Spontaneous development of Epstein-Barr Virus associated human lymphomas in a prostate cancer xenograft program

Prostate cancer research is hampered by the lack of in vivo preclinical models that accurately reflect patient tumour biology and the clinical heterogeneity of human prostate cancer. To overcome these limitations we propagated and characterised a new collection of patient-derived prostate cancer xenografts. Tumour fragments from 147 unsupervised, surgical prostate samples were implanted subcutaneously into immunodeficient Rag2-/-γC-/- mice within 24 hours of surgery. Histologic and molecular characterisation of xenografts was compared with patient characteristics, including androgen-deprivation therapy, and exome sequencing. Xenografts were established from 47 of 147 (32%) implanted primary prostate cancers. Only 14% passaged successfully resulting in 20 stable lines; derived from 20 independent patient samples. Surprisingly, only three of the 20 lines (15%) were confirmed as prostate cancer; one line comprised of mouse stroma, and 16 were verified as human donor-derived lymphoid neoplasms. PCR for Epstein-Barr Virus (EBV) nuclear antigen, together with exome sequencing revealed that the lymphomas were exclusively EBV-associated. Genomic analysis determined that 14 of the 16 EBV+ lines had unique monoclonal or oligoclonal immunoglobulin heavy chain gene rearrangements, confirming their B-cell origin. We conclude that the generation of xenografts from tumour fragments can commonly result in B-cell lymphoma from patients carrying latent EBV. We recommend routine screening, of primary outgrowths, for latent EBV to avoid this phenomenon

What about N? A methodological study of sample-size reporting in focus group studies

<p>Abstract</p> <p>Background</p> <p>Focus group studies are increasingly published in health related journals, but we know little about how researchers use this method, particularly how they determine the number of focus groups to conduct. The methodological literature commonly advises researchers to follow principles of data saturation, although practical advise on how to do this is lacking. Our objectives were firstly, to describe the current status of sample size in focus group studies reported in health journals. Secondly, to assess whether and how researchers explain the number of focus groups they carry out.</p> <p>Methods</p> <p>We searched PubMed for studies that had used focus groups and that had been published in open access journals during 2008, and extracted data on the number of focus groups and on any explanation authors gave for this number. We also did a qualitative assessment of the papers with regard to how number of groups was explained and discussed.</p> <p>Results</p> <p>We identified 220 papers published in 117 journals. In these papers insufficient reporting of sample sizes was common. The number of focus groups conducted varied greatly (mean 8.4, median 5, range 1 to 96). Thirty seven (17%) studies attempted to explain the number of groups. Six studies referred to rules of thumb in the literature, three stated that they were unable to organize more groups for practical reasons, while 28 studies stated that they had reached a point of saturation. Among those stating that they had reached a point of saturation, several appeared not to have followed principles from grounded theory where data collection and analysis is an iterative process until saturation is reached. Studies with high numbers of focus groups did not offer explanations for number of groups. Too much data as a study weakness was not an issue discussed in any of the reviewed papers.</p> <p>Conclusions</p> <p>Based on these findings we suggest that journals adopt more stringent requirements for focus group method reporting. The often poor and inconsistent reporting seen in these studies may also reflect the lack of clear, evidence-based guidance about deciding on sample size. More empirical research is needed to develop focus group methodology.</p

Ex vivo treatment of patient biopsies as a novel method to assess colorectal tumour response to the MEK1/2 inhibitor, Selumetinib

Abstract Although an array of new therapeutics has emerged for the treatment of colorectal cancer, their use is significantly impacted by variability in patient response. Better pre-clinical models could substantially improve efficacy as it may allow stratification of patients into the correct treatment regime. Here we explore acute, ex vivo treatment of fresh, surgically resected human colorectal tumour biopsies as a novel pre-clinical model for identifying patient response to specific therapeutics. The MEK1/2 inhibitor, Selumetinib (AZD6244, ARRY-142886) was used as a tool compound. Firstly, we established an acute treatment protocol and demonstrated this protocol could differentiate phenotypic and pharmacodynamic responses to Selumetinib (0–3uM). We then used the protocol to evaluate Selumetinib response in tumours from 23 colon cancer patients. These studies revealed that the agent inhibited pERK1/2 phosphorylation in all tumours, caused a significant decrease in proliferation in 5/23 (22%) tumours, and that KRAS/BRAF mutant tumours were particularly sensitive to the anti-proliferative effects of the agent. These data are consistent with data from clinical trials of Selumetinib, suggesting that acute treatment of small tumour biopsies is worthy of further exploration as a pre-clinical model to evaluate colorectal cancer response to novel therapies