Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs?

The management of premature birth still remains unsatisfactory. Since the relative lack of efficiency and/or safety of current tocolytic agents have been highlighted, it is necessary to develop new uterorelaxant drugs deprived of important maternal and foetal side effects. Our work reported in this review focuses on a potential new target for tocolytic drugs, the β3-adrenoceptor (ADRB3). This third type of ADRB is shown to be present and functional in human myometrium. We demonstrated that ADRB3 agonists are able to inhibit in-vitro spontaneous contractions of myometrial strips, via a cyclic AMP-mediated pathway. Furthermore, we established that ADRB3 is the predominant subtype over the ADRB2 in human myometrium and that its expression is increased in near-term myometrium, compared to non-pregnant myometrium. Finally, we reported that contrary to ADRB2, the human myometrial ADRB3 is resistant to long-term agonist-induced desensitisation. These compelling data confirm the clinical potential interest of ADRB3 agonists in the pharmacological management of preterm labour

Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

The known breast cancer (BC) susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1,LSP1 and 2q35 confer increased risks of BC for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of three additional SNPs, rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11 and rs10941679 at 5p12 and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased BC risk for BRCA2 carriers (per-allele Hazard Ratio (HR)=1.10, 95%CI:1.03-1.18, p=0.006 and HR=1.09, 95%CI:1.01-1.19, p=0.03, respectively). Neither SNP was associated with BC risk for BRCA1 carriers and rs6504950 was not associated with BC for either BRCA1 or BRCA2 carriers. Of the nine polymorphisms investigated, seven were associated with BC for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, p-values:7×10−11-0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (p=0.0049, 0.03 respectively). All risk associated polymorphisms appear to interact multiplicatively on BC risk for mutation carriers. Based on the joint genotype distribution of the seven risk associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e. between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing BC by age 80, compared with 42-50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences may be sufficient to influence the clinical management of mutation carriers

L'introduction du lipomodelage dans le cadre de la reconstruction mammaire post-cancer au Centre Georges François Leclerc (qualité de vie des patientes opérées et étude de satisfaction des chirurgiens opérateurs)

Introduction :un des problèmes majeurs du cancer du sein reste la mutilation résultant parfois de sa prise en charge. De nombreux progrès ont été réalisés dans le domaine de la reconstruction, notamment avec le développement du lipomodelage .Matériel et méthodes 69 patientes ont eu un lipomodelage au CGFL. Un questionnaire de satisfaction, le Breast-Q, a permis d évaluer la qualité de vie de celles-ci. Puis, la satisfaction des opérateurs quant à la reconstruction effectuée a été évaluée par un questionnaire spécifique. Résultats : les indications de cette technique sont le lipomodelage exclusif, la correction de séquelles de traitement conservateur, la correction secondaire d autres reconstructions et l association à d autres techniques de reconstruction. Le score moyen du Breast-Q est supérieur à 50 sur 100 pour chaque item. Les résultats les plus satisfaisants sont retrouvés en correction secondaire. La qualité de vie est nettement améliorée dans tous les domaines, quelle que soit l indication initiale, avec des effets secondaires fréquents mais transitoires. Pour ce qui est des chirurgiens, l indication préférentielle du lipomodelage est la correction secondaire d autres reconstructions.Discussion : le lipomodelage est une technique simple, fiable et polyvalente. Elle a apporté une satisfaction notable de la quasi-totalité des patientes interrogées, toutes indications confondues. Les chirurgiens interrogés considèrent cette technique comme un outil indispensable de la reconstruction mammaire post-cancer.DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Patient age and breast resection weight affect immediate postmastectomy breast reconstruction in ductal carcinoma in situ

International audiencePurpose: Mastectomy is necessary for 40% of the ductal carcinoma in situ. If immediate breast reconstruction (IBR) is systematically proposed, 81% of the patients would choose immediate versus delayed breast reconstruction, but the actual IBR rate is only approximately 50% of them. Therefore, the aim of this study was to identify objective characteristics that distinguish the patients who actually underwent IBR from those who did not.Methods: Several criteria of 248 patients who have undergone mastectomy for ductal carcinoma were analyzed. Factors studied were age, body mass index, diabetes, tobacco use, and weight of the specimen of resection.Results: The rate of IBR was 43%. An increase in age and weight of the resection specimen, irrespective of the body mass index, was associated with a lower rate of IBR. Thus, an increase of 100 g in the weight of the breast induces a significant reduction of the IBR (33%).Conclusions: In our series, older patients or patients with larger breasts (irrespective of the body mass index) were less likely to undergo IBR. In order to be in line with the patient's desire, the surgeons of our unit should broaden their indications of IBR. The lack of reconstruction of large breasts should certainly be compensated in part with the recent development of free tissue transfers in our unit

Changes in 18F-FDG tumor metabolism after a first course of neoadjuvant chemotherapy in breast cancer: influence of tumor subtypes

International audienc

Beta3-adrenoceptor is the predominant beta-adrenoceptor subtype in human myometrium and its expression is up-regulated in pregnancy.

International audienceTo assess whether pregnancy might influence the functionality and expression of human myometrial beta(2)- and beta(3)-adrenoceptors (beta(2)- and beta(3)-AR), we performed functional, binding, Western blot, and molecular biology experiments in human nonpregnant and near-term pregnant myometrium. Inhibition of spontaneous contractions induced by a beta(3)-AR agonist, SR 59119A, was significantly greater in pregnant, compared with nonpregnant, myometrial strips (E'(max) = 61 +/- 5% vs. 44 +/- 5% for pregnant and nonpregnant myometrium, respectively), whereas salbutamol, a beta(2)-AR agonist, was significantly less efficient in pregnant, compared with nonpregnant, myometrium (E(max) = 29 +/- 4 vs. 54 +/- 8%). Although two populations of binding sites corresponding to beta(2)- and beta(3)-AR were identified in both nonpregnant and pregnant myometrium, we found a clear predominance of the beta(3)-AR subtype. Moreover, beta(3)-AR binding sites were up-regulated 2-fold in myometrium at the end of pregnancy. Both beta(2)- and beta(3)-AR mRNA were expressed in human nonpregnant and pregnant myometrium. Contrary to beta(2)-AR, the expression of the beta(3)-AR transcripts and immunoreactive proteins was increased in pregnant, compared with nonpregnant, myometrium. Such compelling data suggest a predominant role for beta(3)-AR in the regulation of human myometrium contractility, especially at the end of pregnancy, which might have important consequences for the clinical management of preterm labor

Emotional distress and subjective impact of the disease in young women with breast cancer and their spouses

AIM: Evaluate the influence of emotional distress of young women with breast cancer and their spouses on their daily subjective experience of the disease, through application of the Actor-Partner Interdependence Model. PATIENTS & METHODS: A total of 112 women under 45 years of age were diagnosed with nonmetastatic breast cancer and their spouses answered self-reported measures of anxiety, depression and subjective experience of the disease and its treatment. RESULTS: The patient's emotional distress influenced more the subjective experience of her spouse than the spouse's emotional distress influenced the patient. The spouse's difficulties depended as much on his own distress level as on the patient's distress level. CONCLUSION: These data confirm the importance of implementing couple-focused interventions