Expression des métalloprotéinases matricielles dans le cancer du col utérin

Thèse présentée sous la forme d'une "Thèse Article"Objectifs : Comparer l’expression des métalloprotéinases matricielles (MMPs) aux différentes étapes du processus de cancérisation du col utérin et préciser sa localisation au sein des tissus cervicaux.Méthodes : une analyse transcriptomique a été réalisée à partir de 70 prélèvements de cols utérins collectés prospectivement : 17 patientes ayant un col normal (groupe normal), 28 patientes traitées pour une lésion intra-épithéliale de haut grade (groupe HSIL) et 25 patientes traitées pour un cancer invasif (groupe cancer). Les résultats ont été secondairement validés par analyse immunohistochimique (IHC). Le critère de jugement principal était la différence d’expression des MMPs entre les 3 groupes.Résultats : en analyse transcriptomique, par rapport au groupe normal, MMP-1, 9, 10 et 12 sont significativement surexprimées dans le groupe cancer (p < 0,01). Par rapport au groupe HSIL, MMP-1 et 12 sont significativement surexprimées dans le groupe cancer (p<0,005). MMP-9 et 12 sont significativement surexprimées dans le groupe HSIL vs. groupe normal (p<0,01 et p<0,05, respectivement). En IHC, l’expression de MMP-1 augmente de façon significative au cours des différentes étapes de l’histoire naturelle du cancer du col utérin au niveau du stroma (cancer vs. HSIL ; p=0,03, HSIL vs. normal ; p=0,03). MMP-9 et 10 sont surexprimées dans le stroma du groupe cancer vs. groupe normal (p<0,01 et p=0,02, respectivement). Conclusion : au sein du stroma, l’expression de MMP-1 augmente de façon significative au cours des différentes étapes de l’histoire naturelle du cancer du col utérin. Les MMP-9 et 10 sont surexprimées dans le stroma du cancer du col utérin

Les Mutations de NPHP2 et NPH3 dans la néphronophtise infantile

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Statistical Shack-Hartmann wavefront analysis through non-isotropic turbulence

Communication to : SPIE - Remote sensing 2002, Aghia Pelagia, Crete (Grece), September 23-27, 2002SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : 22419, issue : a.2003 n.30 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Endometrial Carcinoma: Immune Microenvironment and Emerging Treatments in Immuno-Oncology

International audienceEndometrial cancer (EC) can easily be cured when diagnosed at an early stage. However, advanced and metastatic EC is a common disease, affecting more than 15,000 patients per year in the United Sates. Only limited treatment options were available until recently, with a taxane–platinum combination as the gold standard in first-line setting and no efficient second-line chemotherapy or hormone therapy. EC can be split into four molecular subtypes, including hypermutated cases with POLE mutations and 25–30% harboring a microsatellite instability (MSI) phenotype with mismatch repair deficiency (dMMR). These tumors display a high load of frameshift mutations, leading to increased expression of neoantigens that can be targeted by the immune system, including (but not limited) to T-cell response. Recent data have demonstrated this impact of programmed death 1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors on chemo-resistant metastatic EC. The uncontrolled KEYNOTE-158 and GARNET trials have shown high response rates with pembrolizumab and dostarlimab in chemoresistant MSI-high tumors. Most responders experiment long responses that last more than one year. Similar, encouraging results were obtained for MMR proficient (MMRp) cases treated with a combination of pembrolizumab and the angiogenesis inhibitor lenvatinib. Approvals have, thus, been obtained or are underway for EC with immune checkpoint inhibitors (ICI) used as monotherapy, and in combination with antiangiogenic agents. Combinations with other targeted therapies are under evaluation and randomized studies are ongoing to explore the impact of ICI-chemotherapy triplets in first-line setting. We summarize in this review the current knowledge of the immune environment of EC, both for MMRd and MMRp tumors. We also detail the main clinical data regarding PD-1/PD-L1 inhibitors and discuss the next steps of development for immunotherapy, including various ICI-based combinations planned to limit resistance to immunotherapy

Association of kidney biopsy findings with short- and medium-term outcomes in children with moderate-to-severe IgA vasculitis nephritis

International audienceAssessing the initial severity of immunoglobulin A vasculitis nephritis (IgAV-N) is important due to its determining effect on kidney management and outcomes. This paper describes a multicentre paediatric cohort of IgAV-N patients and discusses relationships among clinical presentation, histological features, and kidney outcome. We retrospectively studied a cohort of 170 children with biopsy-proven IgAV-N, diagnosed between 2007 and 2017. One-quarter of the cohort (27%) presented with initial nephrotic syndrome (NS). Kidney biopsy revealed International Study of Kidney Disease (ISKDC) grade II or grade III in 83% of cases. Endocapillary proliferation was observed in 73% of patients, and chronic lesions were observed in 25%. Data analysis showed a significant association between NS at onset and endocapillary proliferation and cellular crescents. After a median follow-up of 21 months (IQR 12-39), 30% of patients had persistent proteinuria or decreased eGFR. At the end of follow-up, kidney impairment was more often observed in patients with NS at onset and those with cellular crescents and chronic lesions on initial kidney biopsy.Conclusion: This study highlights the relationship between the clinical and histological presentation of IgAV-N and the factors that affect kidney outcome. The ISKDC classification may be improved by including lesions that are more discriminating for disease severity and prognosis. What is Known: • Nephrotic syndrome (NS) or kidney failure at diagnosis and cellular crescents in more than 50% of the glomeruli are recognized as risk factors for poor kidney outcome in immunoglobulin A vasculitis nephritis (IgAV-N). • The reference histological classification of the International Study of Kidney Disease in Children (ISKDC) is primarily based on the presence and number of affected glomeruli (mesangial proliferation, cellular crescents). The updated Oxford classification, which emphasizes tubular atrophy and interstitial fibrosis, is also used to group pathological features of IgAV-N. Both classifications have limitations. What is New: • Medical treatment should not be postponed in patients with IgAV-N and NS until after biopsy, as NS at diagnosis is associated with initial histological severity and poorer kidney outcome. This proposal needs to be verified in further studies. • Endocapillary proliferation is associated with the initial severity of IgAV-N at diagnosis, while chronic glomerular changes and interstitial fibrosis are associated with poorer short- and medium-term kidney outcomes

SYSIPHE, an airborne hyperspectral imaging system from visible to thermal infrared. Results from the 2015 airborne campaign.

International audienceSYSIPHE is an airborne hyperspectral imaging system covering all atmospheric transmission bands from 0.4μm to 11.5μm. The ground sampling distance is 0.5m over a 500m swath, with higher resolution available in the visible and NIR. SYSIPHE is flown on a Do-228 aircraft operated by DLR. The system also comprises a real-time processing capability and a ground postprocessing chain. The main information products are georeferenced images of spectral radiance, spectral emissivity and reflectance as well as a surface temperature map. After a certification campaign in 2013, qualification airborne campaign for military applications was carried out during the summer of 2015, and this system is now available to external users, representing a significant enhancement of airborne sensing capabilities in Europe. After a brief description of the system and of the 2015 campaign, we present some experimental results from this airborne campaign

Pediatr Nephrol

BACKGROUND: IgA vasculitis (IgAV) is the most common vasculitis in children. IgAV long-term prognosis depends on kidney involvement or IgA vasculitis with nephritis (IgAVN). To date, steroid treatment (oral steroids or methylprednisolone pulses) has not proven to be formally efficient. This study aimed to assess the role of steroids on IgAVN outcome. METHODS: All children with IgAVN diagnosed 2000-2019 in 14 French pediatric nephrology units with minimal follow-up of 6 months were retrospectively included. Outcomes of patients treated with steroids were compared with those of a control group of untreated patients matched for age, sex, proteinuria, eGFR, and histological features. The primary endpoint was IgAVN remission defined as urine protein-to-creatinine ratio < 20 mg/mmol without impaired eGFR one year after disease onset. RESULTS: A total of 359 patients with IgAVN were included with a median follow-up time of 249 days (range 43-809). One hundred eight (30%) patients received oral steroids alone, 207 (51%) patients received three methylprednisolone pulses followed by oral steroids, and 44 patients (12.5%) did not receive steroids. Thirty-two children treated with oral steroids alone were compared with 32 matched control patients who did not receive steroids. One year after disease onset, IgAVN remission proportion was not different between these two groups: 62% versus 68%, respectively. Ninety-three children treated with oral steroids alone were compared with 93 matched patients treated with three methylprednisolone pulses followed by oral corticosteroids. IgAVN remission proportion was not different between these two groups: 77% versus 73%, respectively. CONCLUSION: The benefit of oral steroids alone and methylprednisolone pulses could not be established based on this observational study. Randomized controlled trials are thus required to determine the efficacy of steroids in IgAVN. A higher resolution version of the Graphical abstract is available as Supplementary information