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- Peterziel, H, et al.
(författare)
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Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
- 2022
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Ingår i: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 6:1, s. 94-
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Tidskriftsartikel (refereegranskat)abstract
- The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.
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- Pérez-Escobar, Oscar, et al.
(författare)
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Resolving relationships in an exceedingly young Neotropical orchid lineage using Genotyping-by-sequencing data
- 2020
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- Poor morphological and molecular differentiation in recently diversified lineages is a widespread phenomenon in plants. Phylogenetic relationships within such species complexes are often difficult to resolve because of the low variability in traditional molecular loci. Furthermore, biological phenomena responsible for topological incongruence such as Incomplete Lineage Sorting (ILS) and hybridisation complicate the resolution of phylogenetic relationships among closely related taxa. In this study, we employ a Genotyping-by-sequencing (GBS) approach to disentangle evolutionary relationships within a species complex belonging to the Neotropical orchid genus Cycnoches. This complex includes seven taxa distributed through Central America and the Colombian Choco, and is nested within a Glade estimated to have first diversified in the early Quaternary. Previous phylogenies inferred from few loci failed to provide support for internal relationships within the complex. Our Neighbour-net and coalescent-based analyses inferred from ca. 13,000 GBS loci obtained from 31 individuals belonging to six of the seven traditionally accepted Cycnoches taxa provided a robust phylogeny for this group. The genus Cycnoches includes three main clades that are further supported by morphological traits and geographic distributions. Similarly, a topology reconstructed through maximum likelihood (ML) inference of con-catenated GBS loci produced results that are comparable with those reconstructed through coalescence and network-based methods. Our comparative phylogenetic informativeness analyses suggest that the low support evident in the ML phylogeny might be attributed to the abundance of uninformative GBS loci, which can account for up to 50% of the total number of loci recovered. The phylogenomic framework provided here, as well as morphological evidence and geographical patterns, suggest that the six entities previously thought to be different species or subspecies might actually represent only three distinct segregates. We further discuss the limited phylogenetic informativeness found in our GBS approach and its utility to disentangle relationships within recent and rapidly evolving species complexes. Our study is the first to demonstrate the utility of GBS data to reconstruct relationships within young (similar to 2 Ma) Neotropical plant clades, opening new avenues for studies of species complexes that populate the species-rich orchid family.
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- Keck, Michaela Kristina, et al.
(författare)
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Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
- 2023
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
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- Martinsons, C., et al.
(författare)
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Reconsidering the spectral distribution of light : Do people perceive watts or photons?
- 2024
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Ingår i: Lighting Research and Technology. - : SAGE Publications Ltd. - 1477-1535 .- 1477-0938.
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Tidskriftsartikel (refereegranskat)abstract
- The spectral distribution is a fundamental property of non-monochromatic optical radiation. It is commonly used in research and practical applications when studying how light interacts with matter and living organisms, including humans. In the field of lighting, misconceptions about the spectral distribution of light are responsible for unfounded claims, which pervade the scientific and technical communities. Starting from the definition of the spectral distribution, this paper describes the ambiguities and errors associated with a purely graphical analysis of the spectral distribution. It also emphasizes the importance of considering the particle nature of light in research involving both visual and non-visual effects, which implies using the spectral distribution expressed in the photon system of units, a system that has been seldom used in lighting research for historical reasons. The authors encourage lighting engineers and researchers to determine which system is best suited to their work and then proceed with the correct use of spectral distributions and of spectral weighting functions for applications involving optical radiation. © The Chartered Institution of Building Services Engineers 2024.
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