Accession Number : ADA473202


Title :   Mechanism of Telomerase Inhibition Using a Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization


Descriptive Note : Annual summary rept. 15 Mar 2004-14 Mar 2007


Corporate Author : VIRGINIA COMMONWEALTH UNIV RICHMOND


Personal Author(s) : Poynter, Kennon R ; Holt, Shawn E ; Elmore, L W


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a473202.pdf


Report Date : Apr 2007


Pagination or Media Count : 53


Abstract : Telomerase, a ribonucleoprotein enzyme minimally composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeric repeats onto chromosome ends and is obligatory for continuous tumor cell proliferation, as well as malignant progression of breast cancer cells. Telomerase is an attractive anti-cancer therapeutic target because its activity is present in over 90% of human cancers, including more than 95% of breast carcinomas, but undetectable in most somatic cells. Traditional chemo- and radiotherapies lack the ability to effectively control and cure breast cancer, in part because residual cells are or become resistant to DNA damaging modalities. While various telomerase inhibition strategies cause cancer cells to undergo apoptosis or senescence, there is often a lag period between administration and biologic effect (Corey, 2002). Our goal in this study was to compare the efficacy of different telomerase inhibition strategies in concert with standard chemotherapeutic agents at triggering senescence and/or apoptosis in cultures of breast cancer cells. We hypothesized that telomerase inhibition strategies will sensitize breast cancer cells to traditional chemotherapies, potentially reducing the lag phase, allowing for more potent anti-tumor effects at lower doses, and therefore ultimately imparting less toxicity to the patient.


Descriptors :   *ENZYMES , *CELLS(BIOLOGY) , *RIBONUCLEIC ACIDS , *BREAST CANCER , *RESISTANCE(BIOLOGY) , HUMANS , PROTEINS , NEOPLASMS , RESIDUALS , TEMPLATES , PATIENTS , CHEMOTHERAPEUTIC AGENTS , SENSITIZING , MAMMARY GLANDS , POTENCY , INHIBITION , CURING , DELAY , DOSAGE , CHROMOSOMES , AGING(PHYSIOLOGY) , TOXICITY


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE