Purpose: Extensive work in preclinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to... Show morePurpose: Extensive work in preclinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to therapeutics. In the human setting, this behavior is mainly correlated with the presence of immune cells. Here, in addition to T cells, B cells, macrophages, and mast cells, we identified the relevance of nonimmune cell types for breast cancer survival and therapy benefit, including fibroblasts, myoepithelial cells, muscle cells, endothelial cells, and seven distinct epithelial cell types.Experimental Design: Using single-cell sequencing data, we generated reference profiles for all these cell types. We used these reference profiles in deconvolution algorithms to optimally detangle the cellular composition of more than 3,500 primary breast tumors of patients that were enrolled in the SCAN-B and MATADOR clinical trials, and for which bulk mRNA sequencing data were available.Results: This large data set enables us to identify and subsequently validate the cellular composition of miaoenvironments that distinguish differential survival and treatment benefit for different treatment regimens in patients with primary breast cancer. In addition to immune cells, we have identified that survival and therapy benefit are characterized by various contributions of distinct epithelial cell types.Conclusions: From our study, we conclude that differential survival and therapy benefit of patients with breast cancer are characterized by distinct microenvironments that include specific populations of immune and epithelial cells. Show less
Massive Open Online Course (MOOC) platforms capture the digital traces of millions of learners and generate an avalanche of “numbers” on learner behavior in MOOCs. Yet little is known about the... Show moreMassive Open Online Course (MOOC) platforms capture the digital traces of millions of learners and generate an avalanche of “numbers” on learner behavior in MOOCs. Yet little is known about the dynamics through which MOOCs can support individual learning as the cognitive and social constituents of this complex process and their interplay within this process do not clearly surface in this large mass of “numbers”. This study analyzed the content generated by learners in a MOOC discussion forum with a particular focus on the still under-explored cognitive dimension of learning in MOOCs and demonstrated how certain levels of cognitive engagement relate to learning. It further examined the interplay between the cognitive and social aspects, revealing the moderating role of the social aspect in the association between the lowest level of cognitive engagement and learning in a MOOC environment. The study concludes with discussing the theoretical and practical implications of the findings and with highlighting the need to consider the interdependencies between the cognitive and social variables and learning when designing and evaluating MOOCs. Show less
Massive Open Online Course (MOOC) platforms capture the digital traces of millions of learners and generate an avalanche of “numbers” on learner behavior in MOOCs. Yet little is known about the... Show moreMassive Open Online Course (MOOC) platforms capture the digital traces of millions of learners and generate an avalanche of “numbers” on learner behavior in MOOCs. Yet little is known about the dynamics through which MOOCs can support individual learning as the cognitive and social constituents of this complex process and their interplay within this process do not clearly surface in this large mass of “numbers”. This study analyzed the content generated by learners in a MOOC discussion forum with a particular focus on the still under-explored cognitive dimension of learning in MOOCs and demonstrated how certain levels of cognitive engagement relate to learning. It further examined the interplay between the cognitive and social aspects, revealing the moderating role of the social aspect in the association between the lowest level of cognitive engagement and learning in a MOOC environment. The study concludes with discussing the theoretical and practical implications of the findings and with highlighting the need to consider the interdependencies between the cognitive and social variables and learning when designing and evaluating MOOCs. Show less
Coppens, L.; de Jonge, M.; van Gog, T.; Kester, L. 2020
Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and... Show moreOvarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing all main subtypes of OC. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra-and interpatient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug-screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug-sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine. Show less
Loomans, C.J.M.; Giuliani, N.W.; Balak, J.; Ringnalda, F.; Gurp, L. van; Huch, M.; ... ; Koning, E.J.P. de 2018
