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Electric Field Based Therapies for Cancer: A Selection of Papers...
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Electric Field Based Therapies for Cancer: A Selection of Papers from the 2nd World Congress on Electroporation

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 November 2017) | Viewed by 19963

Special Issue Editors

Prof. Dr. Richard Heller

E-Mail Website
Guest Editor
Department of Medical Engineering, University of South Florida, Tampa, FL 33612, USA
Interests: DNA vaccines; gene electrotransfer; tumor immunology; drug delivery; device and protocol development; immunotherapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Gregor Sersa

E-Mail Website
Guest Editor
1. Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia
2. Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, SI-1000 Ljubljana, Slovenia
Interests: tumor biology; electroporation-based treatments
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Cancers will consist of selected papers from the “2nd World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine, Food and Environmental Technologies”. The meeting was held September 24–28, 2017, in Norfolk, Virginia, USA. This cross-disciplinary meeting was organized to bring together the best in biological, industrial and food processing research to catalyze innovations and stimulate discussions and enhance existing collaborations or initiate new ones. The 2nd World Congress is affiliated and organized by the International Society of Electroporation Based Technologies and Treatments. The major topics included in the Congress were: basic biology of electroporation; basics, modeling of electroporation including MD simulations, technology for PEF and large Treatment capacities; technology for electric pulses for research and medical applications; medical applications; food industry applications; environmental applications; micro and nanotechnologies; and non-thermal plasma. The format of this cross-disciplinary meeting afforded attendees the opportunity to hear about the latest research findings in other related fields and to encourage exchange of ideas. This Special Issue will cover the latest research pertaining to Electroporation Based Technologies and Therapeutic Applications. This will include contributions related to basic, as well as applied, science.

Prof. Richard Heller
Prof. Dr. Gregor Sersa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (4 papers)

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Research

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13 pages, 3095 KiB  
Article
Nano-Pulse Stimulation for the Treatment of Pancreatic Cancer and the Changes in Immune Profile
by Siqi Guo, Niculina I. Burcus, James Hornef, Yu Jing, Chunqi Jiang, Richard Heller and Stephen J. Beebe
Cancers 2018, 10(7), 217; https://doi.org/10.3390/cancers10070217 - 27 Jun 2018
Cited by 24 | Viewed by 4963
Abstract
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 [...] Read more.
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 the induction of immune-mediated protection from a second tumor challenge in orthotopic mouse breast and rat liver cancer models. In the Pan02 model, there were insufficient abscopal effects (1/10) and vaccine-like protective effects (1/15) suggesting that NPS-induced immune mechanisms in this model were limited. To evaluate this further, the immune landscape was analyzed. The numbers of both T regulatory cells (Tregs) and myeloid derived suppressor cells (MDSCs) in blood were significantly reduced, but memory (CD44+) T-cells were absent. Furthermore, the numbers of Tregs and MDSCs did not reduce in spleens compared to tumor-bearing mice. Very few T-cells, but large numbers of MDSCs were present in the NPS treated tumor microenvironment (TME). The number of dendritic cells in the TME was increased and multiple activation markers were upregulated following NPS treatment. Overall, NPS treatments used here are effective for pancreatic tumor ablation, but require further optimization for induction of immunity or the need to include effective combinational NPS therapeutic strategy for pancreatic cancer. Full article
(This article belongs to the Special Issue Electric Field Based Therapies for Cancer: A Selection of Papers from the 2nd World Congress on Electroporation)
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14 pages, 2414 KiB  
Article
Clinically Usable Interleukin 12 Plasmid without an Antibiotic Resistance Gene: Functionality and Toxicity Study in Murine Melanoma Model
by Urska Kamensek, Natasa Tesic, Gregor Sersa and Maja Cemazar
Cancers 2018, 10(3), 60; https://doi.org/10.3390/cancers10030060 - 27 Feb 2018
Cited by 15 | Viewed by 4262
Abstract
Plasmids, which are currently used in interleukin 12 (IL-12) gene electrotransfer (GET) clinical trials in the USA, contain antibiotic resistance genes and are thus, according to the safety recommendation of the European Medicines Agency (EMA), not suitable for clinical trials in the EU. [...] Read more.
Plasmids, which are currently used in interleukin 12 (IL-12) gene electrotransfer (GET) clinical trials in the USA, contain antibiotic resistance genes and are thus, according to the safety recommendation of the European Medicines Agency (EMA), not suitable for clinical trials in the EU. In the current study, our aim was to prepare an IL-12 plasmid without an antibiotic resistance gene and test its functionality and toxicity after GET in a preclinical B16F10 mouse melanoma model. The antibiotic resistance-free plasmid encoding the human IL-12 fusion gene linked to the p21 promoter, i.e., p21-hIL-12-ORT, was constructed using operator-repressor titration (ORT) technology. Next, the expression profile of the plasmid after GET was determined in B16F10 cells and tumors. Additionally, blood chemistry, hematological and histological changes, and antitumor response were evaluated after GET of the plasmid in melanoma tumors. The results demonstrated a good expression and safety profile of the p21-hIL-12-ORT GET and indications of efficacy. We hope that the obtained results will help to accelerate the transfer of this promising treatment from preclinical studies to clinical application in the EU. Full article
(This article belongs to the Special Issue Electric Field Based Therapies for Cancer: A Selection of Papers from the 2nd World Congress on Electroporation)
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14 pages, 2231 KiB  
Article
Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma
by Masa Bosnjak, Tanja Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller and Maja Cemazar
Cancers 2018, 10(2), 37; https://doi.org/10.3390/cancers10020037 - 29 Jan 2018
Cited by 23 | Viewed by 4239
Abstract
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 [...] Read more.
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 determined. GET of all three plasmids caused significant growth delay in melanoma tumors; nevertheless, the effect of pVAX1 was significantly greater than pControl. While DNA sensors in vivo were not upregulated significantly, cytokines IFN β and TNF α were upregulated after GET of pVAX1. In vitro, the mRNAs of some cytosolic DNA sensors were overexpressed after GET; however, with no significant difference among the three plasmids. In summary, although differences in antitumor effects were observed among control plasmids in vivo, no differences in cellular responses to plasmid GET were detected in tumor cells in vitro. Thus, the tumor microenvironment as well as some plasmid properties are most probably responsible for the antitumor effectiveness. Full article
(This article belongs to the Special Issue Electric Field Based Therapies for Cancer: A Selection of Papers from the 2nd World Congress on Electroporation)
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Review

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11 pages, 2951 KiB  
Review
Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review
by Stephen J. Beebe, Brittany P. Lassiter and Siqi Guo
Cancers 2018, 10(4), 97; https://doi.org/10.3390/cancers10040097 - 30 Mar 2018
Cited by 22 | Viewed by 5779
Abstract
Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic [...] Read more.
Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases in memory effector and central memory T-lymphocytes in the blood and spleen. NPS also eliminates immunosuppressive cells in the tumor microenvironment and blood. Finally, NPS treatment of 4T1 breast cancer exhibits an abscopal effect and largely prevents spontaneous metastases to distant organs. NPS with fast rise–fall times and pulse durations near the plasma membrane charging time constant, which exhibits transient, high-frequency components (1/time = Hz), induce responses from mitochondria, endoplasmic reticulum, and nucleus. Such effects may be responsible for release of danger-associated molecular patterns, including ATP, calreticulin, and high mobility group box 1 (HMBG1) from 4T1-Luc cells to induce immunogenic cell death (ICD). This likely leads to immunity and the vaccine-like response. In this way, NPS acts as a unique onco-immunotherapy providing distinct therapeutic advantages showing possible clinical utility for breast cancers as well as for other malignancies. Full article
(This article belongs to the Special Issue Electric Field Based Therapies for Cancer: A Selection of Papers from the 2nd World Congress on Electroporation)
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