Uveal melanoma, as opposed to cutaneous melanoma, is a tumor which is predominantly located in the center of the eye. Given its potential aggressive nature with fatal consequences, it is important... Show moreUveal melanoma, as opposed to cutaneous melanoma, is a tumor which is predominantly located in the center of the eye. Given its potential aggressive nature with fatal consequences, it is important to start treatment in a timely manner. Currently, treatment consists of decreasing the size of the tumor by means of radiation therapy or surgery, but by mapping the genetic makeup of uveal melanoma, personalized treatment potentially becomes possible. In this thesis we tried to solve a piece of this genetic puzzle by focusing on genetic and cellular differences within and between different uveal melanoma. By means of an innovative new technique, digital PCR, we aimed to visualize this so-called heterogeneity. We demonstrate that we can accurately assess which genetic aberrations are present in uveal melanoma. Moreover, we show in what percentage of cells these aberrations are present. Additionally, we illustrate which cell types play an important role in uveal melanoma development. This way, we characterized a substantial amount of different uveal melanoma based on their heterogeneity profile. Lastly, we display whether and how uveal melanomas with a specific heterogeneity profile are susceptible to treatment. Show less
Hemophilia is a sex linked, recessive, hereditary disorder characterizedby excessive bleeding. This bleeding tendency manifestsitself in spontaneous hemorrhages in the joint cavities and muscles... Show moreHemophilia is a sex linked, recessive, hereditary disorder characterizedby excessive bleeding. This bleeding tendency manifestsitself in spontaneous hemorrhages in the joint cavities and muscles,and in excessive bleeding after trauma or surgical procedures.The first written references to the disease can be found in theBabylonian Talmud, in which it can be read that Rabbi Judah thePatriarch exempted the third son from circumcision if his motherhad already lost two sons because they had bled to death afterthis operation ( 1 ) . Rabbi Simon hen Gamaliel even forbade a boyto be circumcised whien sons of his mother's three elder sisters haddied from bleeding after circumcision ( 2).In the 19th century Wardrop discovered the prolonged clottingtime of hemophilic blood. For a long time lack of prothrombin washeld responsible for the clotting defect until in 1935 Quick foundthat the prothrombin time of hemophilic plasma was normal ( 2) .Patek and Taylor reported in 1937 that the prolonged clottingtime of hemophilic plasma could be normalized by the addition ofa globulin fraction of normal blood. For this reason the lackingclotting component was called antihemophilic globulin; later, byinternational agreement, it was named clotting factor VIII (2).In 1944 Pavlovsky observed that a mixture of the blood of twohemophiliacs known to him had a normal clotting time ( 3, 4). Theright interpretation of this finding was given only in 1952 and notby Pavlovsky himself. In that year reports from New York, SanFrancisco, and Oxford described a disease which was clinically andgenetically undistinguishable from hemophilia, but the lackingclotting component was not factor VIII ( 5-7). The missing factorin this new disorder, PTC-deficiency, Christmas disease or hemophiliaB, was later called factor IX. Show less
