Induction of Differentiation in Testicular Germ Cell Tumors and Its Role in Cancer Therapy
| Project/Area Number |
63570760
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
KONDO Naoya Jikei University School of Medicine, Urology, Lecturer, 医学部, 講師 (80138750)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAKAWA Hiroshi Jikei University School of Medicine, Urology, Staff, 医学部, 助手 (60196615)
AKASAKA Yuichiro Jikei University School of Medicine, Urology, Lecturer, 医学部, 講師 (20112807)
YAMAZAKI Haruki Jikei University School of Medicine, Urology, Lecturer, 医学部, 講師 (90159210)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Testicular Gem Cell Tumor / Choriocarcinoma / Induction of Differentiation / HCG / AFP / Yolk Sac Tumor / 絨毛上皮癌 / yolh sac tumor |
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| Research Abstract |
Studies were made to investigate the ability of differentiation in testicular germ cell tumors.
In vitro study, we have found that dibutyryl cyclic adenosine monophosphate (DBcAMP) induces multiple phenotypic changes of testicular choriocarcinoma JHTK-1 cells. Morphological alteration ("broad and elongated cells"), enhancement of human chorionic gonadotropin (HCG) production (15-fold), and inhibition of the cellular proliferation (50%) were seen. These results indicate that DBcAMP induces the differentiation of testicualar choriocarcinoma cells from dividing cytotrophoblastic cells to non-dividing end cells of syncytotrophoblastic cells. Screening of differentiation inducing substances were carried out. The inducers were theophylline, sodium butyrate, vitamin C, vinblastine, and actinomycin D.
In vivo study, alpha-fetoprotein (AFP)-secreting human germ cell tumor xenografts transplanted into nude mice were used. Combination chemotherapy of PVB regimen (CDDP 2mg/kgx5, VBL 0.1mg/X2, and BLM 0.5mg/kgx2) was performed. Histologically, reticular pattern was augmented, and the number of AFP po sitive cells was highly increased. The serum levels and tumor tissue concentrations of AFP increased 2-4 fold and 40-59 fold, respectively. Xenografted tumors continued to regress during 14 days after the initiation of the treatment. These findings also suggests that PVB regimen induces the differentiation of germ cell tumors.
In conclusion, chemical substances including anti-cancer agents can induce the differentiation of testicular germ cell tumors, and inhibit the tumor cell growth as well. This finding will lead to a concept of "differentiation induction inducing therapy" for testicular germ cell tumors.
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Report
(4 results)
Research Products
(9 results)
