The Neurotensin Receptor-1 Pathway Contributes to Human Ductal Breast Cancer Progression

BACKGROUND: The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. METHODS AND RESULTS: we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. CONCLUSION: these data support the activation of neurotensinergic deleterious pathways in breast cancer progression

Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Contraception orale oestroprogestative et risque et risque de mélanome cutané (méta-analyse des études de cohorte et des études cas-témoins)

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Fibroadénome géant chez l adolescente et influence hormonale (analyse d une série de 90 cas)

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

L'évaluation économique des traitements médicaux : méthodes et enjeux

[eng] The Economic Evaluation of Medical Treatment: Methods, Opportunities and Threats . The increase in health spending over the last thirty years is due in the main to health insurance cover becoming widespread and the development of medical techniques. . France has found it particularly difficult to bring this growth under control. It is now vital to evaluate medical practices and compare the cost of new technologies with the improvements they make to the level of health in general. The adoption of a new treatment is a crucial moment for such an approach. It is important at this stage to ensure that the treatment is not only beneficial to health, but that it is sufficiently cost-effective, The case study of hormone treatment for menopause, when used for preventive purposes, shows exactly what methods are available for this type of evaluation and how they can be used to define suitable reimbursement procedures. [fre] L'évaluation économique des traitements médicaux : méthodes et enjeux . La généralisation couverture maladie et pement des techniques médicales sont deux causes majeures de l'expansion des dépenses de santé depuis trente ans. En France, la maîtrise de cette évolution s'est révélée particulièrement difficile. L'évaluation des pratiques médicales et la confrontation du coût des nouvelles technologies à l'amélioration qu'elles apportent au niveau général de la santé s'avèrent dès lors indispensables.L'adoption d'un nouveau traitement constitue un moment crucial pour cette démarche. Il importe en effet de s'assurer à cette étape, non seulement que le traitement est bénéfique en termes de santé, mais que son bilan coût-efficacité est satisfaisant, L'étude du cas-type que constituent les traitements hormonaux de la ménopause, lorsqu'ils sont envisagés dans une perspective de prévention, permet d'illustrer concrètement les méthodes disponibles pour ce type d'évaluation et leur intérêt pour définir des modalités de remboursement adaptées. [ger] Die wirtschaftliche Bewertung der medizinischen Behandlungen: Verfahren und Bedeutung . Die Verallgemeinerung des Versicherungsschutzes im Die Einfûhrung einer neuen Behandlung stellt fur eine sol- Krankheitsfalle und die Fortschritte in der Medizintechnik che Bewertung einen Qberaus wichtigen Zeitpunkt dan denn sind die beiden Hauptursachen fur die Explosion der in dieser Etappe muG nicht nur sichergestellt werden, Gesundheitsausgaben in den letzten dreiBig Jahren. In daB die Behandlung der Gesundheit nQtzt, sondem daB Frankreich hat es sich als besonders schwierig erwiesen, auch das Kosten/Nutzen-Verhâltnis zufriedenstellend ist. diese Entwicklung in den Griff zu bekommen. Somit ist es uneriâBlich, die medizinischen Praktiken einer Bewertung Anhand der Untersuchung des typischen Falles, den die . zu unterziehen und eine GegenQberstellung der Kosten vorbeugende Hormonbehandlung des Klimakteriums der neuen Techniken mit den Verbesserungen, die sie all- darstellt, lassen sich konkret die Verfahren, die fur diese gemein fur die Gesundheit mit sich bringen, vorzu-Art von Bewertung verfûgbar sind, sowiederenNutzen bel nehmen. der Festlegung einer angemessenen Kostenerstattung . veranschaulichen. [spa] La evaluaciôn econômica de los tratamientos médicos : métodos y retos. . La generalization de la cobertura médica y el desarrollo tener la seguridad, no solo de que el tratamiento es de las técnicas en medicina son dos causas mayores del benéfico en términos de sanidad, sino de que el balance au9e de lo.s 9astos de sanidad desde hace treinta anos coste-eficacia es satisfactorio. En Francia, tue especialmente difîcil contener esta evolution. La evaluation de las prâcticas médicas y la El examen del caso experimental que constituyen los comparaciôn del coste de las nuevas tecnologfas con la tratamientos hormonales de la menopausia, cuando se . mejora que estas conllevan para el nivel general de les considéra dentro de una perspectiva de prevention, sanidad, resultan en la actualidad indispensables. permite ilustrar de una manera concreta los métodos de los que se dispone para dicha évaluation, y su interés La adoption de un nuevo tratamiento constituye una cuando se trata de définir unas modalidades de etapa decisiva en este proceso. Importa efectivamente reembolso adaptadas.