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  1. Article ; Online: The Feasibility of Enhancing Susceptibility of Glioblastoma Cells to IRE Using a Calcium Adjuvant.

    Wasson, Elisa M / Ivey, Jill W / Verbridge, Scott S / Davalos, Rafael V

    Annals of biomedical engineering

    2017  Volume 45, Issue 11, Page(s) 2535–2547

    Abstract: Irreversible electroporation (IRE) is a cellular ablation method used to treat a variety of cancers. IRE works by exposing tissues to pulsed electric fields which cause cell membrane disruption. Cells exposed to lower energies become temporarily ... ...

    Abstract Irreversible electroporation (IRE) is a cellular ablation method used to treat a variety of cancers. IRE works by exposing tissues to pulsed electric fields which cause cell membrane disruption. Cells exposed to lower energies become temporarily permeable while greater energy exposure results in cell death. For IRE to be used safely in the brain, methods are needed to extend the area of ablation without increasing applied voltage, and thus, thermal damage. We present evidence that IRE used with adjuvant calcium (5 mM CaCl
    MeSH term(s) Ablation Techniques ; Adjuvants, Pharmaceutic/pharmacology ; Brain Neoplasms/therapy ; Calcium Chloride/pharmacology ; Cell Line, Tumor ; Collagen ; Electroporation ; Glioblastoma/therapy ; Humans ; Models, Theoretical
    Chemical Substances Adjuvants, Pharmaceutic ; Collagen (9007-34-5) ; Calcium Chloride (M4I0D6VV5M)
    Language English
    Publishing date 2017-08-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 185984-5
    ISSN 1573-9686 ; 0191-5649 ; 0090-6964
    ISSN (online) 1573-9686
    ISSN 0191-5649 ; 0090-6964
    DOI 10.1007/s10439-017-1905-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1018: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant.

    Ivey, Jill W / Latouche, Eduardo L / Richards, Megan L / Lesser, Glenn J / Debinski, Waldemar / Davalos, Rafael V / Verbridge, Scott S

    Biophysical journal

    2017  Volume 113, Issue 2, Page(s) 472–480

    Abstract: Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the ... ...

    Abstract Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application.
    MeSH term(s) Animals ; Astrocytes/drug effects ; Astrocytes/pathology ; Biomechanical Phenomena ; Cell Death/drug effects ; Cell Line, Tumor ; Cell Size ; Coculture Techniques ; Collagen ; Electromagnetic Fields ; Electroporation/methods ; Ephrin-A1/pharmacology ; Finite Element Analysis ; Glioma/drug therapy ; Glioma/pathology ; Glioma/therapy ; Humans ; Hydrogels ; Membrane Potentials ; Models, Biological ; Molecular Targeted Therapy/methods ; Rats ; Receptor, EphA2/metabolism
    Chemical Substances Ephrin-A1 ; Hydrogels ; Collagen (9007-34-5) ; Receptor, EphA2 (EC 2.7.10.1)
    Language English
    Publishing date 2017-07-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2017.06.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 235: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 2: Show issues

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  3. Article ; Online: Improving cancer therapies by targeting the physical and chemical hallmarks of the tumor microenvironment.

    Ivey, Jill W / Bonakdar, Mohammad / Kanitkar, Akanksha / Davalos, Rafael V / Verbridge, Scott S

    Cancer letters

    2015  Volume 380, Issue 1, Page(s) 330–339

    Abstract: Tumors are highly heterogeneous at the patient, tissue, cellular, and molecular levels. This multi-scale heterogeneity poses significant challenges for effective therapies, which ideally must not only distinguish between tumorous and healthy tissue, but ... ...

    Abstract Tumors are highly heterogeneous at the patient, tissue, cellular, and molecular levels. This multi-scale heterogeneity poses significant challenges for effective therapies, which ideally must not only distinguish between tumorous and healthy tissue, but also fully address the wide variety of tumorous sub-clones. Commonly used therapies either leverage a biological phenotype of cancer cells (e.g. high rate of proliferation) or indiscriminately kill all the cells present in a targeted volume. Tumor microenvironment (TME) targeting represents a promising therapeutic direction, because a number of TME hallmarks are conserved across different tumor types, despite the underlying genetic heterogeneity. Historically, TME targeting has largely focused on the cells that support tumor growth (e.g. vascular endothelial cells). However, by viewing the intrinsic physical and chemical alterations in the TME as additional therapeutic opportunities rather than barriers, a new class of TME-inspired treatments has great promise to complement or replace existing therapeutic strategies. In this review we summarize the physical and chemical hallmarks of the TME, and discuss how these tumor characteristics either currently are, or may ultimately be targeted to improve cancer therapies.
    MeSH term(s) Ablation Techniques/methods ; Animals ; Antineoplastic Agents/administration & dosage ; Drug Carriers ; Drug Delivery Systems/methods ; Drug Resistance, Neoplasm ; Humans ; Hydrogen-Ion Concentration ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Tumor Hypoxia ; Tumor Microenvironment
    Chemical Substances Antineoplastic Agents ; Drug Carriers
    Language English
    Publishing date 2015-12-24
    Publishing country Ireland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2015.12.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1177: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: High-Frequency Irreversible Electroporation for Intracranial Meningioma: A Feasibility Study in a Spontaneous Canine Tumor Model.

    Latouche, Eduardo L / Arena, Christopher B / Ivey, Jill W / Garcia, Paulo A / Pancotto, Theresa E / Pavlisko, Noah / Verbridge, Scott S / Davalos, Rafael V / Rossmeisl, John H

    Technology in cancer research & treatment

    2018  Volume 17, Page(s) 1533033818785285

    Abstract: High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5- to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death. High-frequency irreversible electroporation ... ...

    Abstract High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5- to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death. High-frequency irreversible electroporation has potential advantages for use in neurosurgery, including the ability to deliver pulses without inducing muscle contraction, inherent selectivity against malignant cells, and the capability of simultaneously opening the blood-brain barrier surrounding regions of ablation. Our objective was to determine whether high-frequency irreversible electroporation pulses capable of tumor ablation could be delivered to dogs with intracranial meningiomas. Three dogs with intracranial meningiomas were treated. Patient-specific treatment plans were generated using magnetic resonance imaging-based tissue segmentation, volumetric meshing, and finite element modeling. Following tumor biopsy, high-frequency irreversible electroporation pulses were stereotactically delivered in situ followed by tumor resection and morphologic and volumetric assessments of ablations. Clinical evaluations of treatment included pre- and posttreatment clinical, laboratory, and magnetic resonance imaging examinations and adverse event monitoring for 2 weeks posttreatment. High-frequency irreversible electroporation pulses were administered successfully in all patients. No adverse events directly attributable to high-frequency irreversible electroporation were observed. Individual ablations resulted in volumes of tumor necrosis ranging from 0.25 to 1.29 cm
    MeSH term(s) Animals ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/pathology ; Brain Neoplasms/radiotherapy ; Disease Models, Animal ; Dogs ; Electrochemotherapy/methods ; Feasibility Studies ; Female ; Humans ; Magnetic Resonance Imaging ; Meningioma/diagnostic imaging ; Meningioma/pathology ; Meningioma/radiotherapy
    Language English
    Publishing date 2018-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2146365-7
    ISSN 1533-0338 ; 1533-0346
    ISSN (online) 1533-0338
    ISSN 1533-0346
    DOI 10.1177/1533033818785285
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    Zs.A 5871: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Targeted cellular ablation based on the morphology of malignant cells.

    Ivey, Jill W / Latouche, Eduardo L / Sano, Michael B / Rossmeisl, John H / Davalos, Rafael V / Verbridge, Scott S

    Scientific reports

    2015  Volume 5, Page(s) 17157

    Abstract: Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on ...

    Abstract Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100 μs) is enhanced for larger cells, short pulses (~1 μs) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors.
    MeSH term(s) Animals ; Brain Neoplasms/pathology ; Brain Neoplasms/therapy ; Brain Neoplasms/veterinary ; Cell Line, Tumor ; Cell Nucleus Size ; Cell Shape ; Cell Survival ; Coculture Techniques ; Dog Diseases/pathology ; Dog Diseases/therapy ; Dogs ; Electroporation ; Finite Element Analysis ; Glioblastoma/pathology ; Glioblastoma/therapy ; Glioblastoma/veterinary ; Humans ; Hydrogels/chemistry ; Single-Cell Analysis
    Chemical Substances Hydrogels
    Language English
    Publishing date 2015-11-24
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep17157
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Treadmill exercise activates subcortical neural networks and improves walking after stroke: a randomized controlled trial.

    Luft, Andreas R / Macko, Richard F / Forrester, Larry W / Villagra, Federico / Ivey, Fred / Sorkin, John D / Whitall, Jill / McCombe-Waller, Sandy / Katzel, Leslie / Goldberg, Andrew P / Hanley, Daniel F

    Stroke

    2008  Volume 39, Issue 12, Page(s) 3341–3350

    Abstract: Background and purpose: Stroke often impairs gait thereby reducing mobility and fitness and promoting chronic disability. Gait is a complex sensorimotor function controlled by integrated cortical, subcortical, and spinal networks. The mechanisms of gait ...

    Abstract Background and purpose: Stroke often impairs gait thereby reducing mobility and fitness and promoting chronic disability. Gait is a complex sensorimotor function controlled by integrated cortical, subcortical, and spinal networks. The mechanisms of gait recovery after stroke are not well understood. This study examines the hypothesis that progressive task-repetitive treadmill exercise (T-EX) improves fitness and gait function in subjects with chronic hemiparetic stroke by inducing adaptations in the brain (plasticity).
    Methods: A randomized controlled trial determined the effects of 6-month T-EX (n=37) versus comparable duration stretching (CON, n=34) on walking, aerobic fitness and in a subset (n=15/17) on brain activation measured by functional MRI.
    Results: T-EX significantly improved treadmill-walking velocity by 51% and cardiovascular fitness by 18% (11% and -3% for CON, respectively; P<0.05). T-EX but not CON affected brain activation during paretic, but not during nonparetic limb movement, showing 72% increased activation in posterior cerebellar lobe and 18% in midbrain (P<0.005). Exercise-mediated improvements in walking velocity correlated with increased activation in cerebellum and midbrain.
    Conclusions: T-EX improves walking, fitness and recruits cerebellum-midbrain circuits, likely reflecting neural network plasticity. This neural recruitment is associated with better walking. These findings demonstrate the effectiveness of T-EX rehabilitation in promoting gait recovery of stroke survivors with long-term mobility impairment and provide evidence of neuroplastic mechanisms that could lead to further refinements in these paradigms to improve functional outcomes.
    MeSH term(s) Aged ; Aged, 80 and over ; Brain/physiopathology ; Cerebellum/physiopathology ; Exercise Therapy ; Female ; Gait Disorders, Neurologic/etiology ; Gait Disorders, Neurologic/therapy ; Humans ; Magnetic Resonance Imaging ; Male ; Mesencephalon/physiopathology ; Middle Aged ; Nerve Net/physiopathology ; Stroke/complications ; Stroke Rehabilitation ; Walking/physiology
    Language English
    Publishing date 2008-08-28
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.108.527531
    Database MEDical Literature Analysis and Retrieval System OnLINE

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