Comprehensive study about the neoplastic characterization of benign and malignant smooth muscle tumor arising in the uterus

子宫良恶性平滑肌瘤肿瘤特征的综合研究

• 批准号: 10470345
• 负责人: FUJII Shingo
• 金额: $ 9.22万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470345/
• 关键词: uterus; leomyoma; heparin; HCG; leiomyosarooma; p53; calponin h1; gene therapy; 子宮平滑筋; 子宮筋腫; 平滑筋肉腫; 肥満細胞; ヘパリン; 増殖抑制; LOH; estrogen receptor; progesterone receptor; カルポニンhl; 腫瘍抑制因子; ゴナドトロピン放出ホルモン; MRI画像; 子宮筋細胞; 子宮筋腫細胞; 子宮平滑筋肉腫細胞; 増

Clinical observations, that a large number of mast cells containing heparin reside in leiomyoma and that leiomyoma often enlarge rapidly during pregnancy, encouraged us to study the effect of heparin and HCG on the growth of leiomyomal cells. Then, heparin inhibited the proliferation of leiomyomal cells through the induction of α-smooth muscle actin (SMA), calponin h1 and p27. This suggests that heparin from mast cells may induce differentiation in leiomyomal cells and may influence tissue remodeling and reconstruction during tumorgenesis of leiomyoma. In contrast, HCG directly promoted the proliferation of leiomyomal cells and the result was compatible with the clinical observation.To determine the genetic difference of smooth muscle tumors the uterus, the expression of estrogen receptors (ER), progesterone receptors (PR), tumor suppressor concogene p53, Ki-67, cyclin E, cyclin A, cdk2, cdc2 and calponin h1 was examined in smooth muscle tumors of the uterus. Then, reduced expression o … More f ER, PR and calponin h1 with increased expression of p53, Ki-67, cyclin E, cyclin A, cdk2, and cdc2 was associated in leiomyosarcomas of the uterus. The vice versa results were obtained in leiomyoma.Uterine leiomyosarcoma is a rare, but lethal, tumor. The genetic analysis of leiomyosarcoma has revealed that this tumor exhibits a diminished expression of calponin h1, which is normally expressed in smooth muscle cells of healthy myometria and in leiomyoma (a benign tumor of smooth muscle). Transfection of the calponin h1 gene into human leiomyosarcoma cells resulted in morphologic modifications that resembled the appearance of cultured normal myometrial smooth muscle cells. Furthermore, in vivo tumorgenicity was significantly reduced by this treatment. Therefore, calponin h1 is a prospective tumor suppressor for leiomyosarcoma. Clinically, the transfer of calponin h1 cDNA into poorly differentiated leiomyosarcoma cells could have therapeutic potential through induction of a normal, differentiated cellular phenotype. Less

临床观察，大量的肥大细胞含有肝素居住在平滑肌瘤和平滑肌瘤往往迅速扩大在怀孕期间，鼓励我们研究肝素和HCG对平滑肌瘤细胞的生长的影响。肝素通过诱导α-平滑肌肌动蛋白（SMA）、钙调蛋白h1和p27的表达抑制平滑肌瘤细胞的增殖。提示肥大细胞来源的肝素可诱导平滑肌细胞分化，并可能影响平滑肌瘤发生过程中的组织重塑和重建。为探讨子宫平滑肌肿瘤的遗传差异，检测了子宫平滑肌肿瘤中雌激素受体（ER）、孕激素受体（PR）、抑癌基因p53、Ki-67、细胞周期蛋白E、细胞周期蛋白A、cdk 2、cdc 2和钙调蛋白h 1的表达。然后，减少表达O ...更多信息 子宫平滑肌瘤中ER、PR和calponin h1与p53、Ki-67、cyclin E、cyclin A、cdk 2和cdc 2的表达增加相关。子宫平滑肌肉瘤是一种罕见但致命的肿瘤。平滑肌肉瘤的基因分析显示，这种肿瘤表现出钙调蛋白h1的表达减少，而钙调蛋白h1通常在健康子宫肌层的平滑肌细胞和平滑肌瘤（平滑肌的良性肿瘤）中表达。将钙调蛋白h1基因转染入人平滑肌肉瘤细胞中，导致类似于培养的正常子宫肌层平滑肌细胞外观的形态学改变。此外，通过这种处理，体内致瘤性显著降低。因此，calponin h1是一种很有前景的平滑肌肉瘤抑癌基因。在临床上，钙调蛋白h1基因转移到低分化平滑肌肉瘤细胞可能有治疗潜力，通过诱导一个正常的，分化的细胞表型。少

项目成果

Ya-Li Zhai et al.: "Uterine leiomyosarcoma has abnormal expression of sex steroid receptors, Ki-67, and p53 compared to the other smooth muscle tumors of the uterus" Internationsl Journal of Gynecologic Pathology. 18. 20-28 (1999)

Ya-Li Zhai 等人：“与其他子宫平滑肌肿瘤相比，子宫平滑肌肉瘤具有性类固醇受体、Ki-67 和 p53 的异常表达”，《国际妇科病理学杂志》。

Akiko Horiuchi et al.: "Reduced expression of calponin h1 in leiomyosarcoma of the uterus" Lavoratory Investigation. 78. 839-846 (1998)

Akiko Horiuchi 等人：“子宫平滑肌肉瘤中钙调蛋白 h1 的表达减少”实验室调查。

Ya-Li Zhai et al.: "Expression of cyclins and cyclin dependent kinases in smooth muscle tumors of the uterus" International Journal of Cancer. in press.

Ya-Li Zhai 等人：“子宫平滑肌肿瘤中细胞周期蛋白和细胞周期蛋白依赖性激酶的表达”国际癌症杂志。

Lu,X, et al.: "Loss of heterozygosity among tumor suppressor genes in invasive and in situ carcinoma of the uterine cervix"International Journal of Gynecologic Cancer. 10. 451-458 (2000)

Lu,X, et al.：“子宫颈浸润性和原位癌中肿瘤抑制基因杂合性的丧失”国际妇科癌症杂志。

Zhai,YL.,Nikaido,T.,Shiozawa,T.,Orii,A.,Toki,T.,Fujii,S.: "Prognostic significance of Bcl-2 expression in leiomyosarcoma of the uterus"British Journal of Cancer. 80. 1658-1664 (1999)

Zhai, YL.、Nikaido, T.、Shiozawa, T.、Orii, A.、Toki, T.、Fujii, S.：“子宫平滑肌肉瘤中 Bcl-2 表达的预后意义”英国癌症杂志。