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Low-intensity pulsed ultrasound-mediated blood-brain barrier opening increases anti programmed death-ligand 1 delivery and efficacy in Gl261 mouse model

ABSTRACT: Low-intensity pulsed ultrasound-mediated blood-brain barrier opening increases anti programmed death-ligand 1 delivery and efficacy in Gl261 mouse model

PROVIDER: PRJNA911839 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22721100_1.fastq.gz	Fastqsanger.gz
	SRR22721100_2.fastq.gz	Fastqsanger.gz
	SRR22721101_1.fastq.gz	Fastqsanger.gz
	SRR22721101_2.fastq.gz	Fastqsanger.gz
	SRR22721102_1.fastq.gz	Fastqsanger.gz

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Low-intensity pulsed ultrasound-mediated blood-brain barrier opening increases anti programmed death-ligand 1 delivery and efficacy in Gl261 mouse model

Project description:Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A Blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10µl/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry.The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly open the BBB. BBB opening was confirmed visually and microscopically using Evans’s blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of the overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients.

2023-02-28 | GSE220909 | GEO

Low-Intensity Pulsed Ultrasound Effects on the Human Blood Brain Barrier

Project description:Analysis of human peritumoral brain following a low-intensity pulsed ultrasound (LIPU) mediated opening of the blood brain barrier, to enhance the delivery of systemic chemotherapies (paclitaxel or carboplatin).

2024-12-02 | GSE208074 | GEO

Identification of early response genes to low-intensity pulsed ultrasound in bone marrow stromal cells

Project description:Low-intensity pulsed ultrasound (LIPUS) has been applied as a therapeutic adjunct to promote fracture healing. However, the detailed molecular mechanisms by which LIPUS promotes bone fracture healing have not yet been fully elucidated. In the present study, the early response genes elicited by low-intensity pulsed ultrasound (LIPUS) in bone marrow stromal cells (BMSCs) were investigated using GeneChip® oligonucleotide microarrays.

2019-08-19 | GSE135935 | GEO

Low-Intensity Pulsed Ultrasound Effects on the Human Blood Brain Barrier

Project description:Low-Intensity Pulsed Ultrasound Effects on the Human Blood Brain Barrier

| PRJNA858102 | ENA

Osteocytes as main responders to Low Intensity Pulsed Ultrasound for the treatment of fracture healing

Project description:Skeletal tissue is known to respond to mechanical stress. Ultrasound stimulation is one of mechanical stress and low intensity pulsed ultrasound (LIPUS) devices have been clinically utilized to promote the fracture healing. However, it is still not clear which skeletal cells, especially osteocytes or osteoblasts, mainly respond to LIPUS stimulation and how they contribute to fracture healing. To examine that, we utilized medaka known to have bones without embedded osteocytes and zebrafish known to have bones with embedded osteocytes as an in vivo model. Interestingly, fracture healing was accelerated by ultrasound stimulation in zebrafish but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocyte, we performed RNA-sequencing with the murine long bone osteocyte Y4 (MLO-Y4) cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation and functional cluster analysis defined that several molecular signatures related in immunity, secretion and transcription. Especially, most of isolated transcription related genes were modulated by LIPUS also in vivo experiments using zebrafish. Target genes analysis showed that inflammatory response and bone formation in fracture healing could be transcriptionally regulated in osteocytes by LIPUS stimulation. Among these transcription genes, early growth response (Egr) 1,2, JunB, Forkhead box Q1 (FoxQ1) and nuclear factor of activated T cells (NFAT) c1 were not altered by LIPUS in medaka unlike zebrafish suggesting that these genes would be key transcriptional regulator of LIPUS-dependent fracture healing through osteocytes. In this study, we revealed bone-equipped osteocytes is necessary for LIPUS-induced promotion of fracture healing through the transcriptional control of target genes presumably to activate neighboring cells involved in fracture healing event.

2021-05-03 | GSE162674 | GEO

Anti-inflammatory role of low intensity pulsed ultrasound in inhibiting LPS-induced M1 polarization of RAW264.7 via Wnt2b/AXIN/β-catenin

Project description:Low-intensity pulsed ultrasound (LIPUS) is a special type of low intensity ultrasound. In periodontal disease, LIPUS was applied as an adjuvant and non-invasive therapeutic treatment. While, the specific mechanism of LIPUS in the treatment of periodontal disease is not quite clear.RAW264.7 cells were induced to M1/M2 macrophage-like polarization by LPS/IL4. LIPUS was performed to stimulate RAW264.7 cells at an intensity of 45 mW/cm2, 25 min, interval 24 h, twice. The polyA mRNA sequencing of LPS induced RAW264.7 cells, LPS induced and LIPUS treated RAW264.7 cells were conducted.Our results suggested that LIPUS played an anti-inflammatory role by inhibiting LPS-induced M1 polarization of RAW264.7 cells in an Wnt2b/AXIN/β-catenin dependent way. LIPUS may inhibit inflammation in periodontal diseases by regulating macrophage differentiation, so as to play a therapeutic role in periodontal diseases.

2024-10-15 | GSE273466 | GEO

Ultrasound-mediated blood–spinal cord barrier opening prolongs survival in an ALS mouse model

Project description:Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. The limited efficacy of recent therapies in clinical development may be linked to lack of drug penetration to the affected motor neurons due to the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). Methods: In this work, the safety and efficacy of repeated short transient opening of the BSCB by low intensity pulsed ultrasound (US, sonication) was studied in females of an ALS mouse model (B6.Cg-Tg(SOD1*G93A)1Gur/J). The BSCB was disrupted using a 1 MHz ultrasound transducer coupled to the spinal cord, with and without injection of insulin-like growth factor 1 (IGF1), a neurotrophic factor that has previously shown efficacy in ALS models. Findings: Results in healthy mouse models demonstrated that the BSCB can be safely disrupted and IGF1 concentrations significantly enhanced after a single session of transient BSCB disruption (176 ±32 µg/g vs. 0.16 ±0.008 µg/g, p<0.0001). Five repeated weekly US performed in female ALS mice demonstrated a survival advantage in mice treated with IGF1 and ultrasound (US+IGF1) compared to treatment with IGF1 alone (176 vs. 166 days, p=0.0038). Surprisingly, this survival advantage was also present in mice treated with ultrasound (US) alone vs untreated mice (178.5 vs. 166.5 days, p=0.0061). Analysis of glial cell immunoreactivity and microglial transcriptome showing reduced cell proliferation pathways, in addition to lymphocyte infiltration, suggested that the beneficial effect of US or US+IGF1 could act through immune cell modulation. Interpretation: These results show the first step towards a possible beneficial impact of transient BSCB opening for ALS therapy and suggest implication of immune cells.

2024-07-15 | GSE269925 | GEO

Gene expression in response to low-intensity pulsed ultrasound treatment of bone marrow cells under osteogenic conditions in vitro

Project description:We performed a comprehensive analysis of gene expression changes following low-intensity pulsed ultrasound (LIPUS) treatment of cultured bone marrow cells under bone formation conditions, using cDNA microarray analysis Bone marrow cells were obtained from the femora of rats and were suspended in an osteogenic medium to make a cell culture. After cultures were established, test cultures were exposed to LIPUS via the base of the cell culture plates for 15 min/day on days 3–9 (LIPUS group). Control cultures (without LIPUS exposure) were otherwise treated identically to the LIPUS group. On day 10, total RNA was extracted from both sets of cultures and hybridized to microarray slides, the data sets were analysed. Markers for differentiated osteoblasts and osteocytes, as well as collagen-related genes, cell adhesion factors were up-regulated in LIPUS group on day 10. Gene expression in response to LIPUS treatment of bone marrow cells were measured on day 10 after cultures were established. Experiments were performed at each conditions (LIPUS or Control).

2015-07-10 | E-GEOD-70662 | biostudies-arrayexpress

Gene expression in response to low-intensity pulsed ultrasound treatment of bone marrow cells under osteogenic conditions in vitro

2015-07-10 | GSE70662 | GEO

Identification of early response genes to low-intensity pulsed ultrasound in bone marrow stromal cells

Project description:Identification of early response genes to low-intensity pulsed ultrasound in bone marrow stromal cells

| PRJNA560688 | ENA