ABSTRACT
BACKGROUND: Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic significance of RXRG in breast cancer. METHODS: Primary breast cancer tissue microarrays (n = 923) were immuno-stained for RXRG protein and correlated with clinicopathological features, and patient outcome. RESULTS: Nuclear RXRG expression was significantly associated with smaller tumour size (p = 0.036), lower grade (p < 0.001), lobular histology (p = 0.016), lower Nottingham Prognostic Index (p = 0.04) and longer breast cancer-specific survival (p < 0.001), and longer time to distant metastasis (p = 0.002). RXRG expression showed positive association with oestrogen receptor (ER)-related biomarkers: GATA3, FOXA1, STAT3 and MED7 (all p < 0.001) and a negative correlation with the Ki67 proliferation marker. Multivariate analysis demonstrated RXRG protein as an independent predictor of longer breast cancer-specific survival and distant metastasis-free survival. In the external validation cohorts, RXRG expression was associated with improved patients' outcome (p = 0.025). In ER-positive tumours, high expression of RXRG was associated with better patient outcome regardless of adjuvant systemic therapy. ER signalling pathway was the top predicted master regulator of RXRG protein expression (p = 0.005). CONCLUSION: This study provides evidence for the prognostic value of RXRG in breast cancer particularly the ER-positive tumours.
Subject(s)
Breast Neoplasms/metabolism , Receptors, Estrogen/metabolism , Retinoid X Receptor gamma/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cohort Studies , Female , Gene Expression , Humans , Immunohistochemistry , Neoplasm Invasiveness , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Retinoid X Receptor gamma/biosynthesis , Retinoid X Receptor gamma/genetics , Tissue Array AnalysisABSTRACT
Amikacin is an important antibiotic, and its use is limited because of the induced nephrotoxicity. Thus, search for natural and synthetic agents that can moderate amikacin toxicity never stopped. The present study aims to investigate the possible ameliorative effects of virgin olive oil and olive leaf extract against the amikacin-induced nephrotoxicity in rat. METHODS: 48 rats were distributed into 6 groups: 1-Animals of control (C) group were injected intraperitoneally (ip) with saline, 2-(AK); injected ip with amikacin {300 mg/kg/day for 12days}, 3-(OO) group: given olive oil {7 ml/kg/day for 16days}, 4-(OOAK) group: given olive oil as in OO and amikacin for 12days, 5-(OL) group: given olive leaf extract {50 mg/kg/day for 16days}, 6-(OLAK) group: given leaf extract as in OL and amikacin for 12days. Animals were fasted and sacrificed. Serum was used for biochemical analysis and kidneys for histopathology. RESULTS: Serum urea and creatinine were significantly (P < 0.001) elevated in AK, and significantly dropped in the OOAK and OLAK groups. Serum uric acid was reduced in AK by 45.29%. Kidneys from AK showed necrosis, whereas, those from OOAK and OLAK showed mild histology. The serum triglyceride was decreased by 17.8% in OL, by 37.02% in OOAK and by 31.48% in OLAK. The calculated amikacin effect showed a significant positive correlation with urea (r = 0.521, P = 0.0004), and a negative correlation with uric acid (r = â¿¿ 0.58, P < 0.0001). CONCLUSION: The study confirmed nephrotoxicity of amikacin in rat which was ameliorated by virgin olive oil and by olive leaf extract. Amikacin did not cause dyslipidemia but reduced serum uric acid.
