Development of chemoimmunothempy against renal cancer by up-regulation of co-stimulatory molecules
| Project/Area Number |
18591757
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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 | Kagawa University |
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Principal Investigator |
WU Xiuxian Kagawa University, Faculty of Medicine, Urology, Associate (10346645)
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| Co-Investigator(Kenkyū-buntansha) |
KAKEHI Yoshiyuki Kagawa University, Faculty of Medicine, Urology, Professor (20214273)
INUI Masashi Kagawa University, Faculty of Medicine, Urology, Assistant Professor (40314918)
TAOKA Rikiya Kagawa University, Faculty of Medicine, Urology, Associate (10403784)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,870,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Renal cell carcinoma cells / PBL / TIL / LFA-3 / ICAM-1 / TRAIL / TRAIL-R2 / Lexatumumab / 共刺激分子 / 末梢血リンパ球 / 腫瘍浸潤リンパ球 / 抗癌剤 |
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| Research Abstract |
In this study, we investigated the effect of adriamycin on the susceptibility of human renal cell carcinoma (RCC) cells to lysis by peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL). We also explored molecular mechanisms involved in adriamycin modulating susceptibility of RCC cells to PBL and TIL. We found that pretreatment of RCC cells with subtoxic concentrations of adriamycin resulted in a potentiation of anticancer activities of PBL and TIL. Adriamycin up-regulated leukocyte function-associated antigen-3 (LFA-3) and intercellular adhesion molecule-1 (ICAM-1) expressions in RCC cells. LFA-3 and ICAM-1 are critical in the binding and killing of cytotoxic T lymphocytes against cancer cells. Up-regulation of LFA-3 and ICAM-1 was also observed in RCC cells treated with two derivatives of adriamycin, epirubicin and pirarubicin. Adriamycin further significantly increased the bindings of PBL to RCC cells. In addition, adriamycin sensitized RCC cells to Fas- and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cytotoxicity. These findings suggest that treatment of RCC patients with low doses of adriamycin may sensitize the RCC cells to killing by PBL and TIL, and may be a novel immunotherapeutic modality for the treatment of drug-resistant and/or immune-resistant RCC. The induction of LFA-3 and ICAM-1 by adriamycin may involve in the enhancement of susceptibility of PBL and TIL-mediated cytolysis in human RCC cells. In the experiments of developing molecular targeted therapy using Lexatumumab, an agonistic TRAIL-receptor 2 (TRAIL-R2) antibody, we demonstrated synergistic cytotoxic effect of adriamycin and Lexatumumab against RCC cells. We further demonstrated that the synergistic cytotoxicity of Lexatumumab and adriamycin was realized by inducing apoptosis through the induction of TRAIL-R2 and the intrinsic caspase pathway.
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Uroplakin III-delta4 messenger RNA as a promising marker to identify nonulcerative interstitial cystitis2007
Author(s)
Zeng, Y, Wu, XX, Homma, Y, Yoshimura, N, Iwaki, H, Kageyama, S, Yoshiki, T, Kakehi, Y
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Journal Title
J Urol 178
Pages: 1322-1327
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Human Agonistic Antibody to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor 2(Trail-R2) Induces Cytotoxicity and Apoptosis in Prostate Cancer and Bladder Cancer Cells2007
Author(s)
Shimada, O, Wu, XX, Jin, XH, Nouh, MA, Fiscella, M, Albert, V, Matsuda, T, Kakehi, Y
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Journal Title
Urology 69
Pages: 395-401
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Anti-tumor effect of vitamin E succinate(VES) against renal cell carcinoma cells2007
Author(s)
Xiuxian, Wu, Yu, Zeng, Ahmed, Mamdouh Hamed, Rikiya, Taoka, Mashashi, Inui, Yoshiyuki, Kakehi
Organizer
Japanese Urological Association 95th Annual Meeting
Year and Date
2007-04-14
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Uroplakin III-Delta4 Messenger RNA as A Promising Marker to Identify Non-Ulcerative Type Interstitial Cystitis2007
Author(s)
Yu, Zeng, Xiuxian, Wu, Yukio, Homma, Naoki, Yoshimura, Hideaki, Iwaki, Susumu, Kageyama, Tatsnhiro, Yoshiki, Yoshiyuki, Kakehi
Organizer
American Urological Association 2007 Annual Meeting
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Enhancement of death receptor 4-mediated apoptosis in renal cell carcinoma cells by low concentrations of adriamycin2007
Author(s)
Xiuxian, Wu, Yoshiuki, Kakehi, Xinghua, Jin, Rikiya, Taoka, Mashashi, Inuiand, Mikio, Sugimoto
Organizer
45th Annual Meeting of Japanese Cancer Therapy Association
Description
「研究成果報告書概要(欧文)」より
Related Report
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