| Project/Area Number |
15390488
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kanazawa University |
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Principal Investigator |
NAMIKI Mikio Kanazawa University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (70155985)
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| Co-Investigator(Kenkyū-buntansha) |
MIZOKAMI Atsushi Kanazawa University, Hospital, Lecturer, 医学部附属病院, 講師 (50248580)
KYO Satoru Kanazawa University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (50272969)
越田 潔 金沢大学, 大学院・医学系研究科, 助教授 (70186667)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2003: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | prostate cancer / relapse / bone metastasis / bisphosphonate / Her-2 / tyrosine kinase inhibitor / 再燃 / hTERT / Bisphosphonate / HER-2 / 遺伝子治療 / 分子様的治療 / アンドロゲン / 分子標的治療 / 胃転移 |
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| Research Abstract |
Since it is not clear why advanced prostate cancer relapses during hormone therapy, we established androgen-independent prostate cancer, LNCaP-SF and LN-REC4 cells from androgen-sensitive cell line, LNCaP. We characterized these cell lines in order to investigate what kinds of mechanisms are involved in progression. LNCaP-SF cells proliferation was stimulated in the absence of androgen and repressed in the presence of androgen. It was suggested that LN-REC4 induced angiogenesis. Now we are investigating the genes which are differentially regulated by androgen.
We also succeeded in establishment of osteoblastic metastatic model of prostate cancer using LNCaP-SF cells. Osteoclast showed important role in osteoblastic metastasis of prostate cancer cells, and we certified that the 3rd generation of bisphosphonates could inhibit osteoblastic bone metastasis as well as osteolytic bone metastasis of prostatic cancer. through inhibition of osteoclast. Furthermore, bisphosphonates not only showed indirect action through osteoclast but also directly induced apoptosis of cancer cells and inhibited invasion through repression of chemokine receptor, CXCR-4 expression. These results indicate that the 3rd generation of bisphosphonates has potency of bone metastasis preventive medicine for prostate cancer.
For development of molecular target drug for oncogene Her-2 assumed that the expression is enhanced in recrudescence prostatic cancer, we also used Her-2 specific-tyrosine kinase inhibitor and confirmed the antitumor effect in vitro and in vivo.
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