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Nanoformulation and Cancer Therapy: Study of DNA Damage and repair Pathway by Expression and Genome Wide Location Analysis (GWLA)
Author(s) -
Tagne JeanBosco,
Kakumanu Srikanth,
Gupta Sumeet,
Volkert Thomas,
Young Richard,
Nicolosi Robert J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb33-a
Subject(s) - dna damage , dna repair , cancer cell , tamoxifen , cancer research , cell , cancer , cell cycle , apoptosis , biology , chemistry , dna , microbiology and biotechnology , pharmacology , breast cancer , biochemistry , genetics
Tamoxifen function by interfering with cell cycle progression by generating DNA strand breaks affecting cell division and DNA synthesis. If the cancer cell is not able to overcome the cell cycle blockage or cell injury caused by the chemotherapeutic compound, the cell will often die via apoptotic mechanisms. The uses of conventional delivery vehicles for chemotherapeutic agents such as tamoxifen in the treatment of cancer have several disadvantages. The cells developed resistance to the agent because all cells don’t receive an initially lethal dose due to misdistribution. This results in the requirement for higher dosages of the drug or renewed spread of the cancer. Cellular resistances result from biochemical metabolism of the agent or functional resistance whereby cells remains unaffected in his presence. The reduction in particle sizes by nanoformulation to less than 100 nm increases surface/volume ratios associated with greater bioavailability and efficacy of pharmaceuticals. Network interaction provides us with greater understanding of gene function. Cancer cells treated with Tamoxifen have detected signal to DNA damage such as activation of the Ataxia Telangiectasia Mutated (ATM), the most important cellular DNA damage response protein activated by double strand breaks (DSBs) but nanoformulation of Tamoxifen doesn’t activate this ATM‐dependent Check2 pathway, indicating little DSBs. We also quantify formulations of the drugs in the blood, brain, liver, spleen, and kidney by High Performance Liquid Chromatography in nude mice xenograft.