A viral aetiology has long been suspected for Alzheimer's disease (AD) but until now, techniques have not been sufficiently sensitive to provide clear evidence for or against the presence of any viral genome in AD brain. We have used the very highly sensitive method of polymerase chain reaction to look for herpes simplex virus type 1 (HSV1) DNA, specifically the viral thymidine kinase (TK) gene, in autopsy brain specimens. DNA-samples from HSV-infected and uninfected Vero cells have been examined concurrently to provide standard "HSV-positive" and "HSV-negative" samples, the latter guarding also against false positives caused by cross-contamination. To preclude false negatives, we have checked the presence of the human gene, hypoxanthine phosphoribosyl transferase. In all specimens from 8 AD patients and 6 normal individuals (temporal, frontal and hippocampal), we have found viral TK sequences. In contrast, in preliminary studies on lymphocytes from normals and AD patients, we did not find TK sequences. It is postulated that factors such as number or expression of viral genes and host susceptibility might be related to incidence of AD.

Objectives To present historical and contemporary hypotheses on the pathogenesis of benign prostatic hyperplasia (BPH), and the potential implications for current medical therapies. Methods The literature on BPH was reviewed. BPH is a prevalent disease with significant health and economic impacts on patients and health organisations across the world, whilst the cause/initiation of the disease process has still not been fully determined. Results In BPH, pathways involving androgens, oestrogens, insulin, inflammation, proliferative reawakening, stem cells and telomerase have been hypothesised in the pathogenesis of the disease. A number of pathways first described >40 years ago have been first rebuked and then have come back into favour. A system of an inflammatory process within the prostate, which leads to growth factor production, stem cell activation, and cellular proliferation encompassing a number of pathways, is currently in vogue. This review also highlights the physiology of the prostate cell subpopulations and how this may account for the delay/failure in treatment response for certain medical therapies. Conclusion BPH is an important disease, and as the pathogenesis is not fully understood it impacts the effectiveness of medical therapies. This impacts patients, with further research potentially highlighting novel therapeutic avenues.

This study examined the initial behaviour of 48 human oral squamous cell carcinomas (SCC) in cell culture. The early outcome of these cultures (contamination, absence of cell growth, epithelial cell senescence/fibroblast overgrowth, extended keratinocyte growth) did not reflect the clinical characteristics of the tumours of origin. Four new human oral SCC cell lines were characterized more extensively. Each cell line was immortal, 3T3-independent, and expressed low degrees of anchorage independence (CFE less than 4 per cent). Two of the four cell lines were tumorigenic in athymic mice. All of the cell lines expressed keratin intermediate filaments and two showed weak co-expression of vimentin. A wide range of keratins were expressed by the tumour xenografts; cornified keratins (K1, K10) were only expressed in the absence of K19 and vimentin, and vice versa. The nuclear:cytoplasmic ratio and the degree of serum independence correlated with each other and with the STNMP clinical grading of the tumours of origin.

Radiotherapy is a mainstay of curative prostate cancer treatment, but risks of recurrence after treatment remain significant in locally advanced disease. Given that tumor relapse can be attributed to a population of cancer stem cells (CSC) that survives radiotherapy, analysis of this cell population might illuminate tactics to personalize treatment. However, this direction remains challenging given the plastic nature of prostate cancers following treatment. We show here that irradiating prostate cancer cells stimulates a durable upregulation of stem cell markers that epigenetically reprogram these cells. In both tumorigenic and radioresistant cell populations, a phenotypic switch occurred during a course of radiotherapy that was associated with stable genetic and epigenetic changes. Specifically, we found that irradiation triggered histone H3 methylation at the promoter of the CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), stimulating its gene transcription. Inhibiting this methylation event triggered apoptosis, promoted radiosensitization, and hindered tumorigenicity of radioresistant prostate cancer cells. Overall, our results suggest that epigenetic therapies may restore the cytotoxic effects of irradiation in radioresistant CSC populations. Cancer Res; 76(9);