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

睾丸癌的研究需要合适的实验系统。我们已经建立了人睾丸肿瘤细胞系，可移植到裸鼠。利用该系统，我们研究了CPT-11（喜树碱衍生物）对该细胞系的体内抗肿瘤作用和诱导分化作用。CPT-11具有与顺铂相似的抗肿瘤作用，与顺铂合用可增强CPT-11的抗肿瘤作用。诱导分化效果不明显。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瘤十分相似。该肿瘤表现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。分离基因的鉴定需要更多的时间。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（UGF 2）和H19基因仅在单侧等位基因中表达。基因组印记的改变是表观遗传变化的一种。我们发现IGF 2和H19基因在睾丸癌中非常频繁地由单侧等位基因表达。我们一直在研究睾丸癌在顺铂或维甲酸诱导分化过程中的基因组印记状态。因此，我们的项目的结果是相当令人满意的。

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.