Clinical trial NCT03254888: Autophagy Bladder Cancer
Official title: Identification of Novel Autophagy Markers in Bladder Cancer Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bladder Cancer
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2017-08-21
Enrollment: 150
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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)

Brief 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 . 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.

Eligibility criteria: 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.

Primary outcomes:
measure: autophagy marker
timeFrame: baseline
Secondary outcomes:
measure: stress markers
timeFrame: baseline
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut
Study officials:
affiliation: Assiut
name: Shaimaa Shakhoun
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: Mizushima N. Autophagy: process and function. Genes Dev. 2007 Nov 15;21(22):2861-73. doi: 10.1101/gad.1599207.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.