Oncology Commons^™

Investigation Of Nanosecond Pulsed Electric Fields (Nspef) Induced Anti-Cancer Mechanism And Enhanced B16f10 Melanoma Cancer Treatment, Kamal Asadipour

Biomedical Engineering Theses & Dissertations

The use of nanosecond pulsed electric fields (nsPEF) has emerged as a promising area of research with vast implications across various scientific disciplines. The ability to generate ultra-short, high-voltage electric pulses has paved the way for numerous applications, ranging from fundamental investigations of biological phenomena to the development of innovative medical therapies. The aim of this thesis is to highlight the importance of nsPEF in two critical areas: 1) Understanding the impact of subtle postpulse waveforms through a comprehensive analysis of two common pulse generators and 2) using this knowledge to advance melanoma treatment by enhancing the therapeutic effect of …

Editorial: Pulsed Electric Field Based Technologies For Oncology Applications, Siqi Guo, Gregor Sersa, Richard Heller

Bioelectrics Publications

No abstract provided.

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Foundations Of Plasmas For Medical Applications, T. Von Woedtke, Mounir Laroussi, M. Gherardi

Electrical & Computer Engineering Faculty Publications

Plasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids …

Qu-Brats: Miccai Brats 2020 Challenge On Quantifying Uncertainty In Brain Tumor Segmentation - Analysis Of Ranking Scores And Benchmarking Results, Raghav Mehta, Angelos Filos, Ujjwal Baid, Chiharu Sako, Richard Mckinley, Michael Rebsamen, Katrin Dätwyler, Raphael Meier, Piotr Radojewski, Gowtham Krishnan Murugesan, Sahil Nalawade, Chandan Ganesh, Ben Wagner, Fang F. Yu, Baowei Fei, Ananth J. Madhuranthakam, Joseph A. Maldjian, Laura Daza, Catalina Gómez, Pablo Arbeláez, Chengliang Dai, Shuo Wang, Hadrien Reynaud, Yuan-Han Mo, Elsa Angelini, Yike Guo, Wenjia Bai, Subhashis Banerjee, Lin-Min Pei, Murat Ak, Sarahi Rosas-González, Ilyess Zemmoura, Clovis Tauber, Minh H. Vu, Tufve Nyholm, Tommy Löfstedt, Laura Mora Ballestar, Veronica Vilaplana, Hugh Mchugh, Gonzalo Maso Talou, Alan Wang, Jay Patel, Ken Chang, Katharina Hoebel, Mishka Gidwani, Nishanth Arun, Sharut Gupta, Mehak Aggarwal, Praveer Singh, Elizabeth R. Gerstner, Jayashree Kalpathy-Cramer, Nicholas Boutry, Alexis Huard, Lasitha Vidyaratne, Md. Monibor Rahman, Khan M. Iftekharuddin, Joseph Chazalon, Elodie Puybareau, Guillaume Tochon, Jun Ma, Mariano Cabezas, Xavier Llado, Arnau Oliver, Liliana Valencia, Sergi Valverde, Mehdi Amian, Mohammadreza Soltaninejad, Andriy Myronenko, Ali Hatamizadeh, Xue Feng, Quan Dou, Nicholas Tustison, Craig Meyer, Nisarg A. Shah, Sanjay Talbar, Marc-André Weber, Abhishek Mahajan, Andras Jakab, Roland Wiest, Hassan M. Fathallah-Shaykh, Arash Nazeri, Mikhail Milchenko1, Daniel Marcus, Aikaterini Kotrotsou, Rivka Colen, John Freymann, Justin Kirby, Christos Davatzikos, Bjoern Menze, Spyridon Bakas, Yarin Gal, Tal Arbel

Electrical & Computer Engineering Faculty Publications

Deep learning (DL) models have provided the state-of-the-art performance in a wide variety of medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder the translation of DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties, could enable clinical review of the most uncertain regions, thereby building trust and paving the way towards clinical translation. Recently, a number of uncertainty estimation methods have been introduced for DL medical image segmentation tasks. …

Uncertainty Estimation In Classification Of Mgnt Using Radiogenomics For Glioblastoma Patients, W. Farzana, Z. A. Shboul, A. Temtam, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Glioblastoma Multiforme (GBM) is one of the most malignant brain tumors among all high-grade brain cancers. Temozolomide (TMZ) is the first-line chemotherapeutic regimen for glioblastoma patients. The methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) gene is a prognostic biomarker for tumor sensitivity to TMZ chemotherapy. However, the standardized procedure for assessing the methylation status of MGMT is an invasive surgical biopsy, and accuracy is susceptible to resection sample and heterogeneity of the tumor. Recently, radio-genomics which associates radiological image phenotype with genetic or molecular mutations has shown promise in the non-invasive assessment of radiotherapeutic treatment. This study proposes a machine-learning framework …

Radiomic Texture Feature Descriptor To Distinguish Recurrent Brain Tumor From Radiation Necrosis Using Multimodal Mri, M. S. Sadique, A. Temtam, E. Lappinen, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Despite multimodal aggressive treatment with chemo-radiation-therapy, and surgical resection, Glioblastoma Multiforme (GBM) may recur which is known as recurrent brain tumor (rBT), There are several instances where benign and malignant pathologies might appear very similar on radiographic imaging. One such illustration is radiation necrosis (RN) (a moderately benign impact of radiation treatment) which are visually almost indistinguishable from rBT on structural magnetic resonance imaging (MRI). There is hence a need for identification of reliable non-invasive quantitative measurements on routinely acquired brain MRI scans: pre-contrast T1-weighted (T1), post-contrast T1-weighted (T1Gd), T2-weighted (T2), and T2 Fluid Attenuated Inversion Recovery (FLAIR) that can …

Trials And Tribulations Of Humanizing Mice For Cancer Research, Brittney Ruedlinger, Steven Warsof, Eric Feliberti, Mary Beth Hughes, Ayobami ‘Edwin’ Oshin, Chunqi Jiang, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

The Graduate School Posters

Cancers are aggressive, evasive, and ruthless killers, claiming millions of lives every year. Cancers are heterogeneous and there is often no single, clearly defined problem as they harness and manipulate a multitude of fundamental mechanisms at the very essence of life. To investigate these mechanisms and vet potential interventive therapies, humanized mice offer a unique model as a prelude to the use of nanosecond pulse stimulation (NPS), a pulse power technology applying nanosecond duration, high electric field pulses, to ablate human tumors. Immunodeficient mouse strains, NSG and NSG-SGM3, were engrafted with human immune cells and human tumors, which would allow …

Modulation Of Ros In Nanosecond-Pulsed Plasma-Activated Media For Dosage-Dependent Cancer Cell Inactivation In Vitro, Chunqi Jiang, Esin Bengisu Sozer, Shutong Song, Nicola Lai, P. Thomas Vernier, Sigi Guo

Bioelectrics Publications

Dosage control of reactive oxygen and nitrogen species (RONS) is critical to low-temperature plasma applications in cancer therapy. Production of RONS by atmospheric pressure, nonequilibrium plasmas in contact with liquid may be modulated via plasma conditions including plasma treatment time and pulse voltage and repetition frequency. In this study, a terephthalic acid-based probe was used to measure hydroxyl radicals [OH_aq] in water exposed to plasma and to demonstrate that the OH_ag concentration increases linearly with treatment time. Fluorometric measurements of hydrogen peroxide concentration in plasma-activated water show a linear relationship between the H₂O₂ production …

Impedance Analysis Of Tissues In Nspef Treatment For Cancer Therapy, Edwin Ayobami Oshin

Biomedical Engineering Theses & Dissertations

Nanosecond pulsed electric field (nsPEF) for cancer therapy is characterized by applications of high voltage pulses with low pulsed energy to induce non-thermal effects on tissues such as tumor ablation. It nonthermally treats tissues via electroporation. Electroporation is the increase in permeabilization of a cell membrane due to the application of high pulsed electric field. The objective of this study was to investigate the effect of nsPEF on tissue by monitoring the tissue’s impedance in real-time. Potato slices (both untreated and electroporated), and tumors extracted from female BALBc mice were studied. 100ns, 1-10kV pulses were applied to the tissues using …

Biomimetic Metal-Organic Nanoparticles Prepared With A 3d-Printed Microfluidic Device As A Novel Formulation For Disulfiram-Based Therapy Against Breast Cancer, Ya Chang, Jizong Jiang, Wu Chen, Wen Yang, Lili Chen, Pengyu Chen, Jianzhong Shen, Shizhi Qian, Teng Zhou, Linfeng Wu, Liang Hong, Yongzhuo Huang, Feng Li

Mechanical & Aerospace Engineering Faculty Publications

Disulfiram (DSF) is currently tested in several clinical trials for cancer treatment in combination with cop-per (Cu) ions. Usually, DSF and Cu are administered in two separate formulations. In the body, DSF andCu ions form diethyldithiocarbamate copper complex [Cu(DDC)₂] which has potent antitumor activities.However, the “two formulation” approach often achieved low Cu(DDC)₂ concentration at tumor regions and resulted in compromised anticancer efficacy. Therefore, preformed Cu(DDC)₂ complex administered in a single formulation will have better anticancer efficacy. However, the poor aqueous solubility of Cu(DDC)₂ is a significant challenge for its clinical use. In this work, a …

Intratumoral Delivery Of Plasmid Il12 Via Electroporation Leads To Regression Of Injected And Noninjected Tumors In Merkel Cell Carcinoma, Shailender Bhatia, Natalie V. Longino, Natalie J. Miller, Rima Kulikauskas, Jayasri G. Iyer, Dafina Ibrani, Astrid Blom, David R. Byrd, Upendra Parvathaneni, Christopher Twitty, Jean S. Campbell, Mai H. Le, Sharron Gargosky, Robert H. Pierce, Richard Heller, Adil Daud, Paul Nghiem

Bioelectrics Publications

Purpose: Interleukin-12 (IL12) promotes adaptive type I immunity and has demonstrated antitumor efficacy, but systemic administration leads to severe adverse events (AE), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer.

Experimental Design: Fifteen patients with MCC with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (cohort A, N = 3) received one cycle before definitive surgery in week 4. …

Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied By Immunogenic Cell Death In Murine Models Of Lymphoma And Colorectal Cancer, Alessandra Rossi, Olga N. Pakhomova, Peter A. Mollica, Maura Casciola, Uma Mangalanathan, Andrei G. Pakhomov, Claudia Muratori

Bioelectrics Publications

Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of …

Il-12 Gene Electrotransfer Triggers A Change In Immune Response Within Mouse Tumors, Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller

Bioelectrics Publications

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell …

Consistent And Reproducible Cultures Of Large-Scale 3d Mammary Epithelial Structures Using An Accessible Bioprinting Platform, John A. Reid, Peter M. Mollica, Robert D. Bruno, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Faculty Publications

Background: Standard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, limitations persist owing to the lack of control over cellular placement within the hydrogel. This results in experimental inconsistencies and random organoid morphology. Robust, high-throughput experimentation requires greater standardization of 3D epithelial culture techniques.

Methods: Here, we detail the use of a 3D bioprinting platform as an investigative tool to control the 3D formation of organoids through the "self-assembly" of human mammary epithelial cells. Experimental bioprinting procedures …

Moderate Heat Application Enhances The Efficacy Of Nanosecond Pulse Stimulation For The Treatment Of Squamous Cell Carcinoma, Chelsea M. Edelblute, Sigi Guo, Embo Yang, Chunqi Jiang, Karl Schoenbach, Richard Heller

Bioelectrics Publications

Nanosecond pulse stimulation as a tumor ablation therapy has been studied for the treatment of various carcinomas in animal models and has shown a significant survival benefit. In the current study, we found that moderate heating at 43°C for 2 minutes significantly enhanced in vitro nanosecond pulse stimulation-induced cell death of KLN205 murine squamous cell carcinoma cells by 2.43-fold at 600 V and by 2.32-fold at 900 V, as evidenced by propidium iodide uptake. Furthermore, the ablation zone in KLN205 cells placed in a 3-dimensional cell-culture model and pulsed at a voltage of 900 V at 43°C was 3 times …

Targeting Ovarian Cancer And Endothelium With An Allosteric Ptp4a3 Phosphatase Inhibitor, Kelley E. Mcqueeney, Joseph M. Salamoun, James C. Burnett, Nektarios Barabutis, Paula Pekic, Sophie L. Lewandowski, Danielle C. Llaneza, Robert Cornelison, Yunpeng Bai, Zhong-Yin Zhang, John D. Catravas

Bioelectrics Publications

Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways. While phosphatases are attractive therapeutic targets, they have been poorly investigated because of a lack of potent and selective chemical probes. In this study, we disclose that a potent, …

Alteration Of Metabolite Profiling By Cold Atmospheric Plasma Treatment In Human Myeloma Cells, Dehui Xu, Yujing Xu, Ning Ning, Qingjie Cui, Zhijie Liu, Xiaohua Wang, Dingxin Liu, Hailan Chen, Michael G. Kong

Bioelectrics Publications

BACKGROUND: Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet.

METHODS: In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and …

Electrotransfer Of Different Control Plasmids Elicits Different Antitumor Effectiveness In B16.F10 Melanoma, Masa Bosnjak, Tanjo Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller, Maja Cemazar

Bioelectrics Publications

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were …

Nano-Pulse Stimulation For The Treatment Of Pancreatic Cancer And The Changes In Immune Profile, Sigi Guo, Niculina I. Burcus, James Hornef, Yu Jing, Chunqi Jiang, Richard Heller, Stephen J. Beebe

Bioelectrics Publications

A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to …

Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma And Induces Innate And Adaptive Memory Immune Mechanisms That Prevent Recurrence, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

Bioelectrics Publications

Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver. NPS induced specific increases in NKs and NKT-cells expressing CD8 and activation receptors CD314-NKG2D and CD161 (NK1.1) in the TME …

Tumor Cell Death After Electrotransfer Of Plasmid Dna Is Associated With Cytosolic Dna Sensor Upregulation, Katarina Znidar, Masa Bosnjak, Nina Semenova, Olga N. Pakhomova, Loree Heller, Maja Cemazar

Bioelectrics Publications

Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA binding …

Upregulation Of Dna Sensors In B16.F10 Melanoma Spheroid Cells After Electrotransfer Of Pdna, Katarina Znidar, Masa Bosnjak, Tanja Jesenko, Loree C. Heller, Maja Cemazar

Bioelectrics Publications

Increased expression of cytosolic DNA sensors, a category of pattern recognition receptor, after control plasmid DNA electrotransfer was observed in our previous studies on B16.F10 murine melanoma cells. This expression was correlated with the upregulation of proinflammatory cytokines and chemokines and was associated with cell death. Here, we expanded our research to include the influence of features of cells in a 3-dimensional environment, which better represents the tumors’ organization in vivo. Our results show that lower number of cells were transfected in spheroids compared to 2-dimensional cultures, that growth was delayed after electroporation alone or after electrotransfer of plasmid …

Electrosensitization Increases Antitumor Effectiveness Of Nanosecond Pulsed Electric Fields In Vivo, Claudia Muratori, Andrei G. Pakhomov, Loree Heller, Maura Casciola, Elena Gianulis, Sergey Grigoryev, Shu Xiao, Olga N. Pakhomova

Bioelectrics Publications

Nanosecond pulsed electric fields are emerging as a new modality for tissue and tumor ablation. We previously reported that cells exposed to pulsed electric fields develop hypersensitivity to subsequent pulsed electric field applications. This phenomenon, named electrosensitization, is evoked by splitting the pulsed electric field treatment in fractions (split-dose treatments) and causes in vitro a 2- to 3-fold increase in cytotoxicity. The aim of this study was to show the benefit of split-dose treatments for in vivo tumor ablation by nanosecond pulsed electric field. KLN 205 squamous carcinoma cells were embedded in an agarose gel or grown subcutaneously as tumors …

Plasma Processes And Polymers Third Special Issue On Plasma And Cancer, Mounir Laroussi, Annemie Bogaerts, Nazir Barekzi

Electrical & Computer Engineering Faculty Publications

(First paragraph) This issue of Plasma Processes and Polymers is the third in a series on the applications of low temperature plasma (LTP) against cancer, or “plasma oncology.” The papers in this issue are inspired from the talks given at the third International Workshop on Plasma for Cancer Treatment (IWPCT) which took place on April 11–12, 2016 in Washington, DC, USA. IWPCT is an international workshop that was created in 2014 as a venue to share cutting edge plasma oncology research. The first IWPCT was held in Washington DC, under the co-chairmanship of Prof. Mounir Laroussi (Old Dominion University) and …

Radio-Frequency Plasma Polymerized Biodegradable Carrier For In Vivo Release Of Cis-Platinum, Sudhir Bhatt, Fatemeh Valamanesh, Jerome Pulpytel, Rea Lo Dico, Aliby Baiyukha, Iman Al-Dybiat, Marc Pocard, Farzaneh Arefi-Khonsari, Massoud Mirshahi

Bioelectrics Publications

A low pressure plasma process based on plasma deposition has been used to develop a drug delivery strategy. In this study, a drug delivery system based on different layers of plasma co-polymerized Poly ε-caprolactone-Polyethylene glycol (PCL-PEG) co-polymers was deposited on biocompatible substrates. Cis-platinum (118 μgm/cm²) was used as an anti-cancer drug and incorporated for local delivery of the chemotherapeutic agent. The co-polymer layers and their interaction with cancer cells were analyzed by scanning electron microscopy. Our study showed that the plasma-PCL-PEG coated cellophane membranes, in which the drug, was included did not modify the flexibility and appearance of …

Electrotransfer Of Single-Stranded Or Double-Stranded Dna Induces Complete Regression Of Palpable B16.F10 Mouse Melanomas, Loree Heller, Vesba Todorovic, Maja Cemazar

Bioelectrics Publications

Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of single-stranded or double-stranded DNA with or without CpG motifs in both …

Synergistic Effect Of Subnanosecond Pulsed Electric Fields And Temperature On The Viability Of Biological Cells, James Thomas Camp

Electrical & Computer Engineering Theses & Dissertations

Pulsed electric fields have been used to induce a biological response in cells, and at sufficient energy, can cause cell death. By reducing the pulse duration from presently used nanosecond to subnanosecond ranges, the electric field can be delivered to biological tissue non-invasively by the use of an antenna instead of electrodes, such as needles. Studies have previously been completed in which the aim was to determine the energy density (electric field strength, number of pulses) required to induce cell death with 800 ps pulses. Based on this data, it was concluded that for pulse durations of 200 ps, with …

A New Pulsed Electric Field Therapy For Melanoma Disrupts The Tumor's Blood Supply And Causes Complete Remission Without Recurrence, Richard Nuccitelli, Xinhua Chen, Andrei G. Pakhomov, Wallace H. Baldwin, Saleh Sheikh, Jennifer L. Pomicter, Wei Ren, Chris Osgood, R. James Swanson, Juergen F. Kolb, Stephen J. Beebe, Karl H. Schoenbach

Bioelectrics Publications

We have discovered a new, ultrafast therapy for treating skin cancer that is extremely effective with a total electric field exposure time of only 180 mu sec. The application of 300 high-voltage (40 kV/cm), ultrashort (300 nsec) electrical pulses to murine melanomas in vivo triggers both necrosis and apoptosis, resulting in complete tumor remission within an average of 47 days in the 17 animals treated. None of these melanomas recurred during a 4-month period after the initial melanoma had disappeared. These pulses generate small, long-lasting, rectifying nanopores in the plasma membrane of exposed cells, resulting in increased membrane permeability to …

The Application Of Innovative High-Throughput Techniques To Serum Biomarker Discovery, Izabela Debkiewicz Karbassi

Theses and Dissertations in Biomedical Sciences

Time-of-flight mass spectrometry continues to evolve as a promising technique for serum protein expression profiling and biomarker discovery. As seen in our initial SELDI-TOF MS and MALDI-TOF MS profiling study of serum for the assessment of breast cancer risk, many profiling strategies typically employ single chemical affinity beads or surfaces to decrease sample complexity of dynamic fluids like serum. However, most proteins, captured on a particular surface or bead, are not resolved in the lower mass range where mass spectrometers are most effective. To this end we have designed an expression profiling workflow that utilizes immobilized trypsin paramagnetic beads in …