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αCT1 Peptide Sensitizes Glioma Cells to Temozolomide in a Glioblastoma Organoid Platform
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  • Jingru Che,
  • Thomas J. DePalma,
  • Hemamylammal Sivakumar,
  • Louisa S. Mezache,
  • Miranda M. Tallman,
  • Monica Venere,
  • Katelyn Swindle-Reilly,
  • Rengasayee Veeraraghavan,
  • Aleksander Skardal
Jingru Che
The Ohio State University

Corresponding Author:[email protected]

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Thomas J. DePalma
The Ohio State University
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Hemamylammal Sivakumar
The Ohio State University
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Louisa S. Mezache
The Ohio State University
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Miranda M. Tallman
The Ohio State University Wexner Medical Center
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Monica Venere
The Ohio State University Comprehensive Cancer Center
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Katelyn Swindle-Reilly
The Ohio State University
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Rengasayee Veeraraghavan
The Ohio State University
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Aleksander Skardal
The Ohio State University
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Abstract

Glioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ) the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a 3-dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and αCT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to analyze changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM.
29 Apr 2022Submitted to Biotechnology and Bioengineering
29 Apr 2022Submission Checks Completed
29 Apr 2022Assigned to Editor
01 May 2022Reviewer(s) Assigned
03 Aug 2022Review(s) Completed, Editorial Evaluation Pending
03 Aug 2022Editorial Decision: Revise Major
07 Dec 20221st Revision Received
07 Dec 2022Submission Checks Completed
07 Dec 2022Assigned to Editor
07 Dec 2022Review(s) Completed, Editorial Evaluation Pending
07 Dec 2022Reviewer(s) Assigned
13 Dec 2022Editorial Decision: Accept
Apr 2023Published in Biotechnology and Bioengineering volume 120 issue 4 on pages 1108-1119. 10.1002/bit.28313