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Research Article
Jerome Canady
Jerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
Intrahepatic cholangiocarcinoma, cancer treatment, adjuvant therapy
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- Table1.png
Drug concentrations of the four FOLFIRINOX components for each dose level in the serial dilution. This corresponds to the [5-FU] notation in Figure 1.
- Table2.png
Chart showing the comparison of the reduction of viability between treatment groups. Whether there is statistical difference p < 0.005 and if that difference is extremely significant p < 1×10-5 (Student’s t test with Bonferroni’s correction).
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View the published article at Scientific Reports.
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Editorial decision: Major revision
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Received 14 Feb, 2021
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Reviewers invited
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On 25 Jan, 2021
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Subject Areas
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A new preprint design is coming!
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See the published version of this preprint at Scientific Reports.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Jerome Canady
Jerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Scientific Reports.
Version 1
Posted 11 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 10 Mar, 2021
Reviews received
Received 04 Mar, 2021
Reviews received
Received 14 Feb, 2021
Reviewers agreed
On 03 Feb, 2021
Reviewers invited
Invitations sent on 29 Jan, 2021
Editor assigned
On 25 Jan, 2021
Editor invited
On 08 Jan, 2021
Submission checks complete
On 07 Jan, 2021
First submitted
On 04 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Biological Chemistry
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Scientific Reports.
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- Table1.png
Drug concentrations of the four FOLFIRINOX components for each dose level in the serial dilution. This corresponds to the [5-FU] notation in Figure 1.
- Table2.png
Chart showing the comparison of the reduction of viability between treatment groups. Whether there is statistical difference p < 0.005 and if that difference is extremely significant p < 1×10-5 (Student’s t test with Bonferroni’s correction).
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