Maura Cotter

Comparative antiproliferative effects of iniparib and olaparib on a panel of triple-negative and non-triple-negative breast cancer cell lines

PARP inhibitors, both as monotherapy and in combination with cytotoxic drugs, are currently undergoing clinical trials in several different cancer types. In this investigation, we compared the antiproliferative activity of two PARP/putative PARP inhibitors, i.e., olaparib and iniparib, in a panel of 14 breast cancer cell lines (seven tripe-negative and seven non-triple-negative). In almost all cell lines investigated, olaparib was a more potent inhibitor of cell growth than iniparib. Inhibition by both drugs was cell line-dependent and independent of the molecular subtype status of the cells, i.e., whether cells were triple-negative or non-triple negative. Although the primary target of PARP inhibitors is PARP1, no significant association was found between baseline levels of PARP1 activity and inhibition with either agent. Similarly, no significant correlation was evident between sensitivity and levels of CDK1, BRCA1 or miR-182. Combined addition of olaparib and either the CDK1 inhibitor, RO-3306 or a pan HER inhibitor (neratinib, afatinib) resulted in superior growth inhibition to that obtained with olaparib alone. We conclude that olaparib, in contrast to iniparib, is a strong inhibitor of breast cancer cell growth and may have efficacy in breast cancer irrespective of its molecular subtype, i.e., whether HER2-positive, estrogen receptor (ER)-positive or triple-negative. Olaparib, in combination with a selective CDK1 inhibitor or a pan HER inhibitor, is a potential new approach for treating breast cancer.

The classification of invasive carcinoma of the breast.

The classification of invasive breast carcinoma assists diagnosis, allows for comparison of different patient groups in clinical trials and facilitates epidemiological analysis. For the individual patient, accurate tumor classification informs clinical decision-making with emphasis on assessment of prognosis and treatment formulation. Tumor grade is an independent prognostic indicator and is calculated by assessing specific tumor characteristics microscopically. The Tumor Node Metastasis staging system, produced by the American Joint Committee on Cancer Union for International Cancer Control, combines information about the primary tumor size, the status of the regional lymph nodes and the presence or absence of distant metastases at diagnosis to classify disease. In recent years, the use of gene expression profiling technology has led to the development of the molecular classification of breast cancer and has highlighted the importance of hormone receptor and HER2 oncogenic pathways, with particular reference to targeted chemotherapy. Tumor typing involves the identification of ‘no special type’ carcinoma with variable clinical, histological and molecular characteristics and ‘special type’ carcinomas that are usually associated with a particular set of prognostic and predictive indices. Some special type carcinomas have unique biological features that influence diagnostic investigation and clinical management.

Anal intraepithelial neoplasia: a single centre 19 year review

There is debate about whether the traditional three‐tiered grading of anal intraepithelial neoplasia (AIN) should be replaced by a more reproducible two‐tiered system. In this study, we review our experience with AIN to determine the most suitable classification system.

Coeliac-like duodenal pathology in orthotopic liver transplant patients on mycophenolic acid therapy.

Diarrhoea following orthotopic liver transplantation (OLT) is a significant clinical problem associated with mycophenolic acid (MPA). The histological injury pattern associated with MPA in the large bowel is well documented in the literature; however, that in the duodenum is less extensively documented. The aim of this study was to investigate the histological spectrum of duodenal injury specifically in symptomatic OLT patients on MPA, and to compare this with the spectrum in patients with coeliac disease and in normal controls.