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Verena Sailer, Emily Eva Holmes, Heidrun Gevensleben, Diane Goltz, Freya Dröge, Luka de Vos, Alina Franzen, Friederike Schröck, Friedrich Bootz, Glen Kristiansen, Andreas Schröck, Dimo Dietrich
BACKGROUND: Squamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients. RESULTS: PITX2 hypermethylation was associated with a better overall survival (hazard ratio, HR = 0...
October 3, 2016: Oncotarget
Bilal O Al-Jiffry, Samah Khayat, Elfatih Abdeen, Tasadooq Hussain, Mohammed Yassin
BACKGROUND: Techniques for diagnosing choledocholithiasis pose significant morbidity and mortality risks. OBJECTIVES: We aimed to develop and validate a clinical scoring system for predicting choledocholithiasis. DESIGN: Data from a prospectively maintained database of all patients with gallstones. SETTING: Patients were admitted to the general surgery department of a military hospital. PATIENTS AND METHODS: We enrolled consecutive patients with symptomatic gallstones, biliary pancreatitis, obstructive jaundice, or cholangitis, who subsequently underwent biochemical testing and ultrasonography...
January 2016: Annals of Saudi Medicine
Layasadat Khorsandi, Sadegh Saremy, Ali Khodadadi, Fereshteh Dehbashi
OBJECTIVE: To evaluate the effect of Exendine-4 (EX-4), a Glucagon-like peptide 1 (GLP-1) receptor agonist, on the differentiation of insulin-secreting cells (IPCs) from rat adipose-derived mesenchymal stem cells(ADMSCs). MATERIALS AND METHODS: In this experimental study, ADMSCs were isolated from rat adi- pose tissue and exposed to induction media with or without EX-4. After induction, the existence of IPCs was confirmed by morphology analysis, expression pattern analysis of islet-specific genes (Pdx-1, Glut-2 and Insulin) and insulin synthesis and secretion...
2016: Cell Journal
Shamone R Gore-Panter, Jeffrey Hsu, John Barnard, Christine S Moravec, David R Van Wagoner, Mina K Chung, Jonathan D Smith
BACKGROUND: Genome-wide studies reveal that genetic variants at chromosome 4q25 constitute the strongest locus associated with atrial fibrillation, the most frequent arrhythmia. However, the mechanisms underlying this association are unknown. Our goal is to find and characterize left atrial-expressed transcripts in the chromosome 4q25 atrial fibrillation risk locus that may play a role in atrial fibrillation pathogenesis. METHODS AND RESULTS: RNA sequencing performed on human left/right pairs identified an intergenic long noncoding RNA adjacent to the PITX2 gene, which we have named PANCR (PITX2 adjacent noncoding RNA)...
January 2016: Circulation. Arrhythmia and Electrophysiology
F Fang, J Pan, G H Su, L X Xu, G Li, Z H Li, H Zhao, J Wang
Numerous studies have focused on the relationship be-tween alcohol dehydrogenase 1C gene (ADH1C) *1/*2 polymorphism (Ile350Val, rs698, also known as ADH1C *1/*2) and pancreatitis risk, but the results have been inconsistent. Thus, we conducted a meta-anal-ysis to more precisely estimate this association. Relevant publications were searched in several widely used databases and 9 eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association...
2015: Genetics and Molecular Research: GMR
Florence Joly, Bénédicte Giffard, Olivier Rigal, Michiel B De Ruiter, Brent J Small, Martine Dubois, Johan LeFel, Sanne B Schagen, Tim A Ahles, Jeffrey S Wefel, Janette L Vardy, Véronique Pancré, Marie Lange, Hélène Castel
CONTEXT: Although cognitive impairments have been identified in patients with non-central nervous system cancer, especially breast cancer, the respective roles of cancer and therapies, and the mechanisms involved in cognitive dysfunction remain unclear. OBJECTIVES: To report a state-of-the-art update from the International Cognitive and Cancer Task Force conference held in 2012. METHODS: A report of the meeting and recent new perspectives are presented...
December 2015: Journal of Pain and Symptom Management
Dhafer Mrizak, Nathalie Martin, Clément Barjon, Anne-Sophie Jimenez-Pailhes, Rami Mustapha, Toshiro Niki, Joël Guigay, Véronique Pancré, Yvan de Launoit, Pierre Busson, Olivier Moralès, Nadira Delhem
BACKGROUND: Regulatory T cells (Treg) and tumor-exosomes are thought to play a role in preventing the rejection of malignant cells in patients bearing nasopharyngeal carcinoma (NPC). METHODS: Treg recruitment by exosomes derived from NPC cell lines (C15/C17-Exo), exosomes isolated from NPC patients' plasma (Patient-Exo), and CCL20 were tested in vitro using Boyden chamber assays and in vivo using a xenograft SCID mouse model (n = 5), both in the presence and absence of anti-CCL20 monoclonal antibodies (mAb)...
January 2015: Journal of the National Cancer Institute
Olivier Morales, Dhafer Mrizak, Violaine François, Rami Mustapha, Céline Miroux, Stéphane Depil, Anne-Valérie Decouvelaere, Pauline Lionne-Huyghe, Claude Auriault, Yvan de Launoit, Véronique Pancré, Nadira Delhem
Epstein-Barr Virus (EBV) is present in the neoplastic cells of around 20-30% of patients with Hodgkin Lymphoma (HL). Although, an immunosuppressive environment is currently described in HL patients, little is known concerning the regulatory mechanism induced by EBV proteins expression in tumour cells. This study aimed to investigate an association between regulatory Type 1 cells (Tr1) and EBV tissue positivity in HL patients. Transcriptomic analysis of both EBV-positive and EBV-negative tumours showed that EBV infection increased gene expression of Tr1-related markers (ITGA2, ITGB2, LAG3) and associated-immunosuppressive cytokines (IL10)...
September 2014: British Journal of Haematology
Houhong Wang, Shuai Wang, Amao Tang, Huihui Gong, Panpan Ma, Li Chen
Despite extensive research and clinical efforts made in the management of acute pancre-atitis during the past few decades, to date no effective cure is available and the mortality from severe acute pancre-atitis remains high. Given that lung is the primary cause of early death in acute pancreatitis patients, novel therapeutic approaches aiming to prevent lung injury have become a subject of intensive investigation. In a previous study, we demonstrated that sivelestat, a specific inhibitor of neutrophil elastase, is effective in protecting against lung failure in rats with taurocholate-induced acute pancreatitis...
August 2014: Experimental Lung Research
C Miroux, O Morales, L Ouaguia, L Aoudjehane, E Boleslawski, V Pancré, Y de Launoit, Y Calmus, F Conti, N Delhem
BACKGROUND: Inevitable hepatitis C virus recurrence after liver transplantation, a major barrier to survival of the transplanted liver may be promoted by immunosuppression and by CD4(+)CD25(+) regulatory T cells (Treg). Treg cells are essential for the induction and maintenance of immunologic self-tolerance as well as transplant tolerance. Moreover, we have previously described low doses of cyclosporine (CsA) to inhibit Treg activity by inducing interleukin-2 and interfron-γ. We investigated here in, the effect of mycophenolate mofetil (MMF) and corticosteroids, usually used in combination with a calcineurin inhibitor on human CD4(+)CD25(+) Treg cells...
November 2012: Transplantation Proceedings
Céline Miroux, Olivier Morales, Khaldoun Ghazal, Samia Ben Othman, Yvan de Launoit, Véronique Pancré, Filomena Conti, Nadira Delhem
BACKGROUND: Liver transplantation is the treatment of end-stage liver diseases, including hepatitis C. Immunosuppression prevents graft rejection but seems to accelerate the recurrence of hepatitis C. Regulatory T cells (Tregs) may be beneficial in tolerance but deleterious in recurrent hepatitis C. We evaluated the effects of cyclosporine or tacrolimus, the principal immunosuppressive drugs, on Treg proliferation and function. METHODS: Human Tregs were isolated from healthy donors and cultured with cyclosporine, tacrolimus, or NIM811, a cyclosporine analog devoid of calcineurin-inhibiting activity...
July 27, 2012: Transplantation
Olivier Moralès, Stéphane Depil, Dhafer Mrizak, Nathalie Martin, Papa Alioune Ndour, Françoise Dufosse, Céline Miroux, Jean Coll, Yvan de Launoit, Claude Auriault, Véronique Pancre, Nadira Delhem
Epstein-Barr virus (EBV) is associated with several malignant diseases that can be distinguished by their patterns of viral latent gene expression. We developed here an original peptidic approach to favor the induction of a specific CD4+ T-cell response against EBV latency II malignancies (Hodgkin's lymphoma, nasopharyngeal carcinoma, T/NK lymphoma). Previously, we selected 6 peptides derived from EBV nuclear antigen-1, latency membrane proteins (LMP)-1, and LMP-2 highly promiscuous for major histocompatibility complex class II molecules and showed their ability to induce interferon-γ-secreting CD4+ T cells...
April 2012: Journal of Immunotherapy
Olivier Moralès, Audrey Richard, Nathalie Martin, Dhafer Mrizak, Magalie Sénéchal, Céline Miroux, Véronique Pancré, Jean Rommelaere, Perrine Caillet-Fauquet, Yvan de Launoit, Nadira Delhem
BACKGROUND: H-1 parvovirus (H-1 PV), a rodent autonomous oncolytic parvovirus, has emerged as a novel class of promising anticancer agents, because of its ability to selectively find and destroy malignant cells. However, to probe H-1 PV multimodal antitumor potential one of the major prerequisites is to decipher H-1 PV direct interplay with human immune system, and so prevent any risk of impairment. METHODOLOGY/PRINCIPAL FINDINGS: Non activated peripheral blood mononuclear cells (PBMCs) are not sensitive to H-1 PV cytotoxic effect...
2012: PloS One
C Miroux, O Moralès, A Carpentier, S Dharancy, F Conti, E Boleslowski, P Podevin, C Auriault, V Pancré, N Delhem
BACKGROUND: Inevitable hepatitis C virus (HCV) recurrence after liver transplantation is a major barrier to the survival of a transplanted liver. It may be promoted by immunosuppression and the emergence of CD4+CD25+ regulatory T cells (Treg). Treg cells can mediate the induction and maintenance of immunological self-tolerance as well as transplant tolerance. We investigated the effects of cyclosporine (CsA), a widely used immunosuppressive agent, on human CD4+CD25+ Treg cells. METHODS: Human CD4+CD25+ cells isolated from healthy donors were cultured in the presence of 40 or 400 ng/mL CsA...
October 2009: Transplantation Proceedings
A Carpentier, F Conti, F Stenard, L Aoudjehane, C Miroux, P Podevin, O Morales, S Chouzenoux, O Scatton, H Groux, C Auriault, Y Calmus, V Pancre, N Delhem
Immune response failure during HCV infection has been associated with the activity of regulatory T cells. Hepatitis C-related cirrhosis is the main reason for liver transplantation. However, 80% of transplanted patients present an accelerated recurrence of the disease. This study assessed the involvement of regulatory T-cell subsets (CD4+CD25+ cells: 'Treg' and CD49b+CD18+ cells: 'T regulatory-1' cells), in the recurrence of HCV after liver transplantation, using transcriptomic analysis, ELISA assays on serum samples and immunohistochemistry on liver biopsies from liver recipients 1 and 5 years after transplantation...
September 2009: American Journal of Transplantation
Arnaud Carpentier, Filoména Conti, Matthieu Carrière, Lynda Aoudjehane, Céline Miroux, Olivier Moralès, Yvon Calmus, Hervé Groux, Claude Auriault, Véronique Pancré, Nadira Delhem, Philippe Podevin
Alternative, non-invasive techniques are necessary to monitor the progression of liver disease during chronic hepatitis C. Firstly, because serum is the most accessible material for studies using qPCR in microplates, gene transcription was compared in 219 selected genes involved in the pathogenesis of hepatitis C virus (HCV) infection between sera, PBMCs and liver samples collected simultaneously from five patients infected chronically. Secondly, using sera, gene profiles were compared between HCV-infected patients (n = 10) and healthy controls (n = 10)...
March 2009: Journal of Medical Virology
N Delhem, A Carpentier, O Moralès, C Miroux, H Groux, C Auriault, V Pancré
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and also the third most common cause of cancer-related death. HCC arises most frequently in males with cirrhosis, which is most often a consequence of chronic hepatitis infection (HBV and HCV) or alcohol abuse. To date, the only effective approaches for patients with HCC are resection or liver transplantation. Immunological mechanisms are important in the surveillance of malignancy and control of tumor progression. Tumor-infiltrating lymphocytes (TILs) have been described in HCC, and extensive infiltration has been associated with reduced tumor recurrence following resection...
December 2008: Bulletin du Cancer
Nadira Delhem, Françoise Cottrez, Arnaud Carpentier, Céline Miroux, Olivier Moralès, Violaine François, Hervé Groux, Claude Auriault, Véronique Pancré
Hepatitis C virus (HCV) becomes chronic in about 85 % of infected individuals, whereas only 15 % of infected people clear spontaneously the virus. The progression of hepatitis C to chronic status is associated to a profound down-regulation of CD4 and CD8 multispecific immune response. This immune defect may participate to the immune tolerance of VHC and consequently to its persistence. Recent findings indicate that T regulatory cells as Tr1 play an inhibitory role on T helper responses notably in the context of auto-immune or inflammatory disorders...
November 2008: Bulletin du Cancer
Véronique Pancré, Nadira Delhem, Yazdan Yazdanpanah, Anne Delanoye, Myriam Delacre, Stéphane Depil, Olivier Moralès, Yves Mouton, Claude Auriault
The ex vivo response to three HLA-DR-restricted Nef peptides (Nef 66-97, Nef 133-159, Nef 180-202) and one HLA-DQ-restricted Nef peptide (Nef 56-68) was evaluated in 28 HIV-seropositive patients and 6 Long-term Non-Progressors (LTNPs). Analyzing specific proliferative response and IFN-gamma secretion, patients were identified as high responders, medium responders and non-responders to peptides. As high responder patients, LTNP patients showed strong proliferative response to all the Nef-peptides as strong IFN-gamma secretion...
August 1, 2007: Vaccine
Stéphane Depil, Olivier Moralès, Florence A Castelli, Nadira Delhem, Violaine François, Bertrand Georges, Françoise Dufossé, Franck Morschhauser, Juergen Hammer, Bernard Maillère, Claude Auriault, Véronique Pancré
The Epstein-Barr virus (EBV) is associated with several malignant diseases, which can be distinguished by their patterns of viral latent gene expression. The latency II program is limited to the expression of the nonimmunodominant antigens EBNA1, LMP1 and LMP2 and is seen in EBV-positive Hodgkin disease, nasopharyngeal carcinomas, and peripheral T/NK-cell lymphomas. CD4 T cells may play a crucial role in controlling these EBV latency II malignancies. In this study, we used the prediction software TEPITOPE to predict promiscuous major histocompatibility complex class II epitopes derived from the latency II antigens EBNA1, LMP1, and LMP2...
February 2007: Journal of Immunotherapy
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