Josiane Denis

Armed Forces Biomedical Research Institute, France | IRBA · lab

Adrenocortical carcinoma (ACC) is a rare malignancy with dismal prognosis. Deregulated microRNA (miRNA) expression has been implicated in ACC aggressiveness. Nevertheless, the mechanisms underlying such deregulations remain unknown. Aberrant Wnt/β-Catenin signaling has been reported in about 40% of ACC and is associated with poor outcome. Here, we...

Introduction Des essais cliniques récents suggèrent que les microARN sont des cibles thérapeutiques prometteuses en oncologie. Nous avons montré que la surexpression de miR-139-5p et miR-483-5p est associée à l’agressivité du carcinome corticosurrénalien (CCS). L’objectif de cette étude est d’évaluer le potentiel thérapeutique d’inhibiteurs de miR-...

Simple Summary Cancer is a complex disease associated with deregulation of numerous genes. In addition, redundant cellular pathways limit efficiency of monotarget drugs in cancer therapy. MicroRNAs are a class of gene expression regulators, which often function by targeting multiple genes. This feature makes them a double-edged sword (a) as attract...

Introduction Certains microARN (miRs) du locus soumis à empreinte parentale 14q32 sont surexprimés dans les carcinomes corticosurrénaliens (CCS) agressifs (récidivants/métastatiques) comparés aux CCS indolents et aux adénomes [1]. Par ailleurs, des mutations activatrices de la voie Wnt/β-caténine (β-cat) sont retrouvées dans 39 % des CCS [2]. Obje...

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the regulation of major pathways in eukaryotic cells through their binding to and repression of multiple mRNAs. With high-throughput methodologies, various outcomes can be measured that produce long lists of miRNAs that are often difficult to interpret. A common question is: after di...

We have previously identified serum miR-483-5p as a preoperative diagnosis and prognosis biomarker for adrenocortical cancer (ACC). Here, we aimed to determine whether circulating miR-483-5p levels measured 3 months post-operatively distinguished patients with good prognosis (no recurrence for at least 3 years; NR3yrs) from patients with poor progn...

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the regulation of major pathways in eukaryotic cells through repression of their target genes at the post-transcriptional level. While high-throughput approaches are broadly used to decipher the biological relevance of miRNAs, extraction of significant information from large miRNA da...

Altered expression of regulatory RNA-binding proteins (RBPs) in cancer leads to abnormal expression of mRNAs encoding many factors involved in cancer hallmarks. While conventional anticancer therapies usually target one pathway at a time, targeting key RBP would affect multiple genes and thus overcome drug resistance. Among the Tristetraprolin fami...

Introduction Le carcinome corticosurrénalien (CCS) a besoin de meilleurs marqueurs diagnostiques et pronostiques. Nous avons récemment démontré que les microARN miR-483-5p et miR-139-5p sont sur-exprimés dans les CCS où ils ciblent les gènes N-myc Downstream-Regulated Gene (NDRG) 2 et 4 (Agosta et al., International Journal of Cancer, 2018). Objec...

Organophosphorus nerve agents still represent a serious risk to human health. In the French armed forces, the current emergency treatment against OP intoxications is a fully licensed wet-dry dual-chambered autoinjector (Ineurope ®), that contains pralidoxime methylsulfate (2-PAM) to reactivate inhibited acetylcholinesterase (AChE), atropine sulfate...

Adrenocortical carcinoma (ACC) is a tumor with poor prognosis in which overexpression of a panel of microRNAs has been associated with malignancy but a very limited number of investigations on their role in ACC pathogenesis have been conducted. We examined the involvement of miR-483-5p and miR-139-5p in adrenocortical cancer aggressiveness. Using b...

TIS11b/BRF1 belongs to the Tristetraprolin (TTP) family of zinc-finger proteins which bind to mRNAs containing AU-rich elements (ARE) in their 3'-untranslated region and target them for degradation. Regulation of TTP family function through phosphorylation by p38 MAPK and PKB/Akt signalling pathways has been extensively studied. In contrast, the ro...

In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hemato-logic support (i.e., mostly TBI victims). To improve the identification and me...

The evolution of organ damage following extensive high-dose irradiation remains largely unexplored and needs further investigation. Wistar rats [with or without partial bone marrow protection (∼20%)] were irradiated at lethal gamma-ray doses (12, 14, and 16 Gy) and received antibiotic support. While total-body-irradiated rats did not survive, bone...

Exposure to organophosphorus (OP) compounds, such as pesticides and the chemical warfare agents (soman and sarin), respectively represents a major health problem and a threat for civilian and military communities. OP poisoning may induce seizures, status epilepticus and even brain lesions if untreated. We recently proved that a combination of atrop...

In case of high-dose radiation exposure, mechanisms controlling late visceral organ damage are still not completely understood and may involve the central nervous system. To investigate the influence of cranial/brain irradiation on late visceral organ damage in case of high-dose exposure, Wistar rats were irradiated at 12 Gy, with either the head a...

In patients suffering from stress-related pathologies and depression, frontal cortex GABA and glutamate contents are reported to decrease and increase, respectively. This suggests that the GABA and/or glutamate content may participate in pathological phenotype expression. Whether differences in frontal cortex GABA and glutamate contents would be as...

A stress management program using cardiac coherence was implemented after an organizational downsizing. The study was conducted in nine voluntary workers in order to evaluate the efficiency of the program. A baseline evaluation was conducted on psychological variables (anxiety, perceived-stress, wellbeing and sleep), endocrine assessments (urinary...

This biodosimetry study used irradiated baboons to investigate the efficacy of a kinetic multiparameter (clinical, physical, and biological) approach for discriminating partial-body irradiation (PBI) and total-body irradiation (TBI). Animals were unilaterally (front) exposed to 60Co gamma rays (8 to 32 cGy min) using either TBI or vertical left hem...

Although zinc is an essential trace element involved in many physiological functions, toxicological data concerning acute exposure are scarce. The aim of our study was to determine the maximal iterative dose of zinc that can be administrated in rats without any adverse effect. Saline (control group) or zinc gluconate at 1, 2 or 4 mg/kg were intrape...

Previous studies have demonstrated the early appearance of inflammatory cytokines in the systemic circulation after thermal injury both in humans and animals. The aim of this study was to evaluate the time course of several cytokines, IL-6, TNF-alpha and IL-1beta in serum, lung, liver and brain of severely burned rats during the first week after th...

The organophosphorus nerve agent soman is an irreversible cholinesterase (ChE) inhibitor that can produce long-lasting seizures and brain damage in which the neurotransmitters acetylcholine and glutamate are involved. These same neurotransmitters play key-roles in the auditory function. It was then assumed that exploring the hearing function may pr...

Preservation of hematopoietic stem and progenitor cell survival is required for recovery from radiation-induced myelosuppression. We recently showed that short-term injection of antiapoptotic cytokine combinations into mice soon after lethal gamma irradiation promoted survival. The present study investigated the hematopoietic response of cynomolgus...

Effects of low to mild doses of soman on central and blood cholinesterase (ChE) activities and anxiety behavior were studied in mice 30 min, 24 h and 7 days after poisoning. At these two latter time points, histopathological consequences of soman intoxication were also studied. The 30-microg/kg dose of soman produced 30 min after intoxication, abou...

1 Neuropharmacology group 2 Neurophysiology of stress group 3 Clinical chemistry laboratory CRSSA 24 avenue des Maquis du Gresivaudan F-38 702 La Tronche FRANCE A domestic swine model for studies on hemorrhagic shock has been developed at CRSSA (L. Bourdon et al.). With some modifications, and based on close contacts with DRDC Suffield (Dr Sawyer a...