Background and AimsPrior studies on the effect of smoking on the risk of colitis-associated colorectal neoplasia (CRN) have reported conflicting results. We aimed to further elucidate the... Show moreBackground and AimsPrior studies on the effect of smoking on the risk of colitis-associated colorectal neoplasia (CRN) have reported conflicting results. We aimed to further elucidate the association between smoking, including possible dose-effects, and the development of colorectal neoplasia in patients with inflammatory bowel disease (IBD).MethodsWe performed a prospective multicenter cohort study including patients with colonic IBD enrolled in a surveillance program in four academic hospitals between 2011 and 2021. The effects of smoking status and pack-years at study entry on subsequent recurrent events of CRN (including indefinite, low- and high-grade dysplasia, and colorectal cancer [CRC]) were evaluated using uni- and multivariable Prentice, Williams, and Peterson total-time Cox proportional hazard models. Adjustment was performed for extensive disease, prior/index dysplasia, sex, age, first-degree relative with CRC, primary sclerosing cholangitis, and endoscopic inflammation.ResultsIn 501 of the enrolled 576 patients, at least one follow-up surveillance was performed after the study index (median follow-up 5 years). CRN occurred at least once in 105 patients. Ever smoking was not associated with recurrent CRN risk (adjusted hazard ratio [aHR] 1.04, 95% confidence interval [CI] 0.75–1.44), but an increasing number of pack-years was associated with an increased risk of recurrent CRN (aHR per 10 pack-years 1.17, 95% CI 1.03–1.32; p < 0.05). Separate analyses per IBD type did not reveal differences.ConclusionsThis study found that an increase in pack-years is associated with a higher risk of recurrent CRN in patients with IBD, independent of established CRN risk factors (NCT01464151). Show less
The TME has increasingly been recognized as an important player in tumor progression and metastasis and a possible target for therapy. The TME consists of multiple cell types secreting growth... Show moreThe TME has increasingly been recognized as an important player in tumor progression and metastasis and a possible target for therapy. The TME consists of multiple cell types secreting growth factors and cytokines that exert either pro- or anti-tumor effects. This thesis mainly focuses on studies of the TME, especially the effects of Endoglin, on several cell types within the TME, including endothelial cells, fibroblasts, and immune cells.The TME has increasingly been recognized as an important player in tumor progression and metastasis and a possible target for therapy. The TME consists of multiple cell types secreting growth factors and cytokines that exert either pro- or anti-tumor effects. This thesis mainly focusses on studies of the TME, especially the effects of Endoglin, on several cell types within the TME, including endothelial cells, fibroblasts, and immune cells. This thesis aims to unravel the role of Endoglin as a possible target on various cell types within the TME of solid tumors. Endoglin is known for its role during angiogenesis, however, an increasing number of studies have shown the importance of Endoglin expression on several other cell types (e.g., immune cells, CAFs, tumor cells). Show less
In dit proefschrift worden studies besproken naar de rol van de TGF-β signaleringsroute in de tumor micro-omgeving in colorectaal kanker. Deze studies hebben zich voornamelijk gefocust op de rol... Show moreIn dit proefschrift worden studies besproken naar de rol van de TGF-β signaleringsroute in de tumor micro-omgeving in colorectaal kanker. Deze studies hebben zich voornamelijk gefocust op de rol van kanker-geassocieerde fibroblasten (CAFs) in kanker. Wij hebben aangetoond dat een co-receptor voor TGF-β, endoglin, een grote rol speelt in het CAF-gemedieerd uitzaaien van darmkanker en dat de expressie van endoglin op CAFs een prognostische marker is voor metastase-vrije overleving in vroeg stadium darmkankerpatienten. Daarnaast werd een nieuwe muizenstam ontwikkeld om specifiek op fibroblasten endoglin uit te schakelen, zodat de rol hiervan in het ontstaan van darmkanker bestudeerd kon worden in een chemisch geinduceerd model voor darmkanker. Samengevat laten de studies in dit proefschrift zien dat endoglin expressie op CAFs een belangrijke rol speelt in het metastaseren van colorectaalkanker en opent het deuren naar therapeutische toepassingen. Show less
Pardieck, I.N.; Jawahier, P.A.; Swets, M.; Velde, C.J.H. van de; Kuppen, P.J.K. 2016
In recent years the international community has paid closer attention to the phenomenon of child-headed households; these are households where a child has taken over the majority of... Show moreIn recent years the international community has paid closer attention to the phenomenon of child-headed households; these are households where a child has taken over the majority of responsibilities of the main caregiver. The primary factors leading to this situation are HIV/AIDS, poverty, conflict and the disintegration of the traditional extended family network. Although children who are deprived of adequate parental care have the right to alternative care, millions of children – including those living in child-headed households – have no recourse to this fundamental right. This study presents an overview of alternative care as well as the factual situation of child-headed households in a selected group of focus countries in sub-Saharan Africa and further provides recommendations aimed at both legal and policymaking issues relating to the existing alternative care systems. This research seeks answers to the question: “What does the internationally recognised right to alternative care for children entail and is the recognition of child-headed households as a form of alternative care in line with the Convention on the Rights of the Child and other international standards which have been adopted as a measure to protect the inherent rights of children to protection, development, survival and participation?” Show less
