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

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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.