Involvement of the Inositol-trisphosphate Receptor in Invasive or Migratory-type Breast Cancers (CarcIno)
Breast cancer is the leading cause of female cancer and female death by cancer in France. Despite the improvement in early detection and therapeutic arsenal, the mortality of this cancer remains high with 11 886 deaths estimated in 2012. Breast cancer is most often a carcinoma born from the lobular or ductal epithelium and is classified In two main categories: non invasive and invasive. Invasive breast cancers account for 75% of the cases. They are usually ductal (75%) and more rarely lobular (25%). The cancer cells are then no longer circumscribed to the galactophoric canals or glands but have invaded neighboring tissues. If they are not treated in time, these cancers can then spread: the cancerous cells will then migrate either by the lymphatic vessels to reach the neighboring ganglia or through the blood vessels to give metastases in other tissues In the liver, lungs and bones). The mortality associated with breast cancer is not due to the growth of the primary tumor but rather to the occurrence of metastases. The study of the mechanisms leading to metastatic invasion (i.e. migration and invasion) is therefore of considerable importance. The development of metastases depends on the acquisition by the cancer cells of various capacities including that of being able to migrate, involving a remodeling of the cytoskeleton highly dependent on the intracellular calcium (Ca2 +) concentration. Several types of signals are able to induce mobilization of Ca2 + from the extracellular medium or endoplasmic reticulum (ER) reserves. At the intracellular level, some of these signals are generated by inositol (1,4,5) -trisphosphate (IP3) from the activation of G protein-coupled receptors or certain receptors with tyrosine kinase activity. Has been shown that the expression, activity and regulation of IP3R receptors (IP3Rs) are involved in the cancerous processes of many tissues, in particular in the phenomena of proliferation of breast cancer cells. Overall, altered expression and / or activity of IP3Rs can be used for the survival, growth, proliferation and migration of cancer cells.
In the laboratory, the investigator showed that regulation of the expression of subtype 3 (IP3R3) by 17β-estradiol (E2) is involved in the growth of the human mammary cancer line MCF-7. E2 triggers the release of Ca2 + in an IP3-dependent mechanism, while prolonged exposure to E2 leads to an increase in the expression of IP3R3. At the same time, the reduction in the expression of IP3R3 cancels the proliferative effect of E2 on MCF-7 cells. More recently, the investigator has established that IP3R3 regulates the proliferation of cells of the human MCF-7 mammary cancer cell line via a molecular and functional interaction with the Ca2 + -dependent BKCa potassium channel. The determination of IP3Rs, including subtype 3, as a mediator / marker of breast carcinogenesis appears to be a major clinical issue.
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Actual)
Enrollment
Contacts and Locations
Study Contact
Study Contact
- Name: Jean GONDRY, PhD
- Phone Number: +33322533694
- Email: gondry.jean@chu-amiens.fr
Study Locations
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Picardie
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Amiens, Picardie, France, 80054
- CHU Amiens Picardie
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- CCI / CLI to be operated
- Grade SBR 1, 2 or 3
- Undifferentiated RE / PR status
- HER2 status undifferentiated
- Ki 67 indifferent
- Metastatic or not
- ADP axillary invaded or not
- Major Patients
Exclusion Criteria:
- CIC / CIL
- Males
Study Plan
How is the study designed?
Design Details
Number of groups / cohorts
Cohorts and Interventions
Group / CohortGroup / Cohort |
Intervention / TreatmentIntervention / Treatment |
|---|---|
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Patient with breast cancer requiring surgery to
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Assess the level of expression of IP3R3 in cancerous tissues and healthy tissues
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Level of expression of IP3R3 defined by an immunohistochemical score
Time Frame: 3 years
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3 years
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Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- PI2015_843_0007
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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