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

在过去，我们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，我们试图开发新的合理的方法来处理子宫平滑肌肿瘤。首先，我们从包含潜在恶性肿瘤并需要特别注意处理的MR图像中设置了唯一的“灰色区域”标准。这一标准允许对一组可能被证明是恶性的子宫平滑肌肿瘤进行临床适当的随访。其次，我们进一步验证了我们的假设，即子宫平滑肌肿瘤起源于月经期间子宫收缩引起的缺氧的影响。P53和p21在月经周期正常子宫肌层的免疫组织化学染色显示，这些蛋白仅在月经周期的滤泡期子宫肌层外层表达，提示子宫这一部分处于低氧应激状态，在周期中容易受损，并可能导致子宫平滑肌肿瘤的发生。根据这一结果，我们研究了PEP-19蛋白和Acroranin在子宫平滑肌肿瘤发生发展中的作用，揭示了这两个基因在子宫平滑肌肿瘤发生的不同阶段中发挥的重要作用。

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.