Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).

Methods: We analyzed >22 million variants for 398,238 women.

Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

Background And Objective: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI.

Durable engraftment after pharmacological pre-transplant immune suppression followed by reduced-toxicity myeloablative haploidentical stem cell transplantation in highly HLA-immunized adults with sickle cell disease.

Allogeneic stem cell transplantation (Allo-SCT) is the only rapidly available curative treatment modality in patients with severe sickle cell disease (SCD). The development of reduced-toxicity myeloablative conditioning (RT-MAC) regimen and the use of partially matched family donors with post-transplantation cyclophosphamide (PT-Cy) have widened the access to Allo-SCT. Antibodies against donor-specific HLA (DSA) increase the risk of engraftment failure in HLA mismatched Allo-SCT.

Efficacy and safety of bosutinib in patients treated with prior imatinib and/or dasatinib and/or nilotinib: Subgroup analyses from the phase 4 BYOND study.

The BYOND study evaluated the efficacy and safety of bosutinib 500 mg once daily in patients with chronic myeloid leukemia (CML) resistant/intolerant to prior tyrosine kinase inhibitors (TKIs). These post-hoc analyses assessed the efficacy and safety of bosutinib by resistance or intolerance to prior TKIs (imatinib-resistant vs dasatinib/nilotinib-resistant vs TKI-intolerant), and cross-intolerance between bosutinib and prior TKIs (imatinib, dasatinib, nilotinib), in patients with Philadelphia chromosome-positive chronic phase CML. Data are reported after ≥3 years' follow-up.

Common single-base insertions in the VNTR of the carboxyl ester lipase (CEL) gene are benign and also likely to arise somatically in the exocrine pancreas.

The CEL gene encodes carboxyl ester lipase, a pancreatic digestive enzyme. CEL is extremely polymorphic due to a variable number tandem repeat (VNTR) located in the last exon. Single-base deletions within this VNTR cause the inherited disorder MODY8, whereas little is known about VNTR single-base insertions in pancreatic disease.

[Pediatric aphereses (workshop SFGM-TC)].

Practice of pediatric aphereses - in particular when caring for low-weight children - differs from the practice of adult aphereses, since pediatric aphereses represent low numbers of procedures, which has practical implications in terms of practical training and retraining for involved healthcare personnel, as needed for habilitation and validation of ongoing competencies. A specific training is mandatory in order to ensure both the child and the staff safety during and after collection, as well as ensure high quality of the collected cell product and that its meets predefined specifications that depend on its intended use. Low and very low-weight children deserve a particular attention for a number of procedural and clinical aspects: the nature and quality of venous accesses to ensure proper operation of the cell separator, management of hemodynamic fluctuations in relation with the relative importance of the extracorporeal blood volume as compared to the total blood volume of the child, risks and clinical manifestations of citrate toxicity, minimization of stress during the procedure that may include but is not limited to pharmacological sedation.

Absence of chromosome axis protein recruitment prevents meiotic recombination chromosome-wide in the budding yeast .

Meiotic recombination shows broad variations across species and along chromosomes and is often suppressed at and around genomic regions determining sexual compatibility such as mating type loci in fungi. Here, we show that the absence of Spo11-DSBs and meiotic recombination on Lakl0C-left, the chromosome arm containing the sex locus of the budding yeast, results from the absence of recruitment of the two chromosome axis proteins Red1 and Hop1, essential for proper Spo11-DSBs formation. Furthermore, cytological observation of spread pachytene meiotic chromosomes reveals that Lakl0C-left does not undergo synapsis.

PEC-PRO: A new prognostic score from a series of 87 patients with localized perivascular epithelioid cell neoplasms (PEComas) treated with curative intent.

Background: Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value.

Methods: This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers.

A novel bioinformatic approach reveals cooperation between Cancer/Testis genes in basal-like breast tumors.

Breast cancer is the most prevalent type of cancer in women worldwide. Within breast tumors, the basal-like subtype has the worst prognosis, prompting the need for new tools to understand, detect, and treat these tumors. Certain germline-restricted genes show aberrant expression in tumors and are known as Cancer/Testis genes; their misexpression has diagnostic and therapeutic applications.

EUS-BD for calibration of benign stenosis of the bile duct in patients with altered anatomy or inaccessible papilla.

In cases of inaccessible papilla, EUS-guided biliary drainage (EUS-BD) has been described as an alternative to calibrate benign biliary stenosis. However, few studies are available. This tw-center, retrospective study was designed to evaluate technical success and clinical success at 1 year.

Nilotinib with or without cytarabine for Philadelphia-positive acute lymphoblastic leukemia.

We previously demonstrated that a reduced-intensity chemotherapy schedule can safely replace hyper-CVAD (cyclophosphamide-vincristine-doxorubicin [Adriamycin]-dexamethasone) cycle 1 when combined with imatinib in adults with Philadelphia-positive acute lymphoblastic leukemia. In the present randomized GRAAPH-2014 trial, we used nilotinib and addressed the omission of cytarabine (Ara-C) in consolidation. The primary objective was the major molecular response (MMR) rate measured by BCR::ABL1 quantification after cycle 4 (end of consolidation).

Primary urethral carcinoma: Recommendations of the oncology committee of the French Urology Association.

Primary urethral carcinoma (PUC) is defined as a tumor process arising within the urethra, with no history of other urinary tract localization or synchronous tumor of the urinary tract. The most common histological types are urothelial carcinoma (UC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). In men, UC predominates, while AC is rare.

A guideline on the molecular ecosystem regulating ferroptosis.

Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.

mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.

Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTert), is expressed from the p21 locus. Expression of either TERT or TERT reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function.

Epitope Identification of an mGlu5 Receptor Nanobody Using Physics-Based Molecular Modeling and Deep Learning Techniques.

The world has witnessed a revolution in therapeutics with the development of biological medicines such as antibodies and antibody fragments, notably nanobodies. These nanobodies possess unique characteristics including high specificity and modulatory activity, making them promising candidates for therapeutic applications. Identifying their binding mode is essential for their development.

Current challenges in cell and gene therapy: a joint view from the European Committee of the International Society for Cell & Gene Therapy (ISCT) and the European Society for Blood and Marrow Transplantation (EBMT).

Cell and gene therapy poses evolving challenges. The current article summarizes the discussions held by European Regional Committee of the International Society for Cell & Gene Therapy and the European Society for Blood and Marrow Transplantation (EBMT) on the current challenges in this field, focusing on the European setting. This article emphasizes the imperative assessment of real-world cell and gene therapy activity, advocating for expanded registries beyond hematopoietic transplantation and chimeric antigen receptor-T-cell therapy.

XIAP overexpressing inflammatory breast cancer patients have high infiltration of immunosuppressive subsets and increased TNFR1 signaling targetable with Birinapant.

Objective: To assess the expression pattern of X-linked inhibitor of apoptosis protein (XIAP), a cellular stress sensor, and delineate the associated changes in the tumor immune microenvironment (TiME) for prognostic value and new therapeutic targets in inflammatory breast cancer (IBC).

Methods: Immunohistochemistry was conducted to assess the spatial localization of immune subsets, XIAP, and PDL1 expression in IBC and non-inflammatory breast cancer (nIBC) pretreatment tumors (n = 142). Validation and further exploration were performed by gene expression analysis of patient tumors along with signaling studies in a co-culture model.

A vertebrate Vangl2 translational variant required for planar cell polarity.

First described in the milkweed bug Oncopeltus fasciatus, planar cell polarity (PCP) is a developmental process essential for embryogenesis and development of polarized structures in Metazoans. This signaling pathway involves a set of evolutionarily conserved genes encoding transmembrane (Vangl, Frizzled, Celsr) and cytoplasmic (Prickle, Dishevelled) molecules. Vangl2 is of major importance in embryonic development as illustrated by its pivotal role during neural tube closure in human, mouse, Xenopus, and zebrafish embryos.

Consore: A Powerful Federated Data Mining Tool Driving a French Research Network to Accelerate Cancer Research.

Background: Real-world data (RWD) related to the health status and care of cancer patients reflect the ongoing medical practice, and their analysis yields essential real-world evidence. Advanced information technologies are vital for their collection, qualification, and reuse in research projects.

Methods: UNICANCER, the French federation of comprehensive cancer centres, has innovated a unique research network: Consore.

Safety and efficacy of nivolumab in elderly patients with metastatic clear cell renal cell carcinoma: Analysis of the NIVOREN GETUG-AFU 26 study.

Introduction: Immune checkpoint inhibitors are standard of care in metastatic renal cell carcinoma but their activity and safety in elderly patients is insufficiently explored. We evaluated outcomes of elderly patients with mRCC treated with nivolumab in the GETUG-AFU 26 NIVOREN phase 2 trial (NCT03013335) and conducted exploratory circulating biomarker analyses.

Methods: Patients with mRCC were treated with nivolumab after at least one antiangiogenic therapy.