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

Gjika, Eda; Pal‐Ghosh, Sonali; Kirschner, Megan; Lin, Li; Sherman, Jonathan H.; Stepp, Mary Ann; Keidar, Michael

doi:10.1038/s41598-020-73457-7

Cited by 50 publications

(50 citation statements)

References 74 publications

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“…[29] Strikingly, we and others identified gas plasma treatment to have an immunological dimension [30,31] by inducing the immunogenic cancer cell death (ICD [32] ) in vitro [33,34] and in vivo. [35,36] Several reports have moreover suggested using gas plasma technology as anticancer agent against internal tumors [37] originating from, for instance, breast, [38][39][40] pancreatic, [41][42][43] colon, [44][45][46] liver, [47][48][49] central nervous, [50][51][52] ovarian, [53][54][55] and prostate [56][57][58] tissue. These and other studies also clearly demonstrated the importance of short-lived ROS/RNS in the induction of ICD.…”

Section: Introductionmentioning

confidence: 99%

Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT‐II T Cell Activation Conferring Tumor Protection in Mice

et al. 2021

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Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken ovalbumin (Ova vs oxOva). Dynamic light scattering and circular dichroism spectroscopy reveal structural modifications in oxOva compared to Ova. T cells from Ova-specific OT-II but not from C57BL/6 or SKH-1 wild type mice presents enhanced activation after Ova addition. OxOva exacerbates this activation when administered ex vivo or in vivo, along with an increased interferon-gamma production, a known anti-melanoma agent. OxOva vaccination of wild type mice followed by inoculation of syngeneic B16F10 Ova-expressing melanoma cells shows enhanced T cell number and activation, decreased tumor burden, and elevated numbers of antigen-presenting cells when compared to their Ova-vaccinated counterparts. Analysis of oxOva using mass spectrometry identifies three hot spots regions rich in oxidative modifications that are associated with the increased T cell activation. Using Ova as a model protein, the findings suggest an immunomodulating role of multi-ROS/RNS modifications that may spur novel research lines in inflammation research and for vaccination strategies in oncology.

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Section: Introductionmentioning

confidence: 99%

Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT‐II T Cell Activation Conferring Tumor Protection in Mice

et al. 2021

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“…Temozolomide is used as the gold standard for the treatment of high-grade GBM. Here, we reasoned that combining CAP with the commonly used chemotherapy drug temozolomide (TMZ) would enhance the treatment of GBM [12,13]. TMZ can extend the overall patient survival rate.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Enhancement of Temozolomide Effect in Human Glioblastoma by Non-Invasive Application of Cold Atmospheric Plasma

Soni

Adhikari

Simonyan

et al. 2021

Cancers

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Glioblastoma (GBM) is one of the most aggressive forms of adult brain cancers and is highly resistant to treatment, with a median survival of 12–18 months after diagnosis. The poor survival is due to its infiltrative pattern of invasion into the normal brain parenchyma, the diffuse nature of its growth, and its ability to quickly grow, spread, and relapse. Temozolomide is a well-known FDA-approved alkylating chemotherapy agent used for the treatment of high-grade malignant gliomas, and it has been shown to improve overall survival. However, in most cases, the tumor relapses. In recent years, CAP has been used as an emerging technology for cancer therapy. The purpose of this study was to implement a combination therapy of CAP and TMZ to enhance the effect of TMZ and apparently sensitize GBMs. In vitro evaluations in TMZ-sensitive and resistant GBM cell lines established a CAP chemotherapy enhancement and potential sensitization effect across various ranges of CAP jet application. This was further supported with in vivo findings demonstrating that a single CAP jet applied non-invasively through the skull potentially sensitizes GBM to subsequent treatment with TMZ. Gene functional enrichment analysis further demonstrated that co-treatment with CAP and TMZ resulted in a downregulation of cell cycle pathway genes. These observations indicate that CAP can be potentially useful in sensitizing GBM to chemotherapy and for the treatment of glioblastoma as a non-invasive translational therapy.

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“…Recently, indirect CAP treatment was effective for the treatment of CCA in vitro , selectively killing CCA cells over normal hepatocytes 25 . Research on CAP in combination with other therapies has shown some potential synergism with anti-neoplastic agents in melanoma cells 26 , drug loaded nanoparticles in breast cancer cells 27 , gemcitabine in murine pancreatic cancer cells 28 , and temozolomide in glioblastoma cells 29 .…”

Section: Introductionmentioning

confidence: 99%

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

Jones¹,

Cheng²,

Murthy³

et al. 2021

Sci Rep

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

Cited by 50 publications

References 74 publications

Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT‐II T Cell Activation Conferring Tumor Protection in Mice

Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT‐II T Cell Activation Conferring Tumor Protection in Mice

In Vitro and In Vivo Enhancement of Temozolomide Effect in Human Glioblastoma by Non-Invasive Application of Cold Atmospheric Plasma

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

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