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Mechanisms of Cancerogenesis of Woodworkers Adenocarcinomas

2016-06-29 20:53:21 | BioPortfolio

Summary

Nasal adenocarcinomas are closely related to wood dust exposure. The precise mechanisms of carcinogenesis leading to the transformation of the respiratory mucosa into a colonic-like mucosa remain unknown: chronic exposure to wood dust may cause chronic inflammation that may lead to pre-degenerative lesions, hypothesis yet unconfirmed. The tumor development requires the activation of a particular gene: CDX2. The working hypothesis is that chronic wood dust exposure is responsible for changes in genes of inflammation, which can in turn lead to changes in the expression of CDX2 and its cofactors, thus making possible the genesis of adenocarcinoma. This work is a pilot study aiming to better understand the mechanisms of carcinogenesis, and to study the feasibility of a larger prospective screening for woodworkers adenocarcinomas. Cells will be obtained from the at risk area (olfactory cleft) by a noninvasive method (brushing) in healthy volunteers (unexposed to wood dust) and in exposed volunteers to compare their genomes and study the genomic changes related to wood dust exposure.

Description

Pilot study, single center, prospective and retrospective, aiming to better understand the mechanisms of carcinogenesis of nasal adenocarcinoma among 2 groups of subjects based on their potential risk of nasal adenocarcinoma.

Patients will be recruited prospectively, in the ENT department (Prof. R. JANKOWSKI-Institut Lorrain Heart and vessels Louis Mathieu -Hospitals Brabois-CHU Nancy), during a visit for another medical reason.

They will be divided into 2 groups as follows:

- Group 1: NON EXPOSED : control group: patients not exposed to wood dust (low risk)

- Group 2: EXPOSED: patients exposed to wood dust (high risk)

After complete information, inclusion in the study will be proposed to patients

If inclusion is accepted, patients will undergo, during the nasal fiber endoscopy (performed for care), and under local anesthesia (performed for care), a brushing of the most accessible olfactory clef (performed for research). These samples will be compared to tumor samples which are already available (REFCOR)

The samples of groups 1 and 2 will be sent directly to the laboratory of Pathological Anatomy Cytology (Pr-J.M. VIGNAUD Hospital Brabois- CHU Nancy). They will briefly vortexed (5 min) and frozen. They will be kept in the laboratory of Pathological Anatomy Cytology (Pr-J.M. VIGNAUD Hospital Brabois- CHU Nancy) until analysis. The samples will be transferred from the laboratory of Pathological Anatomy Cytology (Pr-J.M. VIGNAUD Hospital Brabois- CHU Nancy) to the Genomics Platform (INSERM, U954, Prof. JL GUEANT- Faculty of Medicine, University of Lorraine), for analysis.

RNA will be extracted from olfactory cells , using RNeasy Mini kit (Qiagen) with DNase treatment. The concentration and purity of the DNA / RNA will be measured (OD at 230nm, 260nm and 280nm) with a Nanodrop spectrophotometer (Nyxor). The RNA integrity will be determined from the profiles of ribosomal RNAs (18S & 28S) measured on LabOnChip® (2100 Bioanalyzer System, Agilent Technologies). The RNA samples will be stored at -80 ° C until use.

The transcriptome analysis will be conducted on chips Whole Human Genome 60K * 8 developed by Agilent®, and according to the manufacturer's protocol (single-color Agilent protocol).

At the end of the research samples will be destroyed.

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Conditions

Ethmoid Sinus Adenocarcinoma

Intervention

Brushing of the olfactory cleft

Location

Service ORL-CHRU NANCY
Vandoeuvre Les Nancy
France
54511

Status

Recruiting

Source

Central Hospital, Nancy, France

Results (where available)

View Results

Links

Published on BioPortfolio: 2016-06-29T20:53:21-0400

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Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the VOMERONASAL ORGAN via the vomeronasal nerve, is also included here.

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Air-filled spaces located within the bones around the NASAL CAVITY. They are extensions of the nasal cavity and lined by the ciliated NASAL MUCOSA. Each sinus is named for the cranial bone in which it is located, such as the ETHMOID SINUS; the FRONTAL SINUS; the MAXILLARY SINUS; and the SPHENOID SINUS.

A light and spongy (pneumatized) bone that lies between the orbital part of FRONTAL BONE and the anterior of SPHENOID BONE. Ethmoid bone separates the ORBIT from the ETHMOID SINUS. It consists of a horizontal plate, a perpendicular plate, and two lateral labyrinths.

The numerous (6-12) small thin-walled spaces or air cells in the ETHMOID BONE located between the eyes. These air cells form an ethmoidal labyrinth.

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