The Synergistic Effect of Canady Helios Cold Atmospheric Plasma and A Folfirinox Regimen for The Treatment of Cholangiocarcinoma In Vitro

Abstract Cholangiocarcinoma (CCA) is a rare biliary tract cancer with a low five-year survival rate and high recurrence rate after surgical resection. Currently treatment approaches include systemic chemotherapeutics such as FOLFIRINOX, a chemotherapy regimen is a possible treatment for severe CCA cases. A limitation of this chemotherapy regimen is its toxicity to patients and adverse events. There exists a need for therapies to alleviate the toxicity of a FOLFIRINOX regimen while enhancing or not altering its anticancer properties. Cold Atmospheric plasma (CAP) is a technology with a promising future as a selective cancer treatment. It is critical to know the potential interactions between CAP and adjuvant chemotherapeutics. In this study the aim is to characterize the efficacy of FOLFIRINOX and CAP in combination to understand potential synergetic effect on CCA cells. FOLFIRINOX treatment alone at the highest dose tested (53.8 nM fluorouracil, 13.1 nM Leucovorin, 5.1 nM Irinotecan, and 3.7 nM Oxaliplatin) reduced CCA cell viability to below 20% while CAP treatment alone for 7 min reduced viability to 3% (p < 0.05). An analysis of cell viability, proliferation, and cell cycle demonstrated that CAP in combination with FOLFIRINOX is more effective than either treatment alone at a lower FOLFIRINOX dose of 6.73 nM fluorouracil, 1.71 nM leucovorin, 0.63 nM irinotecan, and 0.47 nM oxaliplatin and a shorter CAP treatment of 1, 3, or 5 minutes. In conclusion, CAP has the potential to reduce the toxicity burden of FOLFIRINOX and warrants further investigation as an adjuvant therapy.

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The synergistic effect of Canady Helios cold atmospheric plasma and a FOLFIRINOX regimen for the treatment of cholangiocarcinoma in vitro

Scientific Reports ◽

10.1038/s41598-021-88451-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Olivia Jones ◽

Xiaoqian Cheng ◽

Saravana R. K. Murthy ◽

Lawan Ly ◽

Taisen Zhuang ◽

...

Keyword(s):

Cell Viability ◽

Chemotherapy Regimen ◽

Synergetic Effect ◽

Atmospheric Plasma ◽

High Recurrence Rate ◽

Cold Atmospheric Plasma ◽

Tract Cancer ◽

Anticancer Properties ◽

Potential Interactions

AbstractCholangiocarcinoma (CCA) is a rare biliary tract cancer with a low five-year survival rate and high recurrence rate after surgical resection. Currently treatment approaches include systemic chemotherapeutics such as FOLFIRINOX, a chemotherapy regimen is a possible treatment for severe CCA cases. A limitation of this chemotherapy regimen is its toxicity to patients and adverse events. There exists a need for therapies to alleviate the toxicity of a FOLFIRINOX regimen while enhancing or not altering its anticancer properties. Cold atmospheric plasma (CAP) is a technology with a promising future as a selective cancer treatment. It is critical to know the potential interactions between CAP and adjuvant chemotherapeutics. In this study the aim is to characterize the efficacy of FOLFIRINOX and CAP in combination to understand potential synergetic effect on CCA cells. FOLFIRINOX treatment alone at the highest dose tested (53.8 µM fluorouracil, 13.7 µM Leucovorin, 5.1 µM Irinotecan, and 3.7 µM Oxaliplatin) reduced CCA cell viability to below 20% while CAP treatment alone for 7 min reduced viability to 3% (p < 0.05). An analysis of cell viability, proliferation, and cell cycle demonstrated that CAP in combination with FOLFIRINOX is more effective than either treatment alone at a lower FOLFIRINOX dose of 6.7 µM fluorouracil, 1.7 µM leucovorin, 0.6 µM irinotecan, and 0.5 µM oxaliplatin and a shorter CAP treatment of 1, 3, or 5 min. In conclusion, CAP has the potential to reduce the toxicity burden of FOLFIRINOX and warrants further investigation as an adjuvant therapy.

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EXTH-10. THE ACTIVATION AND SENSITIZATION OF GLIOBLASTOMA CELLS VIA COLD ATMOSPHERIC PLASMA TREATMENT

Neuro-Oncology ◽

10.1093/neuonc/noz175.344 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi84-vi84

Author(s):

Jonathan Sherman ◽

Dayun Yan ◽

Eda Gjika ◽

Michael Keidar

Keyword(s):

Cell Viability ◽

Plasma Treatment ◽

Cell Activation ◽

Radiation Treatment ◽

In Vitro Study ◽

Atmospheric Plasma ◽

Discharge Process ◽

H2o2 Treatment ◽

Cold Atmospheric Plasma

Abstract BACKGROUND Treatment of glioblastoma multiforme (GBM) continues to remain a challenge using conventional treatment. Through an in vitro study we assessed the efficacy of our novel cold atmospheric plasma technology (CAP) to sensitize GBM cells to temozolomide (TMZ). METHODS The CAP jet is formed through the discharge (Pk-Pk: 5.8 kV) between a ring grounded cathode and a central anode and with He flow through a glass tube. The discharge process is driven by an AC high voltage (3.16 kV) with a frequency of 12.5 kHz. Human glioblastoma (U87MG) cells were cultured in DMEM supplemented by 1% (v/v) penicillin and streptomycin solution and 10% (v/v) FBS. CAP was delivered to U87 cells in a 96-well plate for 1 min in combination with 10 and 15 μM H2O2. The cell viability was measured by using the MTT assay. We then tested TMZ concentrations of 10 and 50 uM. Cell viability was monitored with the Cell Titer Glo 2.0. luminescent assay. All experiments were performed in triplicate and were independently repeated at least 3 times. RESULTS We identified an activation state of U87MG cells after the plasma treatment. This activation state resulted in GBM cells sensitized to reactive species identified by decreased cell viability after treatment with H2O2 as compared to the H2O2 treatment alone (p< 0.005). In addition, the plasma-activated cells were sensitized to TMZ. Cells treated with CAP in combination with TMZ displayed decreased cell viability at TMZ concentrations of (10 uM) (p< 0.05) and (50 uM) (p< 0.005) as compared to TMZ alone. CONCLUSIONS This study demonstrates the activation phenomenon on GBM cells via direct CAP treatment. Due to this activation, the GBM cells were sensitized to both H2O2 and TMZ identified via decreased cell viability. Future work looks to assess this effect of cell activation/sensitization with chemotherapy plus radiation treatment.

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Combination therapy of cold atmospheric plasma (CAP) with temozolomide in the treatment of U87MG glioblastoma cells

Scientific Reports ◽

10.1038/s41598-020-73457-7 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Eda Gjika ◽

Sonali Pal-Ghosh ◽

Megan E. Kirschner ◽

Li Lin ◽

Jonathan H. Sherman ◽

...

Keyword(s):

Combination Therapy ◽

Cell Viability ◽

Cellular Response ◽

Atmospheric Plasma ◽

Treatment Modalities ◽

Glioblastoma Cells ◽

M Cell ◽

Cell Viability Assay ◽

Cold Atmospheric Plasma

Abstract Cold atmospheric plasma (CAP) technology, a relatively novel technique mainly investigated as a stand-alone cancer treatment method in vivo and in vitro, is being proposed for application in conjunction with chemotherapy. In this study, we explore whether CAP, an ionized gas produced in laboratory settings and that operates at near room temperature, can enhance Temozolomide (TMZ) cytotoxicity on a glioblastoma cell line (U87MG). Temozolomide is the first line of treatment for glioblastoma, one of the most aggressive brain tumors that remains incurable despite advancements with treatment modalities. The cellular response to a single CAP treatment followed by three treatments with TMZ was monitored with a cell viability assay. According to the cell viability results, CAP treatment successfully augmented the effect of a cytotoxic TMZ dose (50 μM) and further restored the effect of a non-cytotoxic TMZ dose (10 μM). Application of CAP in conjunction TMZ increased DNA damage measured by the phosphorylation of H2AX and induced G2/M cell cycle arrest. These findings were supported by additional data indicating reduced cell migration and increased αvβ3 and αvβ5 cell surface integrin expression as a result of combined CAP–TMZ treatment. The data presented in this study serve as evidence that CAP technology can be a suitable candidate for combination therapy with existing chemotherapeutic drugs. CAP can also be investigated in future studies for sensitizing glioblastoma cells to TMZ and other drugs available in the market.

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INNV-08. COMPARATIVE STUDY OF THE CANCER TREATMENT POTENTIAL EFFECT OF TUMOR-TREATING FIELDS AND COLD ATMOSPHERIC PLASMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.492 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii118-ii118

Author(s):

Xiaoliang Yao ◽

Isaac Goldstein ◽

Li Lin ◽

Jonathan Sherman ◽

Michael Keidar

Keyword(s):

Cell Viability ◽

Cancer Treatment ◽

Brain Cancer ◽

Room Temperature ◽

Treatment Time ◽

In Vitro Study ◽

Atmospheric Plasma ◽

Cold Atmospheric Plasma ◽

Tumor Treating Fields

Abstract INTRODUCTION Cold Atmospheric Plasma (CAP) is ionized gas close to room temperature that generates reactive oxygen and nitrogen species, an electromagnetic field (EMF) and UV, which are selectively cytotoxic to cancer cells. Tumor Treating Fields (TTFields) is an FDA approved cancer treatment that utilizes “low intensity” and “intermediate frequency” alternating electric fields to produce an inhibitory effect on cancerous cells. OBJECTIVES In this study, we directly compared CAP and TTFields treatments using U87 glioblastoma tumor cells. We aimed to assess the relative merits of both technologies as potential approaches for brain cancer treatment. METHODS In this in vitro study, the cells were treated with either CAP or TTFields at room temperature. In both cases in order the optimize the treatment parameters, the energy we applied was varied for both methods by changing the power and time of the treatment. The resulting cell viability changes were measured 72 hours after treatment. RESULTS The results revealed that increased energy resulted in decreased cell viability of U87 glioblastoma tumor cells with both CAP and TTFields treatment. The rate of U87 glioblastoma tumor cell viability under CAP treatment was 80% of the original viability after using 4.8J of energy, compared with 15,752J of energy with TTFields treatment. Additionally, the CAP displayed significantly greater time-efficiency as compared to TTFields. For instance, the most effective TTFields treatment took 4 hours, while the CAP treatment displayed a comparable effect on tumor cell viability with a treatment time of 30 seconds. CONCLUSIONS This preliminary in vitro study indicates that CAP treatment is potentially a more favorable effective method of brain cancer therapy. This data indicates that CAP is significantly more energy-efficient and requires significantly less treatment time than TTFields. Future research looks to compare the 2 treatments in an intracranial mouse xenograft model.

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

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170731115233 ◽

2018 ◽

Vol 18 (6) ◽

pp. 769-775 ◽

Cited By ~ 13

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.

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Cold atmospheric plasma coupled with air abrasion in liquid medium for the treatment of peri-implantitis model grown with a complex human biofilm: an in vitro study

Clinical Oral Investigations ◽

10.1007/s00784-021-03949-x ◽

2021 ◽

Author(s):

Wang Lai Hui ◽

Vittoria Perrotti ◽

Adriano Piattelli ◽

Kostya (Ken) Ostrikov ◽

Zhi Fang ◽

...

Keyword(s):

Liquid Medium ◽

Statistical Significance ◽

Atmospheric Plasma ◽

Air Abrasion ◽

Implant Surface ◽

Cold Atmospheric Plasma ◽

Surface Features ◽

Treatment Groups ◽

Surface Decontamination

Abstract Objective Treatment of implants with peri-implantitis is often unsuccessful due to residual microbial biofilm hindering re-osseointegration. The aim of this study was to treat biofilm-grown titanium (Ti) implants with different modalities involving air abrasion (AA) and cold atmospheric plasma (CAP) to compare the effectiveness in surface decontamination and the alteration/preservation of surface topography. Materials and methods Saliva collected from a peri-implantitis patient was used to in vitro develop human biofilm over 35 implants with moderately rough surface. The implants were then mounted onto standardized acrylic blocks simulating peri-implantitis defects and treated with AA (erythritol powder), CAP in a liquid medium, or a combination (COM) of both modalities. The remaining biofilm was measured by crystal violet (CV). Surface features and roughness before and after treatment were assessed by scanning electron microscope (SEM). The data were statistically analyzed using Kruskal-Wallis followed by Tukey’s multiple comparison test. Results In the present peri-implantitis model, the human complex biofilm growth was successful as indicated by the statistical significance between the negative and positive controls. All the treatment groups resulted in a remarkable implant surface decontamination, with values very close to the negative control for AA and COM. Indeed, statistically significant differences in the comparison between the positive control vs. all the treatment groups were found. SEM analysis showed no post-treatment alterations on the implant surface in all the groups. Conclusions Decontamination with AA delivering erythritol with or without CAP in liquid medium demonstrated compelling efficacy in the removal of biofilm from implants. All the tested treatments did not cause qualitative alterations to the Ti surface features. No specific effects of the CAP were observed, although further studies are necessary to assess its potential as monotherapy with different settings or in combination with other decontamination procedures. Clinical relevance CAP is a promising option in the treatment of peri-implantitis because it has potential to improve the elimination of bacterial plaque from implant surfaces, in inaccessible pockets or during open-flap debridement, and should stimulate the process of the re-osseointegration of affected dental implants by not altering surface features and roughness.

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In Vitro Anticancer Properties of Table Grape Powder Extract (GPE) in Prostate Cancer

Nutrients ◽

10.3390/nu10111804 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1804 ◽

Cited By ~ 7

Author(s):

Avinash Kumar ◽

Melinee D’silva ◽

Kshiti Dholakia ◽

Anait Levenson

Keyword(s):

Prostate Cancer ◽

Cell Viability ◽

Epidemiological Data ◽

Grape Seed ◽

Dependent Manner ◽

Anticancer Activities ◽

Anticancer Properties ◽

Vegetables And Fruits ◽

Powder Extract

Although the link between diet and cancer is complex, epidemiological data confirm that diet is a risk factor for prostate cancer and indicate a reduced prostate cancer incidence associated with a diet rich in vegetables and fruits. Because of the known protective effect of grape seed extract (GSE) against prostate cancer, we evaluated the effects of grape powder extract (GPE) on cell viability, proliferation, and metastatic capability. Importantly, we explored the possible novel mechanism of GPE through metastasis-associated protein 1 (MTA1) downregulation in prostate cancer, since our previous studies indicated resveratrol (Res)- and pterostilbene (Pter)-induced MTA1-mediated anticancer activities in prostate cancer. We found that GPE inhibited the cell viability and growth of prostate cancer cells only at high 100 μg/mL concentrations. However, at low 1.5–15 μg/mL concentrations, GPE significantly reduced the colony formation and wound healing capabilities of both DU145 and PC3M cells. Moreover, we found that GPE inhibited MTA1 in a dose-dependent manner in these cells, albeit with considerably less potency than Res and Pter. These results indicate that stilbenes such as Res and Pter specifically and potently inhibit MTA1 and MTA1-associated proteins compared to GPE, which contains low concentrations of Res and mainly consists of other flavonoids and anthocyanidins. Our findings support continued interest in GPE as a chemopreventive and anti-cancer agent against prostate cancer but also emphasize the unique and specific properties of stilbenes on MTA1-mediated anticancer effects on prostate cancer.

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