ABSTRACT
Estrogen receptor status is a diagnostic parameter in breast cancer treatment. Estrogen receptor presence is related to a better prognosis because the principal treatments attacking breast cancer tumors have their action site directed at the estrogen receptor. However, the two different subtypes of estrogen receptor, ERα and ERß, have different functions. In this work an alternative point of view focusing on oxidative stress is shown, given that estrogen receptors regulate several proteins related to this oxidative stress, such as antioxidant enzymes, sirtuins, and uncoupling proteins. Postmenopausal human breast tumors with different ERα/ERß ratios were analyzed to characterize the amount of oxidative stress, mitochondrial function, and proliferation-related and oxidative stress-activated signaling pathways. Results showed that tumors with a low ERα/ERß ratio have greater oxidative damage and higher antioxidant enzyme protein levels, as well as uncoupling protein (UCP) and sirtuin 3 (SIRT3), and have high studied signaling pathway activation. Glutathione peroxidase, Complex V, Complex III, Complex II, Complex IV, AKT, SAPK, and ERα were significantly and positively correlated with ERα/ERß ratio. However, carbonyl groups, catalase, CuZn-superoxide dismutase, UCP5, SIRT3, and ERß were significantly and negatively correlated with ERα/ERß ratio. From the independent variables included in the step-by-step stepwise multiple linear regression analysis, only the ERα/ERß ratio was independently associated with carbonyl groups. Surprisingly, these low ERα/ERß ratio tumors have poor prognosis for the patient, and these results and those of other authors suggest that these tumors are adapted to conditions of increased oxidative stress.
Subject(s)
Breast Neoplasms/metabolism , Estrogen Receptor alpha/physiology , Estrogen Receptor beta/physiology , Oxidative Stress , Aged , Estrogen Receptor alpha/analysis , Estrogen Receptor beta/analysis , Female , Humans , Ion Channels/physiology , Middle Aged , Mitochondrial Proteins/physiology , Postmenopause , Proto-Oncogene Proteins c-akt/metabolism , Sirtuin 3/physiology , Uncoupling Protein 1ABSTRACT
BACKGROUND/AIM: Ovarian carcinoma is the main cause of gynecological cancer related deaths. The aim of this study was to determine the activation status of the antioxidant response in samples of ovarian serous carcinoma from paraffin-embedded biopsies and compare them with the response of patients to carboplatin-paclitaxel treatment. MATERIALS AND METHODS: Estrogen receptor alpha (ERα), antioxidant enzymes, and uncoupling protein (UCP) levels were analyzed by western blotting and the presence of estrogen receptor beta (ERß) was investigated by immunohistochemistry (IHC). RESULTS: Lower levels of ERα, antioxidant enzymes and UCPs were found in patients resistant to treatment in comparison to the carboplatin/paclitaxel-sensitive ones; IHC revealed a greater presence of ERß in sensitive patients. CONCLUSION: These results indicate that patients resistant to treatment have a lower level of antioxidant response activation compared to sensitive patients, fact which may be related to the efficacy of this treatment.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antioxidants/therapeutic use , Carboplatin/therapeutic use , Ovarian Neoplasms/drug therapy , Paclitaxel/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antioxidants/pharmacology , Blotting, Western , Carboplatin/pharmacology , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/metabolism , Drug Resistance, Neoplasm/drug effects , Estrogen Receptor alpha/metabolism , Female , Humans , Immunohistochemistry , Ion Channels/metabolism , Mitochondrial Proteins/metabolism , Ovarian Neoplasms/metabolism , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Oxidative Stress/physiology , Paclitaxel/pharmacology , Uncoupling Protein 1ABSTRACT
Synovial sarcoma (SS) is an uncommon malignant neoplasm of the soft tissues. It mainly affects the periarticular tissues of the extremities in young adults, but has been described at nearly all sites; nevertheless, the gastrointestinal tract is an exceptional location. We report a case of a primary synovial sarcoma of the duodenum in a 69-year-old woman. Histological study showed a monophasic pattern. The tumor cells demonstrated diffuse vimentin and Bcl-2 expression, partial EMA expression and focal AE1/3 positivity. The differential diagnosis includes gastrointestinal stromal tumors. Cytogenetic analysis confirmed the diagnosis, with detection of the X;18 translocation. The patient presented postoperative complications and died one month following the intervention.