235 results match your criteria: "Centre de Recherche sur L'Inflammation CRI[Affiliation]"

Article Synopsis
  • GemPred is a predictive transcriptomic signature designed to assess the effectiveness of adjuvant gemcitabine in pancreatic cancer, validated through samples from 350 patients in a clinical trial comparing gemcitabine and mFOLFIRINOX treatments.* -
  • Out of the patients studied, 25.5% were found to be GemPred+, showing significantly longer disease-free and cancer-specific survival when treated with gemcitabine compared to those who were GemPred-, but GemPred did not predict outcomes for those receiving mFOLFIRINOX.* -
  • The study concludes that while GemPred+ patients experienced better survival rates with gemcitabine, they also suffered from more severe adverse events when treated with
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Background: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine.

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The immunological landscape in pancreatic ductal adenocarcinoma and overcoming resistance to immunotherapy.

Lancet Gastroenterol Hepatol

December 2023

Gastrointestinal Oncology, Medical Oncology Department, Institut Curie, Université Versailles Saint-Quentin-Université Paris-Saclay, Saint-Cloud, France; Molecular Oncology, PSL Research University, CNRS, UMR 144, Institut Curie, Paris, France. Electronic address:

Pancreatic ductal adenocarcinoma is associated with a poor prognosis and there are few treatment options. The development of immunotherapy in pancreatic ductal adenocarcinoma has been difficult, and immune checkpoint inhibitors are only effective in a very small subset of patients. Most obstacles for treatment have been related to intertumoural and intratumoural heterogeneity, the composition of tumour stroma, and crosstalk with cancer cells.

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Purpose: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single-cell RNA sequencing has uncovered the coexistence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach.

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A 'classical' and a 'basal-like' subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient and intra-patient inter-ductal heterogeneity, intraductal spatial phenotypes exist with anti-correlating expression levels of GATA6 and KRAS .

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Roles of systemic inflammatory and metabolic responses in the pathophysiology of acute-on-chronic liver failure.

JHEP Rep

September 2023

European Foundation for the Study of Chronic Liver Failure (EF CLIF), Grifols Chair, Barcelona, Spain.

Acute-on-chronic liver failure (ACLF) is the most severe form of acutely decompensated cirrhosis and is characterised by the presence of one or more organ failures, intense systemic inflammation, peripheral blood lymphopenia, and a high risk of death without liver transplantation within 28 days. Herein, we propose the hypothesis that intense systemic inflammation may lead to organ failures through five different non-mutually exclusive mechanisms. First, pathogen-associated molecular patterns and inflammatory mediators ( cytokines and lipid mediators) stimulate the production of the vasorelaxant nitric oxide in the walls of splanchnic arterioles, leading to enhanced splanchnic and systemic vasodilation which, in turn, induces enhanced activity of endogenous vasoconstrictor systems causing renal vasoconstriction and acute kidney injury.

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Article Synopsis
  • Neutrophils are special cells that help fight infections by moving to areas in the body where there is inflammation.
  • This study looked at a molecule called CD31, which helps neutrophils detach and move away from blood vessels to reach the inflamed areas.
  • The researchers discovered that CD31 helps neutrophils change shape and detach properly, showing it plays an important role in how these cells migrate where they are needed the most.
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Background & Aims: Liver regeneration is a repair process in which metabolic reprogramming of parenchymal and inflammatory cells plays a major role. Monoacylglycerol lipase (MAGL) is an ubiquitous enzyme at the crossroad between lipid metabolism and inflammation. It converts monoacylglycerols into free fatty acids and metabolises 2-arachidonoylglycerol into arachidonic acid, being thus the major source of pro-inflammatory prostaglandins in the liver.

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Dendritic cell type 3 arises from Ly6C monocyte-dendritic cell progenitors.

Immunity

August 2023

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore; Gustave Roussy Cancer Campus, Villejuif 94800, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore. Electronic address:

Conventional dendritic cells (cDCs) are professional antigen-presenting cells that control the adaptive immune response. Their subsets and developmental origins have been intensively investigated but are still not fully understood as their phenotypes, especially in the DC2 lineage and the recently described human DC3s, overlap with monocytes. Here, using LEGENDScreen to profile DC vs.

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Background & Aims: Diabetes mellitus is a major risk factor for fatty liver disease development and progression. A novel machine learning method identified five clusters of patients with diabetes, with different characteristics and risk of diabetic complications using six clinical and biological variables. We evaluated whether this new classification could identify individuals with an increased risk of liver-related complications.

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This narrative review addresses the definition of acute-on-chronic liver failure, a condition associated with high short-term mortality in patients with chronic liver disease and/or cirrhosis. We provide two major points of view: the East and the West perspective. Both definitions vary regarding the underlying patient population and organ failure(s) definition.

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Background: Molecular understanding of muscle-invasive (MIBC) and non-muscle-invasive (NMIBC) bladder cancer is currently based primarily on transcriptomic and genomic analyses.

Objective: To conduct proteogenomic analyses to gain insights into bladder cancer (BC) heterogeneity and identify underlying processes specific to tumor subgroups and therapeutic outcomes.

Design, Setting, And Participants: Proteomic data were obtained for 40 MIBC and 23 NMIBC cases for which transcriptomic and genomic data were already available.

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Article Synopsis
  • Researchers identified two main subtypes of Pancreatic adenocarcinoma (PDAC) based on tumor and stroma characteristics, which can influence patient prognosis and treatment strategies.
  • They developed a deep learning model called PACpAInt to quickly classify PDAC using more accessible methods, trained on a diverse set of biopsy data from 202 patients and validated on additional cohorts.
  • The model effectively predicts tumor subtypes and survival outcomes while revealing complex tumor-stroma interactions, including new categories like Hybrid and Intermediate tumors that suggest varied evolution in PDAC.
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Inflammatory bowel diseases are chronic inflammation of the intestinal mucosa characterized by relapsing-remitting cycle periods of variable duration. Infliximab (IFX) was the first monoclonal antibody used for the treatment of Crohn's disease and ulcerative colitis (UC). High variability between treated patients and loss of IFX efficiency over time support the further development of drug therapy.

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Prediction of response to immune checkpoint blockade in patients with metastatic colorectal cancer with microsatellite instability.

Ann Oncol

August 2023

Sorbonne Université, INSERM, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris; Molecular Biology and Medical Genetics, Sorbonne Université, AP-HP, Hospital Pitié-Salpêtrière, Paris. Electronic address:

Background: Mismatch repair-deficient (dMMR) tumors displaying microsatellite instability (MSI) represent a paradigm for the success of immune checkpoint inhibitor (ICI)-based immunotherapy, particularly in patients with metastatic colorectal cancer (mCRC). However, a proportion of patients with dMMR/MSI mCRC exhibit resistance to ICI. Identification of tools predicting MSI mCRC patient response to ICI is required for the design of future strategies further improving this therapy.

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Priming therapy by targeting enhancer-initiated pathways in patient-derived pancreatic cancer cells.

EBioMedicine

June 2023

Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Parc Scientifique et Technologique de Luminy, Aix-Marseille Université and Institut Paoli-Calmettes, Marseille, France; Hospital de Alta Complejidad El Cruce, Florencio Varela, BA, Argentina; University Arturo Jauretche, Florencio Varela, BA, Argentina. Electronic address:

Background: Systems biology leveraging multi-OMICs technologies, is rapidly advancing development of precision therapies and matching patients to targeted therapies, leading to improved responses. A new pillar of precision oncology lies in the power of chemogenomics to discover drugs that sensitizes malignant cells to other therapies. Here, we test a chemogenomic approach using epigenomic inhibitors (epidrugs) to reset patterns of gene expression driving the malignant behavior of pancreatic tumors.

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Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling.

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Introduction: Amoebic liver abscess (ALA) is the fourth cause of mortality by parasitic infection. This study aimed to assess clinical, radiological and therapeutic characteristics of patients admitted for amoebic liver abscess compared to pyogenic abscess in a French digestive tertiary care-centre.

Material And Method: The charts of patients hospitalized for a liver abscess between 2010 and 2020 were retrospectively assessed then separated in two groups: amoebic liver abscess and pyogenic liver abscess from portal underlying cause.

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Recent data have shown that liver fibrosis can regress even at later stages of cirrhosis and shifting the immune response from pro-inflammatory towards a resolutive profile is considered as a promising option. The immune regulatory networks that govern the shift of the inflammatory phenotype and thus potential reversal of liver fibrosis are lesser known. Here we show that in precision-cut human liver slices obtained from patients with end-stage fibrosis and in mouse models, inhibiting Mucosal-Associated Invariant T (MAIT) cells using pharmacological or antibody-driven approaches, limits fibrosis progression and even regresses fibrosis, following chronic toxic- or non-alcoholic steatohepatitis (NASH)-induced liver injury.

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Trop-2 is a ubiquitous and promising target in pancreatic adenocarcinoma.

Clin Res Hepatol Gastroenterol

April 2023

Department of Hepato-Gastroenterology and Digestive Oncology, Pitié Salpêtrière Hospital, APHP, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Sorbonne University, UPMC University, 15-21 Rue de l'École de Médecine, Paris 75006, France. Electronic address:

Background: Trop-2 is overexpressed in tumor cells of various cancers, including pancreatic ductal adenocarcinoma (PDAC), and has emerged as a potent therapeutic target. We evaluated Trop-2 expression both at the transcriptomic and protein levels, and its correlation with tumor features and patients' outcomes in a large cohort of PDAC.

Methods: We included patients undergoing pancreatic resection for PDAC in 5 academic hospitals in France and Belgium.

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Intratumoral microbiome is driven by metastatic site and associated with immune histopathological parameters: An ancillary study of the SHIVA clinical trial.

Eur J Cancer

April 2023

Molecular Oncology, PSL Research University, CNRS, UMR 144, Institut Curie, Paris 75005, France; Paris Center for Microbiome Medicine, Fédération Hospitalo-Universitaire, Paris, France; Medical Oncology Department, Institut Curie, Saint-Cloud 92210, France.

Background: Data on the role of the microbiota in cancer have accumulated in recent years, with particular interest in intratumoral bacteria. Previous results have shown that the composition of intratumoral microbiome is different depending on the type of primary tumour and that bacteria from the primary tumour could migrate to metastatic sites.

Methods: Seventy-nine patients with breast, lung, or colorectal cancer and available biopsy samples from lymph node, lung, or liver site, treated in the SHIVA01 trial were analysed.

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Proteinase 3 (PR3) is the main target antigen of antineutrophil cytoplasmic antibodies (ANCAs) in PR3-ANCA-associated vasculitis. A small fraction of PR3 is constitutively exposed on the surface of quiescent blood neutrophils in a proteolytically inactive form. When activated, neutrophils expose an induced form of membrane-bound PR3 (PR3) on their surface as well, which is enzymatically less active than unbound PR3 in solution due to its altered conformation.

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Circulating monocytes are recruited in damaged tissues to generate macrophages that modulate disease progression. Colony-stimulating factor-1 (CSF-1) promotes the generation of monocyte-derived macrophages, which involves caspase activation. Here, we demonstrate that activated caspase-3 and caspase-7 are located to the vicinity of the mitochondria in CSF1-treated human monocytes.

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In low-risk myelodysplastic syndrome (LR-MDS), erythropoietin (EPO) is widely used for the treatment of chronic anemia. However, initial response to EPO has time-limited effects. Luspatercept reduces red blood cell transfusion dependence in LR-MDS patients.

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Objectives: Inflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 (), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown.

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