EXTH-11. COLD ATMOSPHERIC PLASMA SELECTIVELY INDUCES APOPTOSIS AND FERROPTOSIS THROUGH REACTIVE OXYGEN SPECIES IN HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi165-vi165
Author(s):  
Sophie Peeters ◽  
Zhitong Chen ◽  
Richard Obenchain ◽  
Blake Haist ◽  
Robert Prins ◽  
...  

Abstract INTRODUCTION Cold atmospheric plasma (CAP) selectively induces reactive oxygen and nitrogen species (ROS/RNS) in many types of cancerous cells. ROS-mediated lipid peroxidation is thought to induce ferroptosis, apoptosis, and autophagy. We hypothesize that ferroptosis and apoptosis are key mechanisms of CAP-mediated cytotoxicity in high-grade glioma (HGG). METHODS B16, U87, GL261, EPD-210FHTC and human astrocyte NHA hTERT cells were treated with CAP for 10, 30, 60, 90, and 180 seconds. Proliferation and propidium iodide (PI)/annexin V flow cytometry assays were employed to quantify cytotoxicity, cell cycle phases and apoptosis. Mitochondrial superoxide concentration was measured using MitoSOX Red. Cells were pre-treated with ferroptosis inhibitors Ferrostatin-1 and Deferoxamine (DFO) in rescue assays. RESULTS Survival of GL261 and U87 cells after 90 seconds of CAP treatment was 3.7% and 7%, respectively, compared to 62% in NHA cells. A CAP dose-dependent increase in mitochondrial superoxide concentration was observed in GL261 and NHA (R2=0.88 and 0.99, respectively). A shift of EPD and NHA cells into G0 phase was noted after 180 seconds of treatment, compared to baseline (55.4% versus 1.2%, 100% vs. 27.5% respectively). Early apoptosis was more prominent in NHA cells (79% of dead cells), and late apoptosis in EPD cells after 60 seconds of treatment (86% of dead cells). DFO pre-treatment significantly reduced CAP cytotoxicity in GL261 (93% vs. 58% after 10 seconds) and U87 cells (85% vs. 13% after 60 seconds). DFO pre-treatment had no effect on NHA response to CAP. CONCLUSION CAP treatment induces dose-dependent increases in ROS and apoptosis in HGG lines tested more significantly than in NHA cells. CAP induces G1-phase cell cycle arrest in treated HGG cells and G0 arrest in non-cancerous cells. CAP-mediated cytotoxicity was significantly mitigated with DFO pre-treatment in HGG cells, suggesting that ferroptosis plays a critical role in the mechanism of CAP treatment in HGG.

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 41
Author(s):  
Edgar Tavares-da-Silva ◽  
Eurico Pereira ◽  
Ana S. Pires ◽  
Ana R. Neves ◽  
Catarina Braz-Guilherme ◽  
...  

Antitumor therapies based on Cold Atmospheric Plasma (CAP) are an emerging medical field. In this work, we evaluated CAP effects on bladder cancer. Two bladder cancer cell lines were used, HT-1376 (stage III) and TCCSUP (stage IV). Cell proliferation assays were performed evaluating metabolic activity (MTT assay) and protein content (SRB assay). Cell viability, cell cycle, and mitochondrial membrane potential (Δψm) were assessed using flow cytometry. Reactive oxygen and nitrogen species (RONS) and reduced glutathione (GSH) were evaluated by fluorescence. The assays were carried out with different CAP exposure times. For both cell lines, we obtained a significant reduction in metabolic activity and protein content. There was a decrease in cell viability, as well as a cell cycle arrest in S phase. The Δψm was significantly reduced. There was an increase in superoxide and nitric oxide and a decrease in peroxide contents, while GSH content did not change. These results were dependent on the exposure time, with small differences for both cell lines, but overall, they were more pronounced in the TCCSUP cell line. CAP showed to have a promising antitumor effect on bladder cancer, with higher sensitivity for the high-grade cell line.


2017 ◽  
Vol 7-8 ◽  
pp. 46-51
Author(s):  
Leila Karami-Gadallo ◽  
Mahmood Ghoranneviss ◽  
Leila Ataie-Fashtami ◽  
Majid Pouladian ◽  
Dariush Sardari

2016 ◽  
Vol 94 (2) ◽  
pp. 297-304 ◽  
Author(s):  
Roshan Karunamuni ◽  
Hauke Bartsch ◽  
Nathan S. White ◽  
Vitali Moiseenko ◽  
Ruben Carmona ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2543-2543
Author(s):  
Seema Nagpal ◽  
Reena Parada Thomas ◽  
Sophie Bertrand ◽  
Hari Priya Yerraballa ◽  
Michael Iv ◽  
...  

2543 Background: BPM31510 is an ubidecarenone-lipid conjugate nanodispersion in clinical development for advanced malignancies, including high grade glioma (HGG). BPM31510’s anti-cancer effect is mediated by induction of mitochondrial superoxide and activation of cell death in glioblastoma models. Herein, we present preliminary pharmaco-kinetic and dynamic data, and survival from a phase I study of BPM31510 + Vitamin K in HGG with progression after bevacizumab (BEV). Methods: This was an open-label phase I study of BPM31510 continuous infusion with Vitamin K (10mg IM qweek) using a mTPI design, starting at 110mg/kg 2X/week, allowing 2 dose escalations & 1 de-escalation. Patients had received ChemoRT and were in recurrence after BEV. Results: Of 12 patients treated with BPM31510, 9 completed the 28-day DLT period. 2 patients came off study for progressive disease; 1 patient after asymptomatic hemorrhage into tumor bed (G1). 10 patients had primary GB, 2 had AA. Median age was 54.5yo (27-67) and KPS 70 (60-90). On Day 1 of BPM31510, a dose dependent increase in Cmax was observed; Tmax values were similar for all doses. AUC was linear with dose escalation. For all doses, Day 4 Cmax values were higher compared to Day 1. In contrast there was variable decrease in Tmax (table). Of evaluable patients, 4 patients received the highest dose 171mg/kg, where a single patient experienced DLT: G3 AST & ALT. The most common grade 1/2 AEs were elevated AST, rash, and fatigue, each occurring in 4 patients. The mOS for 9 eligible/evaluable patients was 128 days (95% CI: 48-209) while PFS was 34 days (95% CI of mean 8.9). Two patients are currently alive >12 months. Conclusions: BPM31510 + vitamin K demonstrated a safe profile to maximum dose of 171mg/kg twice/week with potential therapeutic utility in treatment-refractory HGG patients. Multi-omic molecular profiles characterizing AE and response to be reported from the study will be investigated for next phase of clinical development. Clinical trial information: NCT03020602 . [Table: see text]


2020 ◽  
Author(s):  
Meng Ning ◽  
Zhifa Zhang ◽  
Lihui Yu ◽  
Peiyu Han ◽  
xiaofeng Dai

Abstract BackgroundAndrogen receptor-independent prostate cancers do not respond to androgen blockage therapies and suffer from high recurrence rate. We aim to contribute to the establishment of novel therapeutic approaches against such malignancies.Methods We examined whether and how cold atmospheric plasma delivers selectivity against AR-independent prostate cancers using human normal epithelial prostatic cells PNT1A and AR-negative DU145 prostate cancer cells.ResultsWe show that cold atmospheric plasma could selectively halt cell proliferation and migration in androgen receptor-independent cells as a result of induced cell apoptosis and G0/G1 stage cell cycle arrest, and such outcomes were achieved through modulations on the MAPK and NF-kB pathways in response to physical plasma induced intracellular redox level. ConclusionOur study reports cold atmospheric plasma induced reduction on the proliferation and migration of androgen receptor-independent prostate cancer cells that offers novel therapeutic insights on the treatment of such cancers, and provides the first evidence on physical plasma induced cell cycle G0/G1 stage arrest that warrants the exploration on the synergistic use of cold atmospheric plasma and drugs such as chemotherapies in eradicating such cancer cells.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii359-iii359
Author(s):  
John Lucas ◽  
Chih-Yang Hsu ◽  
Jared Becksfort ◽  
Scott Hwang ◽  
Zhaohua Lu ◽  
...  

Abstract PURPOSE/OBJECTIVES Pediatric supratentorial high-grade glioma (stHGG) is a biologically heterogeneous disease defined by unique mutations, natural history and prognosis. Prior work by our group outlined a role for qualitative imaging features in aiding prognostication. We build on that work by evaluating the prognostic utility of radiomic features (RM) when paired with clinical factors. MATERIALS/ METHODS Ninety-one patients age < 21 years with stHGG treated between 1980–2007 were retrospectively reviewed. Prognostic clinical, qualitative imaging (Visually AcceSAble Rembrandt Images, VASARI), and treatment characteristics were evaluated in concert with manual and automatically segmented (DeepMedic), tumor-derived semi-quantitative radiomic features (Pyradiomics) extracted from MR images. Prognostic RM were limited to stable imaging features which were subsequently selected using bootstrapped least absolute shrinkage and selection operator (LASSO). Nonparametric descriptive statistics and prognostication model evaluation, incorporating RM and clinical variables, were developed using random forest (RF), Cox proportional hazards (CPH), and deep learning (deepsurv) algorithms and assessed for goodness of fit using (c-index). RESULTS A subset (N=80) of 386 intensity, shape, and texture derived RM were stable between pre-treatment MR. 28 RM features were independently predictive of survival when compared to models utilizing combinations of clinical, VASARI and had comparable model fit statistics. CPH, RF and deepsurv showed comparable utility in modelling RM features. Combined modelling of clinical, VASARI and RM features using CPH, RF, and deepsurv resulted in c-indices of 0.68, 0.67, 0.68, respectively. CONCLUSION RM features are stable and independently prognostic. Combined modelling of clinical, VASARI, and RM features improves prognostication in stHGG.


2021 ◽  
Author(s):  
Bibo Ge ◽  
Jie Bao ◽  
Jinwu Chen ◽  
Xinzhong Xu ◽  
Juehua Jing ◽  
...  

Abstract Cold atmospheric plasma (CAP) is an emerging technology that has attracted the attention of many researchers in many fields and disciplines. In this study, a dielectric barrier discharge (DBD) plasma device was used to treat Schwann cells (SCs) cultured in vitro, and the effect of CAP on SCs proliferation was evaluated by cell morphology, cell viability, cell cycle and expression of related proteins in SCs. The results showed that the production of intracellular ROS and RNS increased with the increase of CAP treatment time. Compared with the control group, the proliferation of SCs treated with CAP for less than 14 s significantly increased, and and then gradually decreased. Besides, the cell cycle results also showed that more cells were in the S+G2/M phase at this time.The PI3K/Akt/mTOR pathway was activated by low-dose CAP, and the expression of cyclinD1 was consistent with the trend of cell proliferation. In addition, n-acetyl-L-cysteine (NAC) preconditioning significantly prevented CAP-induced cellular changes. In conclusion, low-dose CAP-induced of SCs proliferation was closely related to the PI3K/Akt/mTOR signaling pathway. This study provides a new idea for the treatment of peripheral nerve injury.


2020 ◽  
Vol 53 (12) ◽  
pp. 125202
Author(s):  
Hao Zhang ◽  
Jishen Zhang ◽  
Jie Ma ◽  
Jie Shen ◽  
Yan Lan ◽  
...  

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