Language：Japanese   Publisher：The Crystallographic Society of Japan  

DOI： 10.5940/jcrsj.66.171

Language：Japanese   Publisher：Scientific Reports  

Understanding human genome alterations is necessary to optimize genome-based cancer therapeutics. However, some newly discovered mutations remain as variants of unknown significance (VUS). Here, the mutation c.1403A > G in exon 10 of the platelet-derived growth factor receptor-alpha (PDGFRA) gene, a VUS found in adult glioblastoma multiforme (GBM), was introduced in human embryonal kidney 293 T (HEK293T) cells using genome editing to investigate its potential oncogenic functions. Genome editing was performed using CRISPR/Cas9; the proliferation, drug sensitivity, and carcinogenic potential of genome-edited cells were investigated. We also investigated the mechanism underlying the observed phenotypes. Three GBM patients carrying the c.1403A > G mutation were studied to validate the in vitro results. The c.1403A > G mutation led to a splice variant (p.K455_N468delinsN) because of the generation of a 3’-acceptor splice site in exon 10. PDGFRA-mutated HEK293T cells exhibited a higher proliferative activity via PDGFRα and the cyclin-dependent kinase (CDK)4/CDK6-cyclin D1 signaling pathway in a ligand-independent manner. They showed higher sensitivity to multi-kinase, receptor tyrosine kinase, and CDK4/CDK6 inhibitors. Of the three GBM patients studied, two harbored the p.K455_N468delinsN splice variant. The splicing mutation c.1403A > G in PDGFRA is oncogenic in nature. Kinase inhibitors targeting PDGFRα and CDK4/CDK6 signaling should be evaluated for treating GBM patients harboring this mutation.

DOI： 10.1038/s41598-022-05391-9

Scopus

PubMed

Language：Japanese   Publisher：BMC Microbiology  

Background: The microbial population of the intestinal tract and its relationship to specific diseases has been extensively studied during the past decade. However, reports characterizing the bile microbiota are rare. This study aims to investigate the microbiota composition in patients with pancreaticobiliary cancers and benign diseases by 16S rRNA gene amplicon sequencing and to evaluate its potential value as a biomarker for the cancer of the bile duct, pancreas, and gallbladder. Results: We enrolled patients who were diagnosed with cancer, cystic lesions, and inflammation of the pancreaticobiliary tract. The study cohort comprised 244 patients. We extracted microbiome-derived DNA from the bile juice in surgically resected gallbladders. The microbiome composition was not significantly different according to lesion position and cancer type in terms of alpha and beta diversity. We found a significant difference in the relative abundance of Campylobacter, Citrobacter, Leptotrichia, Enterobacter, Hungatella, Mycolicibacterium, Phyllobacterium and Sphingomonas between patients without and with lymph node metastasis. Conclusions: There was a significant association between the relative abundance of certain microbes and overall survival prognosis. These microbes showed association with good prognosis in cholangiocarcinoma, but with poor prognosis in pancreatic adenocarcinoma, and vice versa. Our findings suggest that pancreaticobiliary tract cancer patients have an altered microbiome composition, which might be a biomarker for distinguishing malignancy.

DOI： 10.1186/s12866-022-02557-3

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：FEBS Journal  

DOI： 10.1111/febs.15315

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oncology Letters  

DOI： 10.3892/ol.2020.11352

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PubMed

Language：Japanese   Publisher：Nature Communications  

Correction to: Nature Communications, published online 19 September 2023 The original version of the Supplementary Information associated with this Article contained an error on page 38, which incorrectly read ‘The details of the experimental conditions and analysis of these SEC-SAXS experiments are summarized in Supplementary Table 4.’ The correct version states ‘Dataset 1’ in place of ‘Supplementary Table 4’. The HTML has been updated to include a corrected version of the Supplementary Information. The original version of this Article contained an error in the Data Availability statement, which incorrectly omitted the following: ‘The SAXS data has been submitted to SASBDB with the deposition ID of SASDQQ8 []’. This has been corrected in both the PDF and HTML versions of the Article.

DOI： 10.1038/s41467-023-42065-0

Scopus

PubMed

Event date： 2016.5 - 2016.6

Language：Japanese   Presentation type：Poster presentation  

Event date： 2015.9

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2015.3

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2014.11

Language：English   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Oral presentation (general)  

Application no：2016-172195  Date applied：2016.9

Date registered：2020.10