Misregulation of DNA damage repair pathways in HPV-positive head and neck squamous cell carcinoma contributes to cellular radiosensitivity

Patients with human papillomavirus type 16 (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCC) display increased sensitivity to radiotherapy and improved survival rates in comparison to HPV-negative forms of the disease. However the cellular mechanisms responsible for this characteristic difference are unclear. Here, we have investigated the contribution of DNA damage repair pathways to the in vitro radiosensitivity of OPSCC cell lines. We demonstrate that two HPV-positive OPSCC cells are indeed more radiosensitive than two HPV-negative OPSCC cells, which correlates with reduced efficiency for the repair of ionising radiation (IR)-induced DNA double strand breaks (DSB). Interestingly, we show that HPV-positive OPSCC cells consequently have upregulated levels of the proteins XRCC1, DNA polymerase β, PNKP and PARP-1 which are involved in base excision repair (BER) and single strand break (SSB) repair. This translates to an increased capacity and efficiency for the repair of DNA base damage and SSBs in these cells. In addition, we demonstrate that HPV-positive but interestingly more so HPV-negative OPSCC display increased radiosensitivity in combination with the PARP inhibitor olaparib. This suggests that PARP inhibition in combination with radiotherapy may be an effective treatment for both forms of OPSCC, particularly for HPV-negative OPSCC which is relatively radioresistant

Mammographic density and breast cancer risk: current understanding and future prospects

Variations in percent mammographic density (PMD) reflect variations in the amounts of collagen and number of epithelial and non-epithelial cells in the breast. Extensive PMD is associated with a markedly increased risk of invasive breast cancer. The PMD phenotype is important in the context of breast cancer prevention because extensive PMD is common in the population, is strongly associated with risk of the disease, and, unlike most breast cancer risk factors, can be changed. Work now in progress makes it likely that measurement of PMD will be improved in the near future and that understanding of the genetics and biological basis of the association of PMD with breast cancer risk will also improve. Future prospects for the application of PMD include mammographic screening, risk prediction in individuals, breast cancer prevention research, and clinical decision making

Social media for pediatric research: what, who, why, and #?

In the age of Facebook congressional hearings and “Twitter diplomacy,” the impact of social media on society is difficult to ignore. Although social media isn’t new and its role in health care continues to grow, misconceptions of its purpose and utility in medicine are common, and some remain skeptical of its value.1 We provide a brief overview of the potential for social media to advance pediatric research and describe the use of hashtags, elaborating with an example from the neonatal clinical research community

The SOUDAN 2 detector - The design and construction of the tracking calorimeter modules

SOUDAN 2 is a 960-ton tracking calorimeter which has been constructed to search for nucleon decay and other phenomena. The full detector consists of 224 calorimeter modules each weighing 4.3 tons. The design and construction of the modules are described. The modules consist of finely segmented iron instrumented with 1 m long drift tubes of 15 mm internal diameter. The tubes enable three spatial coordinates and dE/dx to be recorded for charged particles traversing the tubes