Intraoperative ketorolac in high-risk breast cancer patients : A prospective, randomized, placebo-controlled clinical trial

Funding: This work is financed by grants received by PF, in the name of his institution: the Anticancer Fund (no grant number) (www.anticancerfund.org); the Belgian Society of Anaesthesia and Resuscitation (no grant number) (www.sarb.be); the Fondation Saint-Luc (no grant number) (www.uclouvain.be); the Commission du Patrimoine of the Université catholique de Louvain, St-Luc Hospital (exceptional grant, no number) (www.uclouvain.be). None of the funders had any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript except the scientific advise of GB, scientific director of the Anticancer Fund.Peer reviewedPublisher PD

A microRNA profile of human CD8(+) regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes.

Recently, regulatory T (Treg) cells have gained interest in the fields of immunopathology, transplantation and oncoimmunology. Here, we investigated the microRNA expression profile of human natural CD8(+)CD25(+) Treg cells and the impact of microRNAs on molecules associated with immune regulation. We purified human natural CD8(+) Treg cells and assessed the expression of FOXP3 and CTLA-4 by flow cytometry. We have also tested the ex vivo suppressive capacity of these cells in mixed leukocyte reactions. Using TaqMan low-density arrays and microRNA qPCR for validation, we could identify a microRNA 'signature' for CD8(+)CD25(+)FOXP3(+)CTLA-4(+) natural Treg cells. We used the 'TargetScan' and 'miRBase' bioinformatics programs to identify potential target sites for these microRNAs in the 3'-UTR of important Treg cell-associated genes. The human CD8(+)CD25(+) natural Treg cell microRNA signature includes 10 differentially expressed microRNAs. We demonstrated an impact of this signature on Treg cell biology by showing specific regulation of FOXP3, CTLA-4 and GARP gene expression by microRNA using site-directed mutagenesis and a dual-luciferase reporter assay. Furthermore, we used microRNA transduction experiments to demonstrate that these microRNAs impacted their target genes in human primary Treg cells ex vivo. We are examining the biological relevance of this 'signature' by studying its impact on other important Treg cell-associated genes. These efforts could result in a better understanding of the regulation of Treg cell function and might reveal new targets for immunotherapy in immune disorders and cancer

Focal Expression and Final Activity of Matrix Metalloproteinases May Explain Irregular Dysfunctional Endometrial Bleeding

Irregular dysfunctional bleeding of the endometrium (ie, metrorrhagia without organic lesion) is common in women, whether treated or not with ovarian hormones. Several matrix metalloproteinases (MMPs) become normally expressed and/or activated at menstruation and cause extracellular matrix breakdown. We therefore explored whether episodes of irregular dysfunctional bleeding could be associated with untimely MMP activity. By histology, foci of stromal breakdown were exclusively found in the endometrium of metrorrhagic women at bleeding. In these foci, 1) expression of estrogen receptor-α and progesterone receptor was altered; 2) collagenase-1 (MMP-1), stromelysin-1 (MMP-3), and gelatinase B (MMP-9) became detected in stromal cells, together with MMP-9 in neutrophils; and 3) gelatinase A (MMP-2) was more expressed and immunolocalized at the membrane of stromal cells. By biochemistry, endometrial lysates from nonbleeding metrorrhagic patients contained more latent and active MMP-2 and -9 than age-matched controls; at bleeding, collagenase activity, MMP-9, and active MMP-2 were strikingly increased whereas tissue inhibitor of metalloproteinases-1 (TIMP-1) was considerably decreased. As a functional assay, in situ gelatin zymography revealed large areas of gelatinolytic activity only in endometrium of bleeding patients. Altogether, these results strongly suggest that inappropriate focal expression and activation of several MMPs, combined with decreased inhibition, trigger irregular dysfunctional endometrial bleeding

Complete hydatidiform mole and coexisting normal fetuses: A report of two cases with contrasting outcomes

BACKGROUND: Multiple pregnancies consisting of a complete hydatidiform mole and coexisting fetuses are relatively rare but may become more common due to the increasing use of ovulation induction agents. CASES: We report on a twin and a triplet pregnancy, conceived using clomiphene citrate, with contrasting outcomes. The twin pregnancy resulted in a term delivery of a healthy singleton and the triplet pregnancy in a termination at 17 weeks followed by the development of choriocarcinoma. CONCLUSION: The few cases available suggest that a subgroup of complete moles follows a more benign course and can be managed conservatively, allowing the pregnancy to go to term with appropriate follow-up, whereas other cases follow a more aggressive course. Larger case series are needed to develop definitive protocols.SCOPUS: cp.jinfo:eu-repo/semantics/publishe