Therapy increases poly-ADP-ribose and p53-Ser392-P levels in recurrent squamous cell lung cancer
| Autor: | A, Holownia, R M, Mroz, M, Kozlowski, E, Chyczewska, J, Laudanski, L, Chyczewski, J J, Braszko |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Poly Adenosine Diphosphate Ribose Lung Neoplasms Radiotherapy Biopsy Vinorelbine DNA Neoplasm Middle Aged Vinblastine Combined Modality Therapy Antineoplastic Combined Chemotherapy Protocols Carcinoma Squamous Cell Serine Humans Cisplatin Neoplasm Recurrence Local Tumor Suppressor Protein p53 Aged Neoplasm Staging |
| Zdroj: | Neoplasma. 50(4) |
| ISSN: | 0028-2685 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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