CENETIC ALTERATIONS OF TESTICULAR CANCER RELATING TO ITS GROWTH AND DIFFERENTIATION,AND THE POSSIBILITY OF DIFFERENTIATION-INDUCING THERAPY.
Project/Area Number |
08457423
|
Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Urology
|
Research Institution | Osaka University |
Principal Investigator |
MIKI Tsuneharu Osaka University Medical School, Associate Professor, 医学部, 助教授 (10243239)
|
Co-Investigator(Kenkyū-buntansha) |
KOJIMA Yasuyuki Osaka University Medical School, Assistant Professor, 医学部, 助手 (50273628)
NONOMURA Norio Osaka University Medical School, Assistant Professor, 医学部, 助手 (30263263)
OKUYAMA Akihiko Osaka University Medical School, Professor, 医学部, 教授 (20093388)
|
Project Period (FY) |
1996 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1997: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
Keywords | testicular cancer / chemotherapy / genetic alterations / genomic imprinting / imprinting / epigenetic / differentiation / insulin-like growth factor II / 分化誘導 / ゲノムインプリンティング / IGF2 / H19 |
Research Abstract |
Appropriate experimental system is necessary for the study of testicular cancer. We have already established the human testicular tumor cell line which is transplantable to a nude mouse. Using this system, we have investigated the antitumor effect and differentiation-inducing effect of CPT-11 (a camptothecin derivative) on this cell line in vivo. CPT-11 showed marked anitumor effect like cisplatin, and its antitumor effect was enhanced by the concomitant use of cisplatin. Differentiation-inducing effect was not clear. This effect is still being investigated further. These data strongly support the possibility of practical application of CPT-11 in the clinical field. The histopathological features of the spontaneous testicular tumor in the F344 rat is quite similar to that of human gonadal stromal cell tumor. This tumor showed coexpression of multiple Sertoli cell and Leydig cell marker genes and the evidence of phenotypic bifurcation of the interstitial cell tumor. Cloning of testicular cancer-specific genes is still on going. The characterization of the isolated genes needs much more time. Genomic imprinting is a new entity of genetic regulation, in which certain genes such as insulin-like growth factor II (UGF2) and H19 genes are expressed only from unilateral allele. Alteration of genomic imprinting is one of the epigenetic changes. We found that IGF2 and H19 genes are very frequently expressed from unilateral allele in testicular cancers. We have been studying genomic imprinting status in testicular cancer during the differentiation-inducing stimuli by cisplatin or retinoic acid. Thus the results of our projects is quite satisfactory.
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Report
(3 results)
Research Products
(21 results)