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。

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457423/
• 关键词: 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

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.

睾丸癌的研究需要合适的实验系统。我们已经建立了可移植到裸鼠体内的人睾丸肿瘤细胞系。利用该系统，我们研究了喜树碱衍生物CPT-11对该细胞株的体内抗肿瘤作用和诱导分化作用。CPT-11具有明显的顺铂抗肿瘤作用，与顺铂合用可增强其抗肿瘤作用。诱导分化效果不明显。这一影响仍在进一步调查中。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基质细胞瘤十分相似。肿瘤表现为多种支持细胞和间质细胞标记基因的共表达，间质细胞肿瘤的表型分叉。睾丸癌特异性基因的克隆仍在进行中。对分离的基因进行表征需要更多的时间。基因组印迹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基因只在单侧等位基因中表达。基因组印迹的改变是表观遗传学改变的一种。我们发现IGF2和H19基因在睾丸癌中以单侧等位基因的形式表达。我们一直在研究顺铂或维甲酸诱导分化过程中睾丸癌的基因组印迹状态。因此，我们的项目结果是相当令人满意的。

项目成果

Nonomura Norio: "Loss of imprinting of the insulin-like growth factor II gene in renal cell carcinoma." Cancer Research. Vol.57, No.13. 2575-2577 (1997)

Nonomura Norio：“肾细胞癌中胰岛素样生长因子 II 基因的印记丢失。”

三木 恒治: "精巣腫瘍(リンパ節郭清)" オペナーシング. 12・7. 4-7 (1997)

Tsuneharu Miki：“睾丸肿瘤（淋巴结切除）”开放护理12・7（1997）。

野々村祝夫: "Alfered imprinting of the H19 and insulin-like growth factor genes in testicular tumors." Journal of Urology. 157(in press). (1997)

Norio Nonomura：“睾丸肿瘤中 H19 和胰岛素样生长因子基因的阿尔法印记”，《泌尿学杂志》157（出版中）。

Norio Nonomura: "Secondary acute monocytic leukemia occurring during the treatment of a festicular germ cell tumor." Urologia Internationalis. 58・4. 239-242 (1997)

Norio Nonomura：“治疗脓疱生殖细胞肿瘤期间发生的继发性急性单核细胞白血病”，58・4（1997）。

Norio Nonomura: "Secondary acute monocytic leukemia occurring during the treatment of a testicular germ cell tumor." Urologia Internationalis. 58・4. 239-242 (1997)

Norio Nonomura：“睾丸生殖细胞肿瘤治疗过程中发生的继发性急性单核细胞白血病。” 58・4 (1997)。