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Signaling Pathways Targeting Colorectal Cancer in Egypt

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ClinicalTrials.gov Identifier: NCT03467308
Recruitment Status : Not yet recruiting
First Posted : March 16, 2018
Last Update Posted : March 16, 2018
Sponsor:
Information provided by (Responsible Party):
Asmaa Alaaeldeen Kamal Thabet, Assiut University

Tracking Information
First Submitted Date February 20, 2018
First Posted Date March 16, 2018
Last Update Posted Date March 16, 2018
Estimated Study Start Date April 1, 2018
Estimated Primary Completion Date March 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 9, 2018)
  • Measure TIGAR in the study groups. [ Time Frame: 1 YEAR ]
    Measure TIGAR expression in colorectal cancer patients and risky group patients.
  • Measure TRIM59 in the study groups. [ Time Frame: 1Year ]
    Measure TRIM59 expression in colorectal cancer patients and risky group patients.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: March 9, 2018)
Targeting new prognostic and therapeutic markers for colorectal cancer. [ Time Frame: 1 year ]
Finding a relationship between TIGAR and TRIM 59 expression and PI3K/AKT pathway as a major signaling mechanism in tumorigenesis for targeting new prognostic and therapeutic markers for colorectal cancer.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Signaling Pathways Targeting Colorectal Cancer in Egypt
Official Title Identification of New Signaling Pathways Targeting Colorectal Cancer in Egyptian Patients
Brief Summary Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide. In Egypt, CRC constitutes 4.2% of all cancers with median age is 50 years old.
Detailed Description

The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a transcriptional target of p53. TIGAR functions as a fructose-2,6-bisphosphatase, decreasing the flux through the main glycolytic pathway. Consequently, glucose metabolism diverted into the pentose phosphate pathway (PPP). This results in TIGAR-mediated increase in cellular NADPH production, which contributes to the scavenging of ROS by reduced glutathione and thus a lower sensitivity of cells to oxidative stress-associated apoptosis. PPP also produce ribose phosphate for DNA synthesis and repair that play a role in tumor development and cell survival in tumor microenvironment. A high expression level of TIGAR was observed in cancers such as breast cancer, hepatocellular carcinoma, intestinal cancer, and glioblastoma. These studies suggested that TIGAR may act as an oncogene that support cancer progression.

The tripartite motif containing 59 (TRIM) proteins have been implicated in many biological processes including cell differentiation, apoptosis, transcriptional regulation, and signaling pathways.

It is related to several cancers. The oncogenic effect of TRIM59 on tumor proliferation and migration has been studied in various cancers, including gastric cancer, osteosarcoma, lung and CRC. The biological activity of TRIM59 has been observed to be closely associated with the regulation of P53. TRIM59 interacts with P53, leading to P53 ubiquitination and degradation, and consequently promotes tumor growth and migration. TRIM59 functions as an oncogene in CRC progression. It also activates the PI3K/AKT pathway. Increased activity of this pathway is often associated with tumor progression and resistance to cancer therapies. AKT can control TIGAR protein translation by activation of mTOR.

Targeting TRIM59 inhibition will inhibit PI3K-Akt pathway downregulate TIGAR protein translation. This is in turn downregulates GSH levels, increases ROS production, leading to cell death and blocks the cellular proliferation and survival of cancer cells leading to tumor regression. Therefore, TRIM59 protein can serve as a new potential therapeutic target for CRC.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
tumor tissue samples and normal intestinal tissue samples from the safety margin around the tumor
Sampling Method Non-Probability Sample
Study Population
  • All Patients confirmed histopathologically to have early stages of colorectal cancer admitted to General Surgery Department -Assiut University Hospital for CRC resection.
  • Risky group patients (including those with ulcerative colitis, chron's disease, familial adenomatous polyposis) undergoing diagnostic colonoscopy.
Condition Colorectal Cancer
Intervention Genetic: Markers in tissue samples: (TIGAR , TRIM59, P53, AKT, GSH)

The followings markers will be investigated in tissue samples:

  1. TIGAR expression using quantitative real-time polymerase chain reaction (q Rt PCR) and immunohistochemistry.
  2. TRIM59 expression using quantitative real-time polymerase chain reaction (q Rt PCR) and immunohistochemistry.

P53 expression using immunohistochemistry. P53 nuclear localization is essential for its normal function in growth inhibition or induction of apoptosis.

  • Akt expression using western blot.
  • GSH using chemical methods.
Study Groups/Cohorts
  • Colorectal cancer patients
    50 Patients confirmed histopathologically to have early stages of colorectal cancer.
    Intervention: Genetic: Markers in tissue samples: (TIGAR , TRIM59, P53, AKT, GSH)
  • Risky group
    20 risky patients (those with ulcerative colitis, chron's disease, familial adenomatous polyposis).
    Intervention: Genetic: Markers in tissue samples: (TIGAR , TRIM59, P53, AKT, GSH)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: March 9, 2018)
70
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 1, 2020
Estimated Primary Completion Date March 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • All Patients confirmed histopathologically to have early stages of colorectal cancer.
  • Risky group patients (including those with ulcerative colitis, chron's disease, familial adenomatous polyposis).

Exclusion Criteria:

  • Patients with previous history of CRC treated with chemotherapy or presence of other types of cancer.
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts
Contact: Ragaa Hamdy Salama, Professor (MD) 00201063492008 ragaa_2002@yahoo.com
Contact: Maha Ali Essam al-Din, lecturer (MD) 00201091570963 mahabadari@hotmail.com
Listed Location Countries Egypt
Removed Location Countries  
 
Administrative Information
NCT Number NCT03467308
Other Study ID Numbers CRC18
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Asmaa Alaaeldeen Kamal Thabet, Assiut University
Study Sponsor Assiut University
Collaborators Not Provided
Investigators
Principal Investigator: Asmaa Alaaeldeen Kamal, MD (PhD student) Assiut University
Study Director: Ragaa Hamdy Salama, Professor (MD) Assiut University
Study Director: Maha Ali Essam al-Din, lecturer (MD) Assiut University
Study Director: Marwa AbdelHafiz Abdel Hassan, lecturer (MD) Assiut University
Study Director: Ahmed Ali Abdel Motelb, lecturer (MD) Assiut University
PRS Account Assiut University
Verification Date March 2018