Annual Report 2019
Department of Innovative Seeds Evaluation
Tadashi Kondo
Introduction
The Department of Innovative Seeds Evaluation focuses on two projects: establishing a patient-derived cancer model of rare cancers, and characterizing developed cancer models for the preclinical study. Patient-derived cancer models are an essentially important tool to evaluate novel innovative seeds, and many anti-cancer drugs and biomarkers have been developed using patient-derived cancer models. However, patient-derived cancer models are available only for a limited portion of cancers. In view of this, we launched this project to establish and characterize patient-derived cancer models. One of the most important applications of patient-derived cancer models is to examine the efficacy of anti-cancer drugs as part of a pre-clinical study. The pre-clinical study of rare cancers has been hampered by the lack of patient-derived cancer models. To address this issue, we created a system to evaluate the efficacy of anti-cancer drugs using our original patient-derived cancer models.
Research activities
Surgically dissected tumor tissues obtained in the National Cancer Center Hospital (NCCH) were used to develop patient-derived cancer models. Tumor tissues vary quite widely in terms of substances contained and the heterogeneity of cell populations depending on the original tissue samples, and individual histological methods are required to establish cancer models. The molecular characterization is also important when using the cancer models in research. Given the fact that molecular backgrounds are altered while establishing the cancer model, knowing how the cancer models developed retain the original molecular backgrounds is important. This is why we employ a multi-omics approach. The DNA, RNA, and proteins are comprehensively and intensively examined and the original tissue samples are compared with established models. Our cancer models are included in collaborative studies with pharmaceutical companies. The research activity of our department is linked to that of the Division of Rare Cancer Research. Ideas and fundamental research tools are shared between two laboratories to develop novel innovative seeds.
Future prospects
Our research activities will benefit patients with rare cancers by contributing to the development of novel cancer drugs. We will establish more collaborative studies with companies as well as academic research groups.
List of papers published in 2019
Journal
1. Oyama R, Kito F, Takahashi M, Sakumoto M, Shiozawa K, Qiao Z, Noguchi R, Kubo T, Toki S, Nakatani F, Yoshida A, Kawai A, Kondo T. Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, NCC-dCS1-C1. Hum Cell, 32:202-213, 2019
2. Shiozawa K, Oyama R, Takahashi M, Kito F, Hattori E, Yoshida A, Kawai A, Ono M, Kondo T. Species-Specific Quantitative Proteomics Profiles of Sarcoma Patient-Derived Models Closely Reflect Their Primary Tumors. Proteomics Clin Appl, 13:e1900054, 2019
3. Asano N, Matsuzaki J, Ichikawa M, Kawauchi J, Takizawa S, Aoki Y, Sakamoto H, Yoshida A, Kobayashi E, Tanzawa Y, Nakayama R, Morioka H, Matsumoto M, Nakamura M, Kondo T, Kato K, Tsuchiya N, Kawai A, Ochiya T. A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes. Nat Commun, 10:1299, 2019
4. Oyama R, Kito F, Qiao Z, Sakumoto M, Shiozawa K, Toki S, Yoshida A, Kawai A, Kondo T. Establishment of novel patient-derived models of dermatofibrosarcoma protuberans: two cell lines, NCC-DFSP1-C1 and NCC-DFSP2-C1. In Vitro Cell Dev Biol Anim, 55:62-73, 2019
5. Hattori E, Oyama R, Kondo T. Systematic Review of the Current Status of Human Sarcoma Cell Lines. Cells, 8:pii: E157, 2019
6. Patel N, Wang J, Shiozawa K, Jones KB, Zhang Y, Prokop JW, Davenport GG, Nihira NT, Hao Z, Wong D, Brandsmeier L, Meadows SK, Sampaio AV, Werff RV, Endo M, Capecchi MR, McNagny KM, Mak TW, Nielsen TO, Underhill TM, Myers RM, Kondo T, Su L. HDAC2 Regulates Site-Specific Acetylation of MDM2 and Its Ubiquitination Signaling in Tumor Suppression. iScience, 13:43-54, 2019
7. Qiao Zhiwei, Kondo Tadashi. Identification of cantharidin as a drug candidate for glioblastoma by using a Connectivity Map-based approach. Journal of Electrophoresis, 63:9-14, 2019
8. Qiao Zhiwei, Kondo Tadashi. Screening of a growth inhibitor library of sarcoma cell lines to identify potent anti-cancer drugs. Journal of Electrophoresis, 63:1-7, 2019
9. Oyama Rieko, Takahashi Mami, Kito Fusako, Sakumoto Marimu, Takai Yoko, Shiozawa Kumiko, Qiao Zhiwei, Toki Shunichi, Tanzawa Yoshikazu, Yoshida Akihiko, Kawai Akira, Kondo Tadashi. ESTABLISHMENT AND CHARACTERIZATION OF PATIENT-DERIVED PLEOMORPHIC RHABDOMYOSARCOMA MODELS. 組織培養研究, 38:1-12, 2019
10. Kito F, Oyama R, Sakumoto M, Shiozawa K, Qiao Z, Toki S, Yoshida A, Kawai A, Kondo T. Establishment and characterization of a novel cell line, NCC-MFS1-C1, derived from a patient with myxofibrosarcoma. Hum Cell, 32:214-222, 2019
11. Tajima T, Kito F, Yoshida A, Kawai A, Kondo T. Calreticulin as A Novel Potential Metastasis-Associated Protein in Myxoid Liposarcoma, as Revealed by Two-Dimensional Difference Gel Electrophoresis. Proteomes, 7:pii: E13, 2019
12. Jia X, Chen C, Chen L, Yu C, Kondo T. Decorin as a prognostic biomarker in patients with malignant peripheral nerve sheath tumors. Oncol Lett, 17:3517-3522, 2019
13. Okimoto RA, Wu W, Nanjo S, Olivas V, Lin YK, Ponce RK, Oyama R, Kondo T, Bivona TG. CIC-DUX4 oncoprotein drives sarcoma metastasis and tumorigenesis via distinct regulatory programs. J Clin Invest, 129:3401-3406, 2019
14. Hirata M, Asano N, Katayama K, Yoshida A, Tsuda Y, Sekimizu M, Mitani S, Kobayashi E, Komiyama M, Fujimoto H, Goto T, Iwamoto Y, Naka N, Iwata S, Nishida Y, Hiruma T, Hiraga H, Kawano H, Motoi T, Oda Y, Matsubara D, Fujita M, Shibata T, Nakagawa H, Nakayama R, Kondo T, Imoto S, Miyano S, Kawai A, Yamaguchi R, Ichikawa H, Matsuda K. Integrated exome and RNA sequencing of dedifferentiated liposarcoma. Nat Commun, 10:5683, 2019
15. Asano N, Takeshima H, Yamashita S, Takamatsu H, Hattori N, Kubo T, Yoshida A, Kobayashi E, Nakayama R, Matsumoto M, Nakamura M, Ichikawa H, Kawai A, Kondo T, Ushijima T. Epigenetic reprogramming underlies efficacy of DNA demethylation therapy in osteosarcomas. Sci Rep, 9:20360, 2019