31 research outputs found
The socio-educational experience of Algerian immigrants' children in France and Algeria
SIGLEAvailable from British Library Document Supply Centre- DSC:DX87465 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
DNA methylation as a triage tool for cervical cancer screening - A meeting report.
INTRODUCTION: DNA methylation is proposed as a novel biomarker able to monitor molecular events in human papillomavirus (HPV) infection pathophysiology, enabling the distinction between HPV-induced lesions with regression potential from those that may progress to HPV-related cancer. METHODS: This meeting report summarises the presentations and expert discussions during the HPV Prevention and Control Board-focused topic technical meeting on DNA methylation validation in clinician-collected and self-collected samples, novel DNA methylation markers discovery, implementation in cervical cancer screening programs, and their potential in women living with human immunodeficiency virus (HIV). RESULTS: Data presented in the meeting showed that HPV-positive, baseline methylation-negative women have a lower cumulative cervical cancer incidence than baseline cytology-negative women, making DNA methylation an attractive triage strategy. However, additional standardised data in different settings (low- versus high-income settings), samples (clinician-collected and self-collected), study designs (prospective, modelling, impact) and populations (immunocompetent women, women living with HIV) are needed. CONCLUSION: Establishing international validation guidelines were identified as the way forward towards accurate validation and subsequent implementation in current screening programs
Glucolipotoxicity initiates pancreatic beta-cell death through TNFR5/CD40-mediated STAT1 and NF-kappa B activation
Funded by Diabetes UK, NovoNordisk UK Research Foundation, and St. Bartholomewâs & The Royal London Charitable
Foundation grant awards
Molecular progression to cervical precancer, epigenetic switch or sequential model?
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Low methylation marker levels among human papillomavirus-vaccinated women with cervical high-grade squamous intraepithelial lesions.
Cervical cancer screening programs, including triage tests, need redesigning as human papillomavirus (HPV)-vaccinated women are entering the programs. Methylation markers offer a potential solution to reduce false-positive rates by identifying clinically relevant cervical lesions with progressive potential. In a nested case-control study, 9242 women who received the three-dose HPV16/18-vaccine at ages 12-15 or 18 in a community-randomized trial were included. Subsequently, they were re-randomized for either frequent or infrequent cervical cancer screening trials. Over a 15-year post-vaccination follow-up until 2022, 17 high-grade squamous intraepithelial lesion (HSIL) and 15 low-grade (LSIL) cases were identified at the 25-year screening round, alongside 371 age and community-matched HPV16/18-vaccinated controls. Methylation analyses were performed on cervical samples collected at age 25, preceding histologically confirmed LSIL or HSIL diagnoses. DNA methylation of viral (HPV16/18/31/33) and host-cell genes (EPB41L3, FAM19A4, and miR124-2) was measured, along with HPV-genotyping. No HPV16/18 HSIL cases were observed. The predominant HPV-genotypes were HPV52 (29.4%), HPV59/HPV51/HPV58 (each 23.5%), and HPV33 (17.7%). Methylation levels were generally low, with no significant differences in mean methylation levels of viral or host-cell genes between the LSIL/HSIL and controls. However, a significant difference in methylation levels was found between HSIL cases and controls when considering a combination of viral genes and EPB41L3 (p valueâ=â.0001). HPV-vaccinated women with HSIL had HPV infections with uncommon HPV types that very rarely cause cancer and displayed low methylation levels. Further investigation is warranted to understand the likely regressive nature of HSIL among HPV-vaccinated women and its implications for management
Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.
Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of âself-eatingâ where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis
Interfaces entre dynamisme des versants et peri-urbanisation dans un bassin versant torrentiel : caractérisation, évolution et perception des risques naturels dans le bassin du Lavanchon (agglomération de Grenoble)
Rapport au Conseil Général de l'IsÚre, programme PÎle risque grenobloi
Consistency of the S5 DNA methylation classifier in formalin-fixed biopsies versus corresponding exfoliated cells for the detection of pre-cancerous cervical lesions
Methylation biomarkers are promising tools for diagnosis and disease prevention. The S5 classifier is aimed at the prevention of cervical cancer by the early detection of cervical intraepithelial neoplasia (CIN). S5 is based on pyrosequencing a promoter region of EPB41L3 and five late regions of HPV types 16, 18, 31, and 33 following bisulfite conversion of DNA. Good biomarkers should perform well in a variety of sample types such as exfoliated cells, fresh frozen or formalinâfixed paraffinâembedded (FFPE) materials. Here, we tested the performance of S5 on 315 FFPE biopsies with paired exfoliated cervical samples using four different conversion kits (Epitect Bisulfite, Epitect Fast Bisulfite, EZ DNA Methylation, and EZ DNA MethylationâLightning). The S5 values from FFPE biopsies for all kits were significantly correlated with those obtained from their paired exfoliated cells. For the EZ DNA Methylation kit, we observed an average increased methylation of 4.4% in FFPE. This was due to incomplete conversion of DNA (73% for FFPE vs. 95% for cells). The other kits had a DNA conversion rate in FFPE similar to the cells (95%â97%). S5 performed well at discriminating <CIN2 lesions from CIN2+ lesions on the FFPE with all kits given optimized adjustments to the cutâoff. The area under the curve (AUC) for S5 on FFPE was not significantly different from the paired cells (0.74â0.79 vs. 0.81). The best sensitivity and specificity were obtained for EZ DNA Methylation after the adjustment of the cutâoff to reflect its lower conversion rate. Consistent methylation results can be obtained from FFPE material regardless of the conversion kit used. The S5 classifier performed as well on FFPE material as on exfoliated cells with adjusted cutâoff allowing easier clinical implementation
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