Brain Tumours Clinical Trial
— HUROfficial title:
Predictive Role and HuR Mechanisms of Regulation in the Brain Tumours
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.
| Status | Recruiting |
| Enrollment | 140 |
| Est. completion date | October 1, 2020 |
| Est. primary completion date | October 1, 2015 |
| Accepts healthy volunteers | |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria - Grade I and II meningiomas (WHO) - Diffuse grade II glioma (astrocytoma, oligodendroglioma) - Grade III anaplastic gliomas (astrocytomas and anaplastic oligodendrogliomas) - Grade IV glioblastoma |
| Country | Name | City | State |
|---|---|---|---|
| France | Guillaume GAUCHOTTE | Vandoeuvre Les Nancy |
| Lead Sponsor | Collaborator |
|---|---|
| Central Hospital, Nancy, France |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | level HuR's immunohistochemical expression | at diagnosis | ||
| Primary | time progression-free | through study completion, an average 3 years | ||
| Primary | time overall survival | through study completion, an average 3 years | ||
| Secondary | methyl-HuR level | 1 day at diagnosis | ||
| Secondary | PHH3 level | 1 day at diagnosis | ||
| Secondary | MCM6 level | 1 day at diagnosis | ||
| Secondary | Ki-67 level | 1 day at diagnosis | ||
| Secondary | cyclin D1 level | 1 day at diagnosis | ||
| Secondary | Bcl-2 | 1 day at diagnosis | ||
| Secondary | pPERK level | 1 day at diagnosis | ||
| Secondary | ATF6 level | 1 day at diagnosis | ||
| Secondary | SIRT1 level | 1 day at diagnosis | ||
| Secondary | IRE-1a level | 1 day at diagnosis | ||
| Secondary | HIF-1a level | 1 day at diagnosis | ||
| Secondary | caspase 3 activated level | 1 day at diagnosis | ||
| Secondary | VEGF level | 1 day at diagnosis | ||
| Secondary | CARM1 level | Vitamin B12 metabolism | 1 day at diagnosis | |
| Secondary | miR16 expression level by qRT-PCR | 1 day at diagnosis | ||
| Secondary | miR519 expression level by qRT-PCR | 1 day at diagnosis |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
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