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Annual Report 2018

Department of Innovative Seeds Evaluation

Tadashi Kondo, Rieko Oyama, Fusako Kito

Introduction

 The Department of Innovative Sees Evaluation focuses on two projects: establishing a patient-derived cancer model for rare cancers and characterizing developed cancer models for the preclinical study. The patient-derived cancer model is a key tool to evaluate novel innovative seeds and many anti-cancer drugs and biomarkers have been developed using patient-derived cancer models. However, patientderived cancer models are only available for a limited portion of cancers, which is why we launched this project to establish and characterize patient-derived cancer models. One of the key applications of patient-derived cancer models is to examine the efficacy of anti-cancer drugs as part of a pre-clinical study. Since the pre-clinical study of rare cancers was hampered by the lack of patient-derived cancer models, 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 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, which 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 the collaborative study with pharmaceutical companies, while the research activity of our department is linked to that of the Division of Rare Cancer Research. Ideas and fundamental research tools are then shared between two laboratories to develop novel innovative seeds.

As well as researching and developing patient-derived cancer models, we engae in contract research on proteogenomics and support the research activity of other researchers in terms of technical assistance about proteogenomics experiments. We run mass spectrometry and other proteomics-relevant technology, generating proteogenomics data.

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 2018

Journal

 1. Kondo T. Cancer biomarker development and two-dimensional difference gel electrophoresis (2D-DIGE). Biochim Biophys Acta Proteins Proteom0, 1867:2-8, 2019

 2. 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

 3. 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

 4. Qiao Z, Kondo T. Identification of cantharidin as a drug candidate for glioblastoma by using a Connectivity Map-based approach. J Electrophoresis, 63:9-14, 2019

 5. Qiao Z, Kondo T. Screening of a growth inhibitor library of sarcoma cell lines to identify potent anti-cancer drugs. J Electrophoresis, 63:1-7, 2019

 6. 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

 7. 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

 8. Kondo T. Current Status of Proteomics in Ewing's Sarcoma. Proteomics Clin Appl, 13:e1700130, 2019

 9. Hattori E, Oyama R, Kondo T. Systematic Review of the Current Status of Human Sarcoma Cell Lines. Cells, 8:2019

10. 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. Tiss Cult Res Commun, 38:1-12, 2019

11. Fujii K, Suzuki N, Jimura N, Idogawa M, Kondo T, Iwatsuki K, Kanekura T. HSP72 functionally inhibits the anti-neoplastic effects of HDAC inhibitors. J Dermatol Sci, 90:82-89, 2018

12. Oyama R, Kito F, Sakumoto M, Shiozawa K, Toki S, Endo M, Yoshida A, Kawai A, Kondo T. Establishment and proteomic characterization of a novel synovial sarcoma cell line, NCC-SS2-C1. In Vitro Cell Dev Biol Anim, 54:392-399, 2018

13. Kito F, Oyama R, Takai Y, Sakumoto M, Shiozawa K, Qiao Z, Uehara T, Yoshida A, Kawai A, Kondo T. Establishment and characterization of the NCC-SS1-C1 synovial sarcoma cell line. Hum Cell, 31:167-174, 2018

14. Qiao Z, Kondo T. Identification of cephalomannine as a drug candidate for glioblastoma via high-throughput drug screening. J Electrophoresis, 62:17-20, 2018

15. Shiozawa K, Yoshioka Y, Qiao Z, Shuting J, Ochiya T, Kondo T. Pazopanib-induced changes in protein expression signatures of extracellular vesicles in synovial sarcoma. Biochem Biophys Res Commun, 506:723-730, 2018

16. Qiao Zhiwei, Parlayan Cuneyd, Saito Shigeru, Kondo Tadashi. Meta-analysis of global gene-expression profiles identify molecular signatures for histological subtypes of sarcomas. J Electrophoresis, 62:21-29, 2018

17. Kondo T. Mass Spectrometry and Proteomics 2018: the Mass Spectrometry Society of Japan, Japanese Proteomics Society, and Asia-Oceania Human Proteome Organization. Expert Rev Proteomics, 15:777-779, 2018

18. Oyama R, Takahashi M, Kito F, Sakumoto M, Shiozawa K, Qiao Z, Yoshida A, Endo M, Kawai A, Kondo T. Establishment and characterization of patient-derived xenograft and its cell line of primary leiomyosarcoma of bone. In Vitro Cell Dev Biol Anim, 54:458- 467, 2018

19. Kito F, Oyama R, Sakumoto M, Takahashi M, Shiozawa K, Qiao Z, Sakamoto H, Hirose T, Setsu N, Yoshida A, Kawai A, Kondo T. Establishment and characterization of novel patient-derived osteosarcoma xenograft and cell line. In Vitro Cell Dev Biol Anim, 54:528-536, 2018

20. Oyama R, Kito F, Qiao Z, Sakumoto M, Noguchi R, Takahashi M, Toki S, Tanzawa Y, Yoshida A, Kawai A, Kondo T. Establishment of a novel patient-derived Ewing's sarcoma cell line, NCCES1-C1. In Vitro Cell Dev Biol Anim, 54:770-778, 2018

21. Kito Fusako, Oyama Rieko, Takahashi Mami, Shiozawa Kumiko, Sakumoto Marimu, Yoshida Akihiko, Setsu Noritaka, Kobayashi Eisuke, Kawai Akira, Kondo Tadashi. ESTABLISHMENT AND CHARACTERIZATION OF A PATIENT-DERIVED CANCER MODEL OF UNDIFFERENTIATED PLEOMORPHIC SARCOMA. Tiss Cult Res Commun, 37:133-145, 2018

22. Hattori E, Kondo T. Current status of cancer proteogenomics: a brief introduction. J Electrophoresis, 63:33-37, 2019