scholarly journals Non-Thermal Plasma Application in Tumor-Bearing Mice Induces Increase of Serum HMGB1

2020 ◽  
Vol 21 (14) ◽  
pp. 5128
Author(s):  
Olga Troitskaya ◽  
Ekaterina Golubitskaya ◽  
Mikhail Biryukov ◽  
Mikhail Varlamov ◽  
Pavel Gugin ◽  
...  
Keyword(s):  
Cultured Cells ◽  
High Mobility ◽  
Atmospheric Plasma ◽  
Hmgb1 Level ◽  
Cold Atmospheric Plasma ◽  
Tumor Bearing ◽  
Non Thermal Plasma ◽  
Dying Cells ◽  
Serum Hmgb1 Level

The application of cold atmospheric plasma (CAP) in cancer therapy could be one of the new anticancer strategies. In the current work, we used cold atmospheric plasma jet for the treatment of cultured cells and mice. We showed that CAP induced the death of MX−7 mouse rhabdomyosarcoma cells with the hallmarks of immunogenic cell death (ICD): calreticulin and heat shock protein 70 (HSP70) externalization and high-mobility group box 1 protein (HMGB1) release. The intensity of HMGB1 release after the CAP treatment correlated directly with the basal extracellular HMGB1 level. Releasing from dying cells, HMGB1 can act as a proinflammatory cytokine. Our in vivo study demonstrated that cold atmospheric plasma induces a short-term two-times increase in serum HMGB1 level only in tumor-bearing mice with no effect in healthy mice. These findings support our hypothesis that CAP-dependent HMGB1 release from dying cancer cells can change the serum HMGB1 level. At the same time, we showed a weak cytokine response to CAP irradiation in healthy mice that can characterize CAP as an immune-safety physical antitumor approach.

Targeting Protective Catalase of Tumor Cells with Cold Atmospheric Plasma- Activated Medium (PAM)

2018 ◽  
Vol 18 (6) ◽  
pp. 784-804 ◽  
Author(s):  
Georg Bauer
Keyword(s):  
Control System ◽  
Singlet Oxygen ◽  
Tumor Cells ◽  
Plasma Potential ◽  
Atmospheric Plasma ◽  
Antitumor Action ◽  
Active Principle ◽  
Reaction Products ◽  
Cold Atmospheric Plasma

Background: Application of cold atmospheric plasma to medium generates “plasma-activated medium” that induces apoptosis selectively in tumor cells and that has an antitumor effect in vivo. The underlying mechanisms are not well understood. Objective: Elucidation of potential chemical interactions within plasma-activated medium and of reactions of medium components with specific target structures of tumor cells should allow to define the active principle in plasma activated medium. Methods: Established knowledge of intercellular apoptosis-inducing reactive oxygen/nitrogen species-dependent signaling and its control by membrane-associated catalase and SOD was reviewed. Model experiments using extracellular singlet oxygen were analyzed with respect to catalase inactivation and their relevance for the antitumor action of cold atmospheric plasma. Potential interactions of this tumor cell-specific control system with components of plasma-activated medium or its reaction products were discussed within the scope of the reviewed signaling principles. Results: None of the long-lived species found in plasma-activated medium, such as nitrite and H2O2, nor OCl- or .NO seemed to have the potential to interfere with catalase-dependent control of apoptosis-inducing signaling of tumor cells when acting alone. However, the combination of H2O2 and nitrite might generate peroxynitrite. The protonation of peroxnitrite to peroxynitrous acid allows for the generation of hydroxyl radicals that react with H2O2, leading to the formation of hydroperoxide radicals. These allow for singlet oxygen generation and inactivation of membrane-associated catalase through an autoamplificatory mechanism, followed by intercellular apoptosis-inducing signaling. Conclusion: Nitrite and H2O2 in plasma-activated medium establish singlet oxygen-dependent interference selectively with the control system of tumor cells.

The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer Treatment

2018 ◽  
Vol 18 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Dayun Yan ◽  
Jonathan H. Sherman ◽  
Michael Keidar
Keyword(s):  
Cancer Treatment ◽  
Atmospheric Plasma ◽  
Current Status ◽  
Cold Atmospheric Plasma ◽  
Anti Cancer ◽  
Long Time ◽  
Key Topics ◽  
The Common

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.

scholarly journals INNV-13. SYNERGISTIC EFFECT OF COLD ATMOSPHERIC PLASMA IN COMBINATION WITH TEMOZOLOMIDE TO TREAT GLIOBLASTOMA IN A NON-INVASIVE MOUSE XENOGRAFT MODEL

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii119-ii119
Author(s):  
Manish Adhikari ◽  
Vikas Soni ◽  
Simonyan Hayk ◽  
Colin Young ◽  
Jonathan Sherman ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Tumor Volume ◽  
Bioluminescence Imaging ◽  
Xenograft Model ◽  
Atmospheric Plasma ◽  
Minimal Effect ◽  
Cold Atmospheric Plasma ◽  
Mouse Xenograft Model ◽  
In Vivo Bioluminescence Imaging

Abstract INTRODUCTION A primary limitation in anti-cancer therapy is the resistance of cancer cells to chemotherapeutic drugs. However, combination therapy may be an effective approach for reducing drug derived toxicity and evading drug resistance, resulting in improved clinical treatment of cancer. Our prior work demonstrated effective treatment of glioblastoma (GBM) with cold atmospheric plasma (CAP) technology with minimal effect to normal cells. Consequently, CAP may serve as a strong candidate for combination therapy with the classical antineoplastic alkylating agent Temozolomide (TMZ) to treat GBM. OBJECTIVES To determine the in vivo co-efficacy of CAP and TMZ to “sensitize” GBM. METHODS An in vivo study was performed using the CAP jet device (He-gas) to determine the effect of combined CAP–TMZ treatment. U87MG-luc glioblastoma cells were implanted intracranially in athymic nude NU(NCr)-Foxn1nu/immunodeficient mice. He-CAP (or control He alone) was non-invasively applied over the skin for 60sec to developed tumors on the first day of the treatment followed with 6.5 mg/kg TMZ or vehicle control treatment for 5 days for two weeks (n=5/group). In vivo bioluminescence imaging was used to monitor tumor volume on the 6th, 9th and 13th treatment day. RESULTS In vivo bioluminescence imaging revealed a marked 8.0±3.2 fold increase in tumor volume in control animals (He-vehicle). Treatment with He-TMZ (6.7±2.5 fold) or CAP-vehicle (4.8±1.7 fold) in isolation had minimal effect in preventing tumor growth. However, combined CAP-TMZ co-treatment virtually prevented increases in tumor volume over 2 weeks (1.8±0.2 fold). CONCLUSIONS Collectively, these findings indicate an effective synergistic treatment method for GBM combining CAP with TMZ. Future investigations look to incorporate radiation into the treatment regimen as well as primary GBM cell models.

scholarly journals The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo

2020 ◽  
Vol 17 (3) ◽  
pp. 851-863 ◽  
Author(s):  
Rui He ◽  
Qin Li ◽  
Wenqi Shen ◽  
Tao Wang ◽  
Huijuan Lu ◽  
...  
Keyword(s):  
Atmospheric Plasma ◽  
Diabetic Wound ◽  
Efficacy And Safety ◽  
Novel Therapy ◽  
Cold Atmospheric Plasma

scholarly journals Comparative Study between Direct and Indirect Treatment with Cold Atmospheric Plasma on In Vitro and In Vivo Models of Wound Healing

2018 ◽  
Vol 8 (4) ◽  
pp. 379-401 ◽  
Author(s):  
Constance Duchesne ◽  
Nadira Frescaline ◽  
Jean-Jacques Lataillade ◽  
Antoine Rousseau
Keyword(s):  
Wound Healing ◽  
Comparative Study ◽  
Atmospheric Plasma ◽  
In Vivo Models ◽  
Cold Atmospheric Plasma ◽  
Indirect Treatment

scholarly journals The Emerging Role of Cold Atmospheric Plasma in Implantology: A Review of the Literature

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1505 ◽  
Author(s):  
Wang Lai Hui ◽  
Vittoria Perrotti ◽  
Flavia Iaculli ◽  
Adriano Piattelli ◽  
Alessandro Quaranta
Keyword(s):  
New Technologies ◽  
Atmospheric Plasma ◽  
Oral Diseases ◽  
Air Plasma ◽  
Review Of The Literature ◽  
Air Abrasion ◽  
Cold Atmospheric Plasma ◽  
Osteoblast Activity

In recent years, cold atmospheric plasma (CAP) technologies have received increasing attention in the field of biomedical applications. The aim of this article is to review the currently available literature to provide an overview of the scientific principles of CAP application, its features, functions, and its applications in systemic and oral diseases, with a specific focus on its potential in implantology. In this narrative review, PubMed, Medline, and Scopus databases were searched using key words like “cold atmospheric plasma”, “argon plasma”, “helium plasma”, “air plasma”, “dental implants”, “implantology”, “peri-implantitis”, “decontamination”. In vitro studies demonstrated CAP’s potential to enhance surface colonization and osteoblast activity and to accelerate mineralization, as well as to determine a clean surface with cell growth comparable to the sterile control on both titanium and zirconia surfaces. The effect of CAP on biofilm removal was revealed in comparative studies to the currently available decontamination modalities (laser, air abrasion, and chlorhexidine). The combination of mechanical treatments and CAP resulted in synergistic antimicrobial effects and surface improvement, indicating that it may play a central role in surface “rejuvenation” and offer a novel approach for the treatment of peri-implantitis. It is noteworthy that the CAP conditioning of implant surfaces leads to an improvement in osseointegration in in vivo animal studies. To the best of our knowledge, this is the first review of the literature providing a summary of the current state of the art of this emerging field in implantology and it could represent a point of reference for basic researchers and clinicians interested in approaching and testing new technologies.

Dynamic Defense System Against HMGB1, a Proinflammatory and Lethal Mediator in Severe Infections and Malignancies.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3827-3827
Author(s):  
Takashi Ito ◽  
Kazuhiro Abeyama ◽  
Ko-ichi Kawahara ◽  
Kamal K. Biswas ◽  
Tomonori Uchimura ◽  
...  
Keyword(s):  
Tissue Injury ◽  
High Mobility ◽  
Inflammatory Cells ◽  
Defense System ◽  
Hmgb1 Level ◽  
Beneficial Effects ◽  
Extracellular Milieu ◽  
Severe Infections ◽  
Serum Hmgb1 Level ◽  
Severe Tissue

Abstract High Mobility Group box 1(HMGB1) is an abundant DNA-binding protein that acts as a proinflammatory cytokine when released in the extracellular milieu by necrotic and inflammatory cells. Moreover, an increased HMGB1 in the circulation of septic patients may induce multi-organ failure and lethality. However, very recent observations suggest that the protein also acts as an innate adjuvant, stem cell chemoattractant and growth factor. Thus only systemic and circulatory HMGB1 may induce morbidity and mortality, however, localized HMGB1 may have beneficial effects. Therefore, we serially examined the serum HMGB1 level in patients with various diseases, and also evaluated the significance of the protein. We demonstrate here how HMGB1 is localized and acts as an immune-adjuvant and a repairing factor in damaged tissue. We first established specific ELISA method to measure HMGB1. An increased level of HMGB1 was detected in the serum from patients with sever sepsis, infections, malignancy and so on. However, serum HMGB1 concentrations were fluctuated during the clinical course, and could not be concluded as a lethal mediator as previously reported. Next we investigated the reason of dynamic fluctuations of the protein in the circulation. Based on our findings, we proposed that this fluctuation of HMGB1 concentrations may be mediated by at least following three fashions; 1) proteolytic degradation by plasmin and thrombin, 2) endothelial thrombomodulin(TM) adsorption, and 3) generation of antibody against the protein. We observed that plasmin efficiently degraded HMGB1 into small fragments. However, interestingly the generated fragments of the protein still possess an ability to produce TNFa in macrophages through an undefined pathway. TM binds the protein on its N-terminus lectin-like domain. Binding of HMGB1 to TM resulted in decrement of TM’s cofactor activity to activate protein C by thrombin. HMGB1 bound to TM was gradually degraded by thrombin. These may be a system to localize HMGB1 only in injury sites where TM is down-regulated or disappeared through endothelial-loss. This may exert endothelial defense system against extracellular HMGB1 in severe tissue injury. Another possibility is that the generated antibody against HMGB1 may neutralize the proinflammatory action of the protein. In this context, we found that some of the antibodies against HMGB1 have the characteristics of P-ANCA(perinuclear anti-neutrophil cytoplasmic antibody). This may alter the phenotype of the underlining diseases. In conclusion, we suggest that HMGB1 is not merely a lethal mediator, but a kind of “testament” mediator of cell necrosis or invasive attacks to dendritic cells.

In vivo skin treatment using two portable plasma devices: Comparison of a direct and an indirect cold atmospheric plasma treatment

2013 ◽  
Vol 1 (2) ◽  
pp. 35-39 ◽  
Author(s):  
Y.-F. Li ◽  
D. Taylor ◽  
J.L. Zimmermann ◽  
W. Bunk ◽  
R. Monetti ◽  
...  
Keyword(s):  
Plasma Treatment ◽  
Atmospheric Plasma ◽  
Cold Atmospheric Plasma

scholarly journals Effects of Cold Atmospheric Plasma (CAP) on ß-Defensins, Inflammatory Cytokines, and Apoptosis-Related Molecules in Keratinocytes In Vitro and In Vivo

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120041 ◽  
Author(s):  
Stephanie Arndt ◽  
Michael Landthaler ◽  
Julia L. Zimmermann ◽  
Petra Unger ◽  
Eva Wacker ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Atmospheric Plasma ◽  
Cold Atmospheric Plasma

scholarly journals Diagnostic value of matrix metalloproteinase-2 and high mobility group box 1 in patients with refractory epilepsy

2020 ◽  
Vol 56 (1) ◽  
Author(s):  
Khalid S. Salih ◽  
Farqad B. Hamdan ◽  
Qasim S. Al-Mayah
Keyword(s):  
Roc Curve ◽  
Refractory Epilepsy ◽  
High Mobility ◽  
Serum Levels ◽  
Diagnostic Value ◽  
High Mobility Group ◽  
Matrix Metalloproteinase 2 ◽  
Hmgb1 Level ◽  
Epileptic Patients ◽  
Serum Hmgb1 Level

Abstract Introduction There are large numbers of inflammatory molecules and humoral mediators that can be involved in the epileptogenesis such as cytokines, matrix metalloproteinases (MMP), and high mobility group box-1 (HMGB1). We aimed to evaluate serum levels and the diagnostic value of MMP-2 and HMGB1 in Iraqi patients with epilepsy. Methods One hundred epileptic patients comprised 60 controlled epileptics and 40 refractory patients to treatment with multi antiepileptic drugs (AEDs). Other 50 family-unrelated age- and sex-matched healthy subjects were selected to represent the control group. Serum levels of MMP-2 and HMGB1 were estimated using ELISA. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of these markers when required. Results MMP-2 level was significantly higher in controls than epileptic patients in general (controlled and refractory patients). ROC curve, showed poor diagnostic value of MMP-2 in discriminating epileptics into responsive or refractory to treatment from controls (AUC = 0.679 (95% CI = 0.536-0.823), and AUC = 0.77 (95% CI = 0.637-902), respectively). Serum HMGB1 level in epileptic patients and controls was in close approximation to each other. Conclusions MMP-2 is significantly decreased in patients particularly those with refractory epilepsy (RE); however, it has poor diagnostic value. No difference in the serum HMGB1 level between epileptic patients and controls.

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