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Annual Report 2022

Division of Rare Cancer Research

Tadashi Kondo, Rei Noguchi, Julia Osaki

Introduction

 We conduct research with the aim of discovering seeds that will help improve treatment outcomes for rare cancers.

Building research infrastructure for rare cancers: We are working on creating patient-derived cancer models, screening a library of approved anticancer drugs, and attempting to identify anticancer drugs and biomarkers that exhibit anti-tumor effects.

 Proteome analysis of rare cancers: We are working on proteome analysis from formalin-fixed specimens. The aim is to solve the problem unique to rare cancers, where it is difficult to obtain clinical specimens due to the small number of cases, and research is not progressing.

 Anticancer drug sensitivity test using fresh tumor tissue: We have established an experimental system to test the sensitivity to anticancer drugs by maintaining tumor tissue outside the body, and are trying to make use of it in personalized medicine. This is a strategy to develop treatments for rare cancers for which clinical trials cannot be conducted due to the extremely small number of cases.

 Biomarker development using clinical samples: We are developing biomarkers for rare cancers through proteome analysis using biobank samples.

Research Activities

 Building research infrastructure for rare cancers: Patient-derived sarcoma cell lines were established. The cell lines published in the paper were licensed to academic institutions and pharmaceutical companies. We also identified an anticancer drug that exhibits growth-inhibiting effects at extremely low concentrations.

 Proteome analysis of rare cancers: We optimized the protein extraction protocol from formalin-fixed specimens.

 Anticancer drug sensitivity test using fresh tumor tissue: Experimental conditions were improved by testing media, coating agents, and perfusion culture.

 Biomarker development using clinical samples: Biomarker development was carried out by proteome analysis using biobank samples.

Education

 Young researchers who have completed their degrees, doctoral students at Nagasaki University and Chiba University, and students at Tokyo College of Biotechnology were supervised.

Future Prospects

 We have successfully established patient-derived cancer models, and are identifying candidate anticancer drugs and biomarkers that can be expanded to accommodate broader indications. Additionally, methods for anticancer drug sensitivity testing using fresh tumor tissue and proteome analysis using old formalin-fixed specimens are being established. Biomarker development using biobank samples is also progressing smoothly. In addition to presenting results in papers and conferences, we also disseminate information as appropriate by constantly holding academic meetings. The training of young researchers is also going well, and students under our supervision have received academic and presidential awards. Such research activities are expected to lead to research results that will improve treatment outcomes for sarcoma.

List of papers published in 2022

Journal

1. Isoyama S, Tamaki N, Noguchi Y, Okamura M, Yoshimatsu Y, Kondo T, Suzuki T, Yaguchi S, Dan S. Subtype-selective induction of apoptosis in translocation-related sarcoma cells induced by PUMA and BIM upon treatment with pan-PI3K inhibitors. Cell Death Dis. 2023 Feb;14,169. doi: https://doi.org/10.1038/s41419-023-05690-7.

2. Akiyama T, Yoshimatsu Y, Noguchi R, Sin Y, Osaki J, Ono T, Adachi Y, Tsuchiya R, Toda Y, Kobayashi E, Kojima N, Yoshida A, Ohtori S, Kawai A, Kondo T. Establishment and characterization of NCC-DSM1-C1: a novel cell line derived from a patient with desmoid fibromatosis. Hum Cell. 2023 Mar;36(2):847-853. doi:10.1007/s13577-022-00850-x. Epub 2023 Jan 11. PMID: 36629983.  

3. Noguchi R, Yoshimura A, Uchino J, Takeda T, Chihara Y, Ota T, Hiranuma O, Gyotoku H, Takayama K, Kondo T. Comprehensive Kinase Activity Profiling Revealed the Kinase Activity Patterns Associated with the Effects of EGFR Tyrosine Kinase Inhibitor Therapy in Advanced Non-Small-Cell Lung Cancer Patients with Sensitizing EGFR Mutations. Proteomes 2023, 11(1), 6; https://doi.org/10.3390/proteomes11010006.  

4. Akiyama T, Yoshimatsu Y, Noguchi R, Sin Y, Osaki J, Adachi Y, Ono T, Tsuchiya R, Sato C, Iwata S, Kojima N, Yoshida A, Ohtori S, Kawai A, Kondo T. Establishment and characterization of NCC-PLPS2-C1: a novel cell line of pleomorphic liposarcoma. Hum Cell. 2023 Jan;36(1):468-475. doi:10.1007/s13577-022-00828-9. Epub 2022 Nov 27. PMID: 36436139.  

5. Akiyama T, Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, Sugaya J, Kobayashi E, Yoshida A, Ohtori S, Kawai A, Kondo T. Establishment and characterization of NCC-PS1-C1: a novel cell line of pleomorphic sarcoma from a patient after neoadjuvant radiotherapy. Hum Cell. 2022 Nov;35(6):2011-2019. doi: 10.1007/s13577-022-00787-1. Epub 2022 Sep 14. PMID: 36103079. [PubMed] (external link)

6. Akiyama T, Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, Sato C, Kojima, N, Yoshida A, Kawai A, Ohtori S, Kondo T. Establishment and characterization of NCC-MRT1-C1: a novel cell line of malignant rhabdoid tumor. Hum Cell. 2022, Nov;35(6):2002-2010. doi: 10.1007/s13577-022-00751-z. Epub 2022 Aug 5. Erratum in: Hum Cell. 2022 Oct 18;: PMID: 35927606. [PubMed] (external link)

7. Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, Akiyama T, Sato C, Kobayashi E, Kojima N, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-MFS6-C1: a novel patient-derived cell line of myxofibrosarcoma. Hum Cell. 2022 Nov;35(6):1993-2001. doi: 10.1007/s13577-022-00749-7. Epub 2022 Aug 10. PMID: 35947340. [Pubmed] (external link)

8. Akiyama T, Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, Fukushima S, Toda Y, Kojima N, Yoshida A, Ohtori S, Kawai A, Kondo T. Establishment and characterization of NCC-GCTB5-C1: a novel cell line of giant cell tumor of bone. Hum Cell. 2022 Jun 2. doi: 10.1007/s13577-022-00724-2. Epub ahead of print. PMID: 35653034. [PubMed] (external link)

9. Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, Akiyama T, Sugaya J, Kojima N, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-SS5-C1: a novel patient-derived cell line of synovial sarcoma. Hum Cell. 2022 Jul;35(4):1290-1297. doi: 10.1007/s13577-022-00721-5. Epub 2022 Jun 2. PMID: 35655041.

10. Noguchi R, Yoshimatsu Y, Sin Y, Tsuchiya R, Ono T, Akiyama T, Hirabayashi K, Ozawa I, Nakagawa R, Kikuta K, Kondo T. Establishment and characterization of two novel patient-derived myxoid liposarcoma cell lines. Hum Cell. 2022 Jul;35(4):1279-1289. doi: 10.1007/s13577-022-00717-1. Epub 2022 May 30. PMID: 35637403.  

11. Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, Akiyama T, Nakagawa R, Kamio S, Hirabayashi K, Ozawa I, Kikuta K, Kondo T. Establishment and characterization of a novel patient-derived cell line of dedifferentiated liposarcoma, NCC-DDLPS6-C1. Hum Cell. 2022 Jul;35(4):1270-1278. doi: 10.1007/s13577-022-00710-8. Epub 2022 May 23. PMID: 35604485.  

12. Paudel D, Kuramitsu Y, Uehara O, Morikawa T, Yoshida K, Giri S, Islam ST, Kitagawa T, Kondo T, Sasaki K, Matsuoka H, Miura H, Abiko Y. Proteomic and microbiota analyses of the oral cavity during psychological stress. PLoS One. 2022 May 25;17(5):e0268155. doi: 10.1371/journal.pone.0268155. PMID: 35613108; PMCID: PMC9132284.  

13. Sin Y, Ono T, Tsuchiya R, Noguchi R, Yoshimatsu Y, Kosako H, Kondo T. Proteomic analysis of spheroids of rhabdomyosarcoma cells cultured with decellularized muscle extracts. J Electrophoresis. 2022:66:1-4. 

14. Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, Akiyama T, Nakagawa R, Kamio S, Hirabayashi K, Ozawa I, Kikuta K, Kondo T. Establishment and characterization of a novel patient-derived Ewing sarcoma cell line, NCC-ES2-C1. Hum Cell. 2022 Jul;35(4):1262-1269. doi: 10.1007/s13577-022-00701-9. Epub 2022 Apr 19. PMID: 35441357.