Activation of the E-cadherin/catenin complex in human MCF-7 breast cancer cells by all-trans-retinoic acid.

All-trans-retinoic acid (RA), like insulin-like growth factor I (IGF-I) and tamoxifen, inhibit invasion of human MCF-7/6 mammary cancer cells in vitro. For tamoxifen and for IGF-I, activation of the invasion-suppressor function of the E-cadherin/catenin complex was shown to be the most probable mechanism of the anti-invasive action. We did a series of experiments to determine whether the anti-invasive effect of RA also implicated the invasion-suppressor E-cadherin/catenin complex. Human MCF-7/6 mammary and HCT-8/R1 colon cancer cells, both with a dysfunctional E-cadherin/catenin complex, were treated with RA and the function of the complex was evaluated through Ca(2+)-dependent fast aggregation. Fast aggregation of both MCF-7/6 and HCT-8/R1 cells was induced by 1 microM RA. This effect was abolished by antibodies against E-cadherin. RA-induced fast aggregation was not sensitive to cycloheximide, tyrosine kinase inhibitors or antibodies against IGF-I or against the IGF-I receptor. RA did not stimulate IGF-I receptor phosphorylation or alter the E-cadherin/catenin complex, as evidenced by immunoprecipitation. RA up-regulates the function of the invasion-suppressor complex E-cadherin/catenin. Its action mechanism is different from that of IGF-I. RA may act as an anti-invasive agent with unique mechanisms of action

Response of AGATA Segmented HPGe Detectors to Gamma Rays up to 15.1 MeV

The response of AGATA segmented HPGe detectors to gamma rays in the energy range 2-15 MeV was measured. The 15.1 MeV gamma rays were produced using the reaction d(11B,ng)12C at Ebeam = 19.1 MeV, while gamma-rays between 2 to 9 MeV were produced using an Am-Be-Fe radioactive source. The energy resolution and linearity were studied and the energy-to-pulse-height conversion resulted to be linear within 0.05%. Experimental interaction multiplicity distributions are discussed and compared with the results of Geant4 simulations. It is shown that the application of gamma-ray tracking allows a suppression of background radiation following neutron capture by Ge nuclei. Finally the Doppler correction for the 15.1 MeV gamma line, performed using the position information extracted with Pulse-shape Analysis, is discussed.Comment: 10 pages, 11 figure

Progression of familial adenomatous polyposis (FAP) colonic cells after transfer of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in invasion.

Little is known about the the signalling pathways driving the adenoma-to-carcinoma sequence in human colonic epithelial cells. Accumulation and activation of the src tyrosine kinase in colon cancer suggest a potential role of this oncogene in this early progression. Therefore, we introduced either activated src (m-src), polyoma-MT alone or combined with normal c-src in the adenoma PC/AA/C1 cell line (PC) to define the function and phenotypic transformations induced by these oncogenes in familial adenomatous polyposis (FAP) colonic epithelial cells. Functional expression of these oncoproteins induced the adenoma-to-carcinoma conversion, overexpression of the hepatocyte growth factor (HGF) receptor Met, but failed to confer invasiveness in vivo and in vitro, or to produce alterations in cell proliferation and differentiation. In contrast, PC-msrc cells became susceptible to the HGF-induced invasion of collagen gels and exhibited sustained activation of the pp60src tyrosine kinase and Tyr phosphorylation of the 120-kDa E-cadherin, which was further increased by HGF Transcripts of HGF were clearly identified by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot in the parental and transformed PC cells, suggesting an autocrine mechanism. Taken together, the data indicate that: (1) experimental activation of src and PyMT pathways directly induces tumorigenicity and Met upregulation in a colon adenoma cell line; (2) HGF-activated Met and src cooperate in inducing invasion; (3) in view of the molecular associations between catenins and cadherin or the tumour-suppressor gene product APC, the cell adhesion molecule E-cadherin may constitute a downstream effector of src and Met

Mangomoments - Preconditions and impact on patients and families, healthcare professionals and organisations: A multi-method study in Flemish hospitals

Objective Understanding how small unexpected acts or gestures by healthcare professionals, known as Mangomoments, are translated into practice, what their preconditions are and what their impact is on patients and families, healthcare professionals and organisations. Design A multi-method design was used based on four phases: (1) A (media)campaign to collect Mangomoment stories (n=1045), of which 94% (n=983) were defined as Mangomoments; (2) Semi-structured interviews (n=120); (3) Focus group interviews (n=3); and (4) A consensus meeting. Setting Respondents from a hospital and primary care setting. Participants Patients, family, healthcare professionals, managers, researchers and a policymaker participated. Results Mangomoments are mainly classified in the dimensions a \u20ac Respect for values, preferences and needs' and a 'Emotional support'. Differences in importance of the dimensions were found between healthcare professionals, oncological patients and family and non-oncological patients and family. The results of the interviews, focus groups and consensus meeting were visualised by the Mangomoment model. It identifies several preconditions on the level of patients, healthcare professionals and leadership. For each of these preconditions a catalyst was identified to increase the prevalence of Mangomoments. In general, Mangomoments improved the patient and family experience and facilitated adherence to therapy and led to a positive perception on the healing process. Positive effects for professionals include personal accomplishment and anti-burnout, joy in work and a positive team atmosphere. This led to positive resonance by a relationship of trust between the patient and the healthcare professionals, feelings of tolerance during negative experiences and open communication and a safe climate. Overall, patients and healthcare workers concluded that Mangomoments led to loyalty to the healthcare organisation. Conclusion Mangomoments do not only have a positive impact on patient and family but also on the healthcare professional. Leadership should shape several preconditions and catalysts which can lead to positive resonance and loyalty of patients and professionals

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro.

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells

Axes determination for segmented true-coaxial HPGe detectors

A fast method to determine the crystallographic axes of segmented true-coaxial high-purity germanium detectors is presented. It is based on the analysis of segment-occupancy patterns obtained by irradiation with radioactive sources. The measured patterns are compared to predictions for different axes orientations. The predictions require a simulation of the trajectories of the charge carriers taking the transverse anisotropy of their drift into account.Comment: 18 pages, 1 table, 31 figures; included background contribution to the occupancy patterns and systematic uncertainties, results slightly change

Electric quadrupole moments of the 21+_{1}^{+} states in 100,102,104^{100,102,104}Cd

Using the REX-ISOLDE facility at CERN the Coulomb excitation cross sections for the 0gs+→21+ transition in the β-unstable isotopes 100,102,104Cd have been measured for the first time. Two different targets were used, which allows for the first extraction of the static electric quadrupole moments Q(21+) in 102,104Cd. In addition to the B(E2) values in 102,104Cd, a first experimental limit for the B(E2) value in 100Cd is presented. The data was analyzed using the maximum likelihood method. The provided probability distributions impose a test for theoretical predictions of the static and dynamic moments. The data are interpreted within the shell-model using realistic matrix elements obtained from a G-matrix renormalized CD-Bonn interaction. In view of recent results for the light Sn isotopes the data are discussed in the context of a renormalization of the neutron effective charge. This study is the first to use the reorientation effect for post-accelerated short-lived radioactive isotopes to simultaneously determine the B(E2) and the Q(21+) values

Isospin dependence of electromagnetic transition strengths among an isobaric triplet

Electric quadrupole matrix elements, M, for the J=2→0, ΔT=0, T=1 transitions across the A=46 isobaric multiplet Cr-V-Ti have been measured at GSI with the FRS-LYCCA-AGATA setup. This allows direct insight into the isospin purity of the states of interest by testing the linearity of M with respect to T. Pairs of nuclei in the T=1 triplet were studied using identical reaction mechanisms in order to control systematic errors. The M values were obtained with two different methodologies: (i) a relativistic Coulomb excitation experiment was performed for Cr and Ti; (ii) a “stretched target” technique was adopted here, for the first time, for lifetime measurements in V and Ti. A constant value of M across the triplet has been observed. Shell-model calculations performed within the fp shell fail to reproduce this unexpected trend, pointing towards the need of a wider valence space. This result is confirmed by the good agreement with experimental data achieved with an interaction which allows excitations from the underlying sd shell. A test of the linearity rule for all published data on complete T=1 isospin triplets is presented.Peer Reviewe