Establishment of radiotherapy combined with antisense bcl-2 oligodeoxynucleotide in prostate cancer
| Project/Area Number |
13671674
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Keio University |
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Principal Investigator |
MARUMO Ken (2002) Keio University School of Medicine, Associate Professor, 医学部, 助教授 (80138130)
菊地 栄次 (2001) 慶應義塾大学, 医学部, 助手 (10286552)
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| Co-Investigator(Kenkyū-buntansha) |
MURAI Masaru Keio University School of Medicine, professor, 医学部, 教授 (90101956)
NAKASHIMA Jun Keio University School of Medicine, assistant professor, 医学部, 講師 (10167546)
NAKAGAWA Ken Keio University School of Medicine, assistant professor, 医学部, 講師 (50227740)
丸茂 健 慶應義塾大学, 医学部, 助教授 (80138130)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | prostate cancer / bcl-2 / apoptosis / radiation / diethylstilbestrol |
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| Research Abstract |
Bc1-2 has been shown to prolong cancer cell survival by blocking apoptosis and to have the function of scavenging reactive oxygen species. Antisense bc1-2 oligodeoxynucleotides (bc1-2 AS ODN) produced dose-dependent increases in cytotoxicity and apoptosis and a dose-dependent decrease in Bc1-2 protein expression in PC-3 cells and JCA-1 cells. Bc1-2 AS ODN significantly augmented the cytotoxicity induced by radiation on JCA-1 cells, which was assessed by the colony forming assay, when compared with controls (bcl-2 sense ODN or cationic lipid)
Diethylstilbestrol (DES) significantly inhibited cell growth in PC-3 cells in a dose dependent fashion and significantly induced reactive oxygen species (ROS) generation. Antisense bc1-2 oligodeoxynucleotides significantly enhanced DES-induced cytotoxicity. A significant increase in apoptotic cells was induced by the combination of bc1-2 AS ODN and DES when compared with bc1-2 AS ODN alone and DES alone. Buthionine sulphoximine (BSO), which is a glutathione depletor, significantly decreased the intracellular concentration of glutathione and augmented the DES-induced cytotoxicity and ROS in PC-3 cells. Neither the generation of ROS nor the intracellular concentration of glutathione was influenced by bc1-2 AS ODN treatment. In conclusion, bc1-2 AS ODN significantly enhanced DES-induced cytotoxicity on hormone-independent prostate cancer cells through the apoptotic pathway, independently of an augmentation of reactive oxygen species generation, whereas the glutathione depletor augments its cytotoxicity and reactive oxygen species generation
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Report
(3 results)
Research Products
(6 results)
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[Publications] Kikuchi,E, Horiguchi,Y, Nakashima,J, Kuroda,K, Oya,M, Ohigashi,T, Takahashi,N, Shima,Y, Umezawa,K, Murai,M: "Suppression of hormone-refractory prostate cancer by a novel nuclear factor kappaB inhibitor in nude mice"Cancer Res,. 63(1). 107-110 (2003)
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[Publications] Kikuchi,Eiji, Nakashima,Jun, Horiguchi,Yutaka, Oya,Mototsugu, Ohigashi,Takashi, Murai,Masaru: "Enhancement of diethylstilbestrol induced cytotoxicity by bcl-2 antisense oligodeoxynucleotides and a glutathione depletor for prostate cancer"J Urol. 169. 730-734 (2003)
Description
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Related Report
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