{"database":"ENA","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Fastqsanger.gz":["ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/081/SRR32913181/SRR32913181.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/080/SRR32913180/SRR32913180.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/083/SRR32913183/SRR32913183.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/076/SRR32913176/SRR32913176.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/077/SRR32913177/SRR32913177.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/082/SRR32913182/SRR32913182.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/084/SRR32913184/SRR32913184.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/079/SRR32913179/SRR32913179.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/078/SRR32913178/SRR32913178.fastq.gz"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["Korea Institute of Radiological & Medical Sciences"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA1243967"],"scientific_name":["Mus musculus"],"tag":["xref:PubMed:40355586"],"long_description":["An elevated extracellular matrix (ECM) and interstitial fluid pressure (IFP) in gastric cancer limits the targeting of HER2-expressing GC cells when radioimmunotherapy (RIT) with Cu-64 trastuzumab (Cu-64 TRZ) is utilized. Here, we used Losartan (LOS) to downregulate ECM and IFP in gastric cancer mice model. In our study we treated the gastric cancer mice model with a dose of 40 mg/kg of LOS. We found that the LOS treatment increases a 2-fold higher Alexa-647-TRZ accumulation which significantly enhanced Cu-64 TRZ. We determined that the LOS-treated samples exhibited reduced mRNA and protein expression of SERPINE1, a gene associated with the ECM degradation. Additionally, LOS treatment resulted in the downregulated mRNA expression of the TGF-β1 and COL13A1, the genes involved in ECM deposition and an upregulated RNA expression of MMP2, a gene associated with the ECM degradation. There were no significant changes in metastatic markers of N-Cadherin and E-Cadherin. Moreover, our study demonstrates that silencing SERPINE1 increases the activity of the MMP2 and decreases COL13A1 with no effect on the N-cadherin and E-cadherin were observed. Our novel combinational therapy of using Cu-64 TRZ with LOS is attributed to the downregulation of SERPINE1 targeting ECM and IFP is highly effective for treatment of gastric cancer. Overall design: Effect of Losartan (40 mg/kg) on ECM and interstitial fluid pressure in a gastric cancer mouse model by assessing its impact on Alexa-647-TRZ and Cu-64 trastuzumab accumulation, SERPINE1, TGF-β1, COL13A1, and MMP2 expression, as well as metastatic markers (N-Cadherin and E-Cadherin), using both LOS-treated and untreated groups, along with SERPINE1-silenced samples to evaluate ECM modulation and radioimmunotherapy efficacy."],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Tumor microenvironment modulation by SERPINE1 increases radioimmunotherapy in murine model of gastric cancer","description":"Tumor microenvironment modulation by SERPINE1 increases radioimmunotherapy in murine model of gastric cancer","dates":{"last_updated":"2025-09-24","first_public":"2025-05-15"},"accession":"PRJNA1243967","cross_references":{"GEO":["GSE293300"],"taxon":["10090"],"PubMed":["40355586"]}}