The Role of RUNX2 in Osteosarcoma Oncogenesis

Osteosarcoma is an aggressive but ill-understood cancer of bone that predominantly affects adolescents. Its rarity and biological heterogeneity have limited studies of its molecular basis. In recent years, an important role has emerged for the RUNX2 “platform protein” in osteosarcoma oncogenesis. RUNX proteins are DNA-binding transcription factors that regulate the expression of multiple genes involved in cellular differentiation and cell-cycle progression. RUNX2 is genetically essential for developing bone and osteoblast maturation. Studies of osteosarcoma tumours have revealed that the RUNX2 DNA copy number together with RNA and protein levels are highly elevated in osteosarcoma tumors. The protein is also important for metastatic bone disease of prostate and breast cancers, while RUNX2 may have both tumor suppressive and oncogenic roles in bone morphogenesis. This paper provides a synopsis of the current understanding of the functions of RUNX2 and its potential role in osteosarcoma and suggests directions for future study

Associations between Ethnic Minority Status and Popularity in Adolescence:The role of Ethnic Classroom Composition and Aggression

Although there are theoretical reasons to expect an association between ethnic minority status and popularity, research on this topic is scarce. Therefore, this association was investigated including the moderating role of the ethnic classroom composition and the mediating role of aggression. Data from the longitudinal Dutch SNARE (Social Network Analysis of Risk behavior in Early adolescence) project were used among first-year students (comparable to 5th grade) (N = 1134, N-classrooms = 51, M = 12.5 years, 137 non-Western ethnic minority students). Popularity and aggression were assessed with peer nominations. Multi-level Structural Equation Models showed that ethnic minority status was indirectly associated with higher popularity, through higher aggression. Moreover, with increasing numbers of ethnic minority students in the classroom, popularity levels of both ethnic majority and ethnic minority students decreased. Only when differences in aggression between ethnic minority and majority students were included in the analyses, while the ethnic classroom composition was not included, lower popularity levels were found for ethnic minority than ethnic majority students. Scientific and practical implications of this study were addressed in the discussion

Virtual Resection: A New Tool for Preparing for Nephron-Sparing Surgery in Wilms Tumor Patients

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome

Integrale afweging van ruimtegebruik. Ontwikkeling van een instrumentarium voor het beoordelen van veranderingen in aanwending van ruimte

Ruimte is gelimiteerd in Nederland en door de grote vraag naar ruimte is de ruimtedruk groot. Dit rapport beschrijft een methode om veranderingen in ruimtegebruik in het landelijk gebied te beoordelen. Een raamwerk is opgesteld om de afweging gestructureerd te kunnen maken. De te vergelijken situaties worden gespecificeerd, de effecten die met de verandering samenhangen worden geïdentificeerd, net als de doelstellingen van de beslisser. Hieruit volgen de criteria, deze worden via indicatoren meetbaar gemaakt en gewaardeerd. Op basis van de scores op de criteria wordt een afweging gemaakt. Voor deze beoordeling zijn MCA en MKBA uitgewerkt en vergeleken. Dit beoordelingskader is toegepast voor de casestudie Kuindermeer. Een rode (meer woningbouw en bedrijven) en een groene (meer natuur) variant zijn ontwikkeld en beoordeeld met MCA en MKBA. De ontwikkelde methode is toepasbaar gebleken en beide afwegingsmethoden komen tot een lichte voorkeur voor de groene variant. De methoden kunnen een belangrijke rol spelen in (interactieve) besluitvormingsprocessen

Genome-wide co-occupancy of AML1-ETO and N-CoR defines the t(8;21) AML signature in leukemic cells

BACKGROUND: Many leukemias result from chromosomal rearrangements. The t(8;21) chromosomal translocation produces AML1-ETO, an oncogenic fusion protein that compromises the function of AML1, a transcription factor critical for myeloid cell differentiation. Because of the pressing need for new therapies in the treatment of acute myleoid leukemia, we investigated the genome-wide occupancy of AML1-ETO in leukemic cells to discover novel regulatory mechanisms involving AML-ETO bound genes. RESULTS: We report the co-localization of AML1-ETO with the N-CoR co-repressor to be primarily on genomic regions distal to transcriptional start sites (TSSs). These regions exhibit over-representation of the motif for PU.1, a key hematopoietic regulator and member of the ETS family of transcription factors. A significant discovery of our study is that genes co-occupied by AML1-ETO and N-CoR (e.g., TYROBP and LAPTM5) are associated with the leukemic phenotype, as determined by analyses of gene ontology and by the observation that these genes are predominantly up-regulated upon AML1-ETO depletion. In contrast, the AML1-ETO/p300 gene network is less responsive to AML1-ETO depletion and less associated with the differentiation block characteristic of leukemic cells. Furthermore, a substantial fraction of AML1-ETO/p300 co-localization occurs near TSSs in promoter regions associated with transcriptionally active loci. CONCLUSIONS: Our findings establish a novel and dominant t(8;21) AML leukemia signature characterized by occupancy of AML1-ETO/N-CoR at promoter-distal genomic regions enriched in motifs for myeloid differentiation factors, thus providing mechanistic insight into the leukemic phenotype