School Of Cancer Sciences

Colorectal cancer is one of the most common cancer types and the second leading cause of cancer-related deaths worldwide. Poor survival of patients highlights the importance of identification of novel prognostic markers. The work in this thesis presents Tspan6 as a potential candidate. Tspan6 is a poorly studied member of the tetraspanin family of proteins that has been implicated in cancer initiation, progression and metastasis. The expression of Tspan6 in a cohort of genetically profiled colorectal adenocarcinomas in this study demonstrated that Tspan6 expression is significantly reduced in tumours vs. adjacent non-cancerous tissues. To illustrate the role of Tspan6 in colorectal cancer (CRC) Tspan6 KO mice carrying APCmin/+ allele were generated. It was found that loss of Tspan6 gene accentuates APC-driven tumorigenesis in vivo. Specifically, these animals developed larger numbers of intestinal and colonic polyps. Interestingly, these polyps were significantly bigger in size and ...

The tumour immune microenvironment is considered to influence cancer behaviour and outcome. Using a panel of markers for innate and adaptive immune cells we set out to characterise and understand the bladder tumour microenvironment of 114 patients from a prospective multicentre cohort of newly-diagnosed bladder cancer patients, followed-up for 4.33±1.71 years. We found IL-17-positive cells were significantly increased in primary and concomitant carcinoma in situ (CIS), p<0.0001, a highly malignant lesion which is the most significant single risk factor for disease progression. Further characterisation of the tumour immunophenotype identified IL-17+ cells as predominantly mast cells rather than T-cells, in contrast to most other tumour types. Expression of the IL-17-receptor in bladder tumours, and functional effects and gene expression changes induced by IL-17 in bladder tumour cells in vitro suggest a role in tumour behaviour. Finally, we assessed the effects of IL-17 in the con...

INTRODUCTION In the 75-80% of urothelial bladder cancers (UBC) presenting as non-muscle invasive bladder cancer (NMIBC), transurethral resection of bladder tumour (TURBT) is the key treatment and staging procedure. In the 20-25% of patients with muscle invasive bladder cancer (MIBC), further cross-sectional imaging is required to complete the staging process before considering radical treatment. Given the adverse effects of ionising radiation, clinicians identify patients believed to have MIBC, and so requiring further imaging pre-TURBT, at the tumour histology/stage based on the tumour's visual characteristics. There is minimal evidence describing the accuracy of such predictions in newly-diagnosed patients. METHODS Over a 6-year period, a database of patients undergoing resection of newly-diagnosed bladder lesions in a single UK centre was prospectively established. Predictions based on histology were simultaneously recorded, and the accuracy of these predictions of histology/...

ImportanceSelenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non–muscle-invasive bladder cancer.ObjectiveTo determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC.Design, Setting, and ParticipantsThis multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 m...

Aim  To assess injection of Durasphere under direct endoanal ultrasound guidance as a treatment for faecal incontinence.Method  A total of 23 patients with varying degrees of persistent faecal leakage and/or soiling were recruited. Durasphere was injected in the intersphincteric plane under direct ultrasound guidance. All patients were given a general anaesthetic. Patients had ano-rectal physiology, endoanal ultrasound, continence scoring and quality of life measures assessed at 0, 1, 3, 6 and 12 months.Results  A total of 21 patients were followed up for at least 12 months, with two being excluded at the follow-up stage. Friedman two-way analysis of variance of the Cleveland Clinic Score, Faecal Incontinence Quality of Life Score and Diary Response Score demonstrated a significant sustained improvement. There was no significant improvement in number of bowel movements. There was a significant difference in anal squeeze pressure after therapy, but no significant difference in anal resting pressure. Six patients reported no improvement after Durasphere therapy.Conclusions  Durasphere gave sustained improvements in quality of life and continence scores in this study group. Strict criteria are needed to ascertain suitability for Durasphere therapy.