Prostate cancer (PCa) is the second most prevalent cancer among men worldwide when assessing age-standardized incidence rates. The primary method for early PCa diagnosis involves measuring the... Show moreProstate cancer (PCa) is the second most prevalent cancer among men worldwide when assessing age-standardized incidence rates. The primary method for early PCa diagnosis involves measuring the serum concentration of prostate-specific antigen (PSA), with elevated levels (> 3 ng/mL in the Netherlands) indicating the potential presence of PCa. However, the conventional PSA test exhibits a low specificity. Thus, clinical challenges persist, including the differentiation between PCa and benign prostatic hyperplasia and distinguishing indolent PCa from aggressive forms. This underscores the need for a more specific biomarker for early PCa detection and stratification. Previous studies have reported altered glycosylation features in two prostate-secreted glycoproteins, PSA and prostatic acid phosphatase (PAP) in PCa patients, e.g. variation in sialylation, fucosylation and the level of LacdiNAc . The aim of this thesis was to identify PCa biomarkers for early detection and to improve patient stratification, focusing specifically on the glycomic profiles of PSA and PAP. In addition, as PSA plays an important role with regard to fertility, its glycosylation -in relation to male infertility- was also touched upon. For this purpose, mass spectrometry (MS) based glycoproteomic methods were established to map the glycoprofiles of PSA and PAP derived from various biofluids. Show less
In this thesis, we focus on novel proteins/mechanisms that regulate integrin-adhesion mediated mechano-transduction. We characterized the role of integrin α6β4/HD and caskin2 in force generation... Show moreIn this thesis, we focus on novel proteins/mechanisms that regulate integrin-adhesion mediated mechano-transduction. We characterized the role of integrin α6β4/HD and caskin2 in force generation via FA, investigated the underlying crosstalk between adhesions and cytoskeletons. Moreover, we also explored the mechanism that drives the integrin αVβ5 clustering in FCLs, in which cell tension is also involved. Last but not the least, we investigated the role of an unexplored protein, caskin2, in the regulation of cellular mechanics. Show less
This thesis illuminates painting inscriptions written in the Ming dynasty (1368-164) in a social context, revealing that inscriptions as a particular genre of text richly encompass themes... Show more This thesis illuminates painting inscriptions written in the Ming dynasty (1368-164) in a social context, revealing that inscriptions as a particular genre of text richly encompass themes relevant but not confined to social history, material culture, early modern publishing, identity construction, and self-knowledge. This thesis argues that painting inscriptions written in the Ming era are not only the result of artistic concerns; on many occasions, the production, utilization, and circulation of inscriptions had social concerns, meanings, and influences. Inscriptions as such are rich of notions, attitudes and thoughts, which can be helpful to understand Ming artists and their world, as well as an important source for scholars to explore social and intellectual history of the Ming era. This study, perhaps for the first time, brings two types of sources of inscriptions—existing paintings and textual anthologies—into the vision of academia. The two sources also represent two categories of inscriptions and their dual nature. Inscriptions are material objects with trajectories of circulation and dissemination; on the other hand, they are the texts of histories of reproduction and dissemination. The two categories of inscriptions are transmittable. A Ming painting is not a closed entity, but rather a dynamic entity. Show less
