Synergistic Inhibition of Tumor Cell Proliferation by Cold Plasma and Gemcitabine

Masur, Kai; Behr, Magdalena von; Bekeschus, Sander; Weltmann, Klaus‐Dieter; Hackbarth, Christine; Heidecke, Claus–Dieter; Bernstorff, Wolfram von; Woedtke, Thomas von; Partecke, Lars Ivo

doi:10.1002/ppap.201500123

Cited by 28 publications

(21 citation statements)

References 31 publications

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“…The mode of action of some chemotherapeutic agents employs partly the production of ROS and therefore enhances their cytotoxic effectiveness (e.g., cisplatin or bleomycin) [35][36][37][38]. Even more so, a synergistic effect of gemcitabine and CAP in killing pancreatic tumour cells has been described recently [39].…”

Section: Discussionmentioning

confidence: 99%

Cold Argon Plasma as Adjuvant Tumour Therapy on Progressive Head and Neck Cancer: A Preclinical Study

et al. 2019

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Investigating cold argon plasma (CAP) for medical applications is a rapidly growing, innovative field of research. The controllable supply of reactive oxygen and nitrogen species through CAP has the potential for utilization in tumour treatment. Maxillofacial surgery is limited if tumours grow on vital structures such as the arteria carotis. Here CAP could be considered as an option for adjuvant intraoperative tumour therapy especially in the case of squamous cell carcinoma of the head and neck. Further preclinical research is necessary to investigate the efficacy of this technology for future clinical applications in cancer treatment. Initially, a variety of in vitro assays was performed on two cell lines that served as surrogate for the squamous cell carcinoma (SCC) and healthy tissue, respectively. Cell viability, motility and the activation of apoptosis in SCC cells (HNO97) was compared with those in normal HaCaT keratinocytes. In addition, induction of apoptosis in ex vivo CAP treated human tissue biopsies of patients with tumours of the head and neck was monitored and compared to healthy control tissue of the same patient. In response to CAP treatment, normal HaCaT keratinocytes differed significantly from their malignant counterpart HNO97 cells in cell motility only whereas cell viability remained similar. Moreover, CAP treatment of tumour tissue induced more apoptotic cells than in healthy tissue that was accompanied by elevated extracellular cytochrome c levels. This study promotes a future role of CAP as an adjuvant intraoperative tumour therapy option in the treatment of head and neck cancer. Moreover, patient-derived tissue explants complement in vitro examinations in a meaningful way to reflect an antitumoral role of CAP.

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Section: Discussionmentioning

confidence: 99%

Cold Argon Plasma as Adjuvant Tumour Therapy on Progressive Head and Neck Cancer: A Preclinical Study

et al. 2019

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“…However, the cell lines with wild-type p53 (769-P/ Figure 3 Esophageal adenocarcinoma MUT Positive [45,52] Further experiments will investigate the effect of CAP on additional cancerous cell lines as well as normal tissues to demonstrate the safety of our cold plasma device. The potential of CAP and chemotherapy combined therapies has been reported repeatedly [53][54][55]. For cell lines that require a higher dose of CAP to effectively reduce viability, that dose may be reduced with the addition of chemotherapy drugs.…”

Section: Discussionmentioning

confidence: 99%

The Canady Helios Cold Plasma Scalpel Significantly Decreases Viability in Malignant Solid Tumor Cells in a Dose-Dependent Manner

Rowe¹,

Cheng²,

Ly³

et al. 2018

Plasma

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Abstract:To determine appropriate treatment doses of cold atmospheric plasma (CAP), the Canady Helios Cold Plasma Scalpel was tested across numerous cancer cell types including renal adenocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma, ovarian adenocarcinoma, and esophageal adenocarcinoma. Various CAP doses were tested consisting of both high (3 L/min) and low (1 L/min) helium flow rates, several power settings, and a range of treatment times up to 5 min. The impact of cold plasma on the reduction of viability was consistently dose-dependent; however, the anti-cancer capability varied significantly between cell lines. While the lowest effective dose varied from cell line to cell line, in each case an 80-99% reduction in viability was achievable 48 h after CAP treatment. Therefore, it is critical to select the appropriate CAP dose necessary for treating a specific cancer cell type.

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“…High species concentrations can be used to exploit apoptotic redox signaling pathways in tumor cells [29], and first cancer patients have benefited from plasma therapy [30]. Plasma treatment can act in concert with other drugs [31][32][33], and plasma-generated reactive species induce pro-immunogenic molecules on tumor cells, such as ecto-calreticulin (CRT) [34][35][36]. Although the release of this and other DAMP signals after plasma treatment in melanoma cells has been shown, evidence of immune cell activation in response to plasma-treated melanoma is scarce.…”

Section: Introductionmentioning

confidence: 99%

Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells

et al. 2019

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Recent advances in melanoma therapy increased median survival in patients. However, death rates are still high, motivating the need of novel avenues in melanoma treatment. Cold physical plasma expels a cocktail of reactive species that have been suggested for cancer treatment. High species concentrations can be used to exploit apoptotic redox signaling pathways in tumor cells. Moreover, an immune-stimulatory role of plasma treatment, as well as plasma-killed tumor cells, was recently proposed, but studies using primary immune cells are scarce. To this end, we investigated the role of plasma-treated murine B16F10 melanoma cells in modulating murine immune cells’ activation and marker profile. Melanoma cells exposed to plasma showed reduced metabolic and migratory activity, and an increased release of danger signals (ATP, CXCL1). This led to an altered cytokine profile with interleukin-1β (IL-1β) and CCL4 being significantly increased in plasma-treated mono- and co-cultures with immune cells. In T cells, plasma-treated melanoma cells induced extracellular signal-regulated Kinase (ERK) phosphorylation and increased CD28 expression, suggesting their activation. In monocytes, CD115 expression was elevated as a marker for activation. In summary, here we provide proof of concept that plasma-killed tumor cells are recognized immunologically, and that plasma exerts stimulating effects on immune cells alone.

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Synergistic Inhibition of Tumor Cell Proliferation by Cold Plasma and Gemcitabine

Cited by 28 publications

References 31 publications

Cold Argon Plasma as Adjuvant Tumour Therapy on Progressive Head and Neck Cancer: A Preclinical Study

Cold Argon Plasma as Adjuvant Tumour Therapy on Progressive Head and Neck Cancer: A Preclinical Study

The Canady Helios Cold Plasma Scalpel Significantly Decreases Viability in Malignant Solid Tumor Cells in a Dose-Dependent Manner

Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells

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