Characterization of tumorigenic features of uterine leiomyoma

子宫肌瘤致瘤特征的表征

• 批准号: 08457438
• 负责人: FUJII Shingo
• 金额: $ 4.74万
• 依托单位: SHINSHU 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-08457438/
• 关键词: Leiomyoma; ball-like aggregations; MR image; Mast cells; GnRH analogue; p53; ovarian steroid receptors; 子宮平滑筋; ステロイドホルモン; サイクリン; サイクリン依存性リン酸化酵素; 腫瘍抑制因子

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 … More 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

利用该子宫肌瘤体外培养系统，研究了GnRH类似物治疗子宫肌瘤过程中肌瘤缩小的机制。以前，我们证明平滑肌瘤细胞形成球状聚集体，我们称之为“球状聚集体（BLA）”。由于平滑肌瘤细胞的球状聚集似乎接近体内子宫平滑肌瘤的特征，这使我们能够评估目前用于子宫平滑肌瘤化疗的GnRH类似物的有效性。结果表明，加入GnRH类似物后，平滑肌瘤细胞的球形聚集体消失。结果还表明，GnRH与培养的平滑肌瘤细胞直接结合，平滑肌瘤细胞中存在GnRH受体，并有GnRH表达。此外，添加小剂量和短剂量的GnRH类似物刺激平滑肌细胞增殖 ...更多信息 高剂量GnRH类似物长期治疗可抑制G1期细胞相关基因的表达。提示GnRH类似物可直接调控子宫肌瘤的生长，子宫肌瘤体内系统可用于评价目前子宫肌瘤化疗药物的疗效。肥大细胞（MC）广泛分布于包括平滑肌瘤在内的大多数人体组织和肿瘤中。GnRHa最近被用于治疗平滑肌瘤。为了阐明MCs在平滑肌瘤中的作用，分析了平滑肌瘤中MCs数量与组织学特征的关系，并比较了未治疗组和GnRHa治疗组的MCs数量。结果表明：未治疗的平滑肌瘤中MC数量分布广泛，但在胶原基质较少、细胞密度较高、T2加权像高信号的平滑肌瘤中MC较多。此外，GnRHa治疗后高度缩小的肌瘤中含有较多的MC，这些MC在GnRHa治疗前并不增加，但在肌瘤中已存在，提示MC可能与肌瘤的增殖活动有关，并在GnRHa治疗后肌瘤的缩小中起一定作用。PR在UL中明确表达，与月经周期的阶段无关。ER和PR在CL、UMP和BL中的表达也呈阳性，而在BL中ER的表达变化不一，而在LMS中ER和PR的表达均明显降低，RT-PCR扩增结果与免疫组化结果一致。LMS中Ki-67阳性细胞数显著高于UMP、BL、CL和UL，P53免疫反应阳性细胞数较少

项目成果

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