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CD3xHER2 bsAb-mediated activation of resting T-cells at HER2 positive tumor clusters is sufficient to trigger bystander eradication of distant HER2 negative clusters through IFNγ and TNFα.
Get PDFBispecific antibodies (bsAbs) bridging CD3 on T-cells to tumor-associated antigens (TAA) on tumor cells can direct T-cell immunity to solid tumors. "Bystander killing", where T-cell targeting of TAA-positive tumor cells also leads to the eradication of TAA-negative cells, may overcome TAA heterogeneity. While bystander activity of activated, engineered T-cells has been shown to be robust and wide-reaching, spatiotemporal aspects of bsAb-mediated bystander activity are unresolved. Here, we developed a model where breast cancer tumoroids varying in HER2 expression were printed in to extracellular matrix (ECM) scaffolds. We generated (1) mixed tumors containing different ratios of HER2+ and HER2- tumor cells, and (2) HER2+ and HER2- tumoroids spaced at different distances within the ECM scaffold. Subsequently, tumors were exposed to peripheral blood-derived T-cells in the presence of CD3xHER2 bsAbs. We find that CD3xHER2 bsAb-mediated interaction of resting, nonactivated T-cells with HER2+ tumor cells is sufficient (1) to eliminate 50% HER2- cells in mixed tumor areas, and (2) to eradicate distant HER2- tumor areas. Such bystander killing involves paracrine IFNγ and TNFα activity but does not require T-cell accumulation in HER2- areas. These findings indicate that bystander eradication of TAA-negative cells can significantly contribute to bsAb therapy for solid tumors.Toxicolog
Immunotherapy for metastatic melanoma and beyond = immunotherapie voor gemetastaseerd melanoom en verder
Get PDFMelanoma is the most aggressive type of skin cancer and can occur in males and females of all ages. The prognosis of these patients is significantly related to disease stage and has greatly improved since the development of immunotherapies and targeted therapies. From the moment that the efficacy of immunotherapy in melanoma became evident, multiple clinical trials have also been conducted to investigate its efficacy in other solid tumors. Despite the advances in the treatment of patients with advanced (non)-melanoma skin cancer in the last decades, it remains a disease with a high mortality rate for which development of novel effective treatment options is still essential. This thesis aims to provide insights into such novel treatment strategies with cellular and non-cellular (immuno)therapies for patients with advanced melanoma and non-melanoma skin cancer.LUMC / Geneeskund
Personalized lifestyle interventions for the prevention and treatment of type 2 diabetes
Get PDFVarious studies have shown that a healthy lifestyle can reduce the incidence of type 2 diabetes and have beneficial effects on blood sugar levels in people with type 2 diabetes, with weight loss, healthy eating, and physical activity playing a role. However, the effects of lifestyle interventions differ significantly between individuals. This is partly due to differences in lifestyle, preferences, genetic characteristics, and physiological responses among individuals. Personalized lifestyle interventions based on personal data led to better adherence to dietary advice and improvements in health, such as weight loss and body composition, in a healthy population. Also, lifestyle interventions work best for people who had a reduced health status. Type 2 diabetes is increasingly recognized as a heterogeneous disease, with individuals differing in glucose metabolism, degree of insulin resistance, and disease progression. Personalized advice based on the diabetes pathophysiology, combined with behavior change support, could be more effective in improving glucose metabolism and achieving and maintaining weight loss than the standard primary care. Continuous glucose monitoring can help provide real-time feedback and optimize glucose levels in people with diabetes. Understanding and measuring individual responses to lifestyle interventions can make these interventions more effective.the Netherlands Organisation for applied scientific research (TNO);
Netherlands Association for the Study of Obesity (NASO) ;
Leiden UniversityLUMC / Geneeskund
Slavery and global history: reflections on the 10th Anniversary of the journal of global slavery
Get PDFCities, Migration and Global Interdependence 1350-200
Exploring new horizons: challenges and opportunities for ehealth in geriatric rehabilitation
Get PDFeHealth holds potential to improving rehabilitation outcomes for older adults receiving geriatric rehabilitation. Blended and simple eHealth interventions are the most promising and feasible. Despite these potentials, the adoption of eHealth in geriatric rehabilitation is still limited. Key barriers need to be overcome, such as the lack of usability outcomes, the lack of an organization-wide implementation strategy and the urgent need for healthcare professionals for reliable information on how to effectively identify, use and evaluate eHealth. Additionally, wearable sensors have proven to be capable of quantifying physical activity, sedentary behaviour and the patterns of sedentary in older adults during and after geriatric rehabilitation. Notably, this population engages in very low levels of physical activity and spends the majority of their waking hours in sedentary behaviour. Finally, The use of wearable sensors show potential in improving the prediction of functional recovery at discharge.LUMC / Geneeskund
Do readers anticipate wh-in-situ questions?: Cross-linguistic reading time evidence from Mandarin Chinese and French
Get PDFThe understanding of wh-in-situ questions relies naturally on contextual and prosodic information for their early discrimination from declarative sentences. However, there is scarce evidence on the parsing processes involved during the online incremental processing of these questions. In this study, we investigate the incremental reading of wh-in-situ sentences with no prosodic or contextual information available to aid the parser by comparing them to their declarative counterparts. We investigated two wh-in-situ languages: Mandarin Chinese (in-situ only) and French (optionally in situ). This comparison allows us to determine whether wh-in-situ questions are processed similarly across languages and whether the parsing process is related to language-specific question formation strategies. Results of four word-by-word self-paced reading experiments on two types of wh-in-situ phrases (simplex or complex) in Mandarin Chinese and French show an interpretation strategy in which the most frequent structure, declarative, is considered in both languages, independently of the available question formation strategy. Nevertheless, the timing of the online interpretation and the observed effects are affected by the nature of the wh-phrases (simplex or complex) and the definiteness of the noun phrases contained in the declaratives, which confirms that several processes occur concurrently introducing a limit on the capability to extract conclusions on the processes based solely on behavioral measures.NWO360-70-480Theoretical and Experimental Linguistic
Comparative wood anatomy and evolution of Apocynaceae and Sapotaceae
Get PDFIn my research, I used a comparative wood anatomical approach to address wood evolution of the (largely) tropical flowering plant families Apocynaceae and Sapotaceae. Both families were chosen because they have valuable timber species that are well-represented in wood collections, occur in diverse habitats, have species with different growth forms, but for which the wood anatomy was understudied. I sectioned and stained wood samples following standardised protocols after which the I described the anatomical variation using light-and scanning electron microscopy. These descriptions were combined with existing ones and I performed ancestral state reconstructions on a large set of wood traits with modern comparative modelling methods that use phylogenies based on molecular differences. This allowed me, for the first time, to present the most complete wood anatomical overview of both families. I made comparisons among species of the same family to investigate intrafamilial relationships and to reconstruct wood anatomical evolutionary trends. Moreover, I investigated the impact of growth form and plant size on wood anatomical variation.Alberta Mennega StichtingNaturali
Elephantine Judaism / Yahwism in the context of Elephantine during the Achaemenid Period
Get PDFThis paper explores the religious identity and practices of the Jewish community in Elephantine during the Achaemenid period, focusing on the archaeological and textual evidence from the site itself, rather than the Hebrew Bible. It critiques previous scholarship’s reliance on biblical texts to interpret Elephantine Judaism, which often viewed it as either a deviation or a purer form of biblical Judaism. The study emphasizes a need for a fresh approach that considers Elephantine’s own cultural context and artifacts, highlighting the diversity of religious practices, including syncretic elements and unique customs, as distinct expressions of Elephantine’s community identity.Religious StudiesMiddle Eastern Studie
Het op atomaire schaal afbeelden van chemische reacties op oppervlakken
Get PDFOratie uitgesproken door bij de aanvaarding van het ambt van hoogleraar Surface and Interface Science of Chemie van oppervlakken en grensvlakken aan de Universiteit Leiden op vrijdag 28 maart 2025Catalysis and Surface Chemistr
The expression of information structure in Makhuwa-Enahara
Get PDFThis chapter describes which morphosyntactic strategies Makhuwa-Enahara usesto structure the information in a sentence. Makhuwa-Enahara is a language inwhich word order plays an important role in expressing information structure:the preverbal domain is reserved for topics, non-topical subjects occur in subjectinversion, and there is an immediate after verb (IAV) focus position. The conjointverb form expresses exclusive focus on the IAV constituent, whereas the disjointverb form is an elsewhere form. A topic doubling construction involving a frontedinfinitive may be used to express verum, and three types of cleft sentences areused to express focus. Pronouns and (emphatic) demonstratives are used to indicatereferent activation and contrast.NWO276-78-001Descriptive and Comparative Linguistic