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Neoplasma Vol.50, p.266-271, 2003 |
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Title: Therapy increases poly-ADP-ribose and p53-Ser392-P levels in recurrent squamous cell lung cancer. | ||
Author: A., HOLOWNIA ; R.M., MROZ ; M., KOZLOWSKI ; E., CHYCZEWSKA ; J., LAUDANSKI ; L., CHYCZEWSKI ; J.J., BRASZKO ; | ||
Abstract: p53 protein is a critical regulator of the cell cycle and apoptosis and its
levels and functions change in response to many stimuli. To assess whether the
cytotoxic drugs induce DNA changes, affect phosphorylation and stability of p53
protein, we determined poly-ADP-ribose levels, the expression of p53 protein and
its carboxyl-terminal Ser-392 phosphate levels in fiberoptic bronchoscopy biopsy
samples taken from patients suffering from recurrent squamous cell lung cancer
before and after radiotherapy and chemotherapy. All 14 patients included in this
study were in IA-IIIA clinical stage prior to surgery. Radiation/chemotherapy
decreased G2/M cell numbers but increased S-phase cells by almost 50% compared
to ploidy status before therapy, while median p53 expression was doubled (109%
increase). p53 phosphorylated on Ser-392 was also increased by approximately 70%
in patients treated with radiotherapy and with chemotherapy and correlated with
elevated poly-ADP-ribose levels. Our data suggest that apart from changes in p53
quantity, posttranslational phosphorylation/dephosphorylation-mediated
alterations may play an important role in neoplastic cell proliferation as well
as in antiproliferative activity of drugs inducing DNA damage and apoptosis.
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Year: 2003, Volume: 50, Issue: | Page From: 266, Page To: 271 | |
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