Paris Descartes University

About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Immune system. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.

3rd ESO–ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3)

Abstract: For the purpose of advanced breast cancer (ABC) guidelines, ABC comprises both inoperable locally advanced breast cancer (LABC) and metastatic breast cancer (MBC)1 , 2 Advanced/metastatic breast cancer remains a virtually incurable disease, with a median overall survival (OS) of about 3 years and a 5-year survival rate of around 25%,3 , 4 even in countries without major accessibility problems Survival is strongly related to breast cancer subtype, with the major advances seen in human epidermal growth factor receptor 2 (HER2)-positive ABC5, 6, 7, 8, 9 ABC is a treatable disease with several available therapies and many others in development However, their impact on survival and quality of life (QoL) of ABC patients has been slow3 and different for de novo versus recurrent ABC, with the latter becoming much harder to treat in recent years10 Outcomes are also strongly related to access to the best available care, which includes not only the most efficacious medicines, but also multidisciplinary, specialised care, implementation of guidelines, high-quality pathology, imaging and radiotherapy (RT) Lack of any of these crucial pillars of modern oncological care inevitably results in substantially worse outcomes, as exemplified in the New Zealand report “I am still here”11 While mortality rates have decreased in the majority of developed countries, most deaths are currently seen in less developed societies, and access issues explain the majority of these inequalities12 The application of the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS)13 to the field of ABC (P Shimon, personal communication) shows that the quality of clinical research has improved over the last decade and that better therapies have been developed, providing hope that a substantial improvement in the median OS of ABC patients might soon be seen However, some clinically relevant questions are still unanswered and may be difficult to address through traditional clinical trials, such as the best sequence of therapies for each individual patient The application of computer analytics to big data and real-world data is one of the potential ways forward In-depth discussion must take place regarding the impact of this ‘new’ level of evidence (LoE) in current treatment guidelines and their integration with clinical trial data The 5th International Consensus Conference for Advanced Breast Cancer (ABC 5) took place in Lisbon, Portugal, on 14th-16th November 2019, bringing together 1500 participants from 94 countries worldwide, including health professionals, patient advocates and journalists Since its first edition in 2011, the main goal of the ABC conference has been the development of high-quality international consensus guidelines for the management of ABC These guidelines are based on available evidence and on expert opinion when evidence is lacking They represent the best management options for ABC patients globally, assuming accessibility to all available therapies Adaptation of these guidelines is often needed in settings where access to care is suboptimal The ABC 5 guidelines are jointly developed by ESO and ESMO, and have been endorsed by several international oncology organisations, such as the European Society of Breast Cancer Specialists (EUSOMA), European Society for Radiotherapy and Oncology (ESTRO), European Society of Gynaecological Oncology (ESGO), Union for International Cancer Control (UICC), Senologic International Society (SIS)/International School of Senology (ISS), Federacion Latino-Americana de Mastologia (FLAM), European Oncology Nursing Society (EONS), European Society of Surgical Oncology (ESSO), Arbeitsgemeinschaft Gynakologische Onkologie eV (AGO) and the International Society of Geriatric Oncology (SIOG), and have official representation from the American Society of Clinical Oncology (ASCO) The ABC 5 conference was also organised under the auspices of the Organisation of European Cancer Institutes (OECI) and with the support of the Breast Cancer Research Foundation (BCRF), Susan G Komen and the ABC Global Alliance This manuscript summarises the guidelines developed at ABC 5, each of which are accompanied by the LoE, grade of recommendation (GoR), percentage of consensus reached at the conference and supporting references In addition, the ESMO-MCBS version 1113 (v11) was used to calculate scores for new therapies/indications approved by the European Medicines Agency (EMA) since the last ABC guidelines, as well as a few new therapies that have been scored but are still under EMA evaluation (https://wwwesmoorg/Guidelines/ESMO-MCBS) A table with these scores is included (see supplementary Table S1, available at https://doi/org/101016/jannonc202009010)

Mesenchymal Transition and Dissemination of Cancer Cells Is Driven by Myeloid-Derived Suppressor Cells Infiltrating the Primary Tumor

Abstract: In order to metastasize, cancer cells need to acquire a motile phenotype. Previously, development of this phenotype was thought to rely on the acquisition of selected, random mutations and thus would occur late in cancer progression. However, recent studies show that cancer cells disseminate early, implying the existence of a different, faster route to the metastatic motile phenotype. Using a spontaneous murine model of melanoma, we show that a subset of bone marrow-derived immune cells (myeloid-derived suppressor cells or MDSC) preferentially infiltrates the primary tumor and actively promotes cancer cell dissemination by inducing epithelial-mesenchymal transition (EMT). CXCL5 is the main chemokine attracting MDSC to the primary tumor. In vitro assay using purified MDSC showed that TGF-β, EGF, and HGF signaling pathways are all used by MDSC to induce EMT in cancer cells. These findings explain how cancer cells acquire a motile phenotype so early and provide a mechanistic explanation for the long recognized link between inflammation and cancer progression.

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.

Abstract: Background Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). Objective We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. Methods We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. Results Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. Conclusion APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment.

Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes

Abstract: Specification of cell identity during development depends on exposure of cells to sequences of extrinsic cues delivered at precise times and concentrations. Identification of combinations of patterning molecules that control cell fate is essential for the effective use of human pluripotent stem cells (hPSCs) for basic and translational studies. Here we describe a scalable, automated approach to systematically test the combinatorial actions of small molecules for the targeted differentiation of hPSCs. Applied to the generation of neuronal subtypes, this analysis revealed an unappreciated role for canonical Wnt signaling in specifying motor neuron diversity from hPSCs and allowed us to define rapid (14 days), efficient procedures to generate spinal and cranial motor neurons as well as spinal interneurons and sensory neurons. Our systematic approach to improving hPSC-targeted differentiation should facilitate disease modeling studies and drug screening assays.