Identification et caractérisation de protéines impliquées dans la dissémination du mélanome (rôle de l'Annexine A1)

Nous avons voulu identifier et caractériser des protéines jouant un rôle dans la formation des métastases du mélanome cutané. Pour ce faire, nous avons réalisé des comparaisons protéomiques de deux lignées génétiquement semblables : B16F10 et B16B16, qui induisent toutes deux la formation d'une tumeur primitive, alors que seules les tumeurs B16B16 génèrent des métastases. Parmi les 37 protéines différentielles identifiées, l'Annexine A1 (ANXA1) est plus exprimée dans les cellules et les tumeurs B16B16. Cette protéine est impliquée dans de nombreuses régulations cellulaires, notamment dans la migration et l'extravasation des neutrophiles en se fixant sur les récepteurs aux peptides formylés (FPR). Nous montrons que la diminution du taux d'ANXA1 par ARN interférents entraîne la réduction de la capacité invasive des cellules B16B16 in vitro, et du nombre de métastases in vivo. Des peptides, soit agonistes des FPR (fMLP), soit correspondants à la région N-terminale d'ANXA1, stimulent l'invasion et la sécrétion de MMP9 des cellules B16B16. L'axe ANXA1-FPR, habituellement rencontré dans les lignages myélocytaires, pourrait participer au processus de dissémination du mélanome. Cette hypothèse est en partie corroborée par une étude rétrospective montrant que la présence d'ANXA1 dans les tumeurs primitives humaines est associée à un risque de métastases 6 fois plus élevé. Nousavons également montré que la Synténine, habituellement intracellulaire et favorisant la dissémination du mélanome, est significativement plus sécrétée dans les surnageants des cellules les moins agressives, B16F10. Elle interagirait avec des protéines d'adhésion, renforçant ainsi les liens matrice-cellules ou cellules-cellules.Proteins involved in melanoma dissemination have been studied and protein profiles of two genetically similar melanoma cell lines have been compared. Both B16F10 and B16B16 cells induced primary tumours after subcutaneous graft, but pulmonary metastases were observed only in mice bearing B16B16 melanoma. Among the 37 identified proteins, we focused on Annexin A1 (ANXA1) which expression increased in both B16B16cell culture and tumours. This protein is involved in leukocyte migration and extravasation, particularly by its binding to the formyl peptide receptor (FPR). Here, using RNA interference strategies, we have shoxn that ANXA1 reduction decreased both in vitro cell invasion and metastasis formation in mice. Moreover, treatment of B16B16 cells by fMLP (FPR agonists) or by ANXA1 N-terminal peptide enhanced cell invasion and MMP9 secretion. ANXA1-FPR binding, usually involved in leukocyte regulation, should also contribute to melanoma dissemination processes. This is partly confirmed by a retrospective study in human primary tumours, showing that ANXA1 expression increased 6 fold the metastasis risk. We have also shown that Syntenin, an adaptater protein, was more present in B16F10 secretomes. Intracellular Syntenin was previously described as a marker for melanoma aggressiveness. Its extracellular localisation should protect melanoma cells from invasion, probably by reinforcing cell-cell adhesion or cell-matrix adhesion.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

Évaluation et utilisation de stratégies en mémoire par des patients schizophrènes âgés

International audienc

Long-Range Orientational Organization of Dipolar and Steric Liquids

International audienceLong-range orientational correlations in liquids have received recent renewed interest, in particular for the neat water case. These long-range orientational correlations, exceeding several tens of nanometers, originate from the presence of the strong permanent water dipolar moment. However, the exact dependence with the dipolar moment and the role of other local forces like steric hindrance has never been addressed. In this work, we experimentally measure long-range correlations for a set of liquids differing by their molecular weight and dipolar moment, in order to reveal the origin of their long-range organization. Hence, we show that the dipolar moment of a solvent molecule is not the unique feature determining the orientational correlation. Steric hindrance significantly helps to structure the liquids as well. In order to quantify these long-range correlations, we also derive theoretically the polarization resolved second harmonic scattering intensity as a function of the rotational invariants describing the dipolar and octupolar interaction

Métamémoire des patients âgés souffrant de schizophrénie

International audienc

Qualité de vie liée à la santé des conjoints de patients âgés souffrant d’un épisode dépressif

International audienc

Metacognitive preserved generation strategy benefits for both younger and elderly participants with schizophrenia

International audienceCognitive memory and introspection disturbances are considered core features of schizophrenia. Moreover, it remains unclear whether or not participants with schizophrenia are more cognitively impaired with ageing than healthy participants. The aims of this study were to use a metacognitive approach to determine whether elderly participants with schizophrenia are able to improve their memory performance using a specific generation strategy and to evaluate the memory benefits for them using this strategy. 20 younger and 20 older participants with schizophrenia and their comparison participants matched for age, gender and education learned paired associates words with either reading or generation, rated judgment of learning (JOL) and performed cued recall. Participants with schizophrenia recalled fewer words than healthy comparison participants, but they benefited more from generation, and this difference was stable with ageing. Their JOL magnitude was lower than that of healthy comparison participants, but JOL accuracy was not affected by either age or the pathology. In spite of their memory deficit, elderly and younger participants with schizophrenia benefited remarkably from the memory generation strategy. This result gives some cause for optimism as to the possibility for participants with schizophrenia to reduce memory impairment if learning conditions lead them to encode deeply

Executive deficits in schizophrenia: mediation by processing speed and its relationships with aging

International audienceBackground: Executive deficits are a core characteristic of schizophrenia. Yet, the origin of these impairments remains unclear as they may be caused by processing slowing. This issue is of particular interest for aging insofar as cognitive aging is also associated with decline in executive functioning and a slowing of processing speed. As schizophrenia patients’ life expectancy increases, a better understanding of the origin of older patients’ cognitive deficits becomes essential so that healthcare can be adapted to suit them. This study aims to determine whether processing speed mediates how schizophrenia affects executive functions, and whether these relationships are moderated by age. Methods: Sixty-two schizophrenia patients (27 women) and 62 healthy comparison subjects matched for age (range: 18 to 76 years), gender and education performed neurocognitive tests to evaluate their executive functions (shifting, updating, inhibition and access) and processing speed.Results: Processing speed mediated the effect of schizophrenia on the four specific executive functions, and age moderated this mediation for shifting, updating and access, but in different ways. Age moderated the effect of processing speed on shifting, the direct effect of schizophrenia on access, and both the effect of processing speed and direct effect of schizophrenia on updating.Conclusions: This research highlights the need to evaluate processing speed routinely during therapeutic follow-up, as it is easy and simple to assess and appears to be at the heart of the cognitive deficits in schizophrenia. Finally, processing speed abilities yield information about the evolution of cognition with aging in schizophrenia

Health-related quality of life among community-dwelling people aged 80 years and over: a cross-sectional study in France.

International audienceThe proportion of people living to a very old age is continuously increasing. One of the possibilities explored in policies and services to meet this health and societal challenge is to encourage the very old to continue living at home. This initiative is in line with the wishes of most elderly people. However, owing to the great changes that occur during old age attention should be paid to health-related quality of life (HRQoL). The aims of this study were to assess HRQoL in French community-dwelling people aged 80 years and over and to investigate the sociodemographic and health characteristics and life events associated with HRQoL

Prevalence and Odds of Signs of Depression and Anxiety in Patients with Lichen Planus: Systematic Review and Meta-analyses

International audienceThe association between certain chronic inflammatory skin diseases and psychiatric disorders or conditions has been well documented. However, the exact magnitude of the association between lichen planus and depression/anxiety symptoms and disorders is un-known. A systematic review and pooled meta-analyses were performed to examine the prevalence and odds of depression and anxiety in patients with lichen planus. The meta-analyses showed a high prevalence of signs of depression (27% [19-36%]) and anxiety (28% [21-36%]). The geographical location of the study may partly explain these vari-ations, but method-ological differences could also be involved. Case-control studies showed a strong association between lichen planus and signs of depression (odds ratio 3.79, 95% confidence interval [2.35; 6.12]) or anxiety (odds ratio 2.54, 95% confidence interval [1.73; 3.72]). These results raise the necessity of screening for the presence of depressive and anxiety symptoms or disorders in patients with lichen planus, and of referring such patients for psychiatric evaluation and appropriate treatment, if necessary

The prevalence and odds of anxiety and depression in children and adults with hidradenitis suppurativa: Systematic review and meta-analysis

International audienceHidradenitis suppurativa (HS) is a chronic inflammatory skin disorder. Previous studies have yielded divergent results on the prevalence of depression and anxiety in patients with HS