Colorectal CancerNCT03467308
Signaling Pathways Targeting Colorectal Cancer in Egypt
An observational study of Colorectal Cancer, run by Assiut University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Markers in tissue samples: (TIGAR , TRIM59, P53, AKT, GSH)
- How many people
- 180 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Mar 2018to 1 Apr 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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).
Who cannot join
- Patients with previous history of CRC treated with chemotherapy or presence of other types of cancer.
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Assiut University- faculty of medicine -Medical biochemistry department
Asyut, 71111
About this study
Official title: Identification of New Signaling Pathways Targeting Colorectal Cancer in Egyptian Patients
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.
Read the 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.
- Conditions
- Colorectal Cancer
- Being tested
- Markers in tissue samples: (TIGAR , TRIM59, P53, AKT, GSH)
- Keywords
- colorectal cancer, TIGAR, TRIM59
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Markers in tissue samples: (TIGAR , TRIM59, P53, AKT, GSH)Genetic
The followings markers will be investigated in tissue samples:
- TIGAR expression using quantitative real-time polymerase chain reaction (q Rt PCR) and immunohistochemistry.
- 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 group | Role | What they receive |
|---|---|---|
| Colorectal cancer patients | 50 Patients confirmed histopathologically to have early stages of colorectal cancer. Receives: 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). Receives: Genetic: Markers in tissue samples: (TIGAR , TRIM59, P53, AKT, GSH) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure TIGAR in the study groups.
Measure TIGAR expression in colorectal cancer patients and risky group patients.
Measured: 1 YEAR
Measure TRIM59 in the study groups.
Measure TRIM59 expression in colorectal cancer patients and risky group patients.
Measured: 1Year
Secondary outcomes (1)
Targeting new prognostic and therapeutic markers for colorectal cancer.
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2018
- Study start1 Mar 2018
- Primary completion1 Jan 2020
- Study completion1 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Asmaa Alaaeldeen Kamal Thabet, Assiut University
- Investigators
- Asmaa Alaaeldeen Kamal, MD (PhD student), Principal investigator, Assiut UniversityRagaa Hamdy Salama, Professor (MD), Study director, Assiut UniversityMaha Ali Essam al-Din, lecturer (MD), Study director, Assiut UniversityMarwa AbdelHafiz Abdel Hassan, lecturer (MD), Study director, Assiut UniversityAhmed Ali Abdel Motelb, lecturer (MD), Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03467308
- Sponsor's protocol ID
- CRC18
- Status last verified
- May 2020
- First submitted
- 20 Feb 2018
- Last updated
- 11 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 28052033Cheung 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.
PubMed 23726973Won 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.
PubMed 21820150Zhao 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.
PubMed 26691054Zhou 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.
PubMed 25046164Liang 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.
PubMed 27121462Zhan 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.
PubMed 26599082Sun 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.
PubMed 28534983Ahmad 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.
PubMed 28153010
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of New Signaling Pathways Targeting Colorectal Cancer in Egyptian Patients
- ClinicalTrials.gov ID
- NCT03467308
- Acronym / sponsor ID
- CRC18
- Conditions
- Colorectal Cancer
- Keywords
- colorectal cancer, TIGAR, TRIM59
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 1 Jan 2020 (actual)
- Study completion
- 1 Apr 2020 (actual)
- First posted
- 16 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Colorectal cancer patients | – | Genetic: Markers in tissue samples: (TIGAR , TRIM59, P53, AKT, GSH)50 Patients confirmed histopathologically to have early stages of colorectal cancer. |
| Risky group | – | Genetic: Markers in tissue samples: (TIGAR , TRIM59, P53, AKT, GSH)20 risky patients (those with ulcerative colitis, chron's disease, familial adenomatous polyposis). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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).
Key exclusion criteria (1 listed)
- Patients with previous history of CRC treated with chemotherapy or presence of other types of cancer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Genetic | Colorectal cancer patients, Risky group |
Primary outcome
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.
1 secondary outcome
Targeting new prognostic and therapeutic markers for colorectal cancer.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2020.
- Background: PubMed 28052033Yang 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.
- Background: PubMed 23726973Cheung 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.
- Background: PubMed 21820150Won 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.
- Background: PubMed 26691054Zhao 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.
- Background: PubMed 25046164Zhou 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.
- Background: PubMed 27121462Liang 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.
- Background: PubMed 26599082Zhan 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.
- Background: PubMed 28534983Sun 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.
- Background: PubMed 28153010Ahmad 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Asmaa Alaaeldeen Kamal, MD (PhD student) principal investigator
Assiut University
Ragaa Hamdy Salama, Professor (MD) study director
Assiut University
Maha Ali Essam al-Din, lecturer (MD) study director
Assiut University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Cancer, run by Assiut University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure TIGAR in the study groups. (time frame: 1 YEAR). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03467308, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2020.