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WIREs Nanomed Nanobiotechnol
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Direct treatment versus indirect: Thermo‐ablative and mild hyperthermia effects

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Abstract Hyperthermia is a rapidly growing field in cancer therapy and many advances have been made in understanding and applying the mechanisms of hyperthermia. Secondary effects of hyperthermia have been increasingly recognized as important in therapeutic effects and multiple studies have started to elucidate their implications for treatment. Immune effects have especially been recognized as important in the efficacy of hyperthermia treatment of cancer. Both thermo‐ablative and mild hyperthermia activate the immune system, but mild hyperthermia seems to be more effective at doing so. This may suggest that mild hyperthermia has some advantages over thermo‐ablative hyperthermia and research into immune effects of mild hyperthermia should continue. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery
Number of original research papers and reviews on hyperthermia applications, published in SciFinder. (https://scifinder‐cas‐org)
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Computational approach subdivided into three main phases (a) geometrical modeling of the tumor slab and generation of the computational meshes of Ω and Λ; (b) simulation of the blood, interstitial flow (only blood velocity field is visualized) and definition of the tumor hyperthermic treatment protocol; and (c) simulation of particle release (right panel) and heating upon irradiation of alternating magnetic field (left panel).(Reprinted with permission from Nabil et al. (2015). Figure 2 Copyright 2015 (CC BY 4.0))
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Infrared thermographic images of BxPC‐3 xenograft treated with MF66 during first alternating magnetic field (AMF) treatment shows inhomogeneous temperature distribution and occurrence of local heat spots in the tumor region. Infrared thermographic images of a BxPC‐3 xenograft injected with MF66 (0.087 mg Fe per 100 mm3) during the first magnetic hyperthermia treatment. (a) Images were taken distally from the tumor using an infrared thermography camera. (b) Over each tumor a polygonal region of interest (ROI, white polygon) was placed in a size specific manner and the corresponding temperature data at 10, 30, and 50 min postonset of the AMF was extracted.(Reprinted with permission from Kossatz et al. (2014). Figure 3 Copyright 2014 (CC BY 4.0))
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Enhanced extravasation of 23‐nm dextran in CAPAN‐1 pancreatic tumors resulting from magnetic hyper thermia (MHT) treatment as studied by intra vital microscopy (IVM) imaging and analyses; (a, b) time lapse IVM images showing increased dextran tumor accumulation in treatment groups 1‐ and 5‐hr postheat versus untreated groups; (c) mean average fluorescent intensities with distinct R values between the treated and untreated group; (d) average intensity acquired over 20 min (1‐hr postheat) and fitted to a mass transport model with a higher Ymax and R for treated group; (e) comparison of treatment groups (1‐ and 5‐hr posttreatment) showed similar average fluorescent intensities and transport enhancement properties with Ymax = 3,816 and 3,661 fluorescent units (FUs) and (R = .325 and .458 min−1), respectively; (f) histological analyses confirm that MHT caused little morphological alterations to tumor microenvironment while thermal ablation caused cellular damage.(Reprinted with permission from Kirui et al. (2014). Copyright 2014 Elsevier)
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43°C 30 min increases and activates CD8+ T cells in dLN and CD8+ T cells are required for treatment efficacy. (a) Experimental design to test if local hyperthermia increases and activates CD4+ and CD8+ T cells. (b) Gating strategy for CD4+ and CD8+ T cells (left) and % CD4+ T cells and % CD8+ T cells among leukocytes (CD45+ cells) in dLN (right). Representative of two experiments. (c) Gating strategy for CD44+ CD69+ cells (left) and % CD44+ CD69+ cells among CD4+ and CD8+ T cells in dLN (right). Representative of two experiments. (d) Experimental design to test if CD8+ T cells are required for treatment efficacy. (e) Growth kinetics of secondary tumors (top) and statistics (bottom). Representative of two experiments.(Reprinted with permission from Toraya‐Brown et al. (2014). Figure 5 Copyright 2014 Elsevier)
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Increased symptom‐free survival postmagnetic hyperthermia treatment in a murine disseminated pancreatic cancer model. Mice treated with magnetic nanoparticles and alternating magnetic field radiation showed significant and substantial increase in survival relative to control groups. Neither magnetic nanoparticles or alternating magnetic field treatment alone showed any survival advantage. Log rank test chi‐square p = .0048
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Physiological effects of mild hyperthermia. CXCLs, chemokine (C‐C motif) ligands; HSPs and gp96, heat shock proteins; ICAM‐1, intracellular adhesion molecule 1; ILs, interleukins; iNOS, inducible nitric oxide (NO) synthase; NKG2D, natural killer lectin‐like receptor gene 2D; TLR, toll‐like receptor; TNF‐α, tumor necrosis factor α; VCAM‐1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery
Therapeutic Approaches and Drug Discovery > Emerging Technologies

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