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Phosphatidylserine Externalization in Pancreatic Ductal Adenocarcinoma: Elucidating Mechanisms of Regulation for Combination Therapy

N'Guessan, Kombo F
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595847418811418

Abstract Details

2020, PhD, University of Cincinnati, Medicine: Pathobiology and Molecular Medicine.
Pancreatic cancer is projected to be second deadliest malignancy in the US by 2020. Pancreatic ductal adenocarcinoma (PDAC) makes up 90% of pancreatic cancers. Current treatments for PDAC are ineffective and new treatments are urgent. Gemcitabine (GEM) used in combination with Abraxane (Abr) is one of the first line treatments for advanced PDAC. Unfortunately, GEM/Abr affords only marginal benefits to patients compared to no treatment. Phosphatidylserine (PS) is exposed by non-apoptotic tumor cells and metastases of malignancies with poor treatment efficacy and is overexpressed on the surface of pancreatic cancer cells compared to healthy cells. PS is normally expressed in the inner leaflet of healthy cells. However, oxidative stress (OS) in the tumor microenvironment is thought to induce PS externalization in cancer cells. In cancer cell lines, variations of surface PS expression is associated with increased intracellular calcium, reduced flippase activity and increased expression of PS synthase genes PTDSS1 and PTDSS2. Studies have shown that OS affects intracellular calcium levels through the regulation of calcium channels and pumps, actin rearrangement and p38 MAPK activation. However, the mechanisms regulating PS externalization in PDAC cells are not clear. Additionally, the effects of OS on PS externalization has not been studied in the context of PDAC and the function for PS externalization in pancreatic cancer progression remains unknown. PS is targetable by several therapeutic agents including SapC-DOPS. Furthermore, existing cancer treatments are known to induce PS externalization, sensitizing cells to PS-targeting drugs. GEM, a first line treatment for metastatic PDAC, has been shown to increase the expression of PS on cancer cells. Although GEM treatment increases PS externalization in cancer cells, the therapeutic effect of combining GEM with a PS-targeting drug for PDAC treatment have not been investigated. The aims of our study were to: 1)
Xiaoyang Qi, Ph.D. (Committee Chair)
Vladimir Bogdanov, Ph.D. (Committee Member)
William Miller, Ph.D. (Committee Member)
Susan Waltz, Ph.D. (Committee Member)
Trisha Wise-Draper, Ph.D. (Committee Member)
125 p.
Dance; Demographics; Molecular Biology; Polymer Chemistry
Pancreatic ductal adenocarcinoma; Phosphatidylserine; SapC-DOPS; Cell cycle; p38 MAPK; Oxidative stress

Recommended Citations

Citations

  • N'Guessan, K. F. (2020). Phosphatidylserine Externalization in Pancreatic Ductal Adenocarcinoma: Elucidating Mechanisms of Regulation for Combination Therapy [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595847418811418

    APA Style (7th edition)

  • N'Guessan, Kombo. Phosphatidylserine Externalization in Pancreatic Ductal Adenocarcinoma: Elucidating Mechanisms of Regulation for Combination Therapy. 2020. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595847418811418.

    MLA Style (8th edition)

  • N'Guessan, Kombo. "Phosphatidylserine Externalization in Pancreatic Ductal Adenocarcinoma: Elucidating Mechanisms of Regulation for Combination Therapy." Doctoral dissertation, University of Cincinnati, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595847418811418

    Chicago Manual of Style (17th edition)

ucin1595847418811418
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© 2020, some rights reserved.Creative Commons License Phosphatidylserine Externalization in Pancreatic Ductal Adenocarcinoma: Elucidating Mechanisms of Regulation for Combination Therapy by Kombo F N'Guessan is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.