Document Detail


Cancer cell dynamics in presence of telomerase inhibitors: analysis of in vitro data.
MedLine Citation:
PMID:  12413877     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The inhibition of telomerase activity in actively dividing cells leads to suppression of cell growth after a time delay (inhibitory delay) required to reach a threshold telomeric DNA size. We developed a mathematical model of the dynamics of telomere size distribution and cell growth in the presence of telomere inhibitors that allowed quantification of the inhibitory delay. The model based on the solution of a system of differential equations described quantitatively recent experimental data on dynamics of cultured cells in presence of telomerase inhibitors. The analysis of the data by this model suggested the existence of at least two distinct subpopulations of cells with different proliferative activity. Size distribution of telomeres, fraction of proliferating cells, and tumor doubling times are of critical importance for the dynamics of cancer cells growth in presence of telomerase inhibitors. Rapidly growing cells with large telomeric DNA heterogeneity and small proliferating fractions as well as those with very short homogeneous telomeres would be the most sensitive to telomerase inhibitors.
Authors:
Igor A Sidorov; Ken S Hirsch; Calvin B Harley; Dimiter S Dimitrov
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of theoretical biology     Volume:  219     ISSN:  0022-5193     ISO Abbreviation:  J. Theor. Biol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-04     Completed Date:  2003-01-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376342     Medline TA:  J Theor Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  225-33     Citation Subset:  IM    
Affiliation:
National Cancer Institute, NIH, Bldg. 469, PO Box B, Frederick, MD 21702, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Death
Cell Division
Cell Line
Enzyme Inhibitors / therapeutic use*
Humans
Models, Genetic*
Neoplasms / drug therapy*,  pathology
Telomerase / antagonists & inhibitors*
Telomere / physiology*,  ultrastructure
Time Factors
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; EC 2.7.7.49/Telomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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