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Circulating tumor cells for the prediction of the response to radiation therapy in prostate cancer
No full textInternational audienceCirculating tumor cells (CTCs) have emerged as a promising biomarker for assessing prognosis and predicting therapeutic efficacy in various cancers, including metastatic prostate cancer. However, predicting patient response to treatment, including radiation therapy remains a significant clinical challenge. This review explores the value of CTCs as prognostic markers in radiation therapy for prostate cancer, discussing their detection methods, biological significance, clinical relevance, and future implications.</div
Disease severity across psychiatric disorders is linked to pro-inflammatory cytokines
No full textInternational audienceImportance: Numerous studies indicate that the traditional categorical classification of severe mental disorders (SMD), such as schizophrenia, bipolar disorders, and major depressive disorders, does not align with the underlying biology of those disorders as they frequently overlap in terms of symptoms and risk factors.Objective: This study aimed to identify transdiagnostic patient clusters based on disease severity and explore the underlying biological mechanisms independently of the traditional categorical classification.Design: We utilized data from 443 participants diagnosed with SMD of the PsyCourse Study, a longitudinal study with deep phenotyping across up to four visits. We performed longitudinal clustering to group patients based on symptom trajectories and cognitive performance. The resulting clusters were compared on cross-sectional variables, including independent measures of severity as well as polygenic risk scores, serum protein quantification, miRNA expression, and DNA methylation.Results: We identified two distinct clusters of patients that exhibited marked differences in illness severity but did not differ significantly in age, sex, or diagnostic proportions. We found 19 serum proteins significantly dysregulated between the two clusters. Functional enrichment pointed to a convergence of immune system dysregulation and neurodevelopmental processes.Conclusion: The observed differences in serum protein expression suggest that disease severity is associated with the convergence of immune system dysregulation and neurodevelopmental alterations, particularly involving pathways related to inflammation and brain plasticity. The identification of pro-inflammatory proteins among the differentially expressed markers underscores the potential role of systemic inflammation in the pathophysiology of SMD. These results highlight the importance of considering illness severity as a core dimension in psychiatric research and clinical practice and suggest that targeting immune-related mechanisms may offer promising new therapeutic avenues for patients with SM
Association of Prolonged Breastfeeding With Early Childhood Caries Using Propensity Score Matching in the French Longitudinal Study of Children ( ELFE Cohort)
No full textInternational audienceABSTRACT Objectives The aim of this study was to investigate the link between prolonged breastfeeding (≥ 12 months) and early childhood caries (ECC) using propensity score matching (PSM) to account for observed confounders, reduce bias, and provide a more reliable estimate of this relationship. Methods This study utilised data from the French Longitudinal Study of Children (ELFE Cohort), comprising 11 718 participants. PSM was employed to pair children who were breastfed for 12 months or longer with those breastfed for less than 12 months or not at all, controlling for shared risk factors such as socioeconomic status and dietary habits. Logistic regression models were conducted to examine the association between ECC, reported by the parents at 3.5 years, and prolonged breastfeeding. Results Infants (7.6%) who were breastfed for 12 months or more exhibited twice the odds of developing ECC at 3.5 years compared to those breastfed for less than 12 months or not at all (OR = 2.20, 95% CI: 1.39, 3.47). Conclusion Children breastfed for 12 or more months are at increased risk of developing ECC. Further research is needed to investigate specific breastfeeding practices that may contribute to this increased risk, with the aim of promoting prolonged breastfeeding while ensuring optimal oral health
Clinical characteristics, healthcare resource use, and survival outcomes among patients with advanced NSCLC tested for KRAS mutations in France, the United Kingdom, and Switzerland
No full textInternational audienceObjective: To evaluate real-world patient characteristics, healthcare resource use (HRU), and clinical outcomes among patients with advanced or metastatic (A/M) nonsmall cell lung cancer (NSCLC) stratified by KRAS mutation status (KRAS G12C, KRAS non-G12C, and KRAS wild-type[WT]). Methods: This retrospective chart review included adults with A/M NSCLC and known KRAS status who received second-or third-line non-targeted therapy (index therapy) in France, the UK, or Switzerland. Patient characteristics, HRU, and key clinical outcomes-including time to treatment discontinuation (TTD), progression-free survival (PFS), and overall survival (OS)-were analyzed using the Kaplan-Meier method and log-rank methods. Exploratory multivariate Cox models adjusted for clinical covariates. Results: The study included 211 patients (France: 192, UK: 13, Switzerland: 6), with 53.1% having KRAS G12C, 21.8% KRAS non-G12C, and 25.1% KRAS WT NSCLC. Median age was 66 years; 62.1% were male, and 95.8% were current/former smokers. Baseline characteristics were comparable across KRAS subgroups. HRU was high, including 125 unplanned healthcare provider visits, primarily to general practitioners (42.4%) and specialists (24.0%). Hospitalization was frequent (70.1% of patients), with 40.8% experiencing unplanned admissions, largely due to disease complications (54.2%) and grade 3/4 adverse events (24.4%). Median TTD, PFS, and OS were comparable across KRAS subgroups for second-line (4.4-4.7 months, 5.3-6.3 months, and 11.2-15.0 months) and third-line (3.2-4.1 months, 3.4-5.2 months, and 5.1-9.2 months) therapy. Multivariate analysis showed that KRAS status, performance status, histology, and comorbidities were not significantly associated with survival outcomes. Conclusions: Patients with advanced NSCLC, regardless of KRAS mutation status, experience a substantial disease burden, frequent hospitalizations, and poor clinical outcomes. These findings highlight the urgent need for more effective treatment options for advanced NSCLC, including therapies tailored to KRAS-mutated disease.</div
Hepatocellular carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
No full textInternational audienceNo abstract availabl
Protoporphyrin IX-Derived Ruthenium(II) Complexes for Photodynamic Therapy in Gastric Cancer Cells
No full textInternational audienceIn recent years, photodynamic therapy (PDT) has emerged as a promising alternative to classical chemotherapy for treating cancer. PDT is based on a nontoxic prodrug called photosensitizer (PS) activated by light at the desired location. Upon irradiation, the PS reacts with the oxygen present in the tumor, producing cytotoxic reactive oxygen species (ROS). Compounds with highly conjugated π-bond systems, such as porphyrins and chlorins, have proven to be excellent light scavengers, and introducing a metal atom in their structure improved the generation of ROS. In this work, a series of tetrapyrrole-ruthenium(II) complexes derived from protoporphyrin IX and the commercial drug verteporfin were designed as photosensitizers for PDT. The complexes were almost nontoxic on human gastric cancer cells under dark conditions, revealing remarkable cytotoxicity upon irradiation with light. The ruthenium atom in the central cavity of the chlorin ligand allowed combined mechanisms in photodynamic therapy, as both singlet oxygen and superoxide radicals were detected. Additionally, one complex produced large amounts of singlet oxygen under hypoxic conditions. Biological assays demonstrated that the ruthenium derivatives caused cell death through a caspase 3 mediated apoptotic pathway and via CHOP, an endoplasmic reticulum stress-inducible transcription factor involved in apoptosis and growth arrest.</div
Advances in Longevity: The Intersection of Regenerative Medicine and Cosmetic Dermatology
No full textInternational audienceBackground: Aging is increasingly recognized as a modifiable biological process influenced by genetic, environmental, and lifestyle factors. Recent advances in regenerative medicine and artificial intelligence (AI) have reshaped the field of cosmetic dermatology, shifting the focus from temporary aesthetic improvements to long-term interventions aimed at preserving skin vitality and longevity. Aim: This narrative review aims to synthesize emerging knowledge from 2010 to 2025 on the integration of regenerative strategies, biological modulators, immunologic regulation, microbiome modulation, and AI-driven personalization in the context of aesthetic longevity. The review also discusses translational potential and ethical considerations surrounding these advancements. Methods: A targeted literature search was conducted using PubMed and Scopus to identify peer-reviewed articles from 2010 to 2025. Search terms included "skin aging," "stem cells," "mitochondrial dysfunction," "epigenetic reprogramming," "artificial intelligence in dermatology," and "skin microbiome." Selected studies focused on regenerative and longevity-based interventions with clinical relevance or future applicability in cosmetic dermatology. Results: Key findings were categorized into six interconnected domains: regenerative medicine, mitochondrial function, epigenetic modulation, immunological balance, microbiome resilience, and AI-driven innovation. These pillars demonstrate a paradigm shift toward biologically informed, personalized strategies that aim to restore and sustain skin health at the molecular level. Conclusion: Cosmetic dermatology is undergoing a transformation toward integrative, proactive care that combines regenerative medicine, AI, and personalized interventions. These approaches offer promising, evidence-based solutions for enhancing both aesthetic outcomes and long-term skin function, while also raising important ethical and regulatory considerations for clinical implementation. | IntroductionLongevity, once a futuristic ideal, has become a clinical reality at the intersection of regenerative medicine and cosmetic dermatology [1-3]. Aging is now increasingly regarded as a modifiable process, shaped by genetic predisposition, lifestyle factors, and molecular pathways. Over the past 15 years, advancements in stem cell therapy, mitochondrial research, This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.</div
Impaired IgA Mucosal Immunity Following Lung Transplantation: A Potential Trigger for Bronchiolitis Obliterans Syndrome
No full textInternational audienceRationale : Bronchiolitis obliterans syndrome (BOS) limits long-term survival after lung transplantation (LuTx) and may be triggered by infections. As immunoglobulin (Ig)A is crucial to ensure adequate mucosal immunity, we explored whether IgA-related mucosal immunity is impaired in BOS. Methods : Sixty LuTx recipients from the COLT cohort were retrospectively included. All participants were in stable condition within the first year post-transplant. At 3.5 years post-LuTx, 30 remained stable and 30 had developed BOS. Bronchoalveolar lavage fluid (BALF) and sera collected pre-transplant and at 6 (M6) and 12 months (M12) post-transplant were assessed for monomeric IgA, secretory (S)-IgA, secretory component (SC) and cytokine profiling. Second, bronchiolar polymeric Ig receptor (pIgR) expression and subepithelial IgA-producing B-cell numbers were compared across graft tissue samples from 54 LuTx recipients classified as stable, pre-BOS, BOS or end-stage BOS. Results : S-IgA levels in BALF decreased between M6 and M12 (p=0.0001) and were reduced in BOS patients at M12 (p=0.0018). Patients with lower S-IgA levels had higher infection rates. BOS patients exhibited elevated SC levels in serum (p<0.01). Both reduced S-IgA in BALF and increased SC in serum were associated with higher risk of BOS. Lastly, a reduction in bronchiolar pIgR expression was observed in BOS patients (p=0.0001), that paralleled BOS severity. Conclusions : This study demonstrates an early impairment of mucosal IgA immunity in LuTx patients, which was linked to the later development of BOS, suggesting that IgA-related markers may serve as early predictors of BOS onset
La flexibilité cognitive : une dimension cognitive clé
No full textInternational audienceCognitive flexibility, an essential executive function, allows adaptation to environmental changes and represents a fundamental pillar of executive function in neuropsychological models. Based on neurobiological advances and clinical observations, it has emerged as a promising transdiagnostic marker for several psychiatric pathologies, including mood disorders, schizophrenia, and autism spectrum disorders. This review examines the specific role of cognitive flexibility among other cognitive functions, explores potential therapeutic approaches, and presents its evaluation in human and animal models as part of PEPR PROPSY. As the chapters unfold, readers will deepen their understanding of cognitive flexibility while discovering promising avenues for both assessment methods and intervention strategies.La flexibilité cognitive est une fonction exécutive fondamentale qui permet de s’adapter aux changements environnementaux, et constitue un marqueur transdiagnostique prometteur dans plusieurs troubles psychiatriques. Cette revue examine le rôle spécifique de la flexibilité cognitive parmi les autres fonctions cognitives. Elle explore les approches thérapeutiques potentielles, et présente son évaluation dans le cadre du PEPR PROPSY. À travers ses différentes sections, le lecteur peut ainsi approfondir ses connaissances sur la flexibilité cognitive, et découvrir des pistes encourageantes, tant pour son évaluation que pour son ciblage dans l’optique d’approches interventionnelles
The kinase domain of TRPM7 interacts with PAK1 and regulates pancreatic cancer cell epithelial-to-mesenchymal transition
No full textInternational audiencePancreatic ductal adenocarcinoma (PDAC) is the main and the deadliest form of pancreatic cancer. This is a major problem of public health since it will become the second leading cause of death by cancer in the next few years, mainly due to the lack of efficient therapies. Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) protein, a cation channel fused with a serine/threonine kinase domain is overexpressed in PDAC and associated with a low survival. In this work, we aim to study the role of kinase domain on pancreatic cell fates by using a model of kinase domain deletion by CRISPR-Cas9. PANC-1 and MIA PaCa-2 PDAC cell lines were used and kinase domain was deleted by CRISPR-Cas9 strategy. Kinase domain deletion (ΔK) was validated by RT-qPCR and western blots. The effect of kinase domain deletion on channel function was studied by patch-clamp and Mn 2+ -quenching. The cell phenotype was studied by MTT and cell migration/invasion assays. Finally, the role of kinase domain was studied in vivo in xenografted mice. Here we show that TRPM7 kinase domain is required to maintain a mesenchymal phenotype in PDAC cells. We also demonstrated that TRPM7 and PAK1 interact in the same protein complexes. Moreover, TRPM7 kinase domain is required for carcinogenesis and cancer cell dissemination in vivo. Intriguingly, the role of TRPM7 kinase is cell specific and may depend on the KRAS oncogene mutation status. In conclusion, TRPM7 kinase domain is required to maintain a mesenchymal and aggressive phenotype in PDAC cells, and it could be a promising target against PDAC