Asbestos‐associated genome‐wide DNA methylation changes in lung cancer

Previous studies have revealed a robust association between exposure to asbestos and human lung cancer. Accumulating evidence has highlighted the role of epigenome deregulation in the mechanism of carcinogen‐induced malignancies. We examined the impact of asbestos on DNA methylation. Our genome‐wide studies (using Illumina HumanMethylation450K BeadChip) of lung cancer tissue and paired normal lung from 28 asbestos‐exposed or non‐exposed patients, mostly smokers, revealed distinctive DNA methylation changes. We identified a number of differentially methylated regions (DMR) and differentially variable, differentially methylated CpGs (DVMC), with individual CpGs further validated by pyrosequencing in an independent series of 91 non‐small cell lung cancer and paired normal lung. We discovered and validated BEND4, ZSCAN31 and GPR135 as significantly hypermethylated in lung cancer. DMRs in genes such as RARB (FDR 1.1 × 10^?19, mean change in beta [Δ] ?0.09), GPR135 (FDR 1.87 × 10^?8, mean Δ ?0.09) and TPO (FDR 8.58 × 10^?5, mean Δ ?0.11), and DVMCs in NPTN , NRG2 , GLT25D2 and TRPC3 (all with p <0.05, t‐test) were significantly associated with asbestos exposure status in exposed versus non‐exposed lung tumors. Hypomethylation was characteristic to DVMCs in lung cancer tissue from asbestos‐exposed subjects. When DVMCs related to asbestos or smoking were analyzed, 96% of the elements were unique to either of the exposures, consistent with the concept that the methylation changes in tumors may be specific for risk factors. In conclusion, we identified novel DNA methylation changes associated with lung tumors and asbestos exposure, suggesting that changes may be present in causal pathway from asbestos exposure to lung cancer.     

Radiographic manifestations of periapical inflammatory lesions

Diagnosis, treatment planning, and treatment monitoring in endodontics depend to a very large extent on results from radiographic examinations. The often complex anatomy in respect to the teeth themselves as well as their surrounding structures may render those tasks difficult. New tomographic techniques hold promises for improvements in all those areas, in particular techniques that can display the object in all its three dimensions and remove disturbing anatomical structures to make it possible to evaluate each root and its closest surroundings in detail. They also provide images, taken at different points in time, that are similar in geometry and contrast making it possible to evaluate differences occurring in the fourth dimension – time. Image‐processing techniques applied to digital images obtained with conventional periapical radiography can be of some help towards improved diagnosis provided that optimal irradiation geometry has been used during image acquisition. When conventional radiographs are used and conventional means employed for their evaluation, one should take radiographs from more than one direction to ensure that at least some three‐dimensional information will be obtained. When evaluating images over time they must be compared side by side to provide best possibilities of subjectively detecting changes occurring over time.     

Lysosomal Gold Accumulations in Pulmonary Macrophages

Although soluble gold has been widely used in the treatment of rheumatoid arthritis, little is known about the distribution of gold deposits in extra-articular tissues. In the synovial lining cells and articular cartilage, the morphology of lysosomes containing gold, the aurosomes, is well documented. Because gold may cause pulmonary injury, the morphology and distribution of gold deposits in pulmonary tissue should be recognized. We found morphologically typical aurosomes with electron-dense membranes and granules, giving the spectrum of gold in electron microprobe analysis, in the interstitial and alveolar macrophages in the open lung biopsies of 3 patients who had received gold treatment but not in 12 patients who had not received gold treatment. In contrast to previous studies, aurosomes were not found in the endothelial cells.     

Experiences and psychological distress of spouses of prostate cancer patients at time of diagnosis and primary treatment

We studied experiences and psychological distress of partners of prostate cancer patients at the time of diagnosis and primary treatment and investigated associates of their psychological wellbeing and the emotional social support they give to and receive from the patient. Using a quantitative questionnaire we studied the spouses’ experiences (psychological response and sources of information and emotional support at diagnosis; impacts of prostate cancer on partnership and sex life; impact of side effects of treatment) and the emotional support given and received, and measured their psychological symptom distress. Many spouses reported distressing experiences and all psychological symptoms. Two thirds perceived no impact of the cancer on the partnership while 29% no change in sex life. Distress was associated with a shock, fear of the man's death and impact of side effects, whereas emotional support from a doctor predicted less distress. More support given to the patient was associated with information and emotional support received from a doctor and the patient's sexual dysfunction and pain, and less with experiences of depression, no impact on the partnership and the patient's irritableness. The spouses’ distress was relieved by emotional support from a doctor, which along with received information also enhanced their capability to support the patient.     

Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients

We have previously demonstrated an association between genomic alterations in 19p13, 2p16, and 9q33.1 and asbestos exposure in patients' lung tumours. This study detected allelic imbalance (AI) in these regions in asbestos-exposed lung cancer (LC) patients' histologically normal pulmonary epithelium. We extended the analyses of tumour tissue to cover a large LC patient cohort and studied DNA copy number alteration (CNA) and AI in 19p13, 2p16, and 9q33.1 for the first time in combination. We found both CNA and AI in ≥2/3 of the regions to be significantly and dose-dependently (P < 0.001) associated with pulmonary asbestos fibre count. Twenty percent of the exposed patients' LC showed CNA in ≥2/3 of the regions, whereas none of the non-exposed patients' LC showed CNA in more than one region. AI was evident in 89% of the exposed and in only 26% of the non-exposed patients' LC. The genomic alterations in 19p13, 2p16, and 9q33.1 in compilation identified asbestos-exposed patients' lung tumours better than each of the regions alone. These alterations form the basis for the development of a combinatorial molecular assay that could be used to identify asbestos-related LC.