Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC), currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ), an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation.</p> <p>Results</p> <p>GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, <it>P </it>< 0.00001, r = 0.56). They were also higher in tumor cells containing large amounts of phosphorylated protein kinase B (p-AKT) (unpaired t test, <it>P </it>< 0.0001). To assess the effect of GILZ on proliferation and AKT activation, we used the BG-1 cell line derived from ovarian tumor cells as a cellular model. GILZ expression was either enhanced by stable transfection or decreased by the use of small interfering (si) RNA targeting GILZ. We found that GILZ increased cell proliferation, phospho-AKT cellular content and AKT kinase activity. Further, GILZ upregulated cyclin D1 and phosphorylated retinoblastoma (p-Rb), downregulated cyclin-dependent kinase inhibitor p21, and promoted the entry into S phase of cell cycle.</p> <p>Conclusion</p> <p>The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.</p

Compliance and treatment satisfaction of post menopausal women treated for osteoporosis. Compliance with osteoporosis treatment

International audienceBackgroundAdherence to anti-osteoporosis treatments is poor, exposing treated women to increased fracture risk. Determinants of poor adherence are poorly understood. The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance.MethodsThis was an observational, cross-sectional pharmacoepidemiological study with a randomly-selected sample of 420 GPs, 154 rheumatologists and 110 gynaecologists practicing in France. Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months. Investigators completed a questionnaire on clinical features, treatments and medical history, and on patient compliance. Patients completed a questionnaire on sociodemographic features, lifestyle, attitudes and knowledge about osteoporosis, treatment compliance, treatment satisfaction and quality of life. Treatment compliance was evaluated with the Morisky Medication-taking Adherence Scale. Variables collected in the questionnaires were evaluated for association with compliance using multivariate logistic regression analysis.Results785 women were evaluated. Physicians considered 95.4% of the sample to be compliant, but only 65.5% of women considered themselves compliant. The correlation between patient and physician perceptions of compliance was low (κ: 0.11 [95% CI: 0.06 to 0.16]). Patient-rated compliance was highest for monthly bisphosphonates (79.7%) and lowest for hormone substitution therapy (50.0%). Six variables were associated with compliance: treatment administration frequency, perceptions of long-term treatment acceptability, perceptions of health consequences of osteoporosis, perceptions of knowledge about osteoporosis, exercise and mental quality of life.ConclusionCompliance to anti-osteoporosis treatments is poor. Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance

CXCL12 expression by healthy and malignant ovarian epithelial cells

<p>Abstract</p> <p>Background</p> <p>CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC), CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ovaries, to assess its prognostic value.</p> <p>Methods</p> <p>Immunohistochemistry was used to analyze CXCL12 expression in the reproductive tracts, including the ovaries and fallopian tubes, of healthy women, in benign and borderline epithelial tumors, and in a series of 183 tumor specimens from patients with advanced primary EOC enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin/gemcitabine-based chemotherapy (GINECO study). Univariate COX model analysis was performed to assess the prognostic value of clinical and biological variables. Kaplan-Meier methods were used to generate progression-free and overall survival curves.</p> <p>Results</p> <p>Epithelial cells from the surface of the ovary and the fallopian tubes stained positive for CXCL12, whereas the follicles within the ovary did not. Epithelial cells in benign, borderline and malignant tumors also expressed CXCL12. In EOC specimens, CXCL12 immunoreactivity was observed mostly in epithelial tumor cells. The intensity of the signal obtained ranged from strong in 86 cases (47%) to absent in 18 cases (<10%). This uneven distribution of CXCL12 did not reflect the morphological heterogeneity of EOC. CXCL12 expression levels were not correlated with any of the clinical parameters currently used to determine EOC prognosis or with HER2 status. They also had no impact on progression-free or overall survival.</p> <p>Conclusion</p> <p>Our findings highlight the previously unappreciated constitutive expression of CXCL12 on healthy epithelia of the ovary surface and fallopian tubes, indicating that EOC may originate from either of these epithelia. We reveal that CXCL12 production by malignant epithelial cells precedes tumorigenesis and we confirm in a large cohort of patients with advanced EOC that CXCL12 expression level in EOC is not a valuable prognostic factor in itself.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00052468">NCT00052468</a></p

Miguel Benasayag, Comprendre est agir, paysages et situations

L’époque se caractérise par le fatalisme et la conscience malheureuse : l’individu, prisonnier de la monotonie, est coupé du monde, conscient de la négativité apporté par le progrès. Deux solutions : l’impuissance de la Belle Ame ou la gestion entrepreneuriale de la vie personnelle. Face à la fascination du pire, il faut réapprendre à percevoir, prendre conscience du rapport entre l’organisme et son environnement que M. Benasayag nomme « paysages », d’autant que la conscience est illusoire et..

Jacques Arènes et Nathalie Sarthou-Lajus, La défaite de la volonté

La modernité s’appuie sur des figures du destin, figures intérieures qui accablent le sujet dépressif, livré à l’absurdité du monde et aux angoisses archaïques. Sans pouvoir se débarrasser de soi, l’individu moderne ne peut donner de sens à la souffrance. Mort vivant, il vit dans une éternité factice, nourri de conduites autodestructrices, de la peur de vieillir, dans une culture mortifère qui voit dans l’idée du suicide la négation de l’échéance finale. Cette attitude, décrite par Houellebec..

L’errance du récit dans l’œuvre de Tahar Ben Jelloun

L’enfant, l’écrivain, Lalla, Bobby, tous les personnages de T. Ben Jelloun vont, viennent, partent vers le Sud, marchent vers une origine historique, mentale ou sexuelle. Pourtant, le voyage qui fonde la plupart des romans, se perd souvent dans les sables et se transforme en errance. C’est que le déplacement spatial redouble un cheminement intérieur, souvent douloureux, mimant les va et vient du récit, voire ses impossibilités. 1. L’errance intérieure Les romans débutent par une crise, concré..

Stefan Fisch, Stadtplanung im 19 Jahr-hundert. Der Beispiel München bis zur Ara Theodor Fischer

Riou Françoise, Gaudin Jean-Pierre. Stefan Fisch, Stadtplanung im 19 Jahr-hundert. Der Beispiel München bis zur Ara Theodor Fischer. In: Annales. Économies, Sociétés, Civilisations. 45ᵉ année, N. 2, 1990. pp. 470-471

Stefan Fisch, Stadtplanung im 19 Jahr-hundert. Der Beispiel München bis zur Ara Theodor Fischer

Riou Françoise, Gaudin Jean-Pierre. Stefan Fisch, Stadtplanung im 19 Jahr-hundert. Der Beispiel München bis zur Ara Theodor Fischer. In: Annales. Économies, Sociétés, Civilisations. 45ᵉ année, N. 2, 1990. pp. 470-471