Different cellular p16(INK4a) localisation may signal different survival outcomes in head and neck cancer.

BACKGROUND: Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status. METHODS: Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS). RESULTS: A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status. CONCLUSION: Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.

Positron emission tomography imaging for herpes virus infection: Implications for oncolytic viral treatments of cancer.

Molecular therapy using viruses would benefit greatly from a non-invasive modality for assessing dissemination of viruses. Here we investigated whether positron emission tomography (PET) scanning using [(124)I]-5-iodo-2'-fluoro-1-beta-d-arabinofuranosyl-uracil (FIAU) could image cells infected with herpes simplex viruses (HSV). Using replication-competent HSV-1 oncolytic viruses with thymidine kinase (TK) under control of different promoters, we demonstrate that viral infection, proliferation and promoter characteristics all interact to influence FIAU accumulation and imaging. In vivo, as few as 1 x 107 viral particles injected into a 0.5-cm human colorectal tumor can be detected by [(124)I]FIAU PET imaging. PET signal intensity is significantly greater at 48 hours compared with that at 8 hours after viral injection, demonstrating that PET scanning can detect changes in TK activity resulting from local viral proliferation. We also show the ability of FIAU-PET scanning to detect differences in viral infectivity at 0.5 log increments. Non-invasive imaging might be useful in assessing biologically relevant distribution of virus in therapies using replication-competent HSV.

Author Correction: Solar superstorm of AD 774 recorded subannually by Arctic tree rings.

The authors became aware of a mistake in the data displayed in Fig. 1 and Supplementary Table 2 of the original version of the Article. Specifically, the 14C production values were printed out in the code before the conversion between the omnidirectional fluence and the flux. As a consequence, the values of the 14C production in Fig. 1 and Supplementary Table 2 were too high by a factor of 4×π = 12.566.. As a result of this, a number of changes have been made to both the PDF and the HTML versions of the Article. A full list of these changes is available online.

Solar superstorm of AD 774 recorded subannually by Arctic tree rings.

Recently, a rapid increase in radiocarbon (14C) was observed in Japanese tree rings at AD 774/775. Various explanations for the anomaly have been offered, such as a supernova, a γ-ray burst, a cometary impact, or an exceptionally large Solar Particle Event (SPE). However, evidence of the origin and exact timing of the event remains incomplete. In particular, a key issue of latitudinal dependence of the 14C intensity has not been addressed yet. Here, we show that the event was most likely caused by the Sun and occurred during the spring of AD 774. Particularly, the event intensities from various locations show a strong correlation with the latitude, demonstrating a particle-induced 14C poleward increase, in accord with the solar origin of the event. Furthermore, both annual 14C data and carbon cycle modelling, and separate earlywood and latewood 14C measurements, confine the photosynthetic carbon fixation to around the midsummer.