Evaluation of Proton MR Spectroscopy for the Study of the Tongue Tissue in Healthy Subjects and Patients With Tongue Squamous Cell Carcinoma: Preliminary Findings

PurposeTo noninvasively assess spectroscopic and metabolic profiles of healthy tongue tissue and in an exploratory objective in nontreated and treated patients with tongue squamous cell carcinoma (SCC).MethodsFourteen healthy subjects (HSs), one patient with nontreated tongue SCC (NT-SCC), and two patients with treated tongue SCC (T-SCC) underwent MRI and single-voxel proton magnetic resonance spectroscopy (1H-MRS) evaluations (3 and 1.5T). Multi-echo-times 1H-MRS was performed at the medial superior part (MSP) and the anterior inferior part (AIP) of the tongue in HS, while 1H-MRS voxel was placed at the most aggressive part of the tumor for patients with tongue SCC. 1H-MRS data analysis yielded spectroscopic metabolite ratios quantified to total creatine.ResultsIn HS, compared to MSP and AIP, 1H-MRS spectra revealed higher levels of creatine, a more prominent and well-identified trimethylamine-choline (TMA-Cho) peak. However, larger prominent lipid peaks were better differentiated in the tongue MSP. Compared to HS, patients with NT-SCC exhibited very high levels of lipids and relatively higher values of TMA-Cho peak. Interestingly, patients with T-SCC showed almost nonproliferation activity. However, high lipids levels were measured, although they were relatively lower than lipids levels measured in patients with NT-SCC.ConclusionThe present study demonstrated the potential use of in-vivo1H-MRS to noninvasively assess spectroscopic and metabolic profiles of the healthy tongue tissue in a spatial location-dependent manner. Preliminary results revealed differences between HS and patients with tongue NT-SCC as well as tongue T-SCC, which should be confirmed with more patients. 1H-MRS could be included, in the future, in the arsenal of tools for treatment response evaluation and noninvasive monitoring of patients with tongue SCC

Pleuro-pulmonary tumours detected by clinical and chest X-ray analyses in rats transplanted with mesothelioma cells

New strategies for cancer therapy must be developed, especially in severe neoplasms such as malignant pleural mesothelioma. Animal models of cancer, as close as possible to the human situation, are needed to investigate novel therapeutical approaches. Orthotopic transplantation of cancer cells is then relevant and efforts should be made to follow up tumour evolution in animals. In the present study, we developed a method for the orthotopic growth of mesothelioma cells in the pleural cavity of Fischer 344 and nude rats, along with a procedure for clinical survey. Two mesothelioma cell lines, of rat and human origin, were inoculated by transthoracic puncture. Body weight determination and chest X-ray analyses permitted the follow-up of tumour evolution by identifying different stages. Autopsies showed that tumours localized on the whole pleural cavity (diaphragm, parietal pleura), mediastinum and pericardium. Tumour morphology and antigenic characteristics were consistent with those of the inoculated cells and were similar in both types of rats inoculated with the same cell type. These results demonstrate that mesothelioma formation in rats can be followed up by clinical and radiographic survey after gentle intrathoracic inoculation of mesothelioma cells, thus allowing the definition of stages of interest for further experimental trials. © 1999 Cancer Research Campaig

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Systematic review of randomized controlled trials in the treatment of dry eye disease in Sjogren syndrome

Primary Sjögren’s syndrome is an autoimmune disease characterized by dry eye and dry mouth. We systematically reviewed all the randomized controlled clinical trials published in the last 15 years that included ocular outcomes. We found 22 trials involving 9 topical, 10 oral, 2 intravenous and 1 subcutaneous modalities of treatment. Fluoromethalone eye drops over 8 weeks were more effective than topical cyclosporine in the treatment of dry eye symptoms and signs; similarly, indomethacin eye drops over 1 month were more efficacious than diclofenac eye drops. Oral pilocarpine 5 mg twice daily over 3 months was superior to use of lubricants or punctal plugs for treating dry eye, but 5% of participants had gastrointestinal adverse effects from pilocarpine, though none discontinued treatment. In contrast, etanercept, a TNF-alpha blocking antibody, administered as subcutaneous injections twice weekly, did not improve dry eye significantly compared to placebo injections. In conclusion, topical corticosteroids have been shown to be effective in dry eye associated with Sjögren’s syndrome. As some topical non-steroidal anti-inflammatory drugs may be more effective than others, these should be further evaluated. Systemic secretagogues like pilocarpine have a role in Sjögren’s syndrome but the adverse effects may limit their clinical use. It is disappointing that systemic cytokine therapy did not produce encouraging ocular outcomes but participants should have assessment of cytokine levels in such trials, as those with higher baseline cytokine levels may respond better.published_or_final_versio

Serum profiling identifies CCL8, CXCL13, and IL-1RA as markers of active disease in patients with systemic lupus erythematosus

IntroductionSystemic lupus erythematosus (SLE) is a clinically heterogeneous disease that presents a challenge for clinicians. To identify potential biomarkers for diagnosis and disease activity in SLE, we investigated a selected yet broad panel of cytokines and autoantibodies in patients with SLE, healthy controls (HC), and patients with other autoimmune diseases (AIDs).MethodsSerum samples from 422 SLE patients, 546 HC, and 1223 other AIDs were analysed within the frame of the European PRECISESADS project (NTC02890121). Cytokine levels were determined using Luminex panels, and autoantibodies using different immunoassays.ResultsOf the 83 cytokines analysed, 29 differed significantly between patients with SLE and HC. Specifically, CCL8, CXCL13, and IL-1RA levels were elevated in patients with active, but not inactive, SLE versus HC, as well as in patients with SLE versus other AIDs. The levels of these cytokines also correlated with SLE Disease Activity Index 2000 (SLEDAI-2K) scores, among five other cytokines. Overall, the occurrence of autoantibodies was similar across SLEDAI-2K organ domains, and the correlations between autoantibodies and activity in different organ domains were weak.DiscussionOur findings suggest that, upon validation, CCL8, CXCL13, and IL-1RA could serve as promising serum biomarkers of activity in SLE

O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

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La main savante et le visage : optique et haptique chirurgicale

Pour le chirurgien de la face, l’ambiguïté du rapport entre main et visage est évidente, car si la première fonde étymologiquement le métier chirurgical, de quel visage s’agit-il ? De celui qui, caché derrière son masque, s’applique à réparer la défiguration ou de celui qui, objet et sujet de son attention, s’efforce de retrouver figure humaine et identité au fil des interventions ? L’analogie s’impose alors, celle du peintre et son modèle, du sculpteur et de la main qu’il façonne, du pianiste et de l’œuvre qu’il interprète, de l’écrivain et du souvenir qui déclenche le roman. C’est de cet affrontement des sens, mais aussi de leur enchevêtrement dans ce qui pourrait être appelé la tactilisation de la vue et la visualisation du toucher, cette communauté nécessaire entre l’optique et l’haptique dont il sera question. Appliquée à la greffe du visage, cette inquiétante étrangeté, l’interrogation schizophrène nous plonge derechef dans un vertige abyssal dont seule l’éthique, cette esthétique du dedans évite de nous y engloutir

Chirurgie reconstructrice des désordres ankylosants de l'articulation temporomandibulaire

L articulation temporomandibulaire (ATM), histologiquement comparable aux autres articulations du corps humain, est une articulation complexe de part son origine embryologique, de part son anatomie, et de part sa biomécanique la rendant finalement unique. Ainsi, les pathologies touchant cette articulation sont encore mal comprises, souvent mal diagnostiquées et surtout mal définies. L ankylose de l articulation temporomandibulaire n y fait pas exception. Atteinte rare, son terme demeure ambigu, employé à tort, sa définition fait encore débat de nos jours. Le traitement de cette pathologie, quant à lui incontestable reste chirurgical. Cependant, la complexité de cette articulation semble être un frein aux techniques chirurgicales reconstructrices. Pourtant débutant dès le XIXème siècle, cette chirurgie a vu bien des techniques décrites : du geste simple d interposition et condyloplastie (interposition de matériels autologues ou alloplastiques) à des gestes complexes (greffes osseuses, lambeaux libres), et à l utilisation de prothèses articulaires. Le nombre de prothèses articulaires et le nombre de techniques chirurgicales décrites montre bien la perfectibilité de chaque technique, nécessitant le développement sans cesse de nouvelles approches reconstructrices. Ce travail concerne l analyse de 16 patients pris en charge entre 1998 et 2010. Utilisant des outils développés à l Université Technologique de Compiègne afin d analyser les surfaces articulaires de l ATM, nous montrerons que les nouvelles technologies, et notamment l utilisation de modèles 3D géométriques et des éléments finis permet une aide à la fois sur le plan diagnostique et thérapeutique mais également au développement de nouvelles prothèses articulaires dans la chirurgie reconstructrice de l ATM. Ainsi sera exposé un algorythme décisionnel des différentes techniques de reconstruction de l ATM après résection du bloc d ankylose en fonction du type et de l étiologie avec une décision complémentaire selon l âge et les antécédents chirurgicaux. S appuyant sur les technologies nouvelles des prothèses personnalisées et sur la recherche dans le domaine de l ingénierie tissulaire, l objectif doit être celui de la fabrication d un substitut biologique ostéochondral répondant aux exigences biomécaniques de l ATM.The temporomandibular joint (TMJ), histologically similar to other joints of the human body is a complex joint due to its embryological origin, due to its anatomy and biomechanics of the hand making it ultimately unique. Thus, conditions affecting the joints are still poorly understood, often misdiagnosed and poorly defined above. Ankylosis of the temporomandibular joint is no exception. Reached rare, the term remains ambiguous, misused, its definition is still under debate today. The treatment of this disease, for his undoubted remains surgical. However, the complexity of this joint seems to be a brake on reconstructive surgical techniques. Yet from the beginning nineteenth century, this surgery has seen many of the techniques described: the simple act of interposition and condyloplastie (interposition of autologous or alloplastic material) to complex gestures (bone grafts, free flaps), and the use of joint prostheses. The number of joint replacements and the number of surgical techniques described shows the perfectibility of each technique, requiring constant development of new approaches reconstructive. This work concerns the analysis of 16 patients treated between 1998 and 2010. Using tools developed at the Technological University of Compiègne to analyze the articular surfaces of the ATM, we will show that new technologies, including 3D models using geometric and finite element allows support for both the diagnostic and therapeutic, but also the development of new joint prostheses in reconstructive surgery of the TMJ. Algorithm and a decision will be exposed to different techniques of reconstruction after resection of the TMJ ankylosis block depending on the type and etiology with a companion case by age and surgical history. Based on new technologies and customized prosthetic research in the field of tissue engineering, the goal should be that of the manufacture of a biological substitute for meeting the requirements osteochondral biomechanics of the TMJ.AMIENS-BU Santé (800212102) / SudocSudocFranceF