Smurf2 Gene Expression in Urinary Tract Tumors

• ClinicalTrials.gov Identifier: NCT05134623
• Recruitment Status: Unknown
• First Posted: November 26, 2021
• Last Update Posted: December 16, 2021
• Sponsor: Ziv Hospital
• Collaborator: Azrieli Faculty of medicine, Bar Ilan University, Safed, IL
• Information provided by (Responsible Party): Ziv Hospital

Tracking Information

• First Submitted Date: November 14, 2021
• First Posted Date: November 26, 2021
• Last Update Posted Date: December 16, 2021
• Estimated Study Start Date: December 2021
• Estimated Primary Completion Date: January 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 14, 2021)

Smurf2 and bladder cancer [ Time Frame: 6 months ]

The presence of SMURF2 in bladder tumor tissue compared to normal surrounding tissue

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 14, 2021)

• Smurf2 and bladder cancer [ Time Frame: 6 months ]
  The distribution of SMURF2 in bladder tumor cells - nucleus to cytoplasm
• Smurf2 and bladder cancer [ Time Frame: 6 months ]
  Identification of the SMURF2 product in the urinary sediment using proteomics and PCR

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Smurf2 Gene Expression in Urinary Tract Tumors
• Official Title: Smurf2 Gene Expression in Urinary Tract Tumors - Tissue Immunohistochemitry and Urinary Sediment Analysis

Brief Summary

Smurf2 and bladder cancer - research proposal summary The Smurf2 gene was recently identified as a tumor suppressor gene. It is an E3 ubiquitin ligase and carries a significant role in major cellular processes such as cell division, genomic stability, DNA repair as well as resistance to anti-tumoral drugs.

Recent studies showed that in several common tumors (prostate, breast, osteosarcoma etc.), a significant decrease in the expression or activity of Smurf2 can be noted, making the cells more susceptible to malignant transformation and the tumors more aggressive and highly resistant to various medications.

Bladder cancer is no. 4 cancer in men and 6 in women, and a major cause of cancer related death. Common risk factors are smoking and occupational exposure to aniline dyes or aromatic amines. Its' most common presentation is painless hematuria. Once the diagnosis of a bladder tumor is made, endoscopic resection of the tumors is performed. Superficial tumors of low malignancy may be treated by repeated resections, highly malignant tumors require additional therapy and aggressive tumors invading the bladder muscle layer require radical surgery and chemo-radiotherapy. Therefore, all patients are closely monitored by repeated cystoscopies (endoscopic inspection of the bladder), each 3 months, lifelong.

In an effort to minimize patients' discomfort, there is a constant search for a reliable biomarker in the urine of patients. A marker with good sensitivity and specificity will predict in a noninvasive fashion early recurrence or absence of bladder tumors, sparing the need for invasive cystoscopy. The presence of a biomarker may be used as prognostic factor or a measure of response to therapy.

The aim of this research is to characterize the presence of smurf2 in bladder tumors and determine whether it may be utilized as a reliable biomarker for bladder cancer.

Detailed Description

Smurf2 and bladder cancer - research proposal summary - detailed

The Smurf2 gene was recently identified as a tumor suppressor gene. It is an E3 ubiquitin ligase and carries a significant role in major cellular processes such as cell division, genomic stability, DNA repair as well as resistance to anti-tumoral drugs.

Recent studies showed that in several common tumors (prostate, breast, osteosarcoma etc.), a significant decrease in the expression or activity of Smurf2 can be noted, making the cells more susceptible to malignant transformation and the tumors more aggressive and highly resistant to various medications.

Bladder cancer is no. 4 cancer in men and 6 in women, and a major cause of cancer related death. Common risk factors are cigarrete smoking and occupational exposure to aniline dyes or aromatic amines. Its' most common presentation is painless hematuria. Once the diagnosis of a bladder tumor is made, endoscopic resection of the tumors is performed. Superficial tumors of low malignancy may be treated by repeated resections, highly malignant tumors require additional therapy and aggressive tumors invading the bladder muscle layer require radical surgery and chemo-radiotherapy. Therefore, all patients are closely monitored by repeated cystoscopies (endoscopic inspection of the bladder.

In an effort to minimize patients' discomfort, there is a constant search for a reliable biomarker in the urine of patients. A marker with good sensitivity and specificity will predict in a noninvasive fashion early recurrence or absence of bladder tumors, sparing the need for invasive cystoscopy. The presence of a biomarker may be used as prognostic factor or a measure of response to therapy.

The aim of this research is to characterize the presence of smurf2 in bladder tumors and determine whether it may be utilized as a reliable biomarker for bladder cancer.

In the study, the investigators will collect samples from bladder tumors of patient referred for transurethral resection of a known bladder tumor. The tissue will be processed routinely yet additional slides will be performed and used for immunohistochemical analysis. The investigators will characterize the expression of SMURF2 in the tissue, its abundance, the distribution between the nucleus and cytoplasm and possible differences between the tumors tissue and surrounding normal margins.

Further on, the investigators will collect urine samples from patients with these tumors and examine the urinary sediment using PCR and proteomic examination. The data will be used for further research using the SMURF2 product as a possible novel bio-marker for the presence of bladder tumors and for non-invasive detection and follow-up of patients on surveillance following surgical treatment.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

parafin sections of bladder tumors obtained during trans urethral resection

• Sampling Method: Non-Probability Sample
• Study Population: Male patients, diagnosed with bladder tumors, referred for transurethral resection
• Condition: Bladder Neoplasm

Intervention

Diagnostic Test: immunohistochemistry of tumors samples

routine resection of tumors, further analysis and immunohisochemical staining of the tissue slides.

• Study Groups/Cohorts: Not Provided
• Publications *: Manikoth Ayyathan D, Koganti P, Marcu-Malina V, Litmanovitch T, Trakhtenbrot L, Emanuelli A, Apel-Sarid L, Blank M. SMURF2 prevents detrimental changes to chromatin, protecting human dermal fibroblasts from chromosomal instability and tumorigenesis. Oncogene. 2020 Apr;39(16):3396-3410. doi: 10.1038/s41388-020-1226-3. Epub 2020 Feb 26.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 14, 2021): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: January 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Identified bladder tumor
• Scheduled for transurethral resection
• Informed consent

Exclusion Criteria:

• Previous bladder, prostate or pelvic irradiation
• Persistent urinary tract infection
• Intravesical therpy with BCG within 6 months prior to surgery.
• Intravesical chemotherapy within 6 months prior to surgery

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT05134623
• Other Study ID Numbers: 0029-20-ZIV
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ziv Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Ziv Hospital
• Original Study Sponsor: Same as current
• Collaborators: Azrieli Faculty of medicine, Bar Ilan University, Safed, IL

Investigators

• Study Director: Ran Katz, MD; Ziv Medical Center

• PRS Account: Ziv Hospital
• Verification Date: November 2021