Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone.

The reasons why tumor cells metastasize to bone remain obscure. There is some evidence to support the theory that integrins (acting as cell surface adhesion receptors) play a role in mediating metastasis in certain organs. Here, we report that overexpression of a functionally active integrin alpha(v)b3 in Chinese hamster ovary (CHO) tumor cells drastically increased the incidence, number, and area of bone metastases in nude mice compared with those observed in mock-transfected CHO cells (CHO dhfr+) or in CHO cells expressing a functionally inactive integrin alpha(v)b3 (CHO beta3Delta744). Moreover, a breast cancer cell line (B02) established from bone metastases caused by MDA-MB-231 cells constitutively overexpressed integrin alpha(v)b3, whereas the cell surface expression level of other integrins remained unchanged. In vivo, the extent of bone metastases in B02-bearing mice was significantly increased compared with that of MDA-MB-231-bearing mice. In vitro, B02 cells and CHO cells expressing a functionally active integrin alpha(v)b3 exhibited substantially increased invasion of and adhesion to mineralized bone, bone sialoprotein, and collagen compared with those found with MDA-MB-231, CHO dhfr+, and CHO beta3Delta744 cells, respectively. Overall, our findings suggest that integrin alpha(v)b3 expression in tumor cells accelerates the development of osteolytic lesions, presumably through increased invasion of and adhesion to bone

Abnormal steroidogenesis and aromatase activity in preeclampsia.

International audienceIntroduction :Estrogens and progesterone play critical roles in angiogenesis and vasodilation. Moreover, placental aromatase deficiency is detected in women with preeclampsia (PE) at delivery. We hypothesized that abnormal steroidogenesis occurs much earlier than typical PE diagnosis. Thus, we investigated whether the circulating steroid profile was already disturbed at 24–29 weeks of gestation in women with subsequent PE, and compared the profile with that of women with “placental” small gestational age (SGA) without PE.Methods :We selected nulliparous women (n = 90) from the MOMA trial, including women with PE (n = 25), SGA (n = 25), and controls (NP; n = 40), for plasma steroid profiling by gas chromatography/mass spectrometry and to measure placental growth factor and soluble fms-like tyrosine kinase-1. Placental aromatase expression was evaluated in a new set of women.Results :Compared with that of controls, the women with PE had a significantly lower estrone/androstenedione ratio, and exhibited a decreasing trend for estradiol and estrone levels. Lower estriol levels were observed in the SGA group compared to the NP group. Compared with that of controls, the women with PE and SGA had significantly higher levels of 20α-dihydroprogesterone (20α-DHP) and 20α-DHP/progesterone ratios. Pregnenolone sulfate levels were lower in the PE group than in the NP and SGA groups. Decreased expression of aromatase was observed in the PE group compared to the control group.Discussion :Preeclampsia appears to be characterized by specific steroidogenesis dysregulation long before PE diagnosis, highlighting potential new biomarkers of PE.

Clinical practice guidelines for contraception by the French National College of Gynecologists and Obstetricians (CNGOF)

International audienceThe French College of Obstetrics and Gynecology (CNGOF) has released its first comprehensive recommendations for clinical practices in contraception, to provide physicians with an updated synthesis of the available data as a basis for their practice. The organizing committee and the working group adopted the objective methodological principles defined by the French Authority for Health (HAS) and selected 12 themes relevant to medical professionals' clinical practices concerning contraception. The available literature was screened through December 2017 and served as the basis of 12 texts, reviewed by experts and physicians from public and private practices, with experience in this field. These texts enabled us to develop evidence based, graded recommendations. Male and female sterilization, as well as the use of hormonal treatments not authorized for contraception ("off-label") were excluded from the scope of our review. Specific practical recommendations are provided for the management of contraception prescription, patient information concerning effectiveness, risks, and benefits of the different methods, patient follow-up, intrauterine contraception, emergency contraception, local and natural methods, contraception in teenagers, in women after 40, for women at high thromboembolism or cardiovascular risk, and for those at of primary cancer or relapse. The short- and mid-term future of contraception depends mainly on improving the use of currently available methods. This includes reinforced information for users and increased access to contraception for women, regardless of their social and clinical contexts. The objective of these guidelines is to aid in enabling this improvement

Virulence of Leishmania infantum Is Expressed as a Clonal and Dominant Phenotype in Experimental Infections

Human Leishmania infantum infection results in a spectrum of clinical expressions ranging from cutaneous to either asymptomatic or fatal visceral disease. In this context, characterization of parasite virulence appears to be relevant as a biological marker of intrinsic parasitic factors that can affect the pathology of leishmaniasis. Since parasite populations in naturally infected hosts are likely to be composed of multiclonal associations, we first explored the biodiversity of parasite virulence at the intrastrain level in vitro and in vivo by using 11 clones isolated from three strains previously known to express different virulence phenotypes in mice. Subsequently, we studied the course of infection in mice inoculated simultaneously or successively with strains or clones showing various virulence phenotypes. Analysis of in vitro growth characteristics showed no differences among clones from the different parental strains. By contrast, in vivo experiments evidenced a marked intrastrain heterogeneity of virulence to mice. One out of five clones obtained from a virulent strain showed a typical virulence phenotype, while the remaining four clones had low-virulence profiles, as did the six clones isolated from two low-virulence strains. In mixed multiclonal infections, the virulence phenotype was expressed as a dominant character over the associated low-virulence clones. After a challenge with either a homologous or a heterologous strain or clone, virulence phenotypes were conserved and expressed as in naive mice independently from the preexisting population. These results strongly suggest that parasite virulence in L. infantum visceral leishmaniasis is clonal and dominant in nature

Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition.

Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis

Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition

Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis

Le français : des mots de chacun, une langue pour tous

Vraie problématique linguistique, socio-économique et culturelle que traitent dans ce volume des chercheurs et des universitaires, des enseignants et des hommes d’affaires, des juristes et des écrivains. Comment faire pour que les mots spécialisés de nos professions, ancrés dans des savoir-faire, deviennent également les formes ouvertes d’une langue à partager ? Comment faire aussi pour que les mots de tous les jours, ceux des enfants des banlieues comme ceux des fils de la terre, soient les gages d’une compréhension et d’une reconnaissance mutuelles, d’un accès à la langue des pères, dans une société en perpétuel mouvement ? Comment faire encore pour mettre en résonance les accents des français régionaux et les échos lointains des français de la francophonie, afin que se déploie plus largement cet idéal linguistique commun ? Autant de questions qui trouvent leur champ de réflexion et leur voie de réponse dans les différentes parties de cet ouvrage : le lecteur chemine d’abord à travers les accents du français parlé, en France et dans la francophonie, pénètre au cœur des particularités de l’écrit, réfléchit aux conditions des échanges et du partage de la langue pour pénétrer enfin dans le monde des poètes et s’initier aux enchantements de la langue littéraire qui n’a cessé de dire la vie, la jouissance et la fortune des mots d’où qu’ils proviennent, ceux de La Pléiade, archaïques, techniques ou dialectaux, ceux des poètes modernes, riches de sensations, constellés d’associations, pleins de fulgurances, ceux de Léopold Sedar Senghor, vibrant aux accords de l’Afrique et de la France, fondues dans une mythologie neuve, faite de valeurs singulières mais partagées, métissées par deux cultures dans une même vision poétique. Finalement, c’est encore là une belle escale dans le temps et l’espace que cette troisième étape du voyage au long cours que constituent les Lyriades renouvelées de la langue française. Cet ouvrage est issu des 3e journées de la langue française, Les Lyriades, qui se sont tenues à Liré en Anjou, les 19-20-21 mai 2006. Il a été conçu sous la direction de Françoise Argod-Dutard, professeur des universités et responsable du comité scientifique avec la collaboration de Dominique Beaumon, coordonnateur des Lyriades