Noëlla Bletard

Human papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma.

The prevalence of human papillomavirus (HPV) in a clinical series of 162 patients with oral squamous cell carcinoma (OSCC) was studied. Furthermore, we analyzed the correlation between the immunohistochemical expression of p16, p53, epidermal growth factor receptor (EGFR), and HPV status to predict survival in OSCC patients.

Differential proteomic analysis of a human breast tumor and its matched bone metastasis identifies cell membrane and extracellular proteins associated with bone metastasis

The classical fate of metastasizing breast cancer cells is to seed and form secondary colonies in bones. The molecules closely associated with these processes are predominantly present at the cell surface and in the extracellular space, establishing the first contacts with the target tissue. In this study, we had the rare opportunity to analyze a bone metastatic lesion and its corresponding breast primary tumor obtained simultaneously from the same patient. Using mass spectrometry, we undertook a proteomic study on cell surface and extracellular protein-enriched material. We provide a repertoire of significantly modulated proteins, some with yet unknown roles in the bone metastatic process as well as proteins notably involved in cancer cell invasiveness and in bone metabolism. The comparison of these clinical data with those previously obtained using a human osteotropic breast cancer cell line highlighted an overlapping group of proteins. Certain differentially expressed proteins are validated in the present study using immunohistochemistry on a retrospective collection of breast tumors and matched bone metastases. Our exclusive set of selected proteins supports the setup of further investigations on both clinical samples and experimental bone metastasis models that will help to reveal the finely coordinated expression of proteins that favor the development of metastases in the bone microenvironment.

Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study.

BACKGROUND & AIMS Mesenchymal stromal cell (MSC) infusion could be a means to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase I study was to evaluate the feasibility, safety and tolerability of a single infusion of MSCs in liver transplant recipients. METHODS Ten liver transplant recipients under standard immunosuppression received 1.5-3×106/kg third-party unrelated MSCs on postoperative day 3±2, and were prospectively compared to a control group of ten liver transplant recipients. As primary endpoints, MSC infusion toxicity was evaluated, and infectious and cancerous complications were prospectively recorded until month 12 in both groups. As secondary endpoints, rejection rate, month-6 graft biopsies, and peripheral blood lymphocyte phenotyping were compared. Progressive immunosuppression weaning was attempted from month 6 to 12 in MSC recipients. RESULTS No variation in vital parameters or cytokine release syndrome could be detected during and after MSC infusion. No patient developed impairment of organ functions (including liver graft function) following MSC infusion. No increased rate of opportunistic infection or de novo cancer was detected. As secondary endpoints, there was no difference in overall rates of rejection or graft survival. Month-6 biopsies did not demonstrate a difference between groups in the evaluation of rejection according to the Banff criteria, in the fibrosis score or in immunohistochemistry (including Tregs). No difference in peripheral blood lymphocyte typing could be detected. The immunosuppression weaning in MSC recipients was not successful. CONCLUSIONS No side effect of MSC infusion at day 3 after liver transplant could be detected, but this infusion did not promote tolerance. This study opens the way for further MSC or Treg-based trials in liver transplant recipients. LAY SUMMARY Therapy with mesenchymal stromal cells (MSCs) has been proposed as a means to improve results of solid organ transplantation. One of the potential MSC role could be to induce tolerance after liver transplantation, i.e. allowing the cessation of several medications with severe side effects. This study is the first-in-man use of MSC therapy in ten liver transplant recipients. This study did not show toxicity after a single MSC infusion but it was not sufficient to allow withdrawal of immunosuppression. CLINICAL TRIAL REGISTRATION NUMBER Eudract: # 2011-001822-81, ClinicalTrials.gov: # NCT 01429038.

Methylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer

Cancer cells generally rely on aerobic glycolysis as a major source of energy. Methylglyoxal (MG), a dicarbonyl compound that is produced as a side product during glycolysis, is highly reactive and induces the formation of advanced glycation end-products that are implicated in several pathologies including cancer. All mammalian cells have an enzymatic defense against MG composed by glyoxalases GLO1 and GLO2 that converts MG to d-lactate. Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality. In this study, we used immunohistochemistry to examine the level of MG protein adducts, in a series of 102 CRC human tumors divided into four clinical stages. We consistently detected a high level of MG adducts and low GLO1 activity in high stage tumors compared to low stage ones suggesting a pro-tumor role for dicarbonyl stress. Accordingly, GLO1 depletion in CRC cells promoted tumor growth in vivo that was efficiently reversed using carnosine, a potent MG scavenger. Our study represents the first demonstration that MG adducts accumulation is a consistent feature of high stage CRC tumors. Our data point to MG production and detoxification levels as an important molecular link between exacerbated glycolytic activity and CRC progression.

Dendritic cells in Barrett's esophagus carcinogenesis: an inadequate microenvironment for antitumor immunity?

Barretts esophagus corresponds to the replacement of the normal esophageal squamous epithelium by a columnar epithelium through a metaplastic process. This tissue remodeling is associated with chronic gastroesophageal reflux and constitutes a premalignant lesion leading to a 30- to 60-fold increase in the risk to evolve into esophageal adenocarcinoma. The present study aimed to investigate a possible immune evasion in Barretts esophagus favoring esophageal adenocarcinoma development. We demonstrated that myeloid and plasmacytoid dendritic cells are recruited during the esophageal metaplasia-dysplasia-carcinoma sequence, through the action of their chemoattractants, macrophage inflammatory protein 3α and chemerin. Next, we showed that, in contrast to plasmacytoid dendritic cells, myeloid dendritic cells, co-cultured with Barretts esophagus and esophageal adenocarcinoma cell lines, display a tolerogenic phenotype. Accordingly, myeloid dendritic cells co-cultured with esophageal adenocarcinoma cell lines stimulated regulatory T cell differentiation from naïve CD4(+) T cells. In agreement with those results, we observed that both metaplastic areas and (pre)malignant lesions of the esophagus are infiltrated by regulatory T cells. In conclusion, soluble factors secreted by epithelial cells during the esophageal metaplasia-dysplasia-carcinoma sequence influence dendritic cell distribution and promote tumor progression by rendering them tolerogenic.

OLFM4, KNG1 and Sec24C identified by proteomics and immunohistochemistry as potential markers of early colorectal cancer stages

AbstractBackgroundDespite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the identification of patients with preneoplastic lesions or with early CRC stages remains challenging and is important for reducing CRC incidence and increasing patient’s survival. MethodsWe analysed 76 colorectal tissue samples originated from early CRC stages, normal or inflamed mucosa by label-free proteomics. The characterisation of three selected biomarker candidates was performed by immunohistochemistry on an independent set of precancerous and cancerous lesions harbouring increasing CRC stages.ResultsOut of 5258 proteins identified, we obtained 561 proteins with a significant differential distribution among groups of patients and controls. KNG1, OLFM4 and Sec24C distributions were validated in tissues and showed different expression levels especially in the two early CRC stages compared to normal and preneoplastic tissues.ConclusionWe highlighted three proteins that require further investigations to better characterise their role in early CRC carcinogenesis and their potential as early CRC markers.

Potential diagnostic biomarkers of Ulcerative colitis-associated colorectal dysplasia

1GIGA-R, ULiège, Translational Gastroenterology, Liège, Belgium, 2CHU de Liège, HepatoGastroenterology and Digestive oncology, Liège, Belgium, 3CHU de Liège, Pathological anatomy and cytology, Liège, Belgium, 4GIGA proteomic facility, ULiège, Liège, Belgium, 5ULiège, Laboratory of mass spectrometry, Chemistry, Liège, Belgium, 6GIGA-R, ULiège, Laboratory of Thrombosis and Hemostasis, Liège, Belgium, 7ULiège, Mammalian cell culture laboratory, Liège, Belgium, 8CHU de Liège, Abdominal Surgery Department, Liège, Belgium, 9CHC de Liège, Gastroenterology, Liège, Belgium, 10CHR Citadelle de Liège, Gastroenterology and Digestive oncology, Liège, Belgium

Alveolar echinococcosis in southern Belgium: retrospective experience of a tertiary center.

Dear Editor, Alveolar Echinococcosis (EA) is a zoonosis due to the larval stage of the fox tapeworm Echinococcus multilocuris. Humans are dead-end hosts and are exposed through sylvatic (fox) or domestic (cat and dog) cycles. Infection is acquired through the fecal-oral route. The metacestodes of E. multilocularis proliferate in the liver, inducing a Btumorlike^ lesion that can invade the neighboring organs or spread away from the primary lesion [1]. Until recently, Belgium was considered as a low-risk country for AE. However, in 2008, Hanosset et al. demonstrated by necropsies of red foxes (Vulpes vulpes), a prevalence of AE at up to 60% in some parts of Wallonia, the Southern part of Belgium [2]. The first indigenous Belgian human AE case was diagnosed in 1999 at the Centre Hospitalier Universitaire (CHU) of Liege, a tertiary university hospital in Wallonia [3]. Since this first case, other patients have been diagnosed with EA and managed by the different departments of the CHU Liege [4]. The aim of this study was to evaluate the overall experience and results of the different teams of the CHU Liege with AE and to better determine the number of indigenous AE cases to provide this information to authorities in charge of public health. After University Hospital Ethical committee approval, the authors retrospectively collecteddata from the laboratoryof clinical microbiology (for Echinococcus serologies and PCR), the hospital pharmacy in charge of supplying albendazole, and by searching through patient files from themedico-economic informationservice. Informationwascollectedfrom1999toFebruary 2018. Belgian regulations do not require patient informed consent for a purely retrospective review of medical files. Between 1999 and February 2018, a total of 22 human indigenous AE cases were recorded and their medical files were studied. In all cases, the diagnosis was established based on Echinococcus sp. serology (inhibition of hemagglutination (Fumouze, France), ELISA specific for E. granulosus (Rbiopharm, Germany) and E. multilocularis (Bordier, Suisse) respectively and Western Blot), clinical imaging, histopathology and in some cases an E. multilocularis specific PCR assay on tissue [5]. According to the criteria of Brunetti et al. [1], 11 possible and 11 confirmed cases were diagnosed. The mean age of the patients at the time of diagnosis was 69 years (ranges: 34–85 years). Sixty-four percent of the patients were male. Some degree of immunosuppression could be identified in 36% of cases (solid or hematologic cancers, chronic inflammatory disease, diabetes, and chronic alcoholism). At least one of the risk factors described by Conraths et al. [6] (owning a dog and/or a cat, living in a rural zone, working as farmer, or forestry worker) was identified in all patients but one (data are missing). Patients lived in rural * Audrey Cambier au.cambier@gmail.com

Hepatic alveolar echinococcosis.

Olivier Detry, Nicolas Meurisse, Jean Delwaide, Jean-Baptiste Giot, Philippe Leonard, Bertrand Losson, Marie-Pierre Hayette, Noella Bletard, Paul Meunier and Pierre Honor e Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Multidisciplinary Unit for Echinococcosis Management and Research of the University of Liege (Echino-Liege), University of Liege, Liege, Belgium; Department of Hepatogastroenterology, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Department of Infectious diseases, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Laboratory of Parasitology and Pathology of Parasitic Diseases, Faculty of Veterinary Medicine, University of Liege (ULg), Liege, Belgium; Department of Microbiology, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Department of Pathology, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Department of Radiology, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium

18-Fluoro-deoxyglucose uptake in inflammatory hepatic adenoma: A case report

Positron emission tomography computed tomography (PET-CT) using 18-Fluoro-deoxyglucose (18FDG) is an imaging modality that reflects cellular glucose metabolism. Most cancers show an uptake of 18FDG and benign tumors do not usually behave in such a way. The authors report herein the case of a 38-year-old female patient with a past medical history of cervical intraepithelial neoplasia and pheochromocytoma, in whom a liver lesion had been detected with PET-CT. The tumor was laparoscopically resected and the diagnosis of inflammatory hepatic adenoma was confirmed. This is the first description of an inflammatory hepatic adenoma with an 18FDG up-take.