Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis.

Significant relief of bone pain in patients with bone metastases was observed in a clinical trial of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in breast cancer. Osteoclast activation and differentiation are regulated by bone marrow stromal cells (BMSC), a heterogeneous cell compartment that comprehends undifferentiated mesenchymal stem cells (MSC) and their specialized progeny. In this regard, we found that human primary BMSCs express immunoreactive EGFR. Expression of EGFR mRNA and protein was also demonstrated in two human, continuous MSC-like cell lines, HDS-1 and HDS-2 cells. Treatment of HDS cells with EGF produced a significant increase in the levels of activated EGFR which was not observed in the presence of gefitinib. A significant reduction in the basal levels of activation of the EGFR and of Akt was observed in HDS cells following treatment with gefitinib. Treatment of HDS cells with gefitinib produced a significant reduction in the levels of secreted macrophage colony-stimulating factor (M-CSF) and cell-associated receptor activator of NF-kappaB ligand (RANKL) in both cell lines, as assessed by using specific ELISA and Western blotting techniques. Finally, the ability to sustain the differentiation of pre-osteoclasts of conditioned medium from gefitinib-treated HDS cells was reduced by approximately 45% as compared with untreated HDS cells. These data have demonstrated for the first time that the EGFR regulates the ability of BMSCs to induce osteoclast differentiation and strongly support clinical trials of gefitinib in breast cancer patients with bone disease

Experience of 170 cases of ductal carcinoma in ' (DCIS)

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Factors determining the 24-h blood pressure profile in normotensive patients with type 1 and type 2 diabetes

Some controversy still exists about factors involved in the abnormal circadian pattern of blood pressure (BP) in diabetes, while prognostic value of non-dipping condition is being increasingly recognised. This study was aimed at evaluating the relative influence of autonomic neuropathy (AN) and albumin excretion on 24-h BP profile in type I and type 2 diabetes. We measured AN cardiovascular tests, 24-h ambulatory BP, and urinary albumin excretion rate (UAE) in 47 type 1 and 34 type 2 normotensive non-proteinuric diabetic patients. In type I diabetic patients day-night differences (Delta) in systolic and diastolic BP were lower in those with AN than in those without (3 +/- 9 vs 10 +/- 6%, P 9 vs 16 +/- 6%, P 214 vs 49 +/- 37%, P BP, while in type 2 diabetic patients it was the unique determinant not only of Delta systolic EP but also of 24-h systolic BP. in conclusion, AN is the pivotal factor of blunted nocturnal fall In BP in both type 1 and type 2 diabetic patients. In type 1 diabetic patients AN is associated with attenuated circadian pattern of albuminuria and with a steeper relationship between albuminuria and BP, in type 2 diabetic patients AN is the only factor related to elevated 24-h BP levels. Longitudinal studies are needed to establish the potential role of autonomic dysfunction as a progression promoter for nephropathy and hypertension in type 1 and type 2 diabetes respectively

Can the Body Mass Index and the waist:hips ratio (WHR) affect the correlation between impedance measurement and anthropometry in the evaluation of body composition? [Possono il Body Mass Index (BMI) ed il rapporto vita/fianchi (WHR) influenzare la correlazione tra impedenziometria ed antropometria nella valutazione della composizione corporea?]

Among the numerous techniques used to measure body composition, this study utilised anthropometric methods (weight, height, circumference and skin folds) and impedance measurement (measurement of bioelectric impedance). Results from the two methods were compared in order to assess whether BMI parameters and the waist/hips ratio (WHR) influenced this correlation. One hundred and eighty patients (133 F, 47 M) were included in the study. Patients were divided into groups according to the degree of obesity expressed as BMI and WHR. Body composition was evaluated using anthropometric methods (according to Garrow Webster, Durnin-Womersley, modified Durnin-Womersley and Jackson-Pollock) and impedance measurement in which resistive bioelectric impedance is measured using a tetrapolar technique. A good correlation was generally observed in the female population between impedance assessment and anthropometric methods, and this correlation was not influenced by either BMI or WHR. In the male group, on the other hand, the correlation between the two methods was limited by BMI greater than 30 and WHR greater than 1. In conclusion, impedance measurement and plicometric methods are generally compatible, but areas of uncertainty arise in the male population with BMI greater than 30 and WHR greater than 1

ETRUSCO-2: An ASI-INFN project of technological development and "SCF-Test" of GNSS Laser retroreflectors arrays

The Satellite/Lunar/GNSS laser ranging and altimetry Characterization Facility (SCF) and SCF-Test are respectively a new test facility and test procedure to characterize and model the detailed thermal behaviour and optical performance of Cube Corner laser Retroreflectors (CCRs) for the Global Navigation Satellite System (GNSS) in laboratory-simulated space conditions, developed by INFN-LNF and in use by NASA, ESA, ASI and ISRO. Our key experimental innovation is the concurrent measurement and modelling of the optical Far Field Diffraction Pattern (FFDP) and the temperature distribution of retroreflector payloads under thermal conditions produced with a close-match solar simulator. The apparatus includes infrared cameras for non-invasive thermometry, thermal control and real-time payload movement to simulate satellite orientation on orbit with respect to solar illumination and laser interrogation beams. These capabilities provide: unique pre-launch performance validation of the space segment of Lunar/Satellite Laser Ranging (LLR/SLR); retroreflector design optimization to maximize ranging efficiency and signal-to-noise conditions in daylight. Extra Terrestrial Ranging to Unified Satellite COnstellations-2 (ETRUSCO-2 ) project goals will be achieved using the innovative test procedure described in [1]