Predictive Role and HuR Mechanisms of Regulation in the Brain Tumours

NCT03615391 | Unknown

• 1 other identifier: 2011/APJC/HUR/GAUCHOTTE/MS
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

The HuR protein binds to AU-rich elements in the untranslated 3' region of messenger RNA, thus allowing their stabilization. Its targets include multiple cell cycle regulating proteins, cytokines and growth factors. In some cancers, its overall expression level but especially its cytoplasmic expression are correlated to a higher grade and constitute a poor prognostic factor. To date, HuR's deregulation mechanisms remain poorly understood. A few experimental studies have shown the role of certain microARNS, or of post-translational modifications. In brain tumours, HuR expression, its prognostic value and its deregulation mechanisms have been little studied to date. The first part of the project will be a monocentric retrospective study of human brain tumour samples collected during biopsies or surgical removal. We will first evaluate HuR expression in 140 brain tumors, including 40 meningiomas and 100 gliomas of increasing grade, and look for a correlation with histological grade and survival. We will then apprehend the consequences of its deregulation by analyzing different factors involved in the cell cycle and stress response markers. Finally, we will study the mechanisms of HuR deregulation by analyzing the expression level of several microRNAs (miR16, miR519) and the methylation state of HuR. The second part of the project will focus on cell lines from human brain tumours. We will first attempt to confirm the interactions between HuR and markers involved in the cell cycle and stress response, then the regulation of HuR by its methylation and by microRNAs (miR16 and miR519). We would also like to study the consequences of HuR inhibition and overexpression on cell proliferation, under various conditions of induced stress (pharmacological agents, physical stress). Finally, we will study the consequences of an experimental vitamin B12 deficiency on HuR expression and tumor cell adaptation to stress.

Conditions

Brain Tumours

Outcome Measures

Primary Outcomes (3)

• level HuR's immunohistochemical expression

  at diagnosis

• time progression-free

  through study completion, an average 3 years

• time overall survival

  through study completion, an average 3 years

Secondary Outcomes (16)

• methyl-HuR level

  1 day at diagnosis

• PHH3 level

  1 day at diagnosis

• MCM6 level

  1 day at diagnosis

• Ki-67 level

  1 day at diagnosis

• cyclin D1 level

  1 day at diagnosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient with braim tumor (meningioma, glioma, glioblastoma)

You may qualify if:

• Grade I and II meningiomas (WHO)
• Diffuse grade II glioma (astrocytoma, oligodendroglioma)
• Grade III anaplastic gliomas (astrocytomas and anaplastic oligodendrogliomas)
• Grade IV glioblastoma

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

Guillaume GAUCHOTTE

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Guillaume GAUCHOTTE, PU-PH

CONTACT

g.gauchotte@chru-nancy.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 3, 2018
• Study Start: October 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2020
• Last Updated: August 3, 2018

Record last verified: 2018-08

Locations

FR (1)