Development of therapeutic and prophylactic method for the uterine smooth muscle tumors bu understanding novel aspect of its etiology

我们过去已经研究了子宫平滑肌肿瘤的各种生物学和临床方面。在目前的研究中，鉴于过去和正在进行的见解，我们试图开发新的和合理的方法来处理子宫平滑肌肿瘤。首先，我们从含有潜在恶性肿瘤的MR图像中设定了独特的“灰色地带”标准，需要特别注意处理。这一标准允许临床适当的随访一组子宫平滑肌肿瘤，可能是恶性的。其次，我们进一步验证了子宫平滑肌肿瘤起源于经期子宫收缩缺氧的假说。对月经周期正常子宫肌层的p53和p21免疫染色发现，这些蛋白仅在月经周期卵泡期子宫肌层外层表达，提示子宫这部分处于缺氧应激状态，在月经周期中容易受到损伤，可能导致子宫平滑肌肿瘤的发生。第三，我们在正常子宫平滑肌、良性平滑肌瘤和肉瘤之间进行了比较微阵列分析。根据结果，我们研究了PEP-19蛋白和丙烯蛋白在子宫平滑肌肿瘤发生发展中的作用，发现这两个基因在子宫平滑肌肿瘤发生的各个阶段都起着重要的作用。

We have investigated various biological and clinical aspects of uterine smooth muscle tumors in the past. In the current study, in view of past and ongoing insights, we tried to develop new and rational approach to handle smooth muscle tumors of the uterus. First, we set unique criteria of "gray zone" from the MR image that contains potentially malignant tumors and calls for handling with special attention. This criterion allows clinically appropriate follow up of a group of uterine smooth muscle tumors that may turn out to be malignant. Second, we further investigated our hypothesis that uterine smooth muscle tumors originate under the influence of hypoxia caused by uterine contraction in the time of menstruation. Immunostaining of p53 and p21 in normal myometrium in menstrual cycle revealed that the expression of these proteins are observed in outer layer of uterine myometrium exclusively in follicular phase of menstrual cycle, suggesting that this part of the uterus are under the hypoxic stress and prone to damage in cycle, and may leads to the development of uterine smooth muscle tumors.Third, we have performed comparative microarray analysis among the normal uterine smooth muscle, benign leiomyomas, and sarcomas. According the result, we investigated the role of PEP-19 protein and Acrogranin in the development of uterine smooth muscle tumors, that revealed that both genes play important roles in various stages of the occurrence of them.