Objectives: The finding of new prognostic factors in human cervix cancer is necessary to improve present conventional treatments. The aim of the present study was to determine the expression and evaluate the prognostic value of hypoxia-inducible factor-1(HIF-1α), vascular endothelial growth factor (VEGF) and eritropoyetin receptor (EpoR) in cervix cancer stages IIA-IIB and in preinvasive high grade squamous intraepithelial lesions (HSIL) Methods: The study included 70 patients with cervix cancer, FIGO stages IIA-IIB, 28 patients with HSIL and normal cervix (n = 28). HIF-1α, VEGF and EpoR expression were analyzed in tissue samples by immunohistochemistry using commercial antibodies. Expression and overexpression of the tumor markers were quantified according to German Immunoreactive Score. Results: HIF-1α, EpoR and VEGF overexpression was detected in 30%, 37% and 51% of cancer patients respectively. Patients with HSIL showed enhanced expression only of EpoR and VEGF (39.2% and 71.4%) while VEGF was overexpressed in 21% of the specimen. No correlation was found between VEGF and EpoR with disease-free overall survival (OS), tumor recurrences or prognostic factors. Only overexpression of HIF-1 was associated with less median survival measured up to 24 months, unless it was not maintained a long time. Conclusion: Although any of the markers could be considered as independent prognostic factor for cervix cancer patients, our data showed a significant increase in their expression from the premalignant lesion up to the invasive stages of tumor progression.
Background: Antineoplastic agents induce oxidative stress in biological systems leading to lipid, carbohydrate, protein and DNA damage and affecting cell structure and function. These adverse effects may fuel up the acquisition of new mutations and the development of treatment resistances and secondary malignancies.Methods: We selected 90 breast cancer patients receiving neoadjuvant, adjuvant or palliative chemotherapy, to test the effect of this treatment on the systemic oxidative stress. The patients were distributed in equal groups and paired blood samples, before and after chemotherapy, were extracted. DNA oxidative damage was assessed by alkaline comet assay and a specific inmnoenzymoassay was employed to determine RPA and Ku86 DNA repair activity.Results: We found that neoadjuvant patients presented a marked raise in DNA damage after chemotherapy (Figure 1A). DNA repair activity of KU86 was significantly higher in the adjuvant setting and significantly lower in the neoadjuvant and metastatic settings after chemotherapy. Before chemotherapy administration, KU86 activity was higher in the metastatic and neoadjuvant groups compared to the adjuvant group (Figure 1B).Discussion: Our results show that chemotherapy induces the production of free radicals to an extent that causes a severe DNA damage. High levels of DNA damage are maintained along successive clinical interventions, due to continued production of free radicals during breast cancer treatment, despite the activation of the repair mechanisms that are not sufficient to overcome the effects of the oxidative stress at this level. Our work shows that breast cancer treatment affects the redox status of the patients and, because of its effects into cellular signaling pathways and gene expression, it must be considered as a potential therapeutic target to improve breast cancer treatment and minimize the associated toxicity.Figure legend 1.- Oxidative DNA damage and DNA repair markers in neoadjuvant, adjuvant and metastatic patients, before and after chemotherapy. (A) Percentage of DNA in the tail of lymphocytes, as measured by comet assay. (B) DNA repair activity of KU86. Intragroup statistical differences owed to chemotherapy are indicated as ‡ (P<0.001) or * (P<0.05). Intergroup statistical differences for each period (before and after chemotherapy) (P<0.05) are indicated by the letters a and b, in such a way that the measures with different superscript letters, are statistically different.Figure legend 2.- Fluorescent microscope images of damaged lymphocytes from a neoadjuvant patient before (A) and after (B) chemotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1123.
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