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Laser Interstitial Thermal Therapy Enhances Bidirectional Blood-Brain Barrier Permeability in Glioblastoma

Listed in NCBI GEO

Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for glioblastoma that increases blood-brain barrier (BBB) permeability.

Description

However, the mechanisms and spatiotemporal features of this effect remain unclear. It is also unknown whether LITT promotes release of circulating tumor DNA (ctDNA).Using our previously developed LITT mouse model, we employed single-cell RNA sequencing (scRNAseq) to investigate gene expression changes in endothelial cells following LITT in naïve mouse brain.

Brains were also harvested at multiple time points to assess LITT effects on tight junction (TJ) integrity and transcytosis via immunofluorescence and transmission electron microscopy. Human glioblastoma tissues were analyzed to monitor ambient caveolae-mediated transcytosis in tumor regions. Finally, ctDNA levels in mouse plasma were quantified using digital droplet PCR following LITT.LITT triggered downregulation of pathways related to cell-cell junctions and upregulation of transcytosis.

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LITT transiently disrupted TJ integrity for 7 days up to 100 µm away from the ablation zone. Further, LITT increased caveolae-mediated transcytosis in endothelial cells for 21 days, peaking at 14 days, in part due to suppression of the transcytosis inhibitor Mfsd2a. LITT facilitated ctDNA detection in mouse plasma at 1 hour, 3 days, 7 days, and 14 days post-procedure.Our study demonstrates that LITT transiently disrupts the BBB in the periphery of the ablation with endothelial TJ disruption and transcytosis upregulation following distinct time courses.

LITT effects on the BBB are bidirectional and enhance ctDNA release in addition to enabling brain entry of agents.

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From keywords
Life Sciences
Inferred from text
Cancer 65% · Microscopy 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 12 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE32985512 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:microscopyenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title