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1.
Anticancer Res ; 29(2): 545-52, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19331201

ABSTRACT

BACKGROUND: Vulvar cancer is a rare disease and knowledge on prognostic factors is therefore limited and inconsistent. The aim of this study was to determine prognostic variables for recurrence and survival and to identify patterns of recurrence in patients with vulvar cancer. PATIENTS AND METHODS: All patients (n = 103) with primary vulvar cancer treated at the University Medical Center Hamburg-Eppendorf between 1996 and 2003 were retrospectively analysed regarding the prognostic relevance of different clinicopathological variables. Recurrences were evaluated with regard to their characteristics and localisation. RESULTS: Age, lymph node metastasis, tumor size, depth of invasion and involvement of resection margins predicted poor disease-free and overall survival in univariate analysis. In multivariate analysis, lymph node status was the most important independent prognostic factor (p = 0.002). No correlation was observed between lymph node metastasis and localization of recurrent disease. Regardless of initial nodal involvement, recurrences occurred primarily in the vulvar region. CONCLUSION: Inguinofemoral lymph node status at initial diagnosis is of critical prognostic importance for patients with vulvar cancer. Further tumour biological characteristics need to be identified to stratify patients with nodal involvement for adjuvant radiotherapy of the vulva to prevent local recurrences.


Subject(s)
Neoplasm Recurrence, Local/pathology , Vulvar Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Disease-Free Survival , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Vulvar Neoplasms/surgery
2.
Am J Physiol Endocrinol Metab ; 292(6): E1790-800, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17311890

ABSTRACT

Aldosterone plays a key role in cardiovascular and renal injury. The underlying mechanisms are not completely understood. Because the epidermal growth factor receptor (EGFR) is involved in the development of fibrosis and vascular dysfunction, upregulation of EGFR expression by aldosterone-bound mineralocorticoid receptor (MR) is an attractive hypothesis. We investigated the effect of aldosterone on EGFR expression in the aorta of adrenalectomized rats and in human aorta smooth muscle cells (HAoSMC) in primary culture. Aldosterone, but not dexamethasone, stimulated EGFR expression in vivo in the aorta as well as in HAoSMC. EGFR degradation was not affected. Aldosterone-induced EGFR expression in HAoSMC was dose dependent and prevented by spironolactone. Furthermore, incubation of HAoSMC with aldosterone led to enhanced EGF-induced ERK1/2 phosphorylation and an EGFR-dependent increase in media fibronectin. EGFR promoter reporter gene assay as well as chromatin immunoprecipitation data indicate that MR interacts with the EGFR promoter. With deletion constructs we gained evidence that this interaction takes place between the hMR and the EGFR promoter regions 316-163 (stronger activation site, EC50 approximately 1.0 nM) and 163-1 (weaker activation site, EC50 approximately 0.7 nM), which do not comprise canonical glucocorticoid response elements and are not activated by the human glucocorticoid receptor. The interactions require in part the NH2-terminal domains of MR. ELISA-based transcription factor DNA binding assay with in vitro synthesized hMR suggest direct binding to region 163-1. Our results indicate that aldosterone leads to enhanced EGFR expression via an interaction with the EGFR promoter, which is MR specific and could contribute to the aldosterone-induced increase in fibronectin abundance.


Subject(s)
Aldosterone/physiology , Aorta/metabolism , ErbB Receptors/genetics , ErbB Receptors/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Promoter Regions, Genetic/physiology , Receptors, Mineralocorticoid/metabolism , Adrenalectomy , Aldosterone/pharmacology , Animals , Cells, Cultured , Chromatin , DNA/metabolism , DNA Fragmentation , Fibronectins/metabolism , Humans , Immunoprecipitation , Ligands , Male , Protein Structure, Tertiary/physiology , Rats , Rats, Wistar , Receptors, Mineralocorticoid/genetics , Tunica Media/cytology , Tunica Media/metabolism
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