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Kaya, E.

Publications and source records attributed to Kaya, E..

2 recordsLinked to original sources

Condition Medium of Glioblastoma Cell Lines Decreases the Viability of Glioblastoma Cells by Modulating Gene Expression Profile

Grade IV neoplasm of the central nervous system, GBM, is associated with poor prognosis and relatively short overall survival. Due to the current limitations in treatment methods, GBM is characterized as an incurable disease, and research to advance therapeutic options is required. Conditioned medium is commonly used in in-vitro studies complementary to animal experiments to simulate tumor microenvironment and has the potential to challenge and expand our current understanding of secretome effect on tumor characteristics. This study aimed to investigate the effects of conditioned mediums of GBM cell lines on each other. Conditioned mediums cellular and molecular effects were evaluated using commonly employed techniques such as MTT assay, colony formation assay, wound healing assay, EdU labeling-based flow cytometry, and qRT-PCR. Our study demonstrated that conditioned medium harvested from U87 or LN229 cells at 48th h exhibited an anti-growth activity on each other by changing the gene expression pattern. Furthermore, the conditioned medium of LN229 decreased the migration capacity of U87 cells, and the conditioned medium of U87 cells significantly suppressed the LN229 proliferation. We believe that this initial work provides new insights for a better understanding of GBM cell lines secretome roles and highlights the necessity of further studies to unveil the secretome content. HighlightsO_LIConditioned medium harvested from GBM cells at different time points displayed various effects. C_LIO_LIConditioned medium of GBM cell lines harvested at 48th h decreased the viability of each other. C_LIO_LIThe expression level of anti-and pro-proliferative genes is altered upon condition medium treatment. C_LI

cancer biology↗

Acetyl-Leucine slows disease progression in lysosomal storage disorders

Acetyl-DL-leucine (ADLL) is a derivative of the branched chain amino acid leucine. In observational clinical studies ADLL improved symptoms of ataxia, in particular in patients with the lysosomal storage disorder (LSD), Niemann-Pick disease type C 1 (NPC1). Here, we investigated ADLL and its enantiomers acetyl-L-leucine (ALL) and acetyl-D-leucine (ADL) in symptomatic Npc1-/- mice and observed an improvement in ataxia with both enantiomers and ADLL. When ADLL and ALL were administered pre-symptomatically to Npc1-/- mice, both treatments delayed disease progression and extended life span, whereas ADL did not. These data are consistent with ALL being the neuroprotective enantiomer. Altered glucose and antioxidant metabolism were found to be implicated as one of the potential mechanisms of action of the L enantiomer in Npc1-/- mice. When miglustat and ADLL were used in combination significant synergy resulted. In agreement with these pre-clinical data, when NPC1 patients were evaluated after 12 months of ADLL treatment, rates of disease progression were slowed, with stabilisation or improvement in multiple neurological domains. A beneficial effect of ADLL on gait was also observed in this study in a mouse model of GM2 gangliosidosis (Sandhoff disease) and in Tay-Sachs and Sandhoff disease patients in individual-cases of off-label-use. Taken together, we have identified an unanticipated neuroprotective effect of acetyl-L-leucine and underlying mechanisms of action in LSDs, supporting its further evaluation in clinical trials in lysosomal disorders.

neuroscience↗