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Effect of BMS-582949 treatment on gene expression in osteoclasts

ABSTRACT: Effect of BMS-582949 treatment on gene expression in osteoclasts

PROVIDER: PRJNA1051041 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27173702_1.fastq.gz	Fastqsanger.gz
	SRR27173702_2.fastq.gz	Fastqsanger.gz
	SRR27173703_1.fastq.gz	Fastqsanger.gz
	SRR27173703_2.fastq.gz	Fastqsanger.gz
	SRR27173704_1.fastq.gz	Fastqsanger.gz

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Effect of BMS-582949 treatment on gene expression in osteoclasts

Project description:Controlling excessive osteoclastic activity is a promising strategy for many bone disease treatments. Here we report that 10 μM BMS-582949, a clinical p38α inhibitor,dromatically suppresses the osteoclast differentiation in vitro. Our results provide a evidence that BMS-582949 could be a candicdate drug for the therapy of osteolytic diseases.

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Expression profile of osteoclasts treated with bisphosphonates

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Project description:To investigate the role of HES1 in osteoclast differentiation and function, bone marrow-derived macrophages (BMMs) were derived from CtskCre/WT;RosaHes1 and control (Rosa[STOP]Hes1 ) mice and were differentiated into mature osteoclasts. We then performed gene expression profiling analysis using data obtained from RNA-seq of conrol and HES1-overexpressing osteoclasts.

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Project description:Background: Targeting tumor-associated macrophages through C-C chemokine receptor type 2 (CCRs) in pancreatic ductal adenocarcinoma (PDAC) improves the efficacy of chemotherapy and restores T cell immunity. Methods: We conducted a phase I/II single institution study (NCT03496662) combining chemotherapy gemcitabine and nab-paclitaxel (GnP), an oral CCR2/5 inhibitor BMS-813160 and nivolumab for four 28-day cycles as a neoadjuvant therapy for patients with borderline resectable (BR) or locally advanced (LA) PDAC. The recommended phase 2 dose (RP2D) of BMS-813160 was established in the standard 3+3 design. Primary end points were safety and objective response rate (ORR). Secondary end points included resection rate, progression-free survival (PFS) and overall survival (OS). Results: 8 patients were treated with GnP alone (control arm) and 31 patients (29 response evaluable) were treated at RP2D. No grade 3 or 4 toxicities attributed to nivolumab or BMS-813160 were identified. After all 4 cycles of study treatment (N=26), ORR was 35.7%, 16.7% among BR- and LA-PDAC patients, compared to 0% of control arm patients. 78.6% BR- and 16.7% of LA-PDAC patients who completed study treatment underwent surgical resection. For intent-to-treat analyses, BR-PDAC patients had a mPFS and mOS of 14.6 and 20.4 months respectively; and LA-PDAC patients had a mPFS and mOS of 14.7 and 17 months respectively. Single cell RNAseq analysis showed enhanced proliferating CD4 and CD8 T cells and gene signatures indicative of effector function. Conclusions: Neoadjuvant BMS-813160/nivolumab/GnP was well tolerated and appears to achieve higher ORR and resectability than historical data, warranting a larger randomized phase II study.

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2017-04-19 | PXD002765 | Pride

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