Anti-oxidative stress pathway in the ovary to conquer inevitable aging
Project/Area Number |
15K10704
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
|
Research Institution | The University of Tokyo |
Principal Investigator |
Hiraike Osamu 東京大学, 医学部附属病院, 准教授 (20529060)
|
Research Collaborator |
HIRANO Mana 東京大学, 医学部附属病院, 助教 (80771253)
AKINO Nana
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | 卵巣 / 加齢性変化 / 酸化ストレス / 抗酸化機能 / 顆粒膜細胞 / Nrf2 / 抗酸化 |
Outline of Final Research Achievements |
Nuclear factor-E2-related factor 2 (Nrf2) and its regulator Kelch-like ECH-associated protein 1 (Keap1) are one of the most important defense mechanisms against oxidative stress (OS). Dimethylfumarates (DMF) is an activator of Nrf2, and we investigated the possibility of DMF as a therapeutic drug for OS in human granulosa cells (GCs). We aimed to determine whether DMF alleviates OS in GCs. The mRNA and protein levels of Nrf2 and antioxidants were upregulated by H2O2 in human GCs, and DMF treatment showed similar results through activation of Nrf2. Knockdown of Nrf2 decreased the mRNA and protein levels of antioxidants in human GCs. DMF treatment of GCs activated Nrf2 and reduced intracellular ROS generation. Our results show that activation of Nrf2 by DMF might lead to alleviated OS in human GCs, and this will lead to better outcomes in infertility treatment.
|
Report
(4 results)
Research Products
(62 results)
-
-
[Journal Article] Therapeutic significance of targeting survivin in cervical cancer and possibility of combination therapy with TRAIL2018
Author(s)
Nakamura H, Taguchi A, Kawana K, Baba S, Kawata A, Yoshida M, Fujimoto A, Ogishima J, Sato M, Inoue T, Nishida H, Furuya H, Yamashita A, Eguchi S, Tomio K, Mori-Uchino M, Adachi K, Arimoto T, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y, Fujii T
-
Journal Title
Oncotarget
Volume: 9
Issue: 17
Pages: 13451-13461
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Journal Article] Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer.2017
Author(s)
Oki S, Sone K, Oda K, Hamamoto R, Ikemura M, Maeda D, Takeuchi M, Tanikawa M, Mori-Uchino M, Nagasaka K, Miyasaka A, Kashiyama T, Ikeda Y, Arimoto T, Kuramoto H, Wada-Hiraike O, Kawana K, Fukayama M, Osuga Y, Fujii T.
-
Journal Title
Oncotarget
Volume: in press
Issue: 25
Pages: 40402-40411
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Preoperative assessment of factors associated with difficulty in performing total laparoscopic hysterectomy.2017
Author(s)
Saito A, Hirata T, Koga K, Takamura M, Fukuda S, Neriishi K, Pastorfide G, Harada M, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y
-
Journal Title
J Obstet Gynaecol Res.
Volume: 43(2)
Issue: 2
Pages: 320-329
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
[Journal Article] Low uptake of fluorodeoxyglucose in positron emission tomography/computed tomography in ovarian clear cell carcinoma may reflect glutaminolysis of its cancer stem cell-like properties,2017
Author(s)
Sato M, Kawana K, Adachi K, Fujimoto A, Taguchi A, Fujikawa T, Yoshida M, Nakamura H, Nishida H, Inoue T, Ogishima J, Eguchi S, Yamashita A, Tomio K, Arimoto T, Wada-Hiraike Osamu, Oda K, Nagamatsu T, Osuga Y, Fujii T
-
Journal Title
Oncol Reports
Volume: 37(3)
Issue: 3
Pages: 1883-1888
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
[Journal Article] Drospirenone reduces inflammatory cytokines, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) expression in human endometriotic stromal cells.2017
Author(s)
Makabe T, Koga K, Miyashita M, Takeuchi A, Sue F, Taguchi A, Urata Y, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
-
Journal Title
J Reprod Immunol
Volume: 119
Pages: 44-48
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] A Potential Role for Endoplasmic Reticulum Stress in Progesterone Deficiency in Obese Women.2017
Author(s)
Takahashi N, Harada M, Hirota Y, Zhao L, Azhary JM, Yoshino O, Izumi G, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
-
Journal Title
Endocrinology
Volume: 158
Pages: 84-97
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Targeting glutamine metabolism and focal adhesion kinase additively inhibits the mammalian target of the rapamycin pathway in spheroid cancer stem-like properties of ovarian clear cell carcinoma2016
Author(s)
Sato M, Kawana K, Adachi K, Fujimoto A, Yoshida M, Nakamura H, Nishida H, Inoue T, Taguchi A, Ogishima J, Eguchi S, Yamashita A, Tomio K, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y , Fujii T,
-
Journal Title
Int J Oncol
Volume: 50(4)
Issue: 4
Pages: 1431-1438
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
[Journal Article] Resveratrol Enhances Apoptosis in Endometriotic Stromal Cells.2016
Author(s)
Taguchi, A., Koga, K., Kawana, K., Makabe, T., Sue, F., Miyashita, M., Yoshida, M., Urata, Y., Izumi, G., Takamura, M., Harada, M., Hirata, T., Hirota, Y., Wada-Hiraike, O., Fujii, T., Osuga, Y
-
Journal Title
American Journal of Reproductive Immunology
Volume: 75
Issue: 4
Pages: 486-492
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Systemic Delivery of Sirna by Actively Targeted Polyion Complex Micelles for Silencing the E6 and E7 Human Papillomavirus Oncogenes2016
Author(s)
Nishida H, Matsumoto Y, Kawana K, Christie RJ, Naito M, Kim BS, Toh K, Min HS, Yi Y, Matsumoto Y, Kim HJ, Miyata K, Taguchi A, Tomio K, Yamashita A, Inoue T, Nakamura H, Fujimoto A, Sato M, Yoshida M, Adachi K, Arimoto T, Wada-Hiraike O, Oda K, Nagamatsu T, Nishiyama N, Kataoka K, Osuga Y, Fujii T
-
Journal Title
J Control Release
Volume: in press
Pages: 29-37
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] A potential role of endoplasmic reticulum stress in development of ovarian hyperstimulation syndrome.2016
Author(s)
Takahashi N, Harada M, Hirota Y, Zhao L, Yoshino O, Urata Y, Izumi G, Takamura M, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
-
Journal Title
Mol Cell Endocrinol
Volume: 428
Pages: 161-169
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Effects of 1,25-dihydroxy vitamin D3 on endometriosis.2016
Author(s)
Miyashita M, Koga K, Izumi G, Sue F, Makabe T, Taguchi A, Nagai M, Urata Y, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
-
Journal Title
J Clin Endocrinol Metab
Volume: 101
Issue: 6
Pages: 2371-2379
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Significance of survivin as a prognostic factor and a therapeutic target in endometrial cancer.2016
Author(s)
Chuwa AH, Sone K, Oda K, Ikeda Y, Fukuda T, Wada-Hiraike O, Inaba K, Makii C, Takeuchi M, Oki S, Miyasaka A, Kashiyama T, Arimoto T, Kuramoto H, Kawana K, Yano T, Osuga Y, Fujii T.
-
Journal Title
Gynecol Oncol
Volume: 141
Issue: 3
Pages: 564-569
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
-
[Journal Article] Synergistic antitumor effects of combination of PI3K/mTOR and MEK inhibition (SAR245409 and pimasertib) in mucinous ovarian carcinoma cells by fluorescence resonance energy transfer imaging.2016
Author(s)
Inaba K, Oda K, Aoki K, Sone K, Ikeda Y, Miyasaka A, Kashiyama T, Fukuda T, Makii C, Arimoto T, Wada-Hiraike O, Kawana K, Yano T, Osuga Y, Fujii T
-
Journal Title
Oncotarget
Volume: 7
Issue: 20
Pages: 29577-29591
DOI
NAID
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Spheroid cancer stem cells display reprogrammed metabolism and obtain energy by actively running the tricarboxylic acid (TCA) cycle2016
Author(s)
Sato M, Kawana K, Adachi K, Fujimoto A, Yoshida M, Nakamura H, Nishida H, Inoue T, Taguchi A, Takahashi J, Kojima S, Yamashita A, Tomio K, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y, Fujii T
-
Journal Title
Oncotarget
Volume: 7(22)
Issue: 22
Pages: 33297-33305
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
[Journal Article] Inhibition of endoplasmic reticulum (ER) stress sensors sensitizes cancer stem-like cells to ER stress-mediated apoptosis.2016
Author(s)
Fujimoto A, Kawana K, Taguchi A, Adachi K, Sato M, Nakamura H, Ogishima J, Yoshida M, Inoue T, Nishida H, Tomio K, Yamashita A, Matsumoto Y, Arimoto T, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y, Fujii T.
-
Journal Title
Oncotarget
Volume: 7
Issue: 32
Pages: 51854-51864
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Neutrophil depletion reduces endometriotic lesion formation in mice.2016
Author(s)
Takamura M, Koga K, Izumi G, Urata Y, Nagai M, Hasegawa A, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
-
Journal Title
Am J Reprod Immunol
Volume: 76
Issue: 3
Pages: 193-198
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Modification of the Tumor Microenvironment in KRAS or c-MYC-Induced Ovarian Cancer-Associated Peritonitis.2016
Author(s)
Yoshida M, Taguchi A, Kawana K, Adachi K, Kawata A, Ogishima J, Nakamura H, Fujimoto A, Sato M, Inoue T, Nishida H, Furuya H, Tomio K, Arimoto T, Koga K, Wada-Hiraike O, Oda K, Nagamatsu T, Kiyono T, Osuga Y, Fujii T
-
Journal Title
Plos One
Volume: Aug 2;11
Issue: 8
Pages: e0160330-e0160330
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Cancer-associated fibroblast suppresses killing activity of natural killer cells through downregulation of poliovirus receptor (PVR/CD155), a ligand of activating NK receptor.2016
Author(s)
Inoue T, Adachi K, Kawana K, Taguchi A, Nagamatsu T, Fujimoto A, Tomio K, Yamashita A, Eguchi S, Nishida H, Nakamura H, Sato M, Yoshida M, Arimoto T, Wada-Hiraike O, Oda K, Osuga Y, Fujii T.
-
Journal Title
Int J Oncol
Volume: 49
Issue: 4
Pages: 1297-1304
DOI
Related Report
Peer Reviewed
-
[Journal Article] Development of ovarian cancer after excision of endometrioma.2016
Author(s)
Haraguchi H, Koga K, Takamura M, Makabe T, Sue F, Miyashita M, Urata Y, Izumi G, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Oda K, Kawana K, Fujii T, Osuga Y.
-
Journal Title
Fertil Steril
Volume: 106
Issue: 6
Pages: 1432-1437
DOI
Related Report
Peer Reviewed
-
[Journal Article] Autophagy inhibition augments resveratrol-induced apoptosis in Ishikawa endometrial cancer cells.2016
Author(s)
Fukuda T, Oda K, Wada-Hiraike O, Sone K, Inaba K, Ikeda Y, Makii C, Miyasaka A, Kashiyama T, Tanikawa M, Arimoto T, Yano T, Kawana K, Osuga Y, Fujii T.
-
Journal Title
Oncol Lett
Volume: 12
Pages: 2560-2566
Related Report
Peer Reviewed
-
[Journal Article] MDM2 is a potential therapeutic target and prognostic factor for ovarian clear cell carcinomas with wild type TP53.2016
Author(s)
Makii C, Oda K, Ikeda Y, Sone K, Hasegawa K, Uehara Y, Nishijima A, Asada K, Koso T, Fukuda T, Inaba K, Oki S, Machino H, Kojima M, Kashiyama T, Mori-Uchino M, Arimoto T, Wada-Hiraike O, Yano KK, Fujiwara K, Aburatani H, Osuga Y, Fujii T.
-
Journal Title
Oncotarget
Volume: 7
Issue: 46
Pages: 75328-75338
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] STAT3 activity regulates sensitivity to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in cervical cancer cells.2016
Author(s)
Nakamura H, Taguchi A, Kawana K, Kawata A, Yoshida M, Fujimoto A, Ogishima J, Sato M, Inoue T, Nishida H, Furuya H, Tomio K, Eguchi S, Mori-Uchino M, Yamashita A, Adachi K, Arimoto T, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y, Fujii T.
-
Journal Title
Int J Oncol
Volume: 49
Issue: 5
Pages: 2155-2162
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells.2016
Author(s)
Sato M, Kawana K, Adachi K, Fujimoto A, Yoshida M, Nakamura H, Nishida H, Inoue T, Taguchi A, Takahashi J, Kojima S, Yamashita A, Tomio K, Nagamatsu T, Wada-Hiraike O, Oda K, Osuga Y, Fujii T.
-
Journal Title
Int J Oncol
Volume: 48
Issue: 2
Pages: 829-835
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] CCAR2 negatively regulates nuclear receptor LXRα by competing with SIRT1 deacetylase.2015
Author(s)
Sakurabashi A, Wada-Hiraike O, Hirano M, Fu H, Isono W, Fukuda T, Morita Y, Tanikawa M, Miyamoto Y, Oda K, Kawana K, Osuga Y, Fujii T.
-
Journal Title
J Steroid Biochem Mol Biol
Volume: 149
Pages: 80-88
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
[Journal Article] The anti-malarial chloroquine suppresses proliferation and overcomes cisplatin resistance of endometrial cancer cells via autophagy inhibition.2015
Author(s)
Fukuda T, Oda K, Wada-Hiraike O, Sone K, Inaba K, Ikeda Y, Miyasaka A, Kashiyama T, Tanikawa M, Arimoto T, Kuramoto H, Yano T, Kawana K, Osuga Y, Fujii T.
-
Journal Title
Gynecol Oncol
Volume: 137
Issue: 3
Pages: 538-545
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] HPV-16 impairs the subcellular distribution and levels of expression of protein phosphatase 1γ in cervical malignancy.2015
Author(s)
Seiki T, Nagasaka K, Kranjec C, Kawana K, Maeda D, Nakamura H, Taguchi A, Matsumoto Y, Arimoto T, Wada-Hiraike O, Oda K, Nakagawa S, Yano T, Fukayama M, Banks L, Osuga Y, Fujii T.
-
Journal Title
BMC Cancer
Volume: 7
Issue: 1
Pages: 230-230
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
[Journal Article] PI3K/mTOR pathway inhibition overcomes radioresistance via suppression of the HIF1-α/VEGF pathway in endometrial cancer.2015
Author(s)
Miyasaka A, Oda K, Ikeda Y, Sone K, Fukuda T, Inaba K, Makii C, Enomoto A, Hosoya N, Tanikawa M, Uehara Y, Arimoto T, Kuramoto H, Wada-Hiraike O, Miyagawa K, Yano T, Kawana K, Osuga Y, Fujii T.
-
Journal Title
Gynecol Oncol
Volume: 138
Issue: 1
Pages: 174-180
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Four Cases of Postoperative Pneumothorax Among 2814 Consecutive Laparoscopic Gynecologic Surgeries: A Possible Correlation Between Postoperative Pneumothorax and Endometriosis.2015
Author(s)
Hirata T, Nakazawa A, Fukuda S, Hirota Y, Izumi G, Takamura M, Harada M, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
-
Journal Title
J Minim Invasive Gynecol
Volume: 22
Issue: 6
Pages: 980-984
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Antitumor activity of a combination of dual PI3K/mTOR inhibitor SAR245409 and selective MEK1/2 inhibitor pimasertib in endometrial carcinomas.2015
Author(s)
Inaba K, Oda K, Ikeda Y, Sone K, Miyasaka A, Kashiyama T, Fukuda T, Uehara Y, Arimoto T, Kuramoto H, Wada-Hiraike O, Kawana K, Yano T, Osuga Y, Fujii T.
-
Journal Title
Gynecol Oncol
Volume: 138
Issue: 2
Pages: 323-331
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Resveratrol Protects Against Pathological Preterm Birth by Suppression of Macrophage-Mediated Inflammation.2015
Author(s)
Furuya H, Taguchi A, Kawana K, Yamashita A, Inoue E, Yoshida M, Nakamura H, Fujimoto A, Inoue T, Sato M, Nishida H, Nagasaka K, Adachi K, Hoya M, Nagamatsu T, Wada-Hiraike O, Yamashita T, Osuga Y, Fujii T.
-
Journal Title
Reprod Sci
Volume: 22
Issue: 12
Pages: 1561-1568
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
[Journal Article] ntegrated copy number and expression analysis identifies profiles of whole-arm chromosomal alterations and subgroups with favorable outcome in ovarian clear cell carcinomas.2015
Author(s)
Uehara Y, Oda K, Ikeda Y, Koso T, Tsuji S, Yamamoto S, Asada K, Sone K, Kurikawa R, Makii C, Hagiwara O, Tanikawa M, Maeda D, Hasegawa K, Nakagawa S, Wada-Hiraike O, Kawana K, Fukayama M, Fujiwara K, Yano T, Osuga Y, Fujii T, Aburatani H.
-
Journal Title
PLoS One
Volume: 10
Issue: 6
Pages: e0128066-e0128066
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
[Journal Article] HAND2-mediated proteolysis negatively regulates the function of estrogen receptor α.2015
Author(s)
Fukuda T, Shirane A, Wada-Hiraike O, Oda K, Tanikawa M, Sakuabashi A, Hirano M, Fu H, Morita Y, Miyamoto Y, Inaba K, Kawana K, Osuga Y, Fujii T.
-
Journal Title
Mol Med Rep
Volume: 12
Issue: 4
Pages: 5538-5544
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Putative tumor suppression function of SIRT6 in endometrial cancer.2015
Author(s)
Fukuda T, Wada-Hiraike O, Oda K, Tanikawa M, Makii C, Inaba K, Miyasaka A, Miyamoto Y, Yano T, Maeda D, Sasaki T, Kawana K, Fukayama M, Osuga Y, Fujii T.
-
Journal Title
FEBS Lett
Volume: 589
Issue: 17
Pages: 2274-2281
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance.2015
Author(s)
Sato M, Kawana K, Fujimoto A, Yoshida M, Nakamura H, Nishida H, Inoue T, Taguchi A, Takahashi J, Adachi K, Nagasaka K, Matsumoto Y, Wada-Hiraike O, Oda K, Osuga Y, Fujii T.
-
Journal Title
Oncol Rep
Volume: 35
Issue: 1
Pages: 391-397
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy.2015
Author(s)
keda Y, Oda K, Ishihara H, Wada-Hiraike O, Miyasaka A, Kashiyama T, Inaba K, Fukuda T, Sone K, Matsumoto Y, Arimoto T, Maeda D, Ikemura M, Fukayama M, Kawana K, Yano T, Aoki D, Osuga Y, Fujii T.
-
Journal Title
Br J Cancer
Volume: 113
Issue: 10
Pages: 1477-1483
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-