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Effective Chemotherapy of Heterogeneous and Drug Resistant Early Colon Cancers by Intermittent Dose Schedules: A Computer Simulation Study

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TypeOfResource
Text
TitleInfo
Title
Effective Chemotherapy of Heterogeneous and Drug Resistant Early Colon Cancers by Intermittent Dose Schedules: A Computer Simulation Study
Identifier (type = pmcid)
PA30CA072720
Name (authority = orcid); (authorityURI = http://id.loc.gov/vocabulary/identifiers/orcid.html); (type = personal); (valueURI = http://orcid.org/0000-0002-0912-3870)
NamePart (type = family)
Axelrod
NamePart (type = given)
David E.
Affiliation
Genetics, Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (type = personal)
NamePart (type = family)
Vedula
NamePart (type = given)
Sudeepti
Affiliation
Biomedical Engineering; Molecular Biology and Biochemistry, Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (type = personal)
NamePart (type = family)
Obaniyi
NamePart (type = given)
James
Role
RoleTerm (authority = marcrt); (type = text)
author
Affiliation
Biomedical Engineering, Rutgers University
Name (authority = RutgersOrg-Department); (type = corporate)
NamePart
Genetics
Name (authority = RutgersOrg-Department); (type = corporate)
NamePart
Biomedical Engineering
Name (authority = RutgersOrg-Department); (type = corporate)
NamePart
Molecular Biology and Biochemistry
Name (authority = RutgersOrg-School); (type = corporate)
NamePart
School of Arts and Sciences (SAS) (New Brunswick)
Name (authority = RutgersOrg-School); (type = corporate)
NamePart
School of Engineering
Genre (authority = RULIB-FS)
Article, Refereed
Genre (authority = NISO JAV)
Accepted Manuscript (AM)
Note (type = peerReview)
Peer reviewed
OriginInfo
DateIssued (encoding = w3cdtf); (keyDate = yes)
2017
Abstract (type = Abstract)
Purpose The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function.

Methods A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug’s effect on the elimination of mutant cells and the maintenance of crypt function.

Results Colon crypts can tolerate a 10 fold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug sensitive and drug resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug.

Conclusions An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
PhysicalDescription
InternetMediaType
application/pdf
Extent
25 p.
Subject (authority = local)
Topic
Drug resistance
Subject (authority = local)
Topic
Heterogeneity
Subject (authority = local)
Topic
Dose schedules
Subject (authority = local)
Topic
Intermittent
Subject (authority = local)
Topic
Colon cancer
Subject (authority = local)
Topic
Adenoma
Subject (authority = local)
Topic
Crypt
Extension
DescriptiveEvent
Type
Citation
DateTime (encoding = w3cdtf)
2017
AssociatedObject
Name
Cancer Chemotherapy and Pharmacology
Type
Journal
Relationship
Has part
Detail
889-898
Identifier (type = volume and issue)
79(5)
Reference (type = url)
http://dx.doi.org/10.1007/s00280-017-3272-2
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
Human Genetics Institute of New Jersey
AssociatedEntity
Role
Originator
Name
David E. Axelrod
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
New Jersey Breast Cancer Research Fund
AssociatedEntity
Role
Originator
Name
David E. Axelrod
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
National Institutes of Health
AssociatedEntity
Role
Originator
Name
David E. Axelrod
Note (type = special display note)
Article also available through the publisher at http://rdcu.be/qn25.
RelatedItem (type = host)
TitleInfo
Title
Axelrod David Collection
Identifier (type = local)
rucore30017800001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3T1563M
Genre (authority = ExL-Esploro)
Accepted Manuscript
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Rights

RightsDeclaration (AUTHORITY = FS); (ID = rulibRdec0004)
Copyright for scholarly resources published in RUcore is retained by the copyright holder. By virtue of its appearance in this open access medium, you are free to use this resource, with proper attribution, in educational and other non-commercial settings. Other uses, such as reproduction or republication, may require the permission of the copyright holder.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsEvent
Type
Permission or license
AssociatedObject
Type
License
Name
Multiple author license v. 1
Detail
I hereby grant to Rutgers, The State University of New Jersey (Rutgers) the non-exclusive right to retain, reproduce, and distribute the deposited work (Work) in whole or in part, in and from its electronic format, without fee. This agreement does not represent a transfer of copyright to Rutgers.Rutgers may make and keep more than one copy of the Work for purposes of security, backup, preservation, and access and may migrate the Work to any medium or format for the purpose of preservation and access in the future. Rutgers will not make any alteration, other than as allowed by this agreement, to the Work.I represent and warrant to Rutgers that the Work is my original work. I also represent that the Work does not, to the best of my knowledge, infringe or violate any rights of others.I further represent and warrant that I have obtained all necessary rights to permit Rutgers to reproduce and distribute the Work and that any third-party owned content is clearly identified and acknowledged within the Work.By granting this license, I acknowledge that I have read and agreed to the terms of this agreement and all related RUcore and Rutgers policies.
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Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
Document
CreatingApplication
Version
1.4
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Mac OS X 10.11.6 Quartz PDFContext
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2017-06-19T14:49:11
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2017-06-19T14:49:11
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