. This study reports amplifying the phototherapeutic efficacy by constructing a near‐infrared (NIR)‐responsive multifunctional nanoplatform for synergistic cancer phototherapy by a single NIR irradiation, which can concurrently achieve mitochondria‐targeting phototherapy, synergistic photothermal therapy (PTT)/photodynamic therapy (PDT), self‐sufficient oxygen‐augmented PDT, and multiple‐imaging guidance/monitoring. Perfluorooctyl bromide based nanoliposomes are constructed for oxygen delivery into tumors, performing the functions of red blood cells (RBCs) for oxygen delivery (“Nano‐RBC” nanosystem), which can alleviate the tumor hypoxia and enhance the PDT efficacy. The mitochondria‐targeting performance for enhanced and synergistic PDT/PTT is demonstrated as assisted by nanoliposomes. In particular, these “Nano‐RBCs” can also act as the contrast agents for concurrent computed tomography, photoacoustic, and fluorescence multiple imaging, providing the potential imaging capability for phototherapeutic guidance and monitoring. This provides a novel strategy to achieve high therapeutic efficacy of phototherapy by the rational design of multifunctional nanoplatforms with the unique performances of mitochondria targeting, synergistic PDT/PTT by a single NIR irradiation (808 nm), self‐sufficient oxygen‐augmented PDT, and multiple‐imaging guidance/monitoring.
“…Since magnetic hyperthermia was widely studied for tumor treatments [26], and the tumor ablation therapeutic technique by RF-induced heating of some charged particles has been clinically used recently [27][28][29], the anticancer mechanism of the RF-assisted GFNCs was primarily proposed as a magnetic hyperthermia effect. However, a series of deliberately designed experiments were performed that completely rule out this mechanism.…”
Section: The Anticancer Mechanism Of Rf-assisted Gfncsmentioning
It has long been a dream to achieve tumor targeting therapy that can efficiently reduce the toxicity and severe side effects of conventional antitumor chemotherapeutic agents. Taking advantage of the abnormalities of tumor vasculature, we demonstrate here a new powerful tumor vascular-targeting therapeutic technique for solid cancers that applies advanced nanotechnology to cut off the nutrient supply of tumor cells by physically destroying the abnormal tumor blood vessels. Water soluble magnetic Gd@C82 nanocrystals of the chosen sizes are deliberately designed with abilities to penetrate into the leaky tumor blood vessels. By triggering the radiofrequency induced phase transition of gadofullerene nanocrystals while extravasating the tumor blood vessel, the explosive structural change of nanoparticles generates a devastating impact on abnormal tumor blood vessels, resulting in a rapid and extensive ischemia necrosis and shrinkage of the tumors. This unprecedented target-specific physiotherapy is found to work perfectly for advanced and refractory solid tumors.
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