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Trial record 72 of 77070 for:    Neoplasms

Role of Sorcin and Annexin A3 in Breast Cancer Patients

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ClinicalTrials.gov Identifier: NCT03598660
Recruitment Status : Not yet recruiting
First Posted : July 25, 2018
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Reham I El-mahdy, Assiut University

Brief Summary:

Breast cancer (BC) is the most common female malignancy worldwide and the second leading cause of cancer death in women. One in eight women in the United States will develop the illness in their lifetimes. In Egypt, 37.7% of total cancer cases among women is breast cancer. A locally advanced disease is very common and total mastectomy is the most commonly performed surgery. Screening methods and adjuvant therapy following surgery led to a remarkable decrease in mortality.

Reliable prognostic and predictive markers are needed to guide the selection of the most appropriate adjuvant therapies for individual patients with breast cancer. In fact, a shift from defining the cancer patients who should receive chemotherapy on the basis of their prognostic characteristics to defining the patients who are likely to benefit most from this modality of adjuvant treatment is currently taking place. Understanding the molecular mechanisms underlying the spread of cancer cells to distant organs, therefore, is a prerequisite for the development of novel cancer therapies.


Condition or disease Intervention/treatment
Breast Cancer Genetic: Sorcin gene expression Other: Annexin A3 serum mesurement

Detailed Description:

Breast cancer is the most common female malignancy worldwide. Despite advances in cancer diagnosis and treatment in recent years, traditional treatments (radiotherapy, chemotherapy, and hormone therapy) are always limited by the resistance of some tumor cells, thus forcing researchers to continue to look for new therapeutic approaches and targets. Soluble resistance-related Calcium-binding protein (Sorcin) is a penta-EF hand calcium binding protein, which participates in the regulation of calcium homeostasis in cells and has molecular mass of 22 kDa. The EF-hand is a common helix-loop-helix structural motif used by proteins to bind calcium. Most proteins are endowed with an even number of EF-hands, which are usually structurally and functionally paired. The penta-EF hand (PEF) family includes sorcin, calpains, programmed cell death protein 6 (PDCD6), peflin and grancalcin.

High sorcin regulates the calcium channels and exchangers located at the plasma membrane and at the endo/sarcoplasmic reticulum (ER/SR) and allows high levels of calcium in the ER to be maintained, preventing ER stress and the unfolded protein response, and increases escape from apoptosis. The 18-kDa variant of sorcin is regulated by Tumor necrosis factor receptor-associated protein 1 (TRAP1), a mitochondrial anti-apoptotic protein upregulated in several human tumors which controls sorcin folding and expression. Conversely, sorcin silencing activates apoptotic proteases as caspase-3 and caspase-12 results in major defects in mitosis and cytokinesis, blocks cell cycle progression in mitosis, increases the number of rounded polynucleated cells and induces apoptosis and cell death shifting the equilibrium between cell life and cell death towards proliferation in MDR cancer cells overexpressing sorcin.

Sorcin is highly expressed in the heart, brain and breast and overexpressed in many cancer cells. The gene for sorcin (SRI) spans about 21.9 kb of human genomic DNA. The gene is located in chromosome 7q21. Sorcin gene is in the same amplicon as other genes involved in the resistance to chemotherapeutics in cancer cells (multi-drug resistance, MDR) such as the ATP-binding cassette (ABC) transporters ABCB4 and ABCB1 (Mdr1, or P-glycoprotein 1).

Annexins are a family of intracellular proteins that bind membrane phospholipids in a Calcium concentration-dependent manner. The human genome encodes for 12 different annexins varying in expression and distribution within the tissues. Some of these are ubiquitously expressed (A1, A2, A5, A6, and A7), while some are selective (A3, A8, A9, A10, and A13). Several annexins play important roles during tumor progression. However, little is known about the clinical implications and biological functions of Annexin A3 (ANXA3) in breast cancer. ANXA3 has a role in cell differentiation, cell migration, immune regulation.

The ANXA3 gene is located on human chromosome 4q13-q22 and encodes a protein of 323 amino acid residues. Annexin A3 participates in various tumor-associated biological processes, including tumor initiation, progression, metastasis and is associated with chemotherapy resistance.

ANXA3 is expressed and secreted by neoplastic mammary cells, and its inhibition halts migration in breast cancer cells. The expression of Annexin A3 in human breast carcinoma closely correlated with tumor size and axillary lymph node metastasis. Elevated serum levels of ANXA3 protein were due to its increased secretion from neoplastic breast cells into the systemic circulation. There is inverse correlation between Annexin A3 expression and overall breast cancer patient survival. Moreover, Annexin A3 might be a novel and potential prognostic marker for patients with breast cancer and is involved in regulating apoptosis by affecting the Bcl-2/Bax balance. It promote the transcription of the anti-apoptotic gene Bcl-2 and downregulate the proapoptotic gene BAX.


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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Role of Sorcin and Annexin A3 in Breast Cancer Patients
Estimated Study Start Date : January 20, 2019
Estimated Primary Completion Date : August 1, 2019
Estimated Study Completion Date : September 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Group/Cohort Intervention/treatment
Breast cancer patients

The present study will be carried on 50 breast cancer patients before surgery.

The followings markers must be estimated:

Sorcin gene expression using real time PCR and Annexin A3 serum mesurement using enzyme linked immuno sorbent assay (ELISA).

Genetic: Sorcin gene expression
Sorcin gene expression Will be measured by real time PCR

Other: Annexin A3 serum mesurement
serum mesurement of Annexin A3 by enzyme linked immuno sorbent assay (ELISA)

Healthy controls

The present study will be carried on 15 age and sex matched controls.

The followings markers must be estimated:

Sorcin gene expression using real time PCR and Annexin A3 serum mesurement using ELISA.

Genetic: Sorcin gene expression
Sorcin gene expression Will be measured by real time PCR

Other: Annexin A3 serum mesurement
serum mesurement of Annexin A3 by enzyme linked immuno sorbent assay (ELISA)

Benign breast diseases

The present study will be carried on 15 patients with benign breast diseases.

The followings markers must be estimated:

Sorcin gene expression using real time PCR and Annexin A3 serum mesurement using ELISA.

Genetic: Sorcin gene expression
Sorcin gene expression Will be measured by real time PCR

Other: Annexin A3 serum mesurement
serum mesurement of Annexin A3 by enzyme linked immuno sorbent assay (ELISA)




Primary Outcome Measures :
  1. Role of SORCIN in patients with breast cancer [ Time Frame: 1 year ]
    genetic expression of SORCIN new biomarker in breast cancer patients


Secondary Outcome Measures :
  1. Role of annexin A3 biomarker in with breast cancer patients [ Time Frame: 1 year ]
    serum measurement of annexin A3 in breast cancer patients



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
breast cancer patients
Criteria

Inclusion Criteria:

  • breast cancer patients before surgery who are admitted to the South Egypt Cancer Institute, Surgery Department, Assiut University

Exclusion Criteria:

  • • Patients with malignancies elsewhere in the body.

    • Patients with chronic cardiac diseases.
    • Getting neoadjuvant chemotherapy.
    • Renal disease.
    • Neurodegenerative disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03598660


Contacts
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Contact: reham elmahdy +201002714637 reham.elmahdy@yahoo.com

Sponsors and Collaborators
Assiut University

Publications:
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Responsible Party: Reham I El-mahdy, Principal Investigator, Assiut University
ClinicalTrials.gov Identifier: NCT03598660     History of Changes
Other Study ID Numbers: Breast cancer
First Posted: July 25, 2018    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Reham I El-mahdy, Assiut University:
Breast cancer, SORCIN, Annexin A3

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases