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Epigenetic regulation of Nrf2 and ursolic acid in skin carcinogenesis

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TitleInfo
Title
Epigenetic regulation of Nrf2 and ursolic acid in skin carcinogenesis
Name (type = personal)
NamePart (type = family)
Ramirez
NamePart (type = given)
Christina N.
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Christina N. Ramirez
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RoleTerm (authority = RULIB)
author
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Cai
NamePart (type = given)
Li
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Li Cai
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Advisory Committee
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RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Liu
NamePart (type = given)
Fang
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Fang Liu
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Kong
NamePart (type = given)
Ah-Ng Tony
DisplayForm
Ah-Ng Tony Kong
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Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Bertino
NamePart (type = given)
Joseph
DisplayForm
Joseph Bertino
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
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Text
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theses
OriginInfo
DateCreated (qualifier = exact)
2018
DateOther (qualifier = exact); (type = degree)
2018-10
CopyrightDate (encoding = w3cdtf)
2018
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Non-melanoma skin cancer (NMSC) is the most common cancer in the United States with over 4.0 million new cases diagnosed in 2012. An increase of exposure to environmental pollutants and sunlight are among the causative agents of the disease. Ursolic acid (UA), a well-known natural triterpenoid found in abundance in fruit peels, cranberries, and blueberries has been shown to possess beneficial health effects against a multitude of disorders including, cardiovascular, neurological, and oncological disorders. However, epigenetic modulation of UA in skin carcinogenesis is still poorly understood. Increasing evidence suggests epigenetics play an important role in the development and progression of cancer including NMSC. Among its many anti-cancer activities, UA has also been shown to have the ability to modulate epigenetic mechanisms in vitro and thus presents an attractive candidate to target the underlying epigenetic mechanisms of skin carcinogenesis. Preliminary data in our laboratory and that of others points to epigenetic regulation of key genes at the center of UA activities: 1) Skin carcinogenesis is enhanced in Nrf2 (-/-) mice; 2) The expression Nrf2 and its target gene HO-1 is reduced in skin tumors of Nrf2 (+/+) mice; 3) UA inhibits TPA-induced ear edema and tumor promotion; 4) Hypermethylation of the promoter region of Nrf2 resulting in reduced expression and its target genes is closely associated with prostate tumor progression; 5) Dietary phytochemicals epigenetically modify the hypermethylation of the Nrf2 promoter region and inhibit TPA-induced transformation. Based on the aforementioned observations, it was hypothesized UA can suppress skin carcinogenesis, in part, through the epigenetic regulation of Nrf2 signaling. We demonstrated for the first time that UA restores the expression of Nrf2 by demethylating CpG islands in the Nrf2 promoter in mouse epidermal cells resulting in an increase in the expression of cytoprotective detoxifying/antioxidant enzymes and suppression of tumor promoter-induced cell transformation. Furthermore, we demonstrate UA is able to suppress skin carcinogenesis in vivo using a relevant and novel B[a]P/TPA skin carcinogenesis model. The long-term goal of this research is to understand some of the underlying epigenetic mechanisms driving skin carcinogenesis and to develop safe and effective strategies to prevent/treat NMSC using phytochemicals such as UA who possess anti-cancer properties.
Subject (authority = RUETD)
Topic
Pharmacology, Cellular and Molecular
Subject (authority = ETD-LCSH)
Topic
Skin -- Cancer
Subject (authority = ETD-LCSH)
Topic
Triterpenoid saponins
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9110
PhysicalDescription
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (122 pages : illustrations)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Christina N. Ramirez
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-rrwe-p725
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Ramirez
GivenName
Christina N.
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-07-24 09:58:49
AssociatedEntity
Name
Christina Ramirez
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
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Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
Type
Embargo
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2019-10-31
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2019.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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