Life Sciences Commons^™

Controllable Moderate Heating Enhances The Therapeutic Efficacy Of Irreversible Electroporation For Pancreatic Cancer, Chelsea M. Edelblute, James Hornef, Niculina I. Burcus, Thomas Norman, Stephen J. Beebe, Karl Schoenbach, Richard Heller, Chunqi Jiang, Sigi Guo

Bioelectrics Publications

Irreversible electroporation (IRE) as a non-thermal tumor ablation technology has been studied for the treatment of pancreatic carcinoma and has shown a significant survival benefit. We discovered that moderate heating (MH) at 43°C for 1-2 minutes significantly enhanced ex vivo IRE tumor ablation of Pan02 cells by 5.67-fold at 750 V/cm and by 1.67-fold at 1500 V/cm. This amount of heating alone did not cause cell death. An integrated IRE system with controllable laser heating and tumor impedance monitoring was developed to treat mouse ectopic pancreatic cancer. With this novel IRE system, we were able to heat and maintain the …

Damage-Free Peripheral Nerve Stimulation By 12-Ns Pulsed Electric Field, Maura Casciola, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

Modern technologies enable deep tissue focusing of nanosecond pulsed electric field (nsPEF) for non-invasive nerve and muscle stimulation. However, it is not known if PEF orders of magnitude shorter than the activation time of voltage-gated sodium channels (VGSC) would evoke action potentials (APs). One plausible scenario requires the loss of membrane integrity (electroporation) and resulting depolarization as an intermediate step. We report, for the first time, that the excitation of a peripheral nerve can be accomplished by 12-ns PEF without electroporation. 12-ns stimuli at 4.1-11 kV (3.3-8.8 kV/cm) evoked APs similarly to conventional stimuli (100-250 mus, 1-5 V, 103-515 V/m), …

Delayed Hypersensitivity To Nanosecond Pulsed Electric Field In Electroporated Cells, Sarah D. Jensen, Vera A. Khorokhorina, Claudia Muratori, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

We demonstrate that conditioning of mammalian cells by electroporation with nanosecond pulsed electric field (nsPEF) facilitates their response to the next nsPEF treatment. The experiments were designed to unambiguously separate the electroporation-induced sensitization and desensitization effects. Electroporation was achieved by bursts of 300-ns, 9 kV/cm pulses (50 Hz, n = 3–100) and quantified by propidium dye uptake within 11 min after the nsPEF exposure. We observed either sensitization to nsPEF or no change (when the conditioning was either too weak or too intense, or when the wait time after conditioning was too short). Within studied limits, conditioning never caused desensitization. …

Hyper-Activation Of Pp60(Src) Limits Nitric Oxide Signaling By Increasing Asymmetric Dimethylarginine Levels During Acute Lung Injury, Sanjiv Kumar, Xutong Sun, Satish Kumar Noonepalle, Qing Lu, Evgeny Zemskov, Ting Wang, Saurabh Aggarwal, Christine Gross, Shruti Sharma, Ankit A. Sesai, John D. Catravas

Bioelectrics Publications

The molecular mechanisms by which the endothelial barrier becomes compromised during lipopolysaccharide (LPS) mediated acute lung injury (ALI) are still unresolved. We have previously reported that the disruption of the endothelial barrier is due, at least in part, to the uncoupling of endothelial nitric oxide synthase (eNOS) and increased peroxynitrite-mediated nitration of RhoA. The purpose of this study was to elucidate the molecular mechanisms by which LPS induces eNOS uncoupling during ALI. Exposure of pulmonary endothelial cells (PAEC) to LPS increased pp60^Src activity and this correlated with an increase in nitric oxide (NO) production, but also an increase in …

Electrotransfer Of Plasmid Dna Radiosensitizes B16f10 Tumors Through Activation Of Immune Response, Monika Savarin, Urska Kamensek, Maja Cemazar, Richard Heller, Gregor Sersa

Bioelectrics Publications

Background. Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors.

Materials and methods. The murine melanoma Bl6F10 tumors, growing on the back of C57BI/6 mice, were treated by triple gene electrotransfer and irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice. Furthermore, histological analysis of tumors (necrosis, apoptosis, …

Nanosecond Pulsed Electric Field Induced Changes In Cell Surface Charge Density, Diganta Dutta, Xavier-Lewis Palmer, Anthony Asmar, Michael Stacey, Shizhi Qian

Bioelectrics Publications

This study reports that the surface charge density changes in Jurkat cells with the application of single 60 nanosecond pulse electric fields, using atomic force microscopy. Using an atomic force microscope tip and Jurkat cells on silica in a 0.01 M KCl ionic concentration, we were able to measure the interfacial forces, while also predicting surface charge densities of both Jurkat cell and silica surfaces. The most important finding is that the pulsing conditions varyingly reduced the cells' surface charge density. This offers a novel way in which to examine cellular effects of pulsed electric fields that may lead to …