Uveal melanoma (UM) is the most common malignancy of the eye in adults and it is the second most common form of melanoma after cutaneous melanoma (CM). The identification of patients who have a... Show moreUveal melanoma (UM) is the most common malignancy of the eye in adults and it is the second most common form of melanoma after cutaneous melanoma (CM). The identification of patients who have a high risk of developing metastases would allow the possibility of providing adjuvant therapies to prevent metastases. The application of FISH on transvitreal fine-needle aspiration biopsies is thought to be a reliable method for assaying genetic parameters such as chromosome 3 loss. However, this is based on the assumption that this chromosomal abnormality is distributed homogeneously throughout the tumor. We show that UM can be heterogeneous for the number of copies of chromosome 3 and investigated whether any evidence can be found for heterogeneity in the regulation of tumor-suppressor genes (TSG). Recently, a segregation study identified a potential locus harboring a TSG. One of the genes in this area, RASEF, was analyzed whether the RASEF gene was affected by mutations or gene silencing due to promoter methylation. The MAPK pathway is involved in the balance between melanocyte proliferation and differentiation. Whereas mutant B-RAF and N-RAS are responsible for the activation of the MAPK pathway in most CM, mutations in these genes are usually absent in UM. Nowadays, an assay with increased potential to identify mutations is available and we set out to reanalyze UM cell lines and primary UM for B-RAF mutations. We set out to explore the MAPK pathway by using MAPK profiling and tyrosine kinase arrays. Finally, conclusions drawn from above mentioned studies are summarized and put into perspective. Show less
Rheumatoid arthritis (RA) is a disease characterized by arthritis of mainly the small joints of the hands and feet, which is thought to be the result of an autoimmune response. It is the most... Show moreRheumatoid arthritis (RA) is a disease characterized by arthritis of mainly the small joints of the hands and feet, which is thought to be the result of an autoimmune response. It is the most common inflammatory arthritis with a prevalence of 0.5-1.0% in European and North-American populations 1. There is substantial geographic variation in the occurrence of RA with very high prevalences reported in native American-Indian populations 2, and very low prevalences in populations from South-East Asia 3. The disease is approximately three times more frequent in women than in men, and the prevalence increases with age. Besides the potentially destructive arthritis, patients can be affected by various extraarticular features such as secondary Sj_gren__s syndrome, interstitial lung disease, pericarditis and pleuritis. Fortunately, the advent of tumor necrosis factor (TNF) inhibitors and other biological agents have led to a therapeutic revolution for patients with rheumatoid arthritis 4. Instead of having to resign to an inevitably progressive and debilitating disease course, modern-day treatment aims at achieving the lowest possible disease activity and ultimately remission. Nonetheless, rheumatoid arthritis continues to be a major cause of (partial) disability and of loss of productivity, and is associated with substantial economic costs 5. Classification criteria for the disease were first phrased in 1956 6 after Sir Alfred Garrod had introduced the term rheumatoid arthritis in 1876 in an attempt to counteract the unsatisfactory use of designations such as __chronic rheumatism__ and __rheumatic gout__ 7. The purpose of the classification criteria was to facilitate both clinical diagnosis and scientific research. For many years since, the 1987 American College of Rheumatology (ACR) classification criteria have been used to this end, despite the fact that the incorporation of items such as erosive radiographic changes led to limited diagnostic value of these criteria for patients with early arthritis 8. In order to facilitate the study of persons with earlier stages of disease, the ACR and the European League Against Rheumatism (EULAR) have recently developed the 2010 classification criteria for RA as shown in Table 1 9. It is worthwhile to note that these criteria are based on patient characteristics which were associated with the decision by the physician to start treatment with methotrexate. These criteria are a reflection of the shift towards increasingly earlier diagnosis and treatment of rheumatoid arthritis. Show less
