Manipulating Protein Acetylation in Breast Cancer: A Promising Approach in Combination with Hormonal Therapies?

Estrogens play an essential role in the normal physiology of the breast as well as in mammary tumorigenesis. Their effects are mediated by two nuclear estrogen receptors, ERα and β, which regulate transcription of specific genes by interacting with multiprotein complexes, including histone deacetylases (HDACs). During the past few years, HDACs have raised great interest as therapeutic targets in the field of cancer therapy. In breast cancer, several experimental arguments suggest that HDACs are involved at multiple levels in mammary tumorigenesis: their expression is deregulated in breast tumors; they interfere with ER signaling in intricate ways, restoring hormone sensitivity in models of estrogen resistance, and they clinically represent new potential targets for HDACs inhibitors (HDIs) in combination with hormonal therapies. In this paper, we will describe these different aspects and underline the clinical interest of HDIs in the context of breast cancer resistance to hormone therapies (HTs)

Agent-Based Simulation as an Implementation of Methodological Individualism

This paper investigates the relationship between methodological individualism (MI) and Agent-Based Simulation (ABS). We discuss and analyze a thesis defended by philosophers Caterina Marchionni and Petri Ylikoski (2013). The thesis maintains that, since MI is often considered to be a reductionist approach, it is confusing and meaningless to assume that ABS, which is a non-reductionist and emergentist explanatory model, is committed to MI. We reject this thesis arguing that, from a philosophical standpoint, addressing the problem of the consistency between MI and ABS from a strictly utilitarian perspective is unsatisfactory. We analyze this problem in more substantial terms, i.e. focusing on its more theoretical and conceptual aspects. Moreover, we maintain that ABS explanations must be regarded as individualist explanations and provide a set of logical and historical arguments against the widespread interpretation of MI in terms of reductionism

Histone-désacétylases et cancer du sein (Expression et régulation dans les lignées tumorales mammaires)

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Infection par le papillomavirus humain chez la femme ménopausée

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

ANALYSE DU SYSTEME DES INSULIN-LIKE GROWTH FACTORS (IGF) ET DU FIBROBLAST GROWTH FACTOR-2 (FGF-2) DANS LA TUMORIGENESE CORTICOSURRENALIENNE (DOCTORAT (ENDOCRINOLOGIE ET INTERACTIONS CELLULAIRES))

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Polarization-induced strain and wall roughness in ferroelectric 180° stripe domains probed by diffuse X-ray scattering

International audienc

Étude des domaines ferroélectriques à basse dimensionnalité: apport de la diffraction de rayons X

International audienc

Diffuse X-ray scattering from 180° ferroelectric stripe domains: polarization-induced strain, period disorder and wall roughness

International audienceA key element in ferroic materials is the presence of walls, separating domains with different orientations of the order parameter. We demonstrate that 180° stripe domains in ferroelectric films give rise to very distinct features in their diffuse X-ray scattering (DXS) intensity distributions. A model is developed that allows to determine not only the domain period but also the period disorder, the thickness and roughness of the domain walls, and the strain induced by the rotation of the polarization. As an example, the model is applied to ferroelectric/paraelectric superlattices. Temperature-dependent DXS measurements reveal that the polarization-induced strain dramatically decreases with increasing temperature and vanishes at the Curie temperature. The motion of ferroelectric domain walls appears as a collective process that does not create any disorder in the domain period, whereas the pinning by structural defects increases the wall roughness. This work will facilitate in-situ quantitative studies of ferroic domains and domain wall dynamics under the application of external stimuli, including electric fields and temperature

Involvement of Estrogen Receptor β in Ovarian Carcinogenesis

Abstract Knockout and expression studies suggest that estrogen receptor β (ERβ) plays a prominent role in ovarian function and pathology. Moreover, ovarian cancers are characterized by high morbidity and low responsiveness to anti-estrogens. Here we demonstrate, using quantitative PCR to measure ERα and ERβ levels in 58 ovarian cancer patients, that ERβ expression decreased in cysts and ovarian carcinomas as compared with normal ovaries and that this decrease is attributable only to a selective loss in ERβ expression during cancer progression. To address the question of a possible involvement of ERβ in ovarian cancers, we restored ERα and ERβ expression in two human ovarian cancer cell lines PEO14 (ERα-negative) and BG1 (ERα-positive) using adenoviral delivery. ERα, but not ERβ, could induce progesterone receptor and fibulin-1C. Moreover, ERα and ERβ had opposite actions on cyclin D1 gene regulation, because ERβ down-regulated cyclin D1 gene expression, whereas ERα increased cyclin D1 levels. Interestingly, ERβ expression strongly inhibited PEO14 and BG1 cell proliferation and cell motility in a ligand-independent manner, whereas ERα had no marked effect. Induction of apoptosis by ERβ also contributed to the decreased proliferation of ovarian cancer cells, as shown by Annexin V staining. This study shows that ERβ is an important regulator of proliferation and motility of ovarian cancer and provides the first evidence for a proapoptotic role of ERβ. The loss of ERβ expression may thus be an important event leading to the development of ovarian cancer

Auto-prélèvement avec test HPV : une nouvelle alternative pour améliorer l’adhésion au dépistage du cancer du col de l’utérus?

International audienceLe dépistage du cancer du col utérin, basé sur le frottis cervico-vaginal, a été mis en place dans les années 60 dans la plupart des pays développés, permettant une diminution spectaculaire du nombre de cancers. Cependant ce dépistage, proposé en France aux femmes de 25 à 65 ans, ne couvre pas la totalité de la population cible puisque 40 % environ des femmes y échappe dans notre pays.Une alternative pour augmenter la couverture du dépistage est de proposer aux femmes un auto-prélèvement, vaginal ou urinaire, puis un test de détection des papillomavirus humains (HPV). De nombreuses publications ont montré que cette approche présentait une bonne sensibilité et bonne spécificité comparée au frottis pour la détection des lésions histologiques de haut grade.Plusieurs facteurs doivent être validés avant la mise en place à grande échelle de l’auto-prélèvement : le type de dispositif utilisé, la technique de détection des HPV, les modalités de mise à disposition et de retour des dispositifs, l’information des femmes, la prise en charge des femmes avec test HPV positif et, comme pour tout dépistage, le coût/bénéfice de l’approche choisie.Plusieurs études sur l’auto-prélèvement ont été faites en France ces dernières années et cette approche sera certainement intégrée au dépistage organisé du cancer du col utérin prévu dès 2018 pour améliorer l’efficacité de ce dépistage