A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations.

Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB).

Comparative transcriptomics coupled to developmental grading via transgenic zebrafish reporter strains identifies conserved features in neutrophil maturation.

Neutrophils are evolutionarily conserved innate immune cells playing pivotal roles in host defense. Zebrafish models have contributed substantially to our understanding of neutrophil functions but similarities to human neutrophil maturation have not been systematically characterized, which limits their applicability to studying human disease. Here we show, by generating and analysing transgenic zebrafish strains representing distinct neutrophil differentiation stages, a high-resolution transcriptional profile of neutrophil maturation.

Mutational spectrum of ATRX aberrations in neuroblastoma and associated patient and tumor characteristics.

Neuroblastoma is the most common extracranial solid tumor in children. The chromatin remodeler ATRX is frequently mutated in high-risk patients with a poor prognosis. Although many studies have reported ATRX aberrations and the associated clinical characteristics in neuroblastoma, a comprehensive overview is currently lacking.

Evaluation of Deep Learning Architectures for Complex Immunofluorescence Nuclear Image Segmentation.

Separating and labeling each nuclear instance (instance-aware segmentation) is the key challenge in nuclear image segmentation. Deep Convolutional Neural Networks have been demonstrated to solve nuclear image segmentation tasks across different imaging modalities, but a systematic comparison on complex immunofluorescence images has not been performed. Deep learning based segmentation requires annotated datasets for training, but annotated fluorescence nuclear image datasets are rare and of limited size and complexity.

An annotated fluorescence image dataset for training nuclear segmentation methods.

Fully-automated nuclear image segmentation is the prerequisite to ensure statistically significant, quantitative analyses of tissue preparations,applied in digital pathology or quantitative microscopy. The design of segmentation methods that work independently of the tissue type or preparation is complex, due to variations in nuclear morphology, staining intensity, cell density and nuclei aggregations. Machine learning-based segmentation methods can overcome these challenges, however high quality expert-annotated images are required for training.

Targeting aggressive osteosarcoma with a peptidase-enhanced cytotoxic melphalan flufenamide.

Background: Low survival rates in metastatic high-grade osteosarcoma (HGOS) have remained stagnant for the last three decades. This study aims to investigate the role of aminopeptidase N (ANPEP) in HGOS progression and its targeting with a novel lipophilic peptidase-enhanced cytotoxic compound melphalan flufenamide (melflufen) in HGOS.

Methods: Meta-analysis of publicly available gene expression datasets was performed to determine the impact of gene expression on metastasis-free survival of HGOS patients.

An evaluation of the effect of bortezomib on radiation-induced urinary bladder dysfunction.

Purpose: The urinary bladder is one major organ at risk in radiotherapy of pelvic malignancies. The radiation response manifests in early and chronic changes in bladder function. These are based on inflammatory effects and changes in urothelial cell function and proliferation.

Systemic administration of heparin ameliorates radiation-induced oral mucositis-preclinical studies in mice.

Purpose: The present study investigates the impact of systemic application of heparins on the manifestation of radiation-induced oral mucositis in a well-established mouse model.

Materials And Methods: Male C3H/Neu mice were irradiated with either single-dose or fractionated irradiation protocols with 5 × 3 Gy/week, given over one (days 0-4) or two (days 0-4, 7-11) weeks. All fractionation protocols were concluded by a local test irradiation (day 7/14) using graded doses to generate complete dose-effect curves.

Early inflammatory changes in radiation-induced oral mucositis : Effect of pentoxifylline in a mouse model.

Purpose: Early inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug.

Local hypoxia in oral mucosa (mouse) during daily fractionated irradiation - Effect of pentoxifylline.

Purpose: A significant reduction of radiation-induced oral mucositis by systemic application of pentoxifylline has been demonstrated in a mouse tongue model. However, the underlying mechanisms remain unclear. The present study focuses on the development of local hypoxia in mouse tongue during daily fractionated irradiation and a potential modulation by pentoxifylline.

Modulation of radiation-induced oral mucositis by pentoxifylline: preclinical studies.

Background And Purpose: Oral mucositis is a frequent early side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is accompanied by inflammatory reactions; their interaction with epithelial processes remains unclear. The aim of the present study was to investigate the effect of pentoxifylline (PTX) on the oral mucosal radiation response in the mouse tongue model.

Dosimetric challenges of small animal irradiation with a commercial X-ray unit.

Introduction: A commercial X-ray unit was recently installed at the Medical University Vienna for partial and whole body irradiation of small experimental animals. For 200 kV X-rays the dose deviations with respect to the reference dose measured in the geometrical center of the potential available field size was investigated for various experimental setup plates used for mouse irradiations. Furthermore, the HVL was measured in mm Al and mm Cu at 200 kV for two types of filtration.

Sequence-based high resolution chromosomal comparative genomic hybridization (CGH).

We aimed to devise an appropriate method to directly link the fluorescence profile of chromosomal copy number alterations detected by chromosomal comparative genomic hybridization (cCGH) or any other hybridization or staining information with the genome sequence data. Our goal was to establish an internal anchoring system that could facilitate profile alignment and thus increase the resolution of cCGH. We were able to achieve the alignment of chromosomes with gene mapping data by superimposition of (a) the fluorescence intensity pattern of a sequence-specific fluorochrome (GGCC binding specificity), (b) the cCGH fluorescence intensity profile of individual chromosomes, and (c) the GGCC motif density profile extracted from a genome sequence database.

Genes proximal and distal to MYCN are highly expressed in human neuroblastoma as visualized by comparative expressed sequence hybridization.

MYCN amplification is associated with poor prognosis in neuroblastoma disease. To improve our understanding of the influence of the MYCN amplicon and its corresponding expression, we investigated the 2p expression pattern of MYCN amplified (n = 13) and nonamplified (n = 4) cell lines and corresponding primary tumors (n = 3) using the comparative expressed sequence hybridization technique. All but one MYCN amplified cell line displayed overexpression at 2p.

A new platform linking chromosomal and sequence information.

We have tested whether a direct correlation of sequence information and staining properties of chromosomes is possible and whether this combined information can be used to precisely map any position on the chromosome. Despite huge differences of compaction between the naked DNA and the DNA packed in chromosomes we found a striking correlation when visualizing the GGCC density on both levels. Software was developed that allows one to superimpose chromosomal fluorescence intensity profiles generated by chromolysin A3 (CMA3) staining with GGCC density extracted from the Ensembl database.