Occurrence of epidermal growth factor receptors in benign and malignant ovarian tumors and normal ovarian tissues: an immunohistochemical study

Epidermal growth factor receptor (EGF-R) was studied with monoclonal antibody 2E9 on 50 ovarian tumors of various histological types and 10 non-tumorous ovarian tissues by immunohistochemistry. Enhanced expression was observed in 26/50 (52%) of the tumors. Only 25 out of 46 epithelial tumors (54%) showed positivity in epithelial tumor cells. Staining was cytoplasmic in all cases. No correlation was established between EGF-R expression and the histological type of the epithelial tumor. Apart from EGF-R expression in tumor cells, low immunoreactivity was also observed in stromal and endothelial cells in both normal and tumorous ovarian tissues. Furthermore in 8/9 specimens containing necrotic areas, EGF-R was noticed in these areas as well. Both of the latter observations may have impact on the evaluation of the prognostic value of EGF-R activity in tumors, when based on EGF-R measurements using biochemical binding studies. We therefore recommend that EGF-R is measured with both methods in studies regarding its clinical value

The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters

To analyse the clinical significance of the presence of androgen receptors (AR) in breast carcinomas, clinical and histological parameters of 153 primary breast carcinomas (median follow-up 46 months) were examined. Oestrogen (ER) and progesterone receptor (PR) levels were determined in cytosol preparations using enzyme immunoassay assays and in cryostat sections by immunohistochemistry. AR and Ki-67 levels were only determined immunohistochemically. Data were analysed by uni- and multivariate models. 94/153 (61%) breast carcinomas were ER+ PR+ AR+, while 14 cases were only positive for AR. All grade III tumours (n = 17) were steroid receptor negative and 14 (76%) of these cases demonstrated high Ki-67 values suggestive of more aggressive behaviour. Strikingly, 14 ductal carcinomas negative for ER and PR were positive for AR. In univariate analysis, AR as well as ER, tumour size, lymph node status, grade and Ki-67 proved to be significant prognostic factors for disease free survival (DFS). Multivariate analysis, however, showed lymph node status, tumour size and ER status to be the only independent prognostic factors for DFS within this model. We conclude that simple histological and cell biological parameters, including AR, can be used to select high- and low-risk patients at the time of primary surgery and can provide valuable information on treatment options

Limiting Kinetic Energy through Control Barrier Functions:Analysis and Experimental Validation

In the context of safety-critical control, we propose and analyse the use of Control Barrier Functions (CBFs) to limit the kinetic energy of torque-controlled robots. The proposed scheme is able to modify a nominal control action in a minimally invasive manner to achieve the desired kinetic energy limit. We show how this safety condition is achieved by appropriately injecting damping in the underlying robot dynamics independently of the nominal controller structure. We present an extensive experimental validation of the approach on a 7-Degree of Freedom (DoF) Franka Emika Panda robot. The results demonstrate that this approach provides an effective, minimally invasive safety layer that is straightforward to implement and is robust in real experiments

The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients

The antigen levels of components of the urokinase-type plasminogen activator (uPA) system of plasminogen activation are correlated with prognosis in several types of cancers, including breast cancer. In the present study involving 2780 patients with primary invasive breast cancer, we have evaluated the prognostic importance of the four major components of the uPA system [uPA, the receptor uPAR (CD87), and the inhibitors PAI-1 and PAI-2]. The antigen levels were determined by ELISA in cytosols prepared from primary breast tumors. The levels of the four factors significantly correlated with each other; the Spearman rank correlation coefficients (r(s)) ranged from 0.32 (between PAI-2 and PAI-1 or uPAR) to 0.59 (between uPA and PAI-1). The median duration of follow-up of patients still alive was 88 months. In the multivariate analyses for relapse-free survival (RFS) and overall survival (OS), we defined a basic model including age, menopausal status, tumor size and grade, lymph node status, adjuvant therapy, and steroid hormone receptor status. uPA, uPAR, PAI-1, and PAI-2 were considered as categorical variables, each with two cut points that were established by isotonic regression analysis. Compared with tumors with low levels, those with intermediate and high levels showed a relative hazard rate (RHR) and 95% confidence interval (95% CI) of 1.22 (1.02-1.45) and 1.69 (1.39-2.05) for uPA, and 1.32 (1.14-1.54) and 2.17 (1.74-2.70) for PAI-1, respectively, in multivariate analysis for RFS in all patients. Compared with tumors with high PAI-2 levels, those with intermediate and low levels showed a poor RFS with a RHR (95% CI) of 1.30 (1.14-1.48) and 1.76 (1.38-2.24), respectively. Similar results were obtained in the multivariate analysis for OS in all patients. Furthermore, uPA and PAI-1 were independent predictive factors of a poor RFS and OS in node-negative and node-positive patients. PAI-2 also added to the multivariate models for RFS in node-negative and node-positive patients, and in the analysis for OS in node-negative patients. uPAR did not further contribute to any of the multivariate models. A prognostic score was calculated based on the estimates from the final multivariate model for RFS. Using this score, the difference between the highest and lowest 10% risk groups was 66% in the analysis for RFS at 10 years and 61% in the analysis for OS. Moreover, separate prognostic scores were calculated for node-negative and node-positive patients. In the 10% highest risk groups, the proportion of disease-free patients was only 27 +/- 6% and 9 +/- 3% at 10 years for node-negative and node-positive patients, respectively. These proportions were 86 +/- 4% and 61 +/- 6% for the corresponding 10% lowest risk groups of relapse. We conclude that several components of the uPA system are potential predictors of RFS and OS in patients with primary invasive breast cancer. Knowledge of these factors could be helpful to assess the individual risk of patients, to select various types of adjuvant treatment and to identify patients who may benefit from targeted therapies that are currently being developed

Zekerheid op Lading: Pandrecht en retentierecht op roerende zaken en cognossement in het handelsverkeer

Een zekerheidsrecht functioneert in het recht ongeveer op dezelfde manier als de grijper van een kraan in de haven. Zoals de machinist van een kraan de grijper kan openen of sluiten, zo heeft de zekerheidshouder de bevoegdheid om de zaken onder zich te houden totdat de verschuldigde vordering is betaald, dan wel om de zaken af te geven aan de schuldenaar of een derde. Door de uitoefening van zijn zekerheidsrecht houdt de schuldeiser dus grip op de lading. Dit aspect van het zekerheidsrecht is van groot belang voor logistieke dienstverleners en banken. De door hen verrichte handelingen, zoals kredietverlening, fysieke distributie, expeditie, vervoer, bewaarneming, laden, lossen, opdracht en lastgeving, brengen kosten met zich mee die in beginsel verhaalbaar zijn op de contractuele wederpartij, de schuldenaar. In veel gevallen wordt het verschuldigde loon echter pas betaald na het verrichten van de handeling ten behoeve van de zaken. Daardoor loopt de schuldeiser steeds het risico dat de schuldenaar, om wat voor reden dan ook, verzuimt zijn verbintenis uit de overeenkomst, namelijk de verplichting tot het betalen van het loon, na te komen. Hier komt het belang van het zekerheidsrecht naar voren: door middel van een zekerheidsrecht kan de schuldeiser het risico van wanbetaling door de schuldenaar beperken. De schuldeiser behoeft de zaken niet af te geven zolang het loon niet is betaald en hij kan zich zelfs onder bepaalde omstandigheden op de zaken verhalen. Uiteraard zal niet in alle gevallen waar sprake is van een betalingsverzuim een zekerheidsrecht worden ingeroepen. Vaak volstaat een commerciële oplossing, zoals het bieden van uitstel van betaling. Het zekerheidsrecht komt pas in beeld wanneer een commerciële oplossing geen resultaat (meer) geeft. Dat is het geval wanneer de schuldenaar failliet is gegaan of op andere wijze ervan blijk geeft niet aan zijn betalingsverplichtingen te kunnen voldoen. In deze gevallen waarin een commerciële oplossing niet meer baat, vervullen zekerheidsrechten een onmisbare rol. Dit boek handelt over twee zekerheidsrechten, het pandrecht en het retentierecht, en hun rol in het internationaal handelsverkeer