Updated on 2022/03/29

写真a

 
YOSHIKAWA Nobuhisa
 
Organization
Nagoya University Hospital Obstetrics and Gynecology Lecturer
Graduate School
Graduate School of Medicine
Title
Lecturer

Degree 1

  1. 博士(医学) ( 2016.9   名古屋大学 ) 

Research Areas 1

  1. Life Science / Obstetrics and gynecology

 

Papers 64

  1. Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy.

    Uno K, Yoshikawa N, Tazaki A, Ohnuma S, Kitami K, Iyoshi S, Mogi K, Yoshihara M, Koya Y, Sugiyama M, Tamauchi S, Ikeda Y, Yokoi A, Kikkawa F, Kato M, Kajiyama H

    Scientific reports   Vol. 12 ( 1 ) page: 4513   2022.3

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    Language:English  

    DOI: 10.1038/s41598-022-08503-7

    PubMed

  2. Adjuvant taxane plus platinum chemotherapy for stage I ovarian clear cell carcinoma with complete surgical staging: are more than three cycles necessary?

    Ukai Mayu, Suzuki Shiro, Yoshihara Masato, Yokoi Akira, Yoshikawa Nobuhisa, Kajiyama Hiroaki, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 27 ( 3 ) page: 609 - 618   2022.3

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  3. Clinical effects of cervical conization with positive margins in cervical cancer

    Nagao Yukari, Yokoi Akira, Yoshida Kosuke, Sumi Masanori, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 23288   2021.12

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  4. Long-term post-recurrence survival outcomes in young women receiving fertility-sparing surgery for epithelial ovarian cancer.

    Shigeyama M, Yoshihara M, Kitami K, Mogi K, Uno K, Iyoshi S, Tano S, Yoshikawa N, Kajiyama H

    European journal of obstetrics, gynecology, and reproductive biology   Vol. 267   page: 221 - 225   2021.12

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    DOI: 10.1016/j.ejogrb.2021.11.015

    PubMed

  5. Achievement of live birth after overcoming two gynecological malignancies treated with radical trachelectomy and medroxyprogesterone acetate therapy

    Tamauchi Satoshi, Moriyama Yoshinori, Suzuki Shiro, Ikeda Yoshiki, Yoshikawa Nobuhisa, Kajiyama Hiroaki

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 47 ( 11 ) page: 4101 - 4105   2021.11

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  6. Is cystectomy an option as conservative surgery for young patients with borderline ovarian tumor? A multi-institutional retrospective study

    Ikeda Yoshiki, Yoshihara Masato, Yoshikawa Nobuhisa, Tamauchi Satoshi, Yokoi Akira, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS     2021.8

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  7. A large-scale multi-institutional study evaluating prognostic aspects of positive ascites cytology and effects of therapeutic interventions in epithelial ovarian cancer

    Yoshihara Masato, Emoto Ryo, Kitami Kazuhisa, Iyoshi Shohei, Uno Kaname, Mogi Kazumasa, Tano Sho, Yoshikawa Nobuhisa, Matsui Shigeyuki, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 15154   2021.7

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  8. Metabolome analysis reveals a diversity of cancer tissues in advanced epithelial ovarian cancer

    Yoshida Kosuke, Yoshikawa Nobuhisa, Kitami Kazuhisa, Tamauchi Satoshi, Ikeda Yoshiki, Yokoi Akira, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    CANCER CELL INTERNATIONAL   Vol. 21 ( 1 ) page: 314   2021.6

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  9. Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer

    Hattori Satomi, Yoshikawa Nobuhisa, Mogi Kazumasa, Yoshida Kosuke, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yokoi Akira, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kajiyama Hiroaki

    CURRENT ONCOLOGY   Vol. 28 ( 3 ) page: 1663 - 1672   2021.6

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  10. Preclinical Verification of the Efficacy and Safety of Aqueous Plasma for Ovarian Cancer Therapy

    Nakamura Kae, Yoshikawa Nobuhisa, Mizuno Yuko, Ito Miwa, Tanaka Hiromasa, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka, Kajiyama Hiroaki

    CANCERS   Vol. 13 ( 5 )   2021.3

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  11. Expression of the chrXq27.3 miRNA cluster in recurrent ovarian clear cell carcinoma and its impact on cisplatin resistance

    Yoshida Kosuke, Yokoi Akira, Sugiyama Mai, Oda Shingo, Kitami Kazuhisa, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka, Yokoi Tsuyoshi, Kajiyama Hiroaki

    ONCOGENE   Vol. 40 ( 7 ) page: 1255 - 1268   2021.2

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  12. Active vitamin D inhibits mesothelial-mesenchymal-transition accelerating peritoneal dissemination in ovarian cancer

    Kitami Kazuhisa, Yoshihara Masato, Sugiyama Mai, Koya Yoshihiro, Iyoshi Shohei, Uno Kaname, Mogi Kazumasa, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page: 351 - 351   2021.2

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    Language:Japanese  

    Web of Science

  13. Visualization of platinum resistance through mapping trace elements

    Uno Kaname, Yoshikawa Nobuhisa, Yoshihara Masato, Tazaki Kei, Kato Masashi, Kitami Kazuhisa, Iyoshi Shohei, Tamauchi Satoshi, Sugiyama Mai, Koya Yoshihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page: 906 - 906   2021.2

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  14. The role of chrXq27.3 miRNA cluster in advanced ovarian clear cell carcinoma

    Yoshida Kosuke, Yokoi Akira, Yoshihara Masato, Tamauchi Satoshi, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Kikkawa Fumitaka, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page: 291 - 291   2021.2

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  15. Intra-tumoral polarity induced by Notch signaling can be a novel therapeutic target for advanced ovarian cancer

    Yoshihara Masato, Sugiyama Mai, Koya Yoshihiro, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Mogi Kazumasa, Tano Sho, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page: 363 - 363   2021.2

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    Web of Science

  16. How do peritoneal mesothelial cells on adipose tissue attract ovarian cancer cells?

    Mogi Kazumasa, Yoshihara Masato, Kitami Kazuhisa, Iyoshi Shohei, Uno Kaname, Tano Sho, Sugiyama Mai, Koya Yoshihiro, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page: 341 - 341   2021.2

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  17. Establishment of a patient-derived xenograft model and cell line of malignant transformation of mature cystic teratoma of the ovary

    Tamauchi Satoshi, Suzuki Shiro, Xuboya Chang, Yoshihara Masato, Yoshida Kosuke, Ikeda Yoshiki, Yoshikawa Nobuhisa, Kajiyama Hiroaki, Kikkawa Fumitaka

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 47 ( 2 ) page: 713 - 719   2021.2

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  18. A uterine pseudotumor of immunoglobulinG4-related disease

    Senda Yasutaka, Ikeda Yoshiki, Tamauchi Satoshi, Yoshikawa Nobuhisa, Kikkawa Fumitaka, Kajiyama Hiroaki

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 47 ( 1 ) page: 430 - 435   2021.1

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  19. The Prognostic Significance of Peritumoral Lymphocytes' Band-like Structure in Type II Endometrial Cancer

    Shimizu Yusuke, Suzuki Shiro, Ukai Mayu, Hattori Satomi, Yoshikawa Nobuhisa, Kajiyama Hiroaki

    ANTICANCER RESEARCH   Vol. 41 ( 1 ) page: 249 - 258   2021.1

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  20. Sarcopenia as a Predictor of Survival Among Patients With Organ Metastatic Cervical Cancer

    Yoshikawa Nobuhisa, Shirakawa Akira, Yoshida Kosuke, Tamauchi Satoshi, Suzuki Shiro, Kikkawa Fumitaka, Kajiyama Hiroaki

    NUTRITION IN CLINICAL PRACTICE   Vol. 35 ( 6 ) page: 1041 - 1046   2020.12

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  21. Does uterine preservation affect survival outcomes of patients with stage I ovarian sex cord-stromal cell tumours? A multi-institutional study

    Yoshihara Masato, Tamauchi Satoshi, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Yoshikawa Nobuhisa, Ikeda Yoshiki, Kawai Michiyasu, Nagasaka Tetsuro, Kajiyama Hiroaki

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY   Vol. 254   page: 52 - 56   2020.11

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  22. Adjusted multiple gases in the plasma flow induce differential antitumor potentials of plasma-activated solutions

    Nakamura Kae, Yoshikawa Nobuhisa, Yoshihara Masato, Ikeda Yoshiki, Higashida Akihiro, Niwa Akihiro, Jindo Takahiro, Tanaka Hiromasa, Ishikawa Kenji, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka, Kajiyama Hiroaki

    PLASMA PROCESSES AND POLYMERS   Vol. 17 ( 10 )   2020.10

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    DOI: 10.1002/ppap.201900259

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  23. Survival after Anticancer Treatment of Terminally Ill Patients with Ovarian Carcinoma

    Kajiyama Hiroaki, Suzuki Shiro, Shimbo Akiko, Utsumi Fumi, Yoshikawa Nobuhisa, Kikkawa Fumitaka

    JOURNAL OF PALLIATIVE MEDICINE   Vol. 23 ( 8 ) page: 1060 - 1065   2020.8

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  24. The impact of systematic retroperitoneal lymphadenectomy on long-term oncologic outcome of women with advanced ovarian clear-cell carcinoma

    Kajiyama Hiroaki, Suzuki Shiro, Yoshikawa Nobuhisa, Tamauchi Satoshi, Shibata Kiyosumi, Kikkawa Fumitaka

    JOURNAL OF GYNECOLOGIC ONCOLOGY   Vol. 31 ( 4 ) page: e47   2020.7

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  25. The Preoperative Prognostic Nutritional Index for the Prediction of Outcomes in Patients with Early-Stage Ovarian Clear Cell Carcinoma

    Yoshikawa Nobuhisa, Yoshida Kosuke, Tamauchi Satoshi, Ikeda Yoshiki, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   Vol. 10 ( 1 ) page: 7135   2020.4

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  26. The Therapeutic Effects of Goreisan, a Traditional Japanese Herbal Medicine, on Lower-Limb Lymphedema after Lymphadenectomy in Gynecologic Malignancies: A Case Series Study

    Yoshikawa Nobuhisa, Kajiyama Hiroaki, Otsuka Naoki, Tamauchi Satoshi, Ikeda Yoshiki, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Utsumi Fumi, Shibata Kiyosumi, Kikkawa Fumitaka

    EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE   Vol. 2020   page: 6298293   2020.4

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  27. Is standard radical surgery necessary for elderly patients with early-stage epithelial ovarian carcinoma? similar to Propensity score matched analysis similar to

    Kajiyama Hiroaki, Yoshihara Masato, Tamauchi Satoshi, Yoshikawa Nobuhisa, Niimi Kaoru, Suzuki Shiro, Shibata Kiyosumi, Kikkawa Fumitaka

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   Vol. 50 ( 4 ) page: 411 - 418   2020.4

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  28. CCL2 secreted from cancer-associated mesothelial cells promotes peritoneal metastasis of ovarian cancer cells through the P38-MAPK pathway

    Yasui Hiroaki, Kajiyama Hiroaki, Tamauchi Satoshi, Suzuki Shiro, Peng Yang, Yoshikawa Nobuhisa, Sugiyama Mai, Nakamura Kae, Kikkawa Fumitaka

    CLINICAL & EXPERIMENTAL METASTASIS   Vol. 37 ( 1 ) page: 145 - 158   2020.2

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  29. The role of additional hysterectomy after concurrent chemoradiation for patients with locally advanced cervical cancer

    Yoshida Kosuke, Kajiyama Hiroaki, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 25 ( 2 ) page: 384 - 390   2020.2

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  30. Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

    Yoshikawa Nobuhisa, Liu Wenting, Nakamura Kae, Yoshida Kosuke, Ikeda Yoshiki, Tanaka Hiromasa, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   Vol. 10 ( 1 ) page: 1614   2020.1

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  31. Impact of age on clinicopathological features and survival of epithelial ovarian neoplasms in reproductive age

    Hanatani Maya, Yoshikawa Nobuhisa, Yoshida Kosuke, Tamauchi Satoshi, Ikeda Yoshiki, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kawai Michiyasu, Kajiyama Hiroaki, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 25 ( 1 ) page: 187 - 194   2020.1

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  32. Clinical Significance of Ubiquitin-associated Protein 2-like in Patients With Uterine Cervical Cancer

    Yoshida Kosuke, Kajiyama Hiroaki, Inami Eri, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Shibata Kiyosumi, Nawa Akihiro, Kikkawa Fumitaka

    IN VIVO   Vol. 34 ( 1 ) page: 109 - 116   2020

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  33. Complete Response of Recurrent Small Cell Carcinoma of the Uterine Cervix to Paclitaxel, Carboplatin, and Bevacizumab Combination Therapy

    Nakao Yuri, Tamauchi Satoshi, Yoshikawa Nobuhisa, Suzuki Shiro, Kajiyama Hiroaki, Kikkawa Fumitaka

    CASE REPORTS IN ONCOLOGY   Vol. 13 ( 1 ) page: 373 - 378   2020

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  34. Fertility-sparing surgery and oncologic outcome among patients with early-stage ovarian cancer similar to propensity score- matched analysis similar to

    Kajiyama Hiroaki, Suzuki Shiro, Yoshikawa Nobuhisa, Kawai Michiyasu, Mizuno Kimio, Yamamuro Osamu, Nagasaka Tetsuro, Shibata Kiyosumi, Kikkawa Fumitaka

    BMC CANCER   Vol. 19 ( 1 ) page: 1235   2019.12

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  35. Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma

    Shimbo Akiko, Kajiyama Hiroaki, Tamauchi Satoshi, Yoshikawa Nobuhisa, Ikeda Yoshiki, Nishino Kimihiro, Suzuki Shiro, Niimi Kaoru, Sakata Jun, Kikkawa Fumitaka

    ONCOLOGY REPORTS   Vol. 42 ( 6 ) page: 2323 - 2332   2019.12

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  36. Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background

    Yoshida Kosuke, Yokoi Akira, Kagawa Takumi, Oda Shingo, Hattori Satomi, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Shibata Kiyosumi, Kajiyama Hiroaki, Yokoi Tsuyoshi, Kikkawa Fumitaka

    CARCINOGENESIS   Vol. 40 ( 12 ) page: 1435 - 1444   2019.12

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  37. COMPREHENSIVE MIRNA SEQUENCING OF SQUAMOUS CELL CARCINOMA ARISING FROM OVARIAN MATURE TERATOMA

    Yoshida K., Yokoi A., Tamauchi S., Ikeda Y., Yoshikawa N., Nishino K., Niimi K., Suzuki S., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 29   page: A544 - A545   2019.11

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  38. REDUCED RESPONSE TO CONTROLLED OVARIAN STIMULATION AFTER RADICAL TRACHELECTOMY

    Tamauchi S., Kajiyama H., Osuka S., Moriyama Y., Yoshihara M., Iyoshi S., Yoshida K., Ikeda Y., Yoshikawa N., Nishino K., Niimi K., Suzuki S., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 29   page: A269 - A270   2019.11

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  39. Prognostic value of neutrophil-to-lymphocyte ratio in early-stage ovarian clear-cell carcinoma

    Yoshida Kosuke, Yoshikawa Nobuhisa, Shirakawa Akira, Niimi Kaoru, Suzuki Shiro, Kajiyama Hiroaki, Kikkawa Fumitaka

    JOURNAL OF GYNECOLOGIC ONCOLOGY   Vol. 30 ( 6 ) page: e85   2019.11

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  40. Relationship between preexisting mental disorders and prognosis of gynecologic cancers: A case-control study

    Tamauchi Satoshi, Kajiyama Hiroaki, Moriyama Yoshinori, Yoshihara Masato, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 45 ( 10 ) page: 2082 - 2087   2019.10

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  41. Fertility-Sparing surgery for young women with ovarian endometrioid carcinoma: a multicenteric comparative study using inverse probability of treatment weighting.

    Kajiyama H, Yoshihara M, Tamauchi S, Yoshikawa N, Suzuki S, Kikkawa F

    European journal of obstetrics & gynecology and reproductive biology: X   Vol. 4   page: 100071   2019.10

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    DOI: 10.1016/j.eurox.2019.100071

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  42. Oxidative stress-dependent and -independent death of glioblastoma cells induced by non-thermal plasma-exposed solutions

    Tanaka Hiromasa, Mizuno Masaaki, Katsumata Yuko, Ishikawa Kenji, Kondo Hiroki, Hashizume Hiroshi, Okazaki Yasumasa, Toyokuni Shinya, Nakamura Kae, Yoshikawa Nobuhisa, Kajiyama Hiroaki, Kikkawa Fumitaka, Hori Masaru

    SCIENTIFIC REPORTS   Vol. 9 ( 1 ) page: 13657   2019.9

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  43. Interleukin-33 expression in ovarian cancer and its possible suppression of peritoneal carcinomatosis

    Sekiya Atsushi, Suzuki Shiro, Tanaka Ayako, Hattori Satomi, Shimizu Yusuke, Yoshikawa Nobuhisa, Koya Yoshihiro, Kajiyama Hiroaki, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF ONCOLOGY   Vol. 55 ( 3 ) page: 755 - 765   2019.9

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  44. Long-term oncologic outcome and its prognostic indicators in reproductive-age women with ovarian clear-cell carcinoma

    Kajiyama Hiroaki, Suzuki Shiro, Yoshikawa Nobuhisa, Niimi Kaoru, Kawai Michiyasu, Shibata Kiyosumi, Kikkawa Fumitaka

    ARCHIVES OF GYNECOLOGY AND OBSTETRICS   Vol. 300 ( 3 ) page: 717 - 724   2019.9

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  45. Comparison of long-term oncologic outcomes between metastatic ovarian carcinoma originating from gastrointestinal organs and advanced mucinous ovarian carcinoma

    Kajiyama Hiroaki, Suzuki Shiro, Utsumi Fumi, Yoshikawa Nobuhisa, Nishino Kimihiro, Ikeda Yoshiki, Niimi Kaoru, Yamamoto Eiko, Kawai Michiyasu, Shibata Kiyosumi, Nagasaka Tetsuro, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 24 ( 8 ) page: 950 - 956   2019.8

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  46. Oncologic outcomes after secondary surgery in recurrent clear-cell carcinoma of the ovary

    Kajiyama Hiroaki, Suzuki Shiro, Yoshikawa Nobuhisa, Kawai Michiyasu, Shibata Kiyosumi, Nagasaka Tetsuro, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 29 ( 5 ) page: 910 - 915   2019.6

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  47. Does postoperative prophylactic irradiation of para-aortic lymph nodes reduce the risk of recurrence in uterine cervical cancer with positive pelvic lymph nodes?

    Yoshida Kosuke, Kajiyama Hiroaki, Yoshihara Masato, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 24 ( 5 ) page: 567 - 574   2019.5

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  48. Epidemiological overview of metastatic ovarian carcinoma: long-term experience of TOTSG database

    Kajiyama Hiroaki, Suzuki Shiro, Utsumi Fumi, Nishino Kimihiro, Niimi Kaoru, Mizuno Mika, Yoshikawa Nobuhisa, Kawai Michiyasu, Oguchi Hidenori, Mizuno Kimio, Yamamuro Osamu, Shibata Kiyosumi, Nagasaka Tetsuro, Kikkawa Fumitaka

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 81 ( 2 ) page: 193 - 198   2019.5

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  49. Endometriosis and cancer

    Kajiyama Hiroaki, Suzuki Shiro, Yoshihara Masato, Tamauchi Satoshi, Yoshikawa Nobuhisa, Niimi Kaoru, Shibata Kiyosumi, Kikkawa Fumitaka

    FREE RADICAL BIOLOGY AND MEDICINE   Vol. 133   page: 186 - 192   2019.3

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  50. Survival impact of capsule status in stage I ovarian mucinous carcinoma-A mulicentric retrospective study

    Kajiyama Hiroaki, Suzuki Shiro, Yoshikawa Nobuhisa, Kawai Michiyasu, Nagasaka Tetsuro, Kikkawa Fumitaka

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY   Vol. 234   page: 131 - 136   2019.3

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  51. PAI-1 secreted from metastatic ovarian cancer cells triggers the tumor-promoting role of the mesothelium in a feedback loop to accelerate peritoneal dissemination

    Peng Yang, Kajiyama Hiroaki, Yuan Hong, Nakamura Kae, Yoshihara Masato, Yokoi Akira, Fujikake Kayo, Yasui Hiroaki, Yoshikawa Nobuhisa, Suzuki Shiro, Senga Takeshi, Shibata Kiyosumi, Kikkawa Fumitaka

    CANCER LETTERS   Vol. 442   page: 181 - 192   2019.2

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  52. Reproductive outcomes of 105 malignant ovarian germ cell tumor survivors: a multicenter study

    Tamauchi Satoshi, Kajiyama Hiroaki, Yoshihara Masato, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY   Vol. 219 ( 4 ) page: 385.e1 - 385.e7   2018.10

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  53. EFFECT OF CONCURRENT CHEMO-RADIOTHERAPY ON CLINICAL OUTCOMES IN SMALL CELL CARCINOMA OF THE UTERINE CERVIX

    Ikeda Y., Kajiyama H., Yoshida K., Yoshikawa N., Nishino K., Utsumi F., Niimi K., Suzuki S., Kawai M., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 294 - 294   2018.9

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  54. PROPENSITY SCORE ADJUSTED ANALYSIS OF PROPHYLACTIC IRRADIATION TO PARA-AORTIC LYMPH NODE AFTER RADICAL HYSTERECTOMY FOR UTERINE CERVICAL CANCER.

    Yoshida K., Yoshihara M., Ikeda Y., Yoshikawa N., Nishino K., Utumi F., Niimi K., Suzuki S., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 447 - 447   2018.9

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  55. The upregulated expression of vascular endothelial growth factor in surgically treated patients with recurrent/radioresistant cervical cancer of the uterus

    Yoshida Kosuke, Suzuki Shiro, Sakata Jun, Utsumi Fumi, Niimi Kaoru, Yoshikawa Nobuhisa, Nishino Kimihiro, Shibata Kiyosumi, Kikkawa Fumitaka, Kajiyama Hiroaki

    ONCOLOGY LETTERS   Vol. 16 ( 1 ) page: 515 - 521   2018.7

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  56. Fertility-sparing surgery of malignant transformation arising from mature cystic teratoma of the ovary.

    Yoshikawa N, Teshigawara T, Ikeda Y, Nishino K, Sakata J, Utsumi F, Niimi K, Sekiya R, Suzuki S, Kawai M, Shibata K, Kikkawa F, Kajiyama H

    Oncotarget   Vol. 9 ( 44 ) page: 27564 - 27573   2018.6

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    DOI: 10.18632/oncotarget.25548

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  57. The possible existence of occult metastasis in patients with ovarian clear-cell carcinoma who underwent complete resection without any residual tumours.

    Kajiyama H, Suzuki S, Yoshihara M, Nishino K, Yoshikawa N, Utsumi F, Niimi K, Mizuno M, Kawai M, Oguchi H, Mizuno K, Yamamuro O, Nagasaka T, Shibata K, Kikkawa F

    Oncotarget   Vol. 9 ( 5 ) page: 6298 - 6307   2018.1

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    DOI: 10.18632/oncotarget.23921

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  58. A novel mechanism of neovascularization in peritoneal dissemination via cancer-associated mesothelial cells affected by TGF-beta derived from ovarian cancer

    Fujikake Kayo, Kajiyama Hiroaki, Yoshihara Masato, Nishino Kimihiro, Yoshikawa Nobuhisa, Utsumi Fumi, Suzuki Shiro, Niimi Kaoru, Sakata Jun, Mitsui Hiroko, Shibata Kiyosumi, Senga Takeshi, Kikawa Fumitaka

    ONCOLOGY REPORTS   Vol. 39 ( 1 ) page: 193 - 200   2018.1

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.3892/or.2017.6104

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  59. PRIMA-1MET INDUCES APOPTOSIS THROUGH ACCUMULATION OF INTRACELLULAR REACTIVE OXYGEN SPECIES IRRESPECTIVE OF P53 STATUS AND CHEMO-SENSITIVITY IN EPITHELIAL OVARIAN CANCER CELLS

    Yoshikawa N., Shimizu Y., Yoshihara M., Nakamura K., Suzuki S., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 27   page: 324-324   2017.11

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  60. PRIMA-1MET INDUCES APOPTOSIS THROUGH ACCUMULATION OF INTRACELLULAR REACTIVE OXYGEN SPECIES IRRESPECTIVE OF P53 STATUS AND CHEMO-SENSITIVITY IN EPITHELIAL OVARIAN CANCER CELLS

    Yoshikawa N., Shimizu Y., Yoshihara M., Nakamura K., Suzuki S., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 27   page: 84-84   2017.11

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  61. ESTABLISHMENT AND CHARACTERISATION OF PATIENT-DERIVED XENOGRAFT MODELS FOR MALIGNANT GYNECOLOGIC TUMORS

    Suzuki S., Tamauchi S., Shimizu Y., Yoshihara M., Nakamura K., Yoshikawa N., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 27   page: 494 - 494   2017.11

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  62. PELVIC EXENTERATION IN PATIENTS WITH RECURRENT OR ADVANCED GYNECOLOGIC MALIGNANCIES

    Takuto N., Shimizu Y., Yoshihara M., Nakamura K., Yoshikawa N., Suzuki S., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 27   page: 896 - 896   2017.11

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  63. EVALUATING THE LONG TERM PROGNOSTIC FACTOR AND THE ROLE OF CYTOREDUCTION IN THE OVERALL POPULATION OF PATIENTS WITH CLINICAL AND SURGICAL STAGE IV ENDOMETRIAL CARCINOMA

    Shimizu Y., Kajiyama H., Suzuki S., Yoshikawa N., Nakamura K., Yoshihara M., Tamauchi S., Yoshida K., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 27   page: 1213 - 1213   2017.11

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  64. ESTABLISHMENT AND CHARACTERISATION OF PATIENT-DERIVED XENOGRAFT MODELS FOR MALIGNANT GYNECOLOGIC TUMORS

    Suzuki S., Tamauchi S., Shimizu Y., Yoshihara M., Nakamura K., Yoshikawa N., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 27   page: 1382 - 1382   2017.11

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KAKENHI (Grants-in-Aid for Scientific Research) 6

  1. 腹腔内細胞コミュニケーションが誘導するオカルト播種の休眠維持環境構築のメカニズム

    Grant number:21K19562  2021.7 - 2024.3

    科学研究費助成事業  挑戦的研究(萌芽)

    梶山 広明, 吉原 雅人, 横井 暁, 芳川 修久

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    本課題は腹腔内微小環境における癌関連腹膜中皮細胞に注目して、腹腔内オカルト播種の休眠の機能および維持メカニズムを追究する研究である。休眠の維持に関する解析項目に「腫瘍-CAMのNotchシグナル」や免疫回避の第一歩として「SDF-1α制御-腫瘍関連マクロファージ」との関連を取り入れた斬新かつ挑戦的な研究である。本課題で得られた知見によって腹膜全体をターゲットとした包括的治療戦略の策定や新規バイオマーカーの同定を目指す。特に腹膜は面積的に広範囲であるため、標的にしえた場合の治療及びQOL改善の効果も大きいと考えられる。さらに本研究は卵巣癌に限らず癌性腹膜炎を形成しうる他癌にも応用可能となりうる。

  2. Interdisciplinary study on the peritoneal metastasis of patients with ovarian cancer based on the adipo-peritoneal crosstalk

    Grant number:20H03824  2020.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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  3. 大気圧プラズマによる微小環境を標的とした難治性腹膜播種制御機構の解明

    Grant number:20K09640  2020.4 - 2023.3

    科学研究費助成事業  基盤研究(C)

    中村 香江, 田中 宏昌, 芳川 修久

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    卵巣がんにおける腹膜播種は難治性・治療抵抗性の象徴的な病態として着目されており、がん細胞と腹膜微小環境に存在する腹膜中皮細胞やその他の免疫系細胞との細胞間相互作用が腹膜播種の形成・進展に重要な役割を担っていることが明らかになっている。本研究において、大気圧プラズマの抗腫瘍活性を液体化したプラズマ活性液が誘導する腹膜微小環境における腫瘍抑制機構を解明し、新規治療技術としての基礎的知見の集積を目指す。
    卵巣がんは腹膜播種を伴った進行がんとして発見される場合が多く、故に難治性であり、新規の治療法が求められている。一方、大気圧プラズマの抗腫瘍活性を汎用性の高い液体化したプラズマ活性液は、これまでの抗腫瘍療法とは全く異なる作用機序でがん細胞を殺傷することが示唆されている。本研究では、腹膜播種の形成・進展において重要な役割を果たす腹膜中皮細胞・免疫系細胞を介した腹膜微小環境におけるプラズマ活性液の抗腫瘍効果を明らかにし、新規治療技術としての基礎的知見の集積を目的とする。
    腹膜播種は、がん細胞のみならず本来なら恒常性維持に関わる細胞が、癌関連腹膜中皮細胞、腫瘍浸潤リンパ球、腫瘍関連マクロファージ等に変化し、難治性・治療抵抗性の基盤となって存在している。一方、これまでの研究において、プラズマ活性液の腹腔内投与は、マウス卵巣がん腹膜播種モデルにおいて、腹腔内へのがん細胞の播種を抑制し、マウスの生存期間を有意に延長すること明らかにしてきた。そこで、本研究において、プラズマ活性液による腹膜微小環境への影響を介した播種抑制効果を明らかにするために、がん細胞の播種巣、特に大網組織中のがん微小環境に着目し、組織中に存在するマクロファージとその特徴について解析を行った。その結果、がん細胞の播種3日後には治療対象群のマウス大網組織において、がん細胞の播種および増殖が確認されたのに対し、プラズマ活性液治療群では、がん細胞の増殖が有為に抑制されていることが明らかとなった。組織学的解析の結果、顕著なM1型マクロファージの浸潤が見られ、抗腫瘍免疫が活性化された可能性が示唆された。これらの結果より、初期のがんの播種に対しプラズマ活性液が免疫応答に変化をもたらすことでがんの進展を抑制する可能性を示した。
    コロナ渦における、実験実施の制限や、物品などの入手が一部困難であった。
    今年度の研究成果により、プラズマ活性液が、がん微小環境に抗腫瘍免疫応答を誘導する可能性を示した。しかし、がんの進展に対する腹膜微小環境は種々の細胞が存在し、それらが相互に影響し活性化や分化を誘導している。次年度以降は、中皮細胞やリンパ球にも焦点をあて、正常腹膜とがん性腹膜での微小環境の違いに着目し、プラズマ活性液が、がん細胞が生きづらい微小環境へと変化を誘導することができるかどうかを、培養中皮細胞並びにリンパ球細胞を用いて検討する。一方で、プラズマ活性液によりがん細胞に誘導されたオートファジー細胞死が、腫瘍内免疫原性細胞死を誘導するかどうかについても検討を行い、がん細胞を介した間接的な免疫活性化の効果とそのメカニズムについても明らかにしていく。

  4. p53変異卵巣癌の細胞外小胞を介した腹膜播種進展の病態解明と新規治療戦略

    Grant number:19K18693  2019.4 - 2022.3

    科学研究費助成事業  若手研究

    芳川 修久

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    卵巣癌の腹膜播種には、上皮間葉転換や癌幹細胞様形質の獲得といった癌細胞自身の悪性形質に加えて、エクソソーム等を介した細胞間コミュニケーションに依存した好腫瘍性の腹膜微小環境の構築が重要な役割を果たしている。特に高悪性度漿液性癌では、ほぼ全例でTP53変異を認め且つその大部分がミスセンス変異による変異型p53タンパク(以下、変異型p53)の蓄積を伴うこと、変異型p53が癌細胞の悪性形質を促進する機能を有することが示されてきた。
    本研究では、p53変異卵巣癌由来エクソソームを介した腹膜播種の進展メカニズムを解明し、以て新規治療法の開発へとつなげることを最終的な目標としている。
    我々は前年度の検討結果よりp53の活性化に伴って上昇するDDIT4タンパクの機能解析に進むこととしていた。p53の活性化はその上流として低酸素ストレスが影響していることが知られており、そのマスターレギュレーターの一つとしてDDIT4という分子が報告されている。複数の癌種において低酸素ストレス反応性にDDIT4が上昇し、悪性形質を増強することが知られておりこれにp53の変異の有無がどのように影響を与えているか検討することとした。DDIT4の発現抑制を得るためにsiRNAをValidationした。また、DDIT4の発現抑制により増殖抑制効果やシスプラチン抵抗性が変化する。また、DDIT4の機能実験として、遊走能・浸潤能にも影響を与えることを確認している。臨床組織検体における発現解析として子宮頸癌臨床組織検体を用いてDDIT4の発現比較を行い、リンパ管侵襲やリンパ節転移といった悪性予後と相関する臨床病理学的因子と有意な相関関係を見出した。以上よりDDIT4はリンパ系の転移を誘導する因子であることが示唆されたため、現在子宮頸癌同所移植モデルマウスを作成し、DDIT4発現の多寡によりリンパ転移が変化するか等について評価を加えていく予定としている。また、RNAの網羅的解析によりDDIT4が制御する重要なパスウェイ・分子の同定を目指したい。
    また、別の観点からプラチナ製剤耐性に関する新たな知見としてレーザーアブレーション質量分析を用いたプラチナ抵抗性予測の可能性を検討を開始しており、組織内プラチナ分布によりその後のプラチナ感受性を予見できる可能性があることを見出している。
    変異型p53の強制発現を用いた系においての進捗は当初の想定より遅れているものの、DDIT4の発現抑制系を確立するとともに、増殖や抗がん剤耐性に関するBiological functionを確認することができたという前年度の実績を受けて、さらなる機能実験を追加した。仮説通りの結果となるものもあったが、マウスモデルの構築やshRNA安定抑制細胞株の樹立等まだ途中のものもあるため、全体としてやや遅れている状況となっている。
    以下の通り推進方策を考えている。
    1.補完的にデータを収集する観点で、微量元素マッピング手法を用いた微量元素分布の評価などを合わせて行っていく。この微量元素マッピング法は、質量分析の技術を用いて腫瘍組織におけるプラチナ・銅・亜鉛などの分布や濃度を詳細に把握することができる最新の技術である。これを活用することにより、抗がん剤耐性や臨床的悪性度に相関する特徴を把握することにつながる可能性がある。これのPreliminaryな知見は上記の通り得ており、今後はそのプラチナ分布をもたらすメカニズムに迫る卵巣癌オルガノイドモデルを用いた研究を進めていく。
    2.DDIT4の機能解析を進める。特に変異型p53の有無により増殖や抗がん剤耐性といった生物学的特徴にどのように影響を与えるかについて、検討を進める。既にDDIT4抑制にともなって生じる変化は細胞レベルで一貫したものを得ており、マウスモデルによるin vivoでの検証やRNA発現解析による関与するパスウェイの評価を行う。
    以上を推進することで、研究課題の達成に繋げていく。

  5. Elucidation of malignancy, peritoneal dissemination and spread mechanism of ovarian cancer by interaction with peritoneal mesothelium.

    Grant number:19H03797  2019.4 - 2022.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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  6. Elucidating mechanism of peritoneal metastasis in mutant p53 ovarian cancer based on cell-to-cell communication

    Grant number:17H06753  2017.8 - 2019.3

    Yoshikawa Nobuhisa

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    Grant amount:\2730000 ( Direct Cost: \2100000 、 Indirect Cost:\630000 )

    To evaluate the effects of exogenous mutant p53 protein on endogenous miRNAs expression, two different mutant p53 protein, R248W and R248Q, were expressed in ovarian cancer cell lines haboring p53-null. We identified eight miRNAs that showed 1.5-fold or more increase in expression and two miRNAs that had two-third or more expression reduction in two forced expression strains of mutant p53.
    As a part of elucidation of the mechanism of peritoneal metastasis, we conducted comprehensive analysis of cancer-related miRNAs using FFPE between patients with mature teratomas and malignant transformations, and identified multiple miRNAs. We also elucidated and reported a novel mechanism by which PAI-1, which is abundantly present in cancerous ascites fluid, promotes changes in peritoneal mesothelial cells to promote the tumor-promoting environment.

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