Centralizing surgery for ovarian cancer in a ‘non-centralizing’ country (Belgium): the UNGO (UCLouvain Network of Gynaecological Oncology) experience

Objective In Belgium there is no centralization of surgery for ovarian cancer, with more than 100 centers treating around 800 cases per year. In 2017 a network with several collaborating hospitals was established to centralize surgery for ovarian cancer (UCLouvain Network of Gynecological Oncology; UNGO) following publication of the European Society of Gynecological Oncology (ESGO) recommendations and quality criteria for surgery of advanced ovarian cancer. We obtained ESGO accreditation in 2019. Methods We retrospectively collected data associated with patients undergoing surgery in our institution from 2007 to 2016, before the creation of the network (cohort 1) and, following the establishment of UNGO (2017–2021), patients undergoing surgery were prospectively registered in a REDCap database (cohort 2). The outcomes of the two cohorts were compared. Results A total of 314 patients underwent surgery in our institution from 2007 and 2021: 7.5 patients/year in cohort 1 (retrospective, 2007–2016) and 40.8 patients/year in cohort 2 (after network creation, 2017–2021). Median disease-free survival was increased from 16.5 months (range 13.2–20.4) in cohort 1 to 27.1 months (range 21.5–33.2) in cohort 2 (p=0.0004). In cohort 2, the rate of patients with residual disease at the end of the surgery was significantly less (18.7% vs 8.8%, p=0.023), although more patients in cohort 1 received neoadjuvant chemotherapy (89% vs 54%, p<0.001). However, there was a higher rate of complications in the patients in cohort 2 (18.8% vs 30%, p=0.041). Conclusion Our study shows that, with the help of ESGO and its recommendations, we have been able to create an efficient advanced ovarian cancer centralized network and this may provide an improvement in the quality of care

A Genome-wide Map of CTCF Multivalency Redefines the CTCF Code

The “CTCF code” hypothesis posits that CTCF pleiotropic functions are driven by recognition of diverse sequences through combinatorial use of its 11 zinc fingers (ZFs). This model, however, is supported by in vitro binding studies of a limited number of sequences. To study CTCF multivalency in vivo, we define ZF binding requirements at ∼50,000 genomic sites in primary lymphocytes. We find that CTCF reads sequence diversity through ZF clustering. ZFs 4–7 anchor CTCF to ∼80% of targets containing the core motif. Nonconserved flanking sequences are recognized by ZFs 1–2 and ZFs 8–11 clusters, which also stabilize CTCF broadly. Alternatively, ZFs 9–11 associate with a second phylogenetically conserved upstream motif at ∼15% of its sites. Individually, ZFs increase overall binding and chromatin residence time. Unexpectedly, we also uncovered a conserved downstream DNA motif that destabilizes CTCF occupancy. Thus, CTCF associates with a wide array of DNA modules via combinatorial clustering of its 11 ZFs

Systèmes interactifs pour la santé à l'ISIR

International audienceThis ISIR lab stand showcases some of the interactive systems developed in the past 5 years in relation to HCI and Health. Two types of medical applications are showcased: surgical procedures (e.g., assistance robots, videos in support of learning) and people suffering from a motor deficit (e.g., motorized prostheses, intelligent walkers, kinesthetic feedback for visually impaired assistance).Le stand du laboratoire ISIR présente certains des systèmes interactifs développés au cours des 5 dernières années à l’intersection de l’IHM et la Santé. Deux types d’applications médicales sont présentées : le geste chirurgical (ex. : robots d’assistance, vidéos d’aide à l’apprentissage) et les personnes souffrant d’un déficit moteur (ex. : prothèses motorisées, déambulateurs intelligents, feedback kinesthésique pour l’assistance aux malvoyants)

B Cell Super-Enhancers and Regulatory Clusters Recruit AID Tumorigenic Activity.

The antibody gene mutator activation-induced cytidine deaminase (AID) promiscuously damages oncogenes, leading to chromosomal translocations and tumorigenesis. Why nonimmunoglobulin loci are susceptible to AID activity is unknown. Here, we study AID-mediated lesions in the context of nuclear architecture and the B cell regulome. We show that AID targets are not randomly distributed across the genome but are predominantly grouped within super-enhancers and regulatory clusters. Unexpectedly, in these domains, AID deaminates active promoters and eRNA(+) enhancers interconnected in some instances over megabases of linear chromatin. Using genome editing, we demonstrate that 3D-linked targets cooperate to recruit AID-mediated breaks. Furthermore, a comparison of hypermutation in mouse B cells, AID-induced kataegis in human lymphomas, and translocations in MEFs reveals that AID damages different genes in different cell types. Yet, in all cases, the targets are predominantly associated with topological complex, highly transcribed super-enhancers, demonstrating that these compartments are key mediators of AID recruitment. Cell 2014 Dec 18; 159(7):1524-37