lhrh--ala(6)-gly(10)-ethylamide- and Uterine-Neoplasms

The study aimed to evaluate the safety and efficiency of ultrasound-guided high-intensity focused ultrasound (USgHIFU) combined with gonadotropin-releasing hormone analogue (GnRHa)-ablating symptomatic uterine leiomyoma with homogeneous hyperintensity on T. A total of 34 patients with 42 symptomatic uterine leiomyomas with homogeneous hyperintensity on T. The treatment time and sonication time of the combination group were 102.0 min (55.8-152.2 min) and 25.4 min (12.2-34.1 min); however, they were 149.0 min (87.0-210.0 min) and 38.9 min (14.0-46.7 min) in the simple USgHIFU group. The treatment and sonication time for the combination group was significantly shorter than that for the simple USgHIFU group. Treatment efficiency, NPV ratio and energy effect ratio were 46.7 mm. Our data suggest that USgHIFU combined with GnRHa may be performed to ablate symptomatic uterine leiomyoma with homogeneous hyperintensity on T

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; High-Intensity Focused Ultrasound Ablation; Humans; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Middle Aged; Ultrasonography, Interventional; Uterine Neoplasms; Young Adult

To investigate the effect of 2 medications; Diphereline and Cabergoline, on uterine leiomyoma growth, and its histologic, sonographic, and intra-operative changes.. In an effort to treat large uterine leiomyoma in symptomatic patients in the Gynecology Clinics of the Alzahra Teaching Hospital of Tabriz University of Medical Sciences, Tabriz, Iran, from September 2007 to November 2008, 60 candidates randomized to receive Diphereline 3.75 mg, 4 times every 28 days (group I), and Cabergoline 0.5 mg, once a week for 6 weeks (group II), were included in this study. Clinical symptoms, feasibility of intra-operative dissection, intraoperative complications, sonographic, and pathologic characteristics of the tumor were evaluated.. Thirteen patients from group I, and 10 patients from group II underwent surgery. There was a significant difference between the groups in the rate of lymphocyte infiltration (p=0.003), but not in other pathologic features. In both groups, the mitotic index was between 0-10. While there was no significant difference between the groups in the number (p=0.30), and volume of leiomyomas (p=0.65), however, changes in the uterine artery circulation was significant (p=0.001 [group I], p=0.026 [group II]). In addition, there was a significant difference between the groups for intra-operative hemorrhage and adhesion of leiomyomas to the uterine wall.. This study found that Cabergoline is as effective as Diphereline in the shrinkage of myomas, accompanied by improvement in the sonographic, clinical, and intra-operative outcomes without any adverse pathological changes, and could be a good medical regimen as an adjunct to surgical management.

Topics: Adult; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Middle Aged; Treatment Outcome; Ultrasonography; Uterine Neoplasms

In this prospective, randomized, double-blind study, we evaluated the effects of tibolone therapy in association with preoperative gonadotropin releasing hormone agonist (GnRHa) therapy on the reduction of myoma volume. Twenty patients with myoma uteri were divided into two groups. Group I was given monthly triptoreline (3.75 mg every 28 days IM) treatment for six months. As for group II, tibolone was added on to this treatment. For all of the patients, physical examinations, pelvic ultrasonography, and hormone analyses were carried out and the myoma volume was measured by ultrasonography. The patients were called every month and physical examination, ultrasonography and hormone analyses were repeated. Side-effects were recorded. The SPSS/PC 6.0 program was used for statistical analysis. Statistical significance was defined as a p < 0.05. The results are expressed as means +/- SD. While the average volume of myoma was 72.97 +/- 68.5 cm3 in group I, 78.83 +/- 74.1 cm3 in group II before treatment; it was reduced to 29.91 +/- 27.8 cm3 in group I at the end of six months of treatment. Reductions of 59.6% in group I and 63.9% in group II were determined, however the difference was not statistically significant (p > 0.05). At the beginning the level of serum estradiol was 65.4 +/- 22.3 pg/ml in group I which decreased to 37.2 +/- 4.2 pg/ml by the end of the first month. Amenorrhea occurred in six patients after the second injection and four patients after the third injection in group I. Whereas the level of estradiol was 60.9 +/- 19.5 pg/ml in group II at the beginning, it was reduced to 40.5 +/- 6.2 pg/ml by the end of the first month. Amenorrhea occurred in four patients after the second injection and four patients after the third injection in group II. In group I the patients had the problem of flushing (80%), vaginal dryness (50%), and night sweats (30%). In group II these rates were 30%, 20%, and 20%, respectively. Triptoreline is a GnRHa which has been found to be effective in reducing myoma volume, but this effect could not be deactivated with tibolone. However, a decrease was observed in the side-effects resulting from hypoestrogenism.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Double-Blind Method; Drug Therapy, Combination; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Norpregnenes; Prospective Studies; Treatment Outcome; Triptorelin Pamoate; Ultrasonography; Uterine Neoplasms

Aberrant expression of microRNAs (miRNAs), including miR-21, and alteration of their target genes stability have been associated with cellular transformation and tumorigenesis. We investigated the expression, regulation and function of miR-21 in leiomyomas which develop from myometrial cellular transformation. The results indicated that miR-21 is over-expressed in leiomyomas with specific elevation during the secretory phase of the menstrual cycle and in women who received Depo-Provera and oral contraceptives, but reduced due to GnRHa therapy (P < 0.05). Bioinformatic analysis of microarray gene expression profiles previously obtained from the above cohorts, and myometrial smooth muscle cells (MSMC) and leiomyoma smooth muscle cells (LSMC) treated with GnRHa, transforming growth factor (TGF)-beta and TGF-beta receptor type II (TGF-betaRII) antisense oligomer, indicated that a number of miR-21-predicted target genes were co-expressed and differentially regulated in these cohorts. Gain- and loss-of-function of miR-21 in MSMC, LSMC, transformed LSMC and leiomyosarcoma cell line (SKLM-S1) resulted in differential expression of many genes, including some of the miR-21-predicted/validated target genes, PTEN, PDCD4 and E2F1, and TGF-betaRII, in a cell-specific manner. Gain-of miR-21 function in MSMC and LSMC reduced TGF-beta-induced expression of fibromodulin and TGF-beta-induced factor (P < 0.05), and moderately altered the rate of cell growth and caspase-3/7 activity in these cells. We concluded that miR-21 is aberrantly expressed and hormonally regulated in leiomyomas where, through functional interaction with ovarian steroids and the TGF-beta signaling pathway, either directly or indirectly regulates a number of genes whose products are critical in leiomyoma growth and regression as well as their potential cellular transformation.

Topics: Adult; Blotting, Western; Cell Proliferation; Cells, Cultured; Computational Biology; E2F1 Transcription Factor; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leiomyosarcoma; MicroRNAs; Middle Aged; Myocytes, Smooth Muscle; Oligonucleotide Array Sequence Analysis; PTEN Phosphohydrolase; Receptors, Transforming Growth Factor beta; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transforming Growth Factor beta; Tumor Cells, Cultured; Uterine Neoplasms

To study the clinical application of GnRHa prior to uterine myomectomy and its effect on the clinical outcome of pregnancy.. A retrospective review of the medical records in 20 cases of uterine myomectomy over a period of 6 years was performed. The changes of uterus and myoma volumes in response to preoperative GnRHa was observed, and the rate of relapse in the follow-up, time of impregnation, spontaneous abortion after the impregnation, time of delivery after the operation and the aura threatening uterine rupture, and uterine rupture during the delivery were assessed.. Application of GnRHa produced significant improvement in the clinical symptoms and resulted in obviously reduced volumes of the uterus and myoma. The myoma volume reduction was close to 50% in these cases, and relapse occurred in only 1 case. No spontaneous abortion was found after GnRHa application. The average time of pregnancy was 34+/-3.5 weeks, and aura for uterine rupture was found in 1 case at 33 weeks of pregnancy after GnRHa application.. Application of GnRHa can correct anemia, decrease the relapse rate of myoma, reduce uterus and myoma volumes, to make possible smaller incision for uterine myomectomy that leaves smaller scar in the uterus and decrease intraoperative bleeding, also relieving endometrial injuries to promote the conditions for impregnation and minimize the risks of uterine rupture and total hysterectomy for the benefit of normal delivery.

Topics: Adult; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Pregnancy; Retrospective Studies; Uterine Neoplasms

GnRH analog (GnRHa) and TGF-beta act directly on leiomyoma/myometrial smooth muscle cells (LSMCs and MSMCs) regulating diverse activities resulting in leiomyoma growth and regression. Because GnRH and TGF-beta receptor signaling is in part mediated through the MAPK pathway, we determined whether the contribution of MAPK/ERK and transcriptional activation of c-fos and c-jun, result in differential regulation of type I collagen, fibronectin, and plasminogen activator inhibitor 1 (PAI-1) gene expression, whose products are known to influence extracellular matrix turnover, which is critical in leiomyoma growth and GnRHa-induced regression. We found that GnRHa and TGF-beta in a dose- and time-dependent manner increased the level of phosphorylated ERK1/2 (pERK1/2) in LSMCs and MSMCs. GnRHa and TGF-beta increased ERK1/2 nuclear accumulation resulting in differential regulation of c-fos and c-jun mRNA expression via downstream signaling from MAPK kinase (MEK)1/2, because pretreatment with U0126, a synthetic inhibitor of MEK1/2, abolished basal and GnRHa- and TGF-beta-induced pERK1/2 and the expression of c-fos and c-jun. LSMCs and MSMCs also express fibronectin, type I collagen, and PAI-1 mRNA, and GnRHa and TGF-beta altered their expression in a cell-specific manner through MEK1/2. We concluded that GnRHa and TGF-beta acting through a MAPK/ERK pathway and transcriptional activation of c-fos/c-jun results in differential regulation of specific genes whose products may in part influence the outcome of leiomyoma growth and regression.

Topics: Collagen Type I; Enzyme Activation; Female; Fibronectins; Gene Expression Regulation; Genes, fos; Genes, jun; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Mitogen-Activated Protein Kinases; Myocytes, Smooth Muscle; Myometrium; Plasminogen Activator Inhibitor 1; Transforming Growth Factor beta; Uterine Neoplasms