Bladder CancerNCT03254888
Autophagy Bladder Cancer
An observational study of Bladder Cancer, run by Assiut University at 1 site in Egypt.
Trial summary
Bladder cancer is the most common malignancy of the urinary tract. It represents the 7th most commonly diagnosed cancer in male population worldwide and drops to the 11th when both genders are considered . Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Bladder Cancer
- How many people
- 150 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Dec 2020to 31 Dec 2021
- 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: patients with confirmed bladder cancer (histopathologically) having LGBC(Low Grade bladder cancer) undergoing either TUR(transurethral resection of Bladder Tumour) or Radical Cystectomy and patients having HGBC(High Grade bladder cancer) undergoing either TUR(transurethral resection of Bladder Tumour) or Radical cystectomy. Healthy controls[age and gender matched](with no previous history of gross hematuria, urolithiasis, or active urinary tract infection)
Who may be able to join
- 1)patients confirmed histopathologically to have bladder cancer. 2) Both sexes. 3) Patients who will accept to participate in the study.
Who cannot join
- Patients with past history of Bladder Cancer with previous chemotherapy or any other types of cancer in the last 5 years.
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Assiut
Asyut, 71111
Shaimaa Shakhoun, 00201001143867, atashaimaa8@gmail.com
About this study
Official title: Identification of Novel Autophagy Markers in Bladder Cancer Patients
- Bladder cancer is the most common malignancy of the urinary tract. It represents the 7th most commonly diagnosed cancer in male population worldwide and drops to the 11th when both genders are considered . According to the American cancer society's estimates of bladder cancer in 2017, the number of the new cases of bladder cancer is 79,030, and the mortality figures reached 16,870 .
Read the detailed description
- In Egypt, Bladder Cancer is the most prevalent malignancy among Egyptian males (16%) producing more than 7900 deaths annually . The majority of patients with bladder cancer about (70-80%) present with non-muscle invasive bladder cancer .
- Autophagy is a highly conserved catabolic process that degrades cellular organelles and proteins to maintain cellular biosynthesis during stress ; cancer cells induced autophagy to counteract with anticancer therapy by helping them to evade apoptotic pathway .Autophagy is achieved by many autophagy-related genes .
- Previous studies found that human bladder cancer cell lines exhibit high basal level of autophagic activity that may contribute to resistance to current anticancer treatment, so targeting basal autophagy may help to develop novel therapeutic strategies . Autophagy is potently induced by activating transcription factor 6(Endoplasmic Reticulum stress marker) , and Malondialdehyde (oxidative stress marker) .
- Recently several studies demonstrated the role of autophagy in Bladder Cancer progression as evidenced by detection of microtubule associated protein and its relevance with muscle invasion beside its grade dependency . Autophagy was grade dependent process . Autophagy related gene 7 is a key protein involved in autophagosomes biogenesis, Knockdown of Autophagy related gene 7 induced apoptotic cell death in bladder cancer cell lines measured by increased caspase 3 level, Based on these previous studies autophagy plays a role in bladder cancer progression so interruption of its pathway may serve a novel target for future therapies.
- Conditions
- Bladder Cancer
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Low Grade group | • 50 tumor tissue samples from patients with Low Grade Bladder Cancer undergoing either trans urethral resection of bladder tumor or Radical Cystectomy , The followings markers must be estimated : 1. Autophagy markers: * ( Atg7) level using (quantitative real time polymerase chain reaction). * (LC3A)level using immunohistochemistry . 2. ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) 3. Oxidative stress Marker:(MDA)using chemical method 4. Apoptotic marker:(caspase 3) using(quantitative real time polymerase chain reaction) . | |
| High Grade group | • 50 tumor tissue samples from patients with High Grade Bladder Cancer undergoing either trans urethral resection of bladder tumor or Radical Cystectomy, The followings markers must be estimated : 1. Autophagy markers: * ( Atg7) level using (quantitative real time polymerase chain reaction). * (LC3A)level using immunohistochemistry . 2. ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) 3. Oxidative stress Marker:(MDA)using chemical method 4. Apoptotic marker:(caspase 3) using (quantitative real time polymerase chain reaction) . | |
| Safety margin group | • 50 normal bladder urothelial tissue samples from the safety margin around the tumor(0.5cm to the tumor), The followings markers must be estimated : 1. Autophagy markers: * ( Atg7) level using (quantitative real time polymerase chain reaction). * (LC3A)level using immunohistochemistry . 2. ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) 3. Oxidative stress Marker:(MDA)using chemical method 4. Apoptotic marker:(caspase 3) using (quantitative real time polymerase chain reaction). | |
| Control group | • 50 (age and sex matched )control The followings markers must be estimated : 1. Autophagy markers: * ( Atg7) level using (quantitative real time polymerase chain reaction). * (LC3A)level using immunohistochemistry . 2. ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) 3. Oxidative stress Marker:(MDA)using chemical method 4. Apoptotic marker:(caspase 3) using (quantitative real time polymerase chain reaction).. |
What is being measured
The primary outcome is the main question the study is designed to answer.
autophagy marker
differences in the level of Atg7(autophagy marker) in Low Grade bladder cancer and High Grade bladder cancer groups in comparison with safety margin and healthy control group.
Measured: baseline
Secondary outcomes (1)
stress markers
Relation between LC3A and muscle invasiveness in bladder cancer progression, and relation between levels of ATF6, activating transcription factor6 (ER stress marker) -MDA malondialdehyde (oxidative stress marker)-Caspase3 (apoptotic marker) in different study groups and bladder cancer development.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start1 Dec 2020 (estimated)
- Primary completion1 Oct 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Bladder 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
- Retrospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shaimaa Ramadan, Assiut University
- Investigators
- Shaimaa Shakhoun, Principal investigator, Assiut
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03254888
- Sponsor's protocol ID
- ABC
- Status last verified
- Jul 2020
- First submitted
- 17 Aug 2017
- Last updated
- 8 Jul 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Woldu SL, Bagrodia A, Lotan Y. Guideline of guidelines: non-muscle-invasive bladder cancer. BJU Int. 2017 Mar;119(3):371-380. doi: 10.1111/bju.13760. Epub 2017 Jan 24.
PubMed 28058776Mathew R, Karantza-Wadsworth V, White E. Assessing metabolic stress and autophagy status in epithelial tumors. Methods Enzymol. 2009;453:53-81. doi: 10.1016/S0076-6879(08)04004-4.
PubMed 19216902Kondo Y, Kanzawa T, Sawaya R, Kondo S. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005 Sep;5(9):726-34. doi: 10.1038/nrc1692.
PubMed 16148885Mizushima N. Autophagy: process and function. Genes Dev. 2007 Nov 15;21(22):2861-73. doi: 10.1101/gad.1599207.
PubMed 18006683Lin YC, Lin JF, Wen SI, Yang SC, Tsai TF, Chen HE, Chou KY, Hwang TI. Inhibition of High Basal Level of Autophagy Induces Apoptosis in Human Bladder Cancer Cells. J Urol. 2016 Apr;195(4 Pt 1):1126-35. doi: 10.1016/j.juro.2015.10.128. Epub 2015 Oct 28.
PubMed 26519656Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007 Sep;8(9):741-52. doi: 10.1038/nrm2239.
PubMed 17717517Yang ZJ, Chee CE, Huang S, Sinicrope FA. The role of autophagy in cancer: therapeutic implications. Mol Cancer Ther. 2011 Sep;10(9):1533-41. doi: 10.1158/1535-7163.MCT-11-0047. Epub 2011 Aug 30.
PubMed 21878654Sivridis E, Koukourakis MI, Mendrinos SE, Touloupidis S, Giatromanolaki A. Patterns of autophagy in urothelial cell carcinomas--the significance of "stone-like" structures (SLS) in transurethral resection biopsies. Urol Oncol. 2013 Oct;31(7):1254-60. doi: 10.1016/j.urolonc.2011.12.016. Epub 2012 Jan 24.
PubMed 22281431Ojha R, Singh SK, Bhattacharyya S, Dhanda RS, Rakha A, Mandal AK, Jha V. Inhibition of grade dependent autophagy in urothelial carcinoma increases cell death under nutritional limiting condition and potentiates the cytotoxicity of chemotherapeutic agent. J Urol. 2014 Jun;191(6):1889-98. doi: 10.1016/j.juro.2014.01.006. Epub 2014 Jan 15.
PubMed 24440234Mukhopadhyay S, Sinha N, Das DN, Panda PK, Naik PP, Bhutia SK. Clinical relevance of autophagic therapy in cancer: Investigating the current trends, challenges, and future prospects. Crit Rev Clin Lab Sci. 2016 Aug;53(4):228-52. doi: 10.3109/10408363.2015.1135103. Epub 2016 Feb 16.
PubMed 26743568
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Novel Autophagy Markers in Bladder Cancer Patients
- ClinicalTrials.gov ID
- NCT03254888
- Acronym / sponsor ID
- ABC
- Conditions
- Bladder Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Dec 2020 (estimated)
- Primary completion
- 1 Oct 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 21 Aug 2017 (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.
- Bladder cancer is the most common malignancy of the urinary tract. It represents the 7th most commonly diagnosed cancer in male population worldwide and drops to the 11th when both genders are considered . According to the American cancer society's estimates of bladder cancer in 2017, the number of the new cases of bladder cancer is 79,030, and the mortality figures reached 16,870 .
Detailed description
- In Egypt, Bladder Cancer is the most prevalent malignancy among Egyptian males (16%) producing more than 7900 deaths annually . The majority of patients with bladder cancer about (70-80%) present with non-muscle invasive bladder cancer .
- Autophagy is a highly conserved catabolic process that degrades cellular organelles and proteins to maintain cellular biosynthesis during stress ; cancer cells induced autophagy to counteract with anticancer therapy by helping them to evade apoptotic pathway .Autophagy is achieved by many autophagy-related genes .
- Previous studies found that human bladder cancer cell lines exhibit high basal level of autophagic activity that may contribute to resistance to current anticancer treatment, so targeting basal autophagy may help to develop novel therapeutic strategies . Autophagy is potently induced by activating transcription factor 6(Endoplasmic Reticulum stress marker) , and Malondialdehyde (oxidative stress marker) .
- Recently several studies demonstrated the role of autophagy in Bladder Cancer progression as evidenced by detection of microtubule associated protein and its relevance with muscle invasion beside its grade dependency . Autophagy was grade dependent process . Autophagy related gene 7 is a key protein involved in autophagosomes biogenesis, Knockdown of Autophagy related gene 7 induced apoptotic cell death in bladder cancer cell lines measured by increased caspase 3 level, Based on these previous studies autophagy plays a role in bladder cancer progression so interruption of its pathway may serve a novel target for future therapies.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low Grade group | – | –• 50 tumor tissue samples from patients with Low Grade Bladder Cancer undergoing either trans urethral resection of bladder tumor or Radical Cystectomy , The followings markers must be estimated : 1. Autophagy markers: * ( Atg7) level using (quantitative real time polymerase chain reaction). * (LC3A)level using immunohistochemistry . 2. ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) 3. Oxidative stress Marker:(MDA)using chemical method 4. Apoptotic marker:(caspase 3) using(quantitative real time polymerase chain reaction) . |
| High Grade group | – | –• 50 tumor tissue samples from patients with High Grade Bladder Cancer undergoing either trans urethral resection of bladder tumor or Radical Cystectomy, The followings markers must be estimated : 1. Autophagy markers: * ( Atg7) level using (quantitative real time polymerase chain reaction). * (LC3A)level using immunohistochemistry . 2. ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) 3. Oxidative stress Marker:(MDA)using chemical method 4. Apoptotic marker:(caspase 3) using (quantitative real time polymerase chain reaction) . |
| Safety margin group | – | –• 50 normal bladder urothelial tissue samples from the safety margin around the tumor(0.5cm to the tumor), The followings markers must be estimated : 1. Autophagy markers: * ( Atg7) level using (quantitative real time polymerase chain reaction). * (LC3A)level using immunohistochemistry . 2. ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) 3. Oxidative stress Marker:(MDA)using chemical method 4. Apoptotic marker:(caspase 3) using (quantitative real time polymerase chain reaction). |
| Control group | – | –• 50 (age and sex matched )control The followings markers must be estimated : 1. Autophagy markers: * ( Atg7) level using (quantitative real time polymerase chain reaction). * (LC3A)level using immunohistochemistry . 2. ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) 3. Oxidative stress Marker:(MDA)using chemical method 4. Apoptotic marker:(caspase 3) using (quantitative real time polymerase chain reaction).. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- patients with confirmed bladder cancer (histopathologically) having LGBC(Low Grade bladder cancer) undergoing either TUR(transurethral resection of Bladder Tumour) or Radical Cystectomy and patients having HGBC(High Grade bladder cancer) undergoing either TUR(transurethral resection of Bladder Tumour) or Radical cystectomy. Healthy controls[age and gender matched](with no previous history of gross hematuria, urolithiasis, or active urinary tract infection)
Key inclusion criteria (1 listed)
- 1)patients confirmed histopathologically to have bladder cancer. 2) Both sexes. 3) Patients who will accept to participate in the study.
Key exclusion criteria (1 listed)
- Patients with past history of Bladder Cancer with previous chemotherapy or any other types of cancer in the last 5 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
autophagy marker
Time frame: baseline
differences in the level of Atg7(autophagy marker) in Low Grade bladder cancer and High Grade bladder cancer groups in comparison with safety margin and healthy control group.
1 secondary outcome
stress markers
Time frame: baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2020.
- Results publication: PubMed 28058776Woldu SL, Bagrodia A, Lotan Y. Guideline of guidelines: non-muscle-invasive bladder cancer. BJU Int. 2017 Mar;119(3):371-380. doi: 10.1111/bju.13760. Epub 2017 Jan 24.
- Results publication: PubMed 19216902Mathew R, Karantza-Wadsworth V, White E. Assessing metabolic stress and autophagy status in epithelial tumors. Methods Enzymol. 2009;453:53-81. doi: 10.1016/S0076-6879(08)04004-4.
- Results publication: PubMed 16148885Kondo Y, Kanzawa T, Sawaya R, Kondo S. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005 Sep;5(9):726-34. doi: 10.1038/nrc1692.
- Results publication: PubMed 18006683Mizushima N. Autophagy: process and function. Genes Dev. 2007 Nov 15;21(22):2861-73. doi: 10.1101/gad.1599207.
- Results publication: PubMed 26519656Lin YC, Lin JF, Wen SI, Yang SC, Tsai TF, Chen HE, Chou KY, Hwang TI. Inhibition of High Basal Level of Autophagy Induces Apoptosis in Human Bladder Cancer Cells. J Urol. 2016 Apr;195(4 Pt 1):1126-35. doi: 10.1016/j.juro.2015.10.128. Epub 2015 Oct 28.
- Results publication: PubMed 17717517Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007 Sep;8(9):741-52. doi: 10.1038/nrm2239.
- Results publication: PubMed 21878654Yang ZJ, Chee CE, Huang S, Sinicrope FA. The role of autophagy in cancer: therapeutic implications. Mol Cancer Ther. 2011 Sep;10(9):1533-41. doi: 10.1158/1535-7163.MCT-11-0047. Epub 2011 Aug 30.
- Results publication: PubMed 22281431Sivridis E, Koukourakis MI, Mendrinos SE, Touloupidis S, Giatromanolaki A. Patterns of autophagy in urothelial cell carcinomas--the significance of "stone-like" structures (SLS) in transurethral resection biopsies. Urol Oncol. 2013 Oct;31(7):1254-60. doi: 10.1016/j.urolonc.2011.12.016. Epub 2012 Jan 24.
- Results publication: PubMed 24440234Ojha R, Singh SK, Bhattacharyya S, Dhanda RS, Rakha A, Mandal AK, Jha V. Inhibition of grade dependent autophagy in urothelial carcinoma increases cell death under nutritional limiting condition and potentiates the cytotoxicity of chemotherapeutic agent. J Urol. 2014 Jun;191(6):1889-98. doi: 10.1016/j.juro.2014.01.006. Epub 2014 Jan 15.
- Results publication: PubMed 26743568Mukhopadhyay S, Sinha N, Das DN, Panda PK, Naik PP, Bhutia SK. Clinical relevance of autophagic therapy in cancer: Investigating the current trends, challenges, and future prospects. Crit Rev Clin Lab Sci. 2016 Aug;53(4):228-52. doi: 10.3109/10408363.2015.1135103. Epub 2016 Feb 16.
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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.
Shaimaa Shakhoun principal investigator
Assiut
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 Bladder 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 1 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: status not confirmed, as of the sponsor's last update on 8 Jul 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact MahaAli Essam-Eldeen Mohamed, lecturer (00201091570963, mahabadari@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
autophagy marker (time frame: baseline). 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 NCT03254888, which also lists 10 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 8 Jul 2020.