Signaling Pathways Targeting Colorectal Cancer in Egypt
NCT ID: NCT03467308
Last Updated: 2020-05-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
180 participants
OBSERVATIONAL
2018-03-01
2020-04-01
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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CASE_CONTROL
PROSPECTIVE
Study Groups
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Colorectal cancer patients
50 Patients confirmed histopathologically to have early stages of colorectal cancer.
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.
Risky group
20 risky patients (those with ulcerative colitis, chron's disease, familial adenomatous polyposis).
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.
Interventions
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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.
Eligibility Criteria
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Inclusion Criteria
* Risky group patients (including those with ulcerative colitis, chron's disease, familial adenomatous polyposis).
Exclusion Criteria
ALL
No
Sponsors
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Assiut University
OTHER
Responsible Party
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Asmaa Alaaeldeen Kamal Thabet
Principal Investigator
Principal Investigators
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Asmaa Alaaeldeen Kamal, MD (PhD student)
Role: PRINCIPAL_INVESTIGATOR
Assiut University
Ragaa Hamdy Salama, Professor (MD)
Role: STUDY_DIRECTOR
Assiut University
Maha Ali Essam al-Din, lecturer (MD)
Role: STUDY_DIRECTOR
Assiut University
Marwa AbdelHafiz Abdel Hassan, lecturer (MD)
Role: STUDY_DIRECTOR
Assiut University
Ahmed Ali Abdel Motelb, lecturer (MD)
Role: STUDY_DIRECTOR
Assiut University
Locations
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Assiut University- faculty of medicine -Medical biochemistry department
Asyut, , Egypt
Countries
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References
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Yang J, Wen J, Tian T, Lu Z, Wang Y, Wang Z, Wang X, Yang Y. GLUT-1 overexpression as an unfavorable prognostic biomarker in patients with colorectal cancer. Oncotarget. 2017 Feb 14;8(7):11788-11796. doi: 10.18632/oncotarget.14352.
Cheung EC, Athineos D, Lee P, Ridgway RA, Lambie W, Nixon C, Strathdee D, Blyth K, Sansom OJ, Vousden KH. TIGAR is required for efficient intestinal regeneration and tumorigenesis. Dev Cell. 2013 Jun 10;25(5):463-77. doi: 10.1016/j.devcel.2013.05.001. Epub 2013 May 30.
Won KY, Lim SJ, Kim GY, Kim YW, Han SA, Song JY, Lee DK. Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer. Hum Pathol. 2012 Feb;43(2):221-8. doi: 10.1016/j.humpath.2011.04.021. Epub 2011 Aug 4.
Zhao M, Fan J, Liu Y, Yu Y, Xu J, Wen Q, Zhang J, Fu S, Wang B, Xiang L, Feng J, Wu J, Yang L. Oncogenic role of the TP53-induced glycolysis and apoptosis regulator in nasopharyngeal carcinoma through NF-kappaB pathway modulation. Int J Oncol. 2016 Feb;48(2):756-64. doi: 10.3892/ijo.2015.3297. Epub 2015 Dec 17.
Zhou Z, Ji Z, Wang Y, Li J, Cao H, Zhu HH, Gao WQ. TRIM59 is up-regulated in gastric tumors, promoting ubiquitination and degradation of p53. Gastroenterology. 2014 Nov;147(5):1043-54. doi: 10.1053/j.gastro.2014.07.021. Epub 2014 Jul 18.
Liang J, Xing D, Li Z, Shen J, Zhao H, Li S. TRIM59 is upregulated and promotes cell proliferation and migration in human osteosarcoma. Mol Med Rep. 2016 Jun;13(6):5200-6. doi: 10.3892/mmr.2016.5183. Epub 2016 Apr 25.
Zhan W, Han T, Zhang C, Xie C, Gan M, Deng K, Fu M, Wang JB. TRIM59 Promotes the Proliferation and Migration of Non-Small Cell Lung Cancer Cells by Upregulating Cell Cycle Related Proteins. PLoS One. 2015 Nov 24;10(11):e0142596. doi: 10.1371/journal.pone.0142596. eCollection 2015.
Sun Y, Ji B, Feng Y, Zhang Y, Ji D, Zhu C, Wang S, Zhang C, Zhang D, Sun Y. TRIM59 facilitates the proliferation of colorectal cancer and promotes metastasis via the PI3K/AKT pathway. Oncol Rep. 2017 Jul;38(1):43-52. doi: 10.3892/or.2017.5654. Epub 2017 May 22.
Ahmad R, Alam M, Hasegawa M, Uchida Y, Al-Obaid O, Kharbanda S, Kufe D. Targeting MUC1-C inhibits the AKT-S6K1-elF4A pathway regulating TIGAR translation in colorectal cancer. Mol Cancer. 2017 Feb 2;16(1):33. doi: 10.1186/s12943-017-0608-9.
Other Identifiers
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CRC18
Identifier Type: -
Identifier Source: org_study_id
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