Search of combined cancer immunotherapy with mouse model induced tumor-specific variant antigen
Project/Area Number |
18K09291
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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Research Institution | Shimane University |
Principal Investigator |
Ishikawa Masako 島根大学, 学術研究院医学・看護学系, 助教 (50467718)
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Co-Investigator(Kenkyū-buntansha) |
中山 健太郎 島根大学, 学術研究院医学・看護学系, 准教授 (70346401)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | がん免疫療法 / 卵巣がん / マウスモデル / 免疫チェックポイント関連分子 / 卵巣癌 / 複合免疫療法 / MSI / 婦人科がん / 腫瘍特異的変異抗原 / 免疫チェックポイント阻害薬 |
Outline of Final Research Achievements |
We investigated effective factor of cancer immunotherapy and the relationship between the effects of cancer immunotherapy and the frequency of somatic mutations and mutation burden in ovarian cancer to find effective treatment groups. The frequency of MSI-High in ovarian cancer was only 4.3%. There was no correlation between MSI status and prognosis and was also no correlation between MSI status and the expression of immune checkpoint-related molecules, so we considered these factors cannot be a predictor for therapeutic effect. We also examined the effects of combination therapy with ICI (immune check point inhibitors) and other anticancer drugs. We prepared mice xenografts which were injected ovarian cancer cell line knocked out POLE, as a model of mutation burden rich. The group of combination therapy could not contribute prognosis improvement. Next, we started to make organoids from ovarian cancer tissue for functional experiments and drug administration experiments.
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Academic Significance and Societal Importance of the Research Achievements |
婦人科癌の中でも死亡率の高い卵巣癌の治療成績向上のため癌免疫療法の効果的な治療群を探索した。癌免疫療法の効果予測因子としてマイクロサテライト不安定性について検討したが、卵巣癌では頻度が少なく、予後との関連も認めなかった。次に、体細胞突然変異の頻度や数が多いPolymerase ε(POLE)変異関連癌のマウスモデルを作製し、抗癌薬と癌免疫療法の併用行ったが、生存期間を延長しなかった。 マウスモデルで一定した結果を得られなかったことから、近年、がん微小環境も含めがんの生物学的特性を反映するとされる三次元培養を行い、卵巣癌からオルガノイドモデルを作製し、さらに併用治療実験を進めるところである。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer.2021
Author(s)
Kurose S, Nakayama K, Razia S, Ishikawa M, Ishibashi T, Yamashita H, Sato S, Sakiyama A, Yoshioka S, Kobayachi M, Nakayama S, Otsuki Y, Ishikawa N, Kyo S.
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Journal Title
Diseases (Basel, Switzerland)
Volume: 9
Issue: 1
Pages: 14-14
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic Value of Peripheral Blood Lymphocyte Telomere Length in Gynecologic Malignant Tumors.2020
Author(s)
Shanta K, Nakayama K, Ishikawa M, Ishibashi T, Yamashita H, Sato S, Sasamori H, Sawada K, Kurose S, Mahmud HM, Razia S, Iida K, Ishikawa N, Kyo S
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Journal Title
Cancers
Volume: 12
Issue: 6
Pages: 1469-1469
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mucinous borderline ovarian tumors with BRAF V600E mutation may have low risk for progression to invasive carcinomas2020
Author(s)
hnishi K, Nakayama K, Ishikawa M, Ishibashi T, Yamashita H, Nakamura K, Minamoto T, Iida K, Razia S, Ishikawa N, Kyo S.
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Journal Title
Arch Gynecol Obstet
Volume: 302
Issue: 2
Pages: 487-495
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.2020
Author(s)
Masako Ishikawa, Kentaro Nakayama, Kohei Nakamura, Hitomi Yamashita, Tomoka Ishibashi, Toshiko Minamoto, Kouji Iida, Sultana Razia, Noriyoshi Ishikawa, Satoru Nakayama, Yoshiro Otsuki, Satoru Kyo
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Journal Title
Archives of gynecology and obstetrics
Volume: 302
Issue: 1
Pages: 209-218
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates.2020
Author(s)
Minamoto T, Nakayama K, Ishibashi T, Ishikawa M, Nakamura K, Yamashita H, Shanta K, Mahmud HM, Razia S, Iida K, Nakamura T, Kanda H, Kyo S.
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Journal Title
International journal of molecular sciences
Volume: 21
Issue: 24
Pages: 9688-9688
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future.2019
Author(s)
Hitomi Yamashita, Kentaro Nakayama, Masako Ishikawa, Tomoka Ishibashi, Kohei Nakamura, Kiyoka Sawada, Yuki Yoshimura, Nagisa Tatsumi, Sonomi Kurose, Toshiko Minamoto, Kouji Iida, Sultana Razia, Noriyoshi Ishikawa, Satoru Ky
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Journal Title
International journal of molecular sciences
Volume: 20
Issue: 20
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients. Diagnostics (Basel). 2019;27;10(1). pii: E13.2019
Author(s)
Ishibashi T, Nakayama K, Razia S, Ishikawa M, Nakamura K, Yamashita H, Dey P, Iida K, Kurioka H, Nakayama S, Otsuki Y, Ishikawa N, Kyo S.
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Journal Title
Diagnostics (Basel).
Volume: 27;10(1)
Issue: 1
Pages: 13-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinicopathological and biological analysis of PIK3CA mutation and amplification in cervical carcinomas.2019
Author(s)
Sultana Razia, Kentaro Nakayama, Kohei Nakamura, Tomoka Ishibashi, Masako Ishikawa, Toshiko Minamoto, Kouji Iida, Yoshiro Otsuki, Satoru Nakayama, Noriyoshi Ishikawa, Satoru Kyo
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Journal Title
Experimental and therapeutic medicine
Volume: 18
Pages: 2278-2284
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies).2019
Author(s)
Ruriko Ono, Kentaro Nakayama, Kohei Nakamura, Hitomi Yamashita, Tomoka Ishibashi, Masako Ishikawa, Toshiko Minamoto, Sultana Razia, Noriyoshi Ishikawa, Yoshiro Otsuki, Satoru Nakayama, Hideyuki Onuma, Hiroko Kurioka, Satoru Kyo
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Journal Title
International journal of molecular sciences
Volume: 20
Issue: 15
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] High frequency of POLE mutations in synchronous endometrial and ovarian carcinoma.2018
Author(s)
Ishikawa M, Nakayama K*, Nakamura K, Ono R, Yamashita H, Ishibashi T, Minamoto T, Iida K, Razia S, Ishikawa N, Kyo S.
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Journal Title
Hum Pathol
Volume: 18
Pages: 30424-30426
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report2018
Author(s)
Nakamura Kohei、Nakayama Kentaro、Minamoto Toshiko、Ishibashi Tomoka、Ohnishi Kaori、Yamashita Hitomi、Ono Ruriko、Sasamori Hiroki、Razia Sultana、Hossain Mohammad Mahmud、Kamrunnahar Shanta、Ishikawa Masako、Ishikawa Noriyoshi、Kyo Satoru
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Journal Title
International Journal of Molecular Sciences
Volume: 19
Issue: 4
Pages: 979-979
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Relationship among microsatellite instability, immune cells infiltration, and expression of immune checkpoint molecules in ovarian carcinoma: immunotherapeutic strategies for the future2020
Author(s)
Yamashita H, Nakayama K, Ishikawa M, Ishibashi T, Sawada K, Yoshimura Y, Tatsumi Nm Kurose S, Sato S, Minamoto T, Iida K, Kyo S.
Organizer
第72回日本産科婦人科学会学術講演会
Related Report
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[Presentation] High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.2020
Author(s)
Ishikawa M, Nakayama K, Yamashita H, Ishibashi T, Sato S, Minamoto T, Iida K, Kurose S, Tatsumi N, Sawada K, Kyo M,
Organizer
第72回日本産科婦人科学会学術講演会
Related Report
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[Presentation] Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies)2019
Author(s)
Ono R, Nakayama K, Nakamura K, Yamashita H, Ishibashi T, Ishikawa M, Minamoto T, Razia S, Ishikawa N, Otsuki Y, Nakayama S, Onuma H, Kurioka H, Kyo S.
Organizer
第71回日本産科婦人科学会
Related Report