Hepatoblastoma (HB) is the most common form of liver cancer in young children.
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Therefore, investigating a large volume (100–1000 pL) of biological tissue in 3D at a high resolution was hardly possible until the development of 3D EM technologies including serial block-face (SBF)-SEM and Focused Ion Beam-SEM 3, 4, 5, 6. Although effective, these techniques produce images only in two dimensions. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are routinely used to collect ultrastructural data from biological specimens at nanoscale resolution and to correlate structural images with biological functions.
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Since its advent in the 1930s, EM has allowed the in-depth analysis of a wide range of biological samples. The applications of 3D electron microscopy (EM) are still under development. To shed light on this critical issue, we investigated the ultrastructural pattern of cancer tissue. Moreover, these interactions are dynamic and vary as the cancer progresses and metastasizes. These observations suggest that the structural organization of tumour tissue changes from one sample to another and is likely controlled by environmental and genetic factors such as the tissue origin, state of differentiation, genetic programme, the mutations they harbour, the activated molecular pathways, and the surrounding stromal components such as blood capillaries. Moreover, pathological tumour atlases display a multitude of 2D images with tumour tissues whose cells are organized differently while belonging to the same category of cancer ( ).
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In recent investigations, we noted that various hepatoma cells engrafted on the chick embryo chorioallantoic membrane (CAM) were arranged histologically and microscopically in a lineage-specific way while growing in a comparable controlled environment 1, 2. Tumour cells establish composite interactions with the surrounding cancerous cells, extracellular matrix and stromal components, including blood capillaries and immune cells. However, tumours often present a complex architecture that 2D imaging cannot capture. In conclusion, this pilot study allowed the identification of bioarchitectural parameters that shape the internal and spatial organization of tumours, thus paving the way for future investigations in the emerging onconanotomy field.ĭiagnostic, prognostic and predictive clinical cancer studies are mainly based on the analysis of tissue sections in two dimensions (2D). Finally, a set of tumour cells polarized in the direction of a hot spot corresponding to a bile canaliculus-like structure. We also found anatomical connections between the blood capillary and the planar alignment and size of tumour cells in their 3D milieu. We found that the size of hepatoblastoma cells correlates with the size of their nucleus, cytoplasm and mitochondrial mass. cytoplasm, nucleus, mitochondria), we report unique 3D ultrastructural data about the organization of tumour tissue. By digitally reconstituting an entire hepatoblastoma sample with a blood capillary, a bile canaliculus-like structure, hundreds of tumour cells and their main organelles (e.g.
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#Virtual cz manual manual
Here, we analysed the spatial organization of patient-derived xenograft tissues generated from hepatoblastoma, the most frequent childhood liver tumour, by serial block-face scanning electron microscopy using an integrated workflow combining 3D imaging, manual and machine learning-based semi-automatic segmentations, mathematics and infographics.
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Despite recent progress in the characterization of tumour components, the tri-dimensional (3D) organization of this pathological tissue and the parameters determining its internal architecture remain elusive.