Autophagy Bladder Cancer

Study Overview
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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.

Official Title
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Identification of Novel Autophagy Markers in Bladder Cancer Patients

Conditions
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Bladder Cancer

Participation Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Low Grade group<br>• 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 : Autophagy markers: ( Atg7) level using (quantitative real time polymerase chain reaction). (LC3A)level using immunohistochemistry . ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) Oxidative stress Marker:(MDA)using chemical method Apoptotic marker:(caspase 3) using(quantitative real time polymerase chain reaction) . | |
| High Grade group<br>• 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 : Autophagy markers: ( Atg7) level using (quantitative real time polymerase chain reaction). (LC3A)level using immunohistochemistry . ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) Oxidative stress Marker:(MDA)using chemical method Apoptotic marker:(caspase 3) using (quantitative real time polymerase chain reaction) . | |
| Safety margin group<br>• 50 normal bladder urothelial tissue samples from the safety margin around the tumor(0.5cm to the tumor), The followings markers must be estimated : Autophagy markers: ( Atg7) level using (quantitative real time polymerase chain reaction). (LC3A)level using immunohistochemistry . ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) Oxidative stress Marker:(MDA)using chemical method Apoptotic marker:(caspase 3) using (quantitative real time polymerase chain reaction). | |
| Control group<br>• 50 (age and sex matched )control The followings markers must be estimated : Autophagy markers: ( Atg7) level using (quantitative real time polymerase chain reaction). (LC3A)level using immunohistochemistry . ER-stress marker: (ATF6) level using ELISA(Enzyme Linked Immuno sorbent Assay) Oxidative stress Marker:(MDA)using chemical method Apoptotic marker:(caspase 3) using (quantitative real time polymerase chain reaction).. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline |