The Granger Causal Effects of Canady Helios Cold Plasma on the Inhibition of Breast Cancer Cell Proliferation

Cold atmospheric plasma (CAP) has become a promising tool for modern medicine. With its recent applications in oncology, regenerative medicine, and immunotherapy, CAP can be used for a myriad of different clinical treatments. When using CAP specifically for the treatment of tumors, it is known to el...

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Main Authors: Annisa Elbedour, Xiaoqian Cheng, Saravana R. K. Murthy, Taisen Zhuang, Lawan Ly, Olivia Jones, Giacomo Basadonna, Michael Keidar, Jerome Canady
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/12/9/4622
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author Annisa Elbedour
Xiaoqian Cheng
Saravana R. K. Murthy
Taisen Zhuang
Lawan Ly
Olivia Jones
Giacomo Basadonna
Michael Keidar
Jerome Canady
author_facet Annisa Elbedour
Xiaoqian Cheng
Saravana R. K. Murthy
Taisen Zhuang
Lawan Ly
Olivia Jones
Giacomo Basadonna
Michael Keidar
Jerome Canady
author_sort Annisa Elbedour
collection DOAJ
description Cold atmospheric plasma (CAP) has become a promising tool for modern medicine. With its recent applications in oncology, regenerative medicine, and immunotherapy, CAP can be used for a myriad of different clinical treatments. When using CAP specifically for the treatment of tumors, it is known to elicit an oxidative response within malignant cancer cells, inducing cell cycle arrest and apoptosis. In this study, data of intracellular reactive oxygen species (ROS), caspase activity, Ki-67 expression, and cell cycle activity in the G1 phase were acquired to determine the causal relationships these intermediates have with cell proliferation and death after Canady Helios Cold Plasma (CHCP) treatment. The data were derived from four different subtypes of breast cancer cell lines: BT-474, MCF-7, MDA-MB-231, and SK-BR-3. Data transformation techniques were conducted on the time-series data for the input into the causal model code. The models were created on the basis of Granger causality principles. Our results demonstrated that there was a Granger causal relationship among all potentially causal variables (ROS, caspase, Ki-67, and G1 activity) and cell proliferation after 5 min CHCP treatment; however, not all variables were causal for the 3 min models. This same pattern did not exist for cell death models, which tested all potentially causal variables (ROS, Ki-67, and G1 activity) vs. caspase activity. All models were validated through a variety of statistical tests and forecasting accuracy metrics. A pseudo data set with defined causal links was also created to test R’s ability in picking up known causal relationships. These models, while nonexhaustive, elucidated the effects cold plasma has on cell activity regulators. Research in causal modeling is needed to help verify the exact mechanism of cold plasma for the ultimate optimization of its application in the treatment of cancers.
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spelling doaj.art-feb16db93cf8477d8214ec6a8f31add42023-11-23T07:51:43ZengMDPI AGApplied Sciences2076-34172022-05-01129462210.3390/app12094622The Granger Causal Effects of Canady Helios Cold Plasma on the Inhibition of Breast Cancer Cell ProliferationAnnisa Elbedour0Xiaoqian Cheng1Saravana R. K. Murthy2Taisen Zhuang3Lawan Ly4Olivia Jones5Giacomo Basadonna6Michael Keidar7Jerome Canady8Jerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912, USAJerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912, USAJerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912, USAJerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912, USAJerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912, USAJerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912, USASchool of Medicine, University of Massachusetts, Worcester, MA 01605, USADepartment of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USAJerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912, USACold atmospheric plasma (CAP) has become a promising tool for modern medicine. With its recent applications in oncology, regenerative medicine, and immunotherapy, CAP can be used for a myriad of different clinical treatments. When using CAP specifically for the treatment of tumors, it is known to elicit an oxidative response within malignant cancer cells, inducing cell cycle arrest and apoptosis. In this study, data of intracellular reactive oxygen species (ROS), caspase activity, Ki-67 expression, and cell cycle activity in the G1 phase were acquired to determine the causal relationships these intermediates have with cell proliferation and death after Canady Helios Cold Plasma (CHCP) treatment. The data were derived from four different subtypes of breast cancer cell lines: BT-474, MCF-7, MDA-MB-231, and SK-BR-3. Data transformation techniques were conducted on the time-series data for the input into the causal model code. The models were created on the basis of Granger causality principles. Our results demonstrated that there was a Granger causal relationship among all potentially causal variables (ROS, caspase, Ki-67, and G1 activity) and cell proliferation after 5 min CHCP treatment; however, not all variables were causal for the 3 min models. This same pattern did not exist for cell death models, which tested all potentially causal variables (ROS, Ki-67, and G1 activity) vs. caspase activity. All models were validated through a variety of statistical tests and forecasting accuracy metrics. A pseudo data set with defined causal links was also created to test R’s ability in picking up known causal relationships. These models, while nonexhaustive, elucidated the effects cold plasma has on cell activity regulators. Research in causal modeling is needed to help verify the exact mechanism of cold plasma for the ultimate optimization of its application in the treatment of cancers.https://www.mdpi.com/2076-3417/12/9/4622cold atmospheric plasma (CAP)reactive oxygen species (ROS)caspaseKi-67cell cycleGranger causality
spellingShingle Annisa Elbedour
Xiaoqian Cheng
Saravana R. K. Murthy
Taisen Zhuang
Lawan Ly
Olivia Jones
Giacomo Basadonna
Michael Keidar
Jerome Canady
The Granger Causal Effects of Canady Helios Cold Plasma on the Inhibition of Breast Cancer Cell Proliferation
Applied Sciences
cold atmospheric plasma (CAP)
reactive oxygen species (ROS)
caspase
Ki-67
cell cycle
Granger causality
title The Granger Causal Effects of Canady Helios Cold Plasma on the Inhibition of Breast Cancer Cell Proliferation
title_full The Granger Causal Effects of Canady Helios Cold Plasma on the Inhibition of Breast Cancer Cell Proliferation
title_fullStr The Granger Causal Effects of Canady Helios Cold Plasma on the Inhibition of Breast Cancer Cell Proliferation
title_full_unstemmed The Granger Causal Effects of Canady Helios Cold Plasma on the Inhibition of Breast Cancer Cell Proliferation
title_short The Granger Causal Effects of Canady Helios Cold Plasma on the Inhibition of Breast Cancer Cell Proliferation
title_sort granger causal effects of canady helios cold plasma on the inhibition of breast cancer cell proliferation
topic cold atmospheric plasma (CAP)
reactive oxygen species (ROS)
caspase
Ki-67
cell cycle
Granger causality
url https://www.mdpi.com/2076-3417/12/9/4622
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