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

临床观察发现，子宫肌瘤中存在大量含肝素的肥大细胞，且子宫肌瘤在妊娠期间往往迅速扩大，这促使我们研究肝素和人绒毛膜促性腺激素对子宫肌瘤细胞生长的影响。然后，肝素通过诱导α-平滑肌肌动蛋白、钙蛋白H1和p27抑制子宫肌瘤细胞的增殖。提示肥大细胞肝素可诱导肌瘤细胞分化，并可能影响肌瘤发生过程中的组织重塑和重建。相反，hCG可直接促进子宫肌瘤细胞的增殖，其结果与临床观察结果一致。为确定子宫平滑肌肿瘤的遗传差异，我们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、细胞周期蛋白CDK2、细胞周期蛋白cdc2和钙蛋白H1的表达。然后，…的约化表达式子宫肌肉瘤中ER、PR和calponin H1表达增加，P53、Ki-67、Cyclin E、Cyclin A、CDK2和CDC2表达增强。子宫平滑肌肉瘤是一种罕见但致命的肿瘤。对子宫肌肉瘤的遗传学分析表明，该肿瘤表现出钙蛋白H1的表达减弱，该蛋白在正常子宫肌层和肌瘤(一种良性的平滑肌肿瘤)的平滑肌细胞中正常表达。将Calponin H1基因导入人子宫平滑肌肉瘤细胞后，细胞形态发生了改变，与培养的正常子宫肌层平滑肌细胞相似。此外，这种治疗显著降低了体内的致瘤性。因此，Calponin H1是一种有希望的平滑肌肉瘤的肿瘤抑制因子。在临床上，通过诱导正常分化的细胞表型，将钙蛋白H1基因转移到低分化的平滑肌肉瘤细胞中可能具有治疗潜力。较少

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