NQ01 expression in endoscopically resected human colorectal tumours
Research type
Research Study
Full title
NQ01 expression in endoscopically resected human colorectal tumours
IRAS ID
168336
Contact name
Mark Hull
Contact email
Sponsor organisation
University of Leeds
Clinicaltrials.gov Identifier
15/NW/0048, NRES Committee North West - Greater Manchester West
Duration of Study in the UK
0 years, 3 months, 30 days
Research summary
Endoscopic mucosal resection (EMR) of benign and malignant non-polypoid colorectal tumours is increasingly performed as an alternative to surgical removal. There is a risk of tumour recurrence at the resection site explained by incomplete removal of neoplastic tissue. Tumour recurrence has been reported in between 0-40% of cases. Risk of recurrence at the resection site necessitates repeat follow-up endoscopy to check the resection site with further resection or tumour ablation required if recurrence has occurred. There is the risk of interval cancer if undetected tumour progresses to malignancy prior to endoscopic follow-up evaluation. There is a need for therapies which could reduce resection site recurrence risk. One possibility is local treatment of the resection site with anti-neoplastic drug therapy which would ablate any remaining neoplastic cells.
One candidate agent for topical therapy at the resection site is the drug E09. E09 has been introduced into clinical trials for local therapy of bladder cancer. E09 is metabolised and inactivated very efficiently in the systemic circulation, such that E09 lacks systemic toxicity and only has activity at sites of expression of the enzyme NQ01, which activates E09 to an active form.
In a preliminary report, NQ01 protein was reported to be localized to normal human colorectal epithelium and in malignant epithelial cells in human colorectal cancer tissue. However, there has been no systematic investigation of NQ01 expression in a large series of human colorectal tissues. We will test the hypotheses that: 1) NQ01 protein is expressed differentially in normal and 2) neoplastic colorectal epithelium and that NQ01 protein is present in recurrent tumour cells at the site of EMR.Results Summary
This project was a short Academic Clinical Trainee research project to be completed in 4 months. The aim was to detect a protein called NQ01 in bowel polyps, which had already been removed. If NQ01 was present in the polyp tissue, it would have opened up the opportunity to use a chemotherapy drug in patients to minimise recurrence.
The method for detection of the NQ01 protein used a commercially available antibody to visualise (stain) the protein in thin sections of the polyp tissue (a technique called immunohistochemistry). Unfortunately, the staining of the polyp sections was non-specific and not accurate so we could not conclude that the antibody was working properly. We did not have sufficient time to try other methods and we were unable to find an alternative junior researcher, who could take the project on, for several years after the original Trainee finished.REC name
North West - Greater Manchester West Research Ethics Committee
REC reference
15/NW/0048
Date of REC Opinion
15 Jan 2015
REC opinion
Favourable Opinion