| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1996: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Research Abstract |
The mechanisms regarding to the shrinkage of leiomyoma during the treatment with GnRH analogue (GnRH) analogue have been investigated using this in vitro system of uterine leiomyoma. Previously, we demonstrated that the cells from leiomyoma formed ball-like aggregations which we named "ball-like aggregations (BLAs)". Since the ball-like aggregations of cells from leiomyoma seem to be close to the features of uterine leiomyoma in vivo, this allows us to evaluate the efficiency of GnRH analogue currently used for chemotherapy of uterine leiomyomas. The results showed that the addition of GnRH analogue caused disappearance of the figure of the ball-like aggregations of cells from leiomyoma. The results also showed that GnRH directly binds to the cultured cells from leiomyoma and that the existence of GnRH receptor as well as GnRH expression in the cells from leiomyomas. Furthermore, the addition of small and short doses of GnRH analogue stimulates the proliferation of smooth muscle cells
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of leiomyoma, but the late G1 phase cell cycle related genes' expression were suppressed by the addition of high doses GnRH analogue for long treatment. These results suggested that GnRH analogue may directly regulate the growth of uterine leiomyomas, and that the in vivo system of uterine leiomyoma is useful to evaluate the efficiency of drugs currently used for chemotherapy of uterine leiomyomas. Mast cells (MCs) are widely distributed in most human tissues and neoplasms, including a leiomyoma. GnRHa has been recently applied for the treatment of a leiomyoma. To elucidate the role of MCs in a leiomyoma, the relationship between the number of MCs in leiomyomas and the histological features was analyzed, furthermore, the number of MCs in untreated leiomyomas was compared with that of MCs in the leiomyomas treated with GnRHa. The results showed that the number of MCs in untreated leiomyomas was widely distributed, but there were more Mcs in leiomyomas with fewer collagen matrix, with higher cellularity, and with high intensity of T2 weighted MR image. In addition, the leiomyomas which had highly shrinked with GnRHa contained a larger number of MCs, and these MCs were not increased by GnRHa, but before therapy they had existed in the leiomyomas The findings suggest that MCs may associated with prolierative activity of leiomyoma and play a role in shirnkage of the size in GnRHa therapy.Both ER and PR are immunohistochemically expressed in all ULs. PR was definitely experssed in UL irrespective of the phase of the menstrual cycle. This staining pattern of PR was also observed in CL,UMP and BL,although BL showed variable staining for ER.Compared to these tumors, the expression of both ER and PR was markedly reduced in LMS.The results of ER and PR transcripts by RT-PCR amplification were compatible with those of immunohistochemistry. The number of Ki-67 positive cells in LMS was extraordinary and significantly higher than in UMP,BL,CL and UL.P53 immunoreactivity was seen Less
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