CENETIC ALTERATIONS OF TESTICULAR CANCER RELATING TO ITS GROWTH AND DIFFERENTIATION,AND THE POSSIBILITY OF DIFFERENTIATION-INDUCING THERAPY.

睾丸癌与其生长和分化有关的遗传性改变，以及分化诱导治疗的可能性。

基本信息

批准号：
08457423
负责人：
MIKI Tsuneharu
金额：
$ 3.46万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

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.

睾丸癌的研究需要适当的实验系统。我们已经建立了可移植到裸鼠的人睾丸肿瘤细胞系。利用该系统，我们研究了CPT-11（一种喜树碱衍生物）对该细胞系的体内抗肿瘤作用和分化诱导作用。 CPT-11与顺铂一样具有显着的抗肿瘤作用，并且与顺铂合用时其抗肿瘤作用增强。分化诱导作用尚不清楚。这种影响仍在进一步研究中。这些数据有力地支持了CPT-11在临床领域实际应用的可能性。 F344大鼠自发性睾丸肿瘤的组织病理学特征与人性腺间质细胞肿瘤非常相似。该肿瘤显示出多个支持细胞和间质细胞标记基因的共表达以及间质细胞肿瘤表型分叉的证据。睾丸癌特异性基因的克隆仍在进行中。分离基因的表征需要更多时间。基因组印记是一种新的遗传调控实体，其中某些基因，如胰岛素样生长因子 II (UGF2) 和 H19 基因仅由单侧等位基因表达。基因组印记的改变是表观遗传变化之一。我们发现 IGF2 和 H19 基因在睾丸癌的单侧等位基因中非常频繁地表达。我们一直在研究顺铂或视黄酸分化诱导刺激过程中睾丸癌的基因组印记状态。因此，我们的项目的结果是相当令人满意的。