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Inhibition of breast cancer progression with Vitamin D compounds
Descriptive
TitleInfo
Title
Inhibition of breast cancer progression with Vitamin D compounds
Name
(type = personal)
NamePart
(type = family)
Wahler
NamePart
(type = given)
Joseph
NamePart
(type = date)
1987-
DisplayForm
Joseph Wahler
Role
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(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Suh
NamePart
(type = given)
Nanjoo
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Nanjoo Suh
Affiliation
Advisory Committee
Role
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chair
Name
(type = personal)
NamePart
(type = family)
Chen
NamePart
(type = given)
Suzie
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Suzie Chen
Affiliation
Advisory Committee
Role
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internal member
Name
(type = personal)
NamePart
(type = family)
Cai
NamePart
(type = given)
Li
DisplayForm
Li Cai
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Liu
NamePart
(type = given)
Fang
DisplayForm
Fang Liu
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Cohick
NamePart
(type = given)
Wendie
DisplayForm
Wendie Cohick
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
Graduate School - New Brunswick
Role
RoleTerm
(authority = RULIB)
school
TypeOfResource
Text
Genre
(authority = marcgt)
theses
OriginInfo
DateCreated
(encoding = w3cdtf);
(qualifier = exact)
2015
DateOther
(qualifier = exact);
(type = degree)
2015-10
CopyrightDate
(encoding = w3cdtf);
(qualifier = exact)
2015
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Early epidemiological studies have shown an inverse correlation of increased vitamin D3 to breast cancer. Since this discovery, many studies have linked 1,25-dihydroxyvitamin D3, the active metabolite of vitamin D, and vitamin D analogs to decreased cell proliferation, invasion, and metastasis. The pharmacological dose of 1,25(OH)2D3 required to elicit a response can induce hypercalcemic toxicity. Therefore, non-calcemic vitamin D analogs, such as BXL0124, have been of interest in the inhibition of breast cancer. Breast cancer is a heterogeneous disease which proceeds through a natural progression, beginning with early hyperplasia and culminating in invasive or metastatic disease. Ductal carcinoma in situ (DCIS) is a non-malignant lesion of the breast with the potential to progress to invasive ductal carcinoma (IDC). Due to the implications of breast cancer stem cells (BCSCs) in breast cancer progression, we investigated the role of vitamin D compounds on these processes. We showed that BXL0124 inhibited the progression of DCIS to IDC in a model of breast cancer progression by maintaining critical DCIS structures through the modulation of matrix metalloproteinases transcription. In addition, BXL0124 treatment decreased cell proliferation and maintained vitamin D receptor (VDR) levels in tumors. VDR was expressed in a variety of clinical breast tumors and was lost during malignant transformation of normal mammary cells to pre-malignant histological types, suggesting vitamin D supplementation as a preventative agent due to higher VDR levels in normal breast tissue. Vitamin D compounds (125(OH)2D3 or BXL0124) reduced the growth and self-renewal of mammospheres, an assay which enriches for BCSCs. The putative CD44+/CD24-/low BCSC population was shifted to a population expressing higher CD24 in vitro and in vivo by treatment with BXL0124. Pluripotency genes such as CD44 and OCT4 were also repressed, contributing to the reduction in cell and tumor growth. We demonstrated the therapeutic potential of Gemini vitamin D analog BXL0124 on the inhibition of breast cancer progression and the ability of vitamin D compounds to repress the BCSC population in vitro and in vivo, potentially contributing to the effects on tumor progression.
Subject
(authority = RUETD)
Topic
Pharmacology, Cellular and Molecular
Subject
(authority = ETD-LCSH)
Topic
Breast--Cancer--Treatment
Subject
(authority = ETD-LCSH)
Topic
Vitamin D
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_6791
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xvi, 171 p. : ill.)
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Joseph Wahler
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3RJ4MGP
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Wahler
GivenName
Joseph
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2015-09-25 21:43:17
AssociatedEntity
Name
Joseph Wahler
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
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ContentModel
ETD
OperatingSystem
(VERSION = 5.1)
windows xp
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