Increased anti-tumour efficacy of doxorubicin when combined with sulindac in a xenograft model of an MRP-1-positive human lung cancer

Background: A number of cellular proteins, including P-glycoprotein (P-gp) and Multiple drug Resistance Protein (MRP-1), act as drug efflux pumps and are important in the resistance of many cancers to chemotherapy. We previously reported that a small number of NSAIDs could inhibit the activity of MRP-1. Materials and Methods: We chose sulindac as a candidate agent for further investigation as it has the most favourable efficacy and toxicity profile of the agents available for a potential specific MRP-1 inhibitor. NCI H460 cells expressed MRP-1 protein (by Western blot) and also the toxicity, of doxorubicin (a substrate of MRP-1) could be potentiated in this line using non-toxic concentrations of the MRP-1 substrate/inhibitor sulindac. These cells were implanted in nude mice and the animals divided into various groups which were administered doxorubicin and/or sulindac. Results: Sulindac was shown to significantly potentiate the tumour growth inhibitor activity of doxorubicin in this MRP-1-overexpressing human tumour xenograft model. Conclusion: Sulindac may be clinically useful as an inhibitor of the MRP-1 cancer resistance mechanism.

Young Women’s Positive and Negative Perceptions of Self in Northern Ireland

This paper represents analysis of one aspect of a larger research project examining the everyday lives and experiences of young women in Northern Ireland. As an introductory exercise within focus groups, 48 young women considered and discussed the good and not so good things about being a young woman in Northern Ireland. Through these accounts many issues emerged, some in direct contrast and contradiction to one another. The area focused upon for the purpose of this paper is the body, particularly with regard to body image (self-expression versus pressure) and becoming a woman (growing up versus menarche). The aim is to illustrate that what young women cite as being potentially positive aspects of growing up or being a young woman often have negative experiences and implications attached to them. In light of the advancements made by young women in Northern Irish society, an opening of opportunities and their awareness of the persistence of gendered messages regarding their bodies, many young women are of the belief that such messages have less impact upon them today and that gender is a barrier that can be overcome. It is illustrated and argued here, however, that dominant cultural messages regarding women’s bodies are more subtle, confusing and perhaps pervasive than they ever have been. As a consequence, this has created more pressure and confusion for young women and tensions exist in terms of young women’s beliefs and their actions. In light of these research findings, this paper considers practice implications for those working with and for young women.

A novel method for isolation of human lung T cells from lung resection tissue reveals increased expression of GAPDH and CXCR6

Lung T lymphocytes are important in pulmonary immunity and inflammation. it has been difficult to study these cells due to contamination with other cell types, mainly alveolar macrophages. We have developed a novel method for isolating lung T cells from lung resection tissue, using a combination of approaches. Firstly the lung tissue was finely chopped and filtered through a nylon mesh. Lymphocytic cells were enriched by Percoll density centrifugation and the T cells purified using human CD3 microbeads, resulting in 90.5% +/- 1.9% (n = 11) pure lymphocytes. The T cell yield from the crude cell preparation was 10.8 +/- 2.1% and viability, calculated using propidium iodide (PI) staining and trypan blue, was typically over 95%. The purification process did not affect expression of CD69 or CD103, nor was there a difference in the proportion of CD4 and CD8 cells between the starting population and the purified cells. Microarray analysis and real time RT-PCR revealed upregulation of GAPDH and CXCR6 of the lung T cells as compared to blood-derived T cells. This technique highly enriches lung T cells to allow detailed investigation of the biology of these cells. (C) 2008 Elsevier B.V. All rights reserved.