Targeting the molecules useful for the diagnosis and treatment of endometrial cancers
Project/Area Number |
17390448
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Kanazawa University |
Principal Investigator |
INOUE Masaki Kanazawa University, Graduate School Of Medical Science, Prof (10127186)
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Co-Investigator(Kenkyū-buntansha) |
KYO Satoru Kanazawa University, Graduate School of Medical Science, Associate (50272969)
TANAKA Masaaki Kanazawa University, OBGYN, Associate (70283140)
中村 充宏 金沢大学, 医学部附属病院, 助手 (50377397)
|
Project Period (FY) |
2005 – 2007
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Project Status |
Completed (Fiscal Year 2007)
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Budget Amount *help |
¥16,750,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2006: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2005: ¥6,400,000 (Direct Cost: ¥6,400,000)
|
Keywords | Molecular carcinogenesis / Molecular targets / Endometrial cancer / Therapeutic agent / Prognostic Markers / 遺伝子治療 / 遺伝子診断 / 遺伝子メチル化 / エピジェネテイック変化 / 早期診断 / テロメラーゼ / K-ras遺伝子 / MEK-ERK |
Research Abstract |
Endometrial cancer is the second most common gynecological malignancy and its incidence has increased dramatically over the last decade in Japan. Although the surgical and chemotherapeutic treatments for endometrial cancers are well-established, the need for molecular-target therapy has increased, especially for recurrent and/or radio- or chemo-resistant diseases. Thus there is a need for a better understanding of the molecular pathway of endometrial carcinogens. The most frequent genetic abnormalities are mutations in PTEN and ERAS. A PTEN mutation and ERAS mutation activates the PI3K pathway and ERK - MAP pathway, respectively. In the present study using the clinical samples, there is no significant association between KRAS or BRAF and p-ERK1/2 expression. Patients with low expression have a favorable prognosis. Thus, the activation of ERK1/2 occurs in a ERAS and BRAF I dependent manner in endometrial cancer. A High level of p-AKT expression was observed in approximately 60% of endometrial cancers. It occurs independently of both PTEN mutations and PIK3CA mutations. Furthermore, p-AKT expression did not correlated with expression of potential downstream targets such as p-mTOR and/or p TORO 1/3a. The high-expression of p-AKT was strongly associated with ERK. The present study revealed the presence of complex signaling pathways other than the conventional carcinogenic pathway. The molecular targeting for the diagnosis and treatment of endometrial cancers is a long way for the success.
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] Analysis of outcome of stage I-III endometrial cancer treated with systematic operation omitting paraaortic lymphadenectomy2007
Author(s)
Kyo, S., Hashimoto, M., Maida, Y., Mizumoto, Y., Nakamura, M., Takakura, M., Inoue, M
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Journal Title
Eur J Gynecol Oncol (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Activation of ERK1/2 occurs independently of KRas orBraf status in endometrial cancer and is associated with favorable prognosis2007
Author(s)
Mizumoto, Y., Kyo, S., Mori, N., Sakaguchi, J., Ohno, S., Maida, Y., Hashimoto, M., Takakura, M., Inoue, M
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Journal Title
Cancer Science 98
Pages: 6652-6658
NAID
Description
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[Journal Article] Creation of tumorigenic human endometrial epithelial cells with intact chromosomes by introducing defined genetic elements2006
Author(s)
Mizumoto, Y., Kyo, S., Ohno, S., Hashimoto, M., Nakamura, M., Maida, Y., Sakaguchi, J., Takakura, M., Inoue, M., Kiyono, T
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Description
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[Journal Article] High Twist expression in involved in infiltrative endometrial, cancer and affects patient survival2006
Author(s)
Kyo, S., Sakaguchi, J., Ohno, S., Mizumoto, Y., Maida, Y., Hashimoto, M., Nakamura, M., Takakura, M., Nakajima, M., Masutomi, K., Inoue, M
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Journal Title
Human Pathol 37
Pages: 431-438
Description
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[Journal Article] Expression of Tn and Sialy-Tn antigens in endometrial cancer. Its relationship with tumor-produced cyclooxygenase-2, tumor-infiltrated lymphocytes and patients prognosis2006
Author(s)
Ohono, S., Ohno, Y., Nakada, H., Suzuki, N., Soma, G., Inoue, M
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Journal Title
Anticancer Research 26
Pages: 4047-4054
Description
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[Journal Article] Distinct telomere length regulation in premalignant cervical and endometrial lesions : implicationsnfor the roles of telomeres in uterine carcinogenesis2006
Author(s)
Maida, Y., Kyo, S., Forsyth, NR., Takakura, M., Sakaguchi, J., Mizumoto, Y., Hashimoto,Y., Nakamura, M., Nakao, S., Inoue, M
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Journal Title
J Pathol 210
Pages: 214-223
Description
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[Journal Article] High Twist expression is involved in infiltrative feature of endometrial cancer and affects patient survival.2006
Author(s)
Kyo S, Sakaguchi J, Ohno S, Miziumoto Y, Maida Y, Hashimoto M, Nakamura M, Takakura M, Nakajima M, Masutomi K, Inoue M.
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Journal Title
Human Pathology 37
Pages: 431-438
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[Journal Article] High Twist expression is involved in infiltrative feature of endometrial cancer and affects patient survival.2006
Author(s)
Kyo S, Sakaguchi J, Ohno S, Miziumoto Y, Maida Y, Hashimoto M, Nakamura M, Takakura M, Nakajima M, Masutomi K, Inoue M.
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Journal Title
Human Pathology (In Press)
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[Journal Article] Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma2005
Author(s)
Ohno, Y., Ohno, S., Suzuki, N., Kamei, T., Inagawa, H., Soma, Q., Inoue, M
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Journal Title
Int J Cancer 114
Pages: 696-701
Description
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[Journal Article] Pharmacokinetics of paclitaxel in ovarian cancer patients and genetic polymorphisms of CYP2C8, CYP3A4, and MDRI2005
Author(s)
Nakajima, M., Fujiki, Y., Kyo, S., Nakamura, M., Maida, Y., Tanaka, M., Inoue, M
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Journal Title
J Clin Pharmacol 45
Pages: 674-682
Description
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[Journal Article] Efficient inhibition of human telomerase reverse transcriptase expression by RNA interference sensitizes cancer cells to ionizing radiation and chemotherapy2005
Author(s)
Nakamura, M., Masutomi, K., Kyo, S., Hashimoto, M., Maida,Y., Kanaya, T., Tanaka, M., Hahn, WC., Inoue, M
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Journal Title
Human gene therapy 16
Pages: 859-868
Description
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[Journal Article] Analysis of telomerase single-strand overhang in human endometrial cancers2005
Author(s)
Hashimoto, M., Kyo, S., Masutomi, K., Maida, Sakaguchi, J., Mizumoto, Y., Nakamura, M., Hahn, WC., Inoue, M
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Journal Title
FEBS letter 579
Pages: 2959-2964
Description
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[Journal Article] Association of mismatch repair deficiency with PTEN frameshift mutations in endometrial cancers and the precursors in a Japanese population2005
Author(s)
Kanaya, T., Kyo, S., Sakaguchi, J., Maida, Y., Nakamura, M., Takakura, M., Hashimoto, M., Mizumoto, Y., Inoue, M
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Journal Title
Am J Clin Pathol 124
Pages: 89-96
Description
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[Journal Article] Aromatase expression in stromal cells of endometrioid endometrial cancer correlates with poor survival2005
Author(s)
Segawa, T., Shozu, M., Murakami, K., Kasai, T., Shinohara, K., Nomura, K., Ohno, S., Inoue, M
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Journal Title
Clin Cancer Res 11
Pages: 2188-2194
Description
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[Journal Article] ADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary2005
Author(s)
Shoat, M., Minami, N., Yokoyama, H., Inoue, M., Kurihara, H., Matsushima, K., Kuno, K
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Journal Title
J Mol Endocrnol 35
Pages: 343-355
Description
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[Journal Article] Establishment of long-term culture model to study endometrial biology and carcinogenesis
Author(s)
Kyo, S., Mizumoto, Y., Kiyono, T., Maida, Y., Hashimoto, M., Sakaguchi, J., Takakura, M., Inoue, M
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Journal Title
Review Article.Reprod Oncol (in press)
Description
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[Book] 10代からのがん予防2007
Author(s)
井上正樹
Total Pages
246
Publisher
NHK出版
Description
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