Autophagy Bladder Cancer

NCT ID: NCT03254888

Last Updated: 2020-07-08

Study Results

Results pending

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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Recruitment Status

UNKNOWN

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-12-01

Study Completion Date

2021-12-31

Brief Summary

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• 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

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* 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

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Bladder Cancer

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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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) .

No interventions assigned to this group

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) .

No interventions assigned to this group

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).

No interventions assigned to this group

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)..

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 1)patients confirmed histopathologically to have bladder cancer. 2) Both sexes. 3) Patients who will accept to participate in the study.

Exclusion Criteria

* Patients with past history of Bladder Cancer with previous chemotherapy or any other types of cancer in the last 5 years.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Shaimaa Ramadan

Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shaimaa Shakhoun

Role: PRINCIPAL_INVESTIGATOR

Assiut

Locations

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Assiut

Asyut, , Egypt

Site Status

Countries

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Egypt

Central Contacts

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MahaAli Essam-Eldeen Mohamed, lecturer

Role: CONTACT

00201091570963

Shaimaa Shakhoun

Role: CONTACT

00201001143867

Facility Contacts

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Shaimaa Shakhoun

Role: primary

00201001143867

References

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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.

Reference Type RESULT
PMID: 28058776 (View on PubMed)

Mathew 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.

Reference Type RESULT
PMID: 19216902 (View on PubMed)

Kondo 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.

Reference Type RESULT
PMID: 16148885 (View on PubMed)

Mizushima N. Autophagy: process and function. Genes Dev. 2007 Nov 15;21(22):2861-73. doi: 10.1101/gad.1599207.

Reference Type RESULT
PMID: 18006683 (View on PubMed)

Lin 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.

Reference Type RESULT
PMID: 26519656 (View on PubMed)

Maiuri 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.

Reference Type RESULT
PMID: 17717517 (View on PubMed)

Yang 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.

Reference Type RESULT
PMID: 21878654 (View on PubMed)

Sivridis 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.

Reference Type RESULT
PMID: 22281431 (View on PubMed)

Ojha 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.

Reference Type RESULT
PMID: 24440234 (View on PubMed)

Mukhopadhyay 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.

Reference Type RESULT
PMID: 26743568 (View on PubMed)

Other Identifiers

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ABC

Identifier Type: -

Identifier Source: org_study_id

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