Docetaxel is one of the most active drugs used to treat breast cancer. The cellular target of docetaxel is the microtubule, specifically the beta-tubulin subunit, that comprises a series of isotypes and that can modulate function. This study has examined the role of alteration in beta-tubulin isotypes in vitro and has sequenced the beta-tubulin gene to determine if there were mutations, both of which may represent important mechanisms of acquired resistance to docetaxel. Breast cancer cells, MCF-7 (oestrogen-receptor positive) and MDA-MB-231, (oestrogen-receptor negative) were made resistant to docetaxel in vitro. Expression of beta-tubulin isotypes (class I, II, III, IVa, IVb, and VI) was determined at the RNA and protein level using RT-PCR and western analysis, respectively. DNA sequencing evaluated the beta-tubulin gene. At the mRNA level, class I, II, III, and IVa beta-tubulin mRNA isotypes were over-expressed in docetaxel-resistant MCF-7 cells when compared with the docetaxel-sensitive parental cells. However, class VI beta-tubulin mRNA isotype expression was decreased in resistant cells. In MDA-MB-231 cells, there was a decrease in expression of the class I and class IVa beta-tubulin mRNA. However, there were increased expressions in class II, IVb, and VI beta-tubulin mRNA isotypes in resistant cells. Western analysis has confirmed corresponding increases in beta-tubulin protein levels in MCF-7 cells. However, in MDA-MB-231 cells, there were decreased protein levels for class II and class III beta-tubulin. This study demonstrates that altered expression of mRNA beta-tubulin isotypes and modulation of beta-tubulin protein levels are associated with acquired docetaxel resistance in breast cancer cells. This allows further understanding and elucidation of mechanisms involved in resistance to docetaxel.

Introduction Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. However, apoptosis and cell cycle regulation are key mechanisms by which most chemotherapeutic agents exert their cytotoxic effects.

Introduction The current Royal College of Surgeons commissioning guideline on colonic diverticular disease suggests that patients should undergo endoscopic evaluation of the colonic lumen after an episode of computed tomography (CT) proven acute diverticulitis to rule out malignancy. The necessity of routine endoscopic assessment of CT proven diverticulitis remains debatable. Aim To establish whether routine endoscopic assessment should be carried out for patients after an episode of acute diverticulitis. Method Data was collected retrospectively from all patients diagnosed with acute diverticulitis on CT and who subsequently had follow up endoscopic assessment from January to July 2019. Results Total number of patients were 64.Median age of the cohort was 58.Of all patients, 48 had diagnosis of uncomplicated diverticulitis whereas 16 patients had diagnosis of complicated diverticulitis on CT scan. All patients had follow up colonoscopy after an acute attack with following findings: 2 patients had no pathology, 56 patients had diagnosis of only diverticulosis, 4 patients had both diverticulosis and polyps and 2 patients had bowel cancer. All 4 cases of polyps had benign pathology and uncomplicated diverticulitis on CT scan. Two bowel cancer patients, one had complicated diverticulitis with thickening of proximal sigmoid and the other patient had abnormal sigmoid colon suggestive of malignancy on CT scan. Conclusion Recent meta-analysis showed no difference between diverticulitis and normal population group in terms of risk of bowel cancer. Routine colonoscopy may not be appropriate in patients with acute uncomplicated diverticulitis but endoscopic assessment after an episode of complicated diverticulitis is necessary.

Utilising over the scope endoclips previously has been thought to be limited by the size of defect. Our experience details novel combination techniques that allow for quick resolution and the expeditious commencement of further management such as chemotherapy. These clips also proved to be cost-effective in our centre, utilising less inpatient and outpatient resources than alternative management plans.

4 Almoudaris AM, Burns EM, Bottle A, Aylin P, Darzi A, Faiz O. A colorectal perspective on voluntary submission of outcome data to clinical registries. Br J Surg 2011; 98: 132-9. 5 Raftery J, Roderick P, Stevens A. Potential use of routine databases in health technology assessment. Heal Technol Assess 2005; 9: 1-92.We would like to thank Dr Dahlia AA Hawezy and Robyn Boyle who designed and drawn diagram of the procedure.