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Kilic, B.

Publications and source records attributed to Kilic, B..

3 recordsLinked to original sources

Quantitative live imaging reveals region-dependent medulloblastoma disseminationin the zebrafish brain

Medulloblastoma is the most common malignant pediatric brain tumor, and relapse is frequently driven by dissemination within the central nervous system. Yet the early dynamics of tumor spread remain difficult to resolve in vivo. Here, we orthotopically transplanted human medulloblastoma cells into larval zebrafish and followed individual xenografts by longitudinal high-resolution confocal imaging. ONS-76 showed particularly robust dissemination, with hindbrain tumors spreading into the developing cerebellum in 81.5% of larvae, more than fourfold the frequency observed for forebrain or midbrain tumors. Disseminating cells extended along brain-surface and leptomeningeal-like regions and frequently associated with cerebral vasculature. Quantitative analysis of tumor area, perimeter, compactness, convex hull area, and fractal dimension captured changes in growth and spatial complexity over time. Dasatinib reduced tumor expansion and dissemination-related features in a concentration-dependent manner, while higher doses revealed host toxicity. These findings establish a powerful in vivo model for resolving medulloblastoma dissemination and therapeutic response.

cancer biology↗

Colour Constancy: Colour Interaction between Local Surround and Illumination in Virtual Reality Scenarios

In our study, we used virtual reality to investigate how the colour of an objects surroundings influences colour constancy. Using Unreal Engine, we manipulated lighting and object properties in computer-generated scenes illuminated by five different light sources and presented them through an HTC Vive Pro Eye virtual reality headset. Participants assessed colour constancy by selecting the object that best matched a neutral reference from among five differently coloured options within the scene. Our results demonstrated a significant decline in colour constancy performance when the illuminant colour was in the opposite direction to that of the local surround, highlighting the interactive effects of surround colour and illumination.

animal behavior and cognition↗

Selective inhibition of histone deacetylase 1 and 3 improves motor phenotype and alleviates transcriptional dysregulation in Huntington's disease mice

Huntingtons disease (HD) is an autosomal dominant neurodegenerative disease characterized by a late clinical onset of psychiatric, cognitive, and motor symptoms. Transcriptional dysregulation is an early and central disease mechanism which is accompanied by epigenetic alterations in HD. Previous studies demonstrated that targeting transcriptional changes by inhibition of histone deacetylases (HDACs), especially the class I HDACs, provides therapeutic effects. Yet, their exact mechanisms of action and the features of HD pathology, on which these inhibitors act remain to be elucidated. Here, using transcriptional profiling, we found that selective inhibition of HDAC1 and HDAC3 by RGFP109 repaired the expression of a number of genes, including the transcription factor genes Neurod2 and Nr4a2, and 43% of the gene sets that were dysregulated by mutant Huntingtin expression in the striatum and improved motor skill learning deficit in the R6/1 mouse model of HD. RGFP109-treated R6/1 mice showed improved coordination on the RotaRod over four consecutive trials, while vehicle-treated R6/1 animals displayed no improvement in coordination skills and fell 50 seconds earlier off the rod in the fourth trial. We also found, by volumetric MRI, a widespread brain atrophy in the R6/1 mice at the symptomatic disease stage, on which RGFP109 showed a modest effect. Collectively, our combined work presents new evidence for specific HDAC1 and HDAC3 inhibition as a therapeutic strategy for alleviating the phenotypic and molecular features of HD.

neuroscience↗