著者

Zhiwei Qiao Tadashi Kondo

出版者

Japanese Electrophoresis Society

雑誌

Journal of Electrophoresis (ISSN:13499394)

巻号頁・発行日

vol.63, no.1, pp.1-7, 2019 (Released:2019-02-06)

参考文献数

34

被引用文献数

2

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There is a need for novel drugs for sarcoma treatment. In the present study, to identify inhibitors with potential therapeutic utility in sarcomas, we screened the growth inhibitory effects of 361 inhibitors, including experimental reagents and anti-cancer drugs approved for use in non-sarcoma malignancies and those under clinical trials. The inhibitors were initially tested using 10 osteosarcoma cell lines. The half-maximal inhibitory concentration (IC50) of leptomycin B, actinomycin D, chetomin, and staurosporine was <100 nM in all the cell lines. As the promiscuous effects of staurosporine on kinases make it unsuitable for clinical applications, the other three inhibitors were tested in an additional 15 sarcoma cell lines derived from synovial sarcoma, fibrosarcoma, liposarcoma, rhabdomyosarcoma, malignant peripheral nerve sheath tumor, leiomyosarcoma, and Ewing’s sarcoma. The IC50 of leptomycin B and actinomycin D was <100 nM in all cell lines and that of chetomin was <100 nM in all but three synovial sarcoma cell lines. Although the clinical development of leptomycin B, a chromosomal region maintenance (CRM)1/exportin (XPO)1 inhibitor, was discontinued because of toxicity, a previous clinical trial revealed that other CRM1/XPO1 inhibitors, such as selinexor, have anti-tumor effects in sarcomas. Actinomycin D has proven clinical utility in the treatment of sarcomas. Chetomin disrupts the interaction of hypoxia-inducible factor-1 with the transcriptional coactivator p300 and its clinical utility has not been established in sarcomas. Chetomin exhibited growth inhibitory effects on sarcoma cells with different histological subtypes. Library screening is a powerful approach to detect the potential utility of anti-cancer drugs in sarcoma treatment.

著者

Yayoi Kimura Tosifusa Toda Hisashi Hirano

出版者

日本電気泳動学会

雑誌

Journal of Electrophoresis (ISSN:13499394)

巻号頁・発行日

vol.60, no.1, pp.1-4, 2016 (Released:2016-03-17)

参考文献数

10

被引用文献数

3

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Protein post-translational modifications (PTMs) play crucial roles in regulation of protein function and cell signaling, and abnormalities in protein PTMs are both causes and consequences of disease. Mass spectrometry (MS) is widely used to analyze protein PTMs. In this study, we developed an original database, ModProt (Post-Translational Modification Map of Proteome), to integrate our laboratory data and literature information regarding PTM sites. To develop the ModProt database, we constructed a web-based laboratory information management system (LIMS). This system allows us to administer the ModProt database and to view PTM site maps and corresponding protein information including amino acid sequences, official gene symbols, UniProt accessions/IDs, chromosome number/positions, and additional description. The ultimate goal of the ModProt database is to achieve PTM-based diagnosis and personalized medicine through detection of abnormal PTMs by comparing PTM site maps in healthy and disease states using the database.