ulipristal and Uterine-Neoplasms

To evaluate novel hormonal therapies in patients with unresectable benign metastasizing leiomyoma (BML) disease.. Case series.. National Institutes of Health (NIH).. Five subjects with the diagnosis of BML based on imaging and/or histopathologic diagnosis.. Four patients were treated with single or combination therapy of leuprolide acetate and/or an aromatase inhibitor. One patient was treated with an antiprogestin (CDB-2914).. Response to therapy was measured by tumor burden on cross-sectional imaging employing RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 guidelines.. Four patients treated with single or combination therapy of leuprolide acetate and/or an aromatase inhibitor demonstrated stable disease with reduction in tumor burden. The fifth patient treated with antiprogestin (CDB-2914) had degeneration of her tumor, progression of its size, and an improvement in symptoms.. Hormone treatment with GnRH agonist and/or aromatase inhibition may be a therapeutic option to reduce tumor burden in unresectable BML disease or for those patients who wish to avoid surgical intervention. RECIST 1.1 guidelines, while traditionally used to evaluate tumor response to cancer therapeutics, may be useful in evaluating BML tumor burden response to hormone therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leiomyomatosis; Leuprolide; Middle Aged; Norpregnadienes; Tomography, X-Ray Computed; Treatment Outcome; Tumor Burden; Uterine Neoplasms

Uterine myomas, the most common benign solid pelvic tumors in women, occur in twenty percent of them in reproductive years and form the most common indication for hysterectomy. Various factors affect the choice of the best treatment modality for a given patient. Asymptomatic myomas may be managed by careful follow up. Medical therapy should be tried as a first line of treatment for symptomatic myomas while surgical treatment should be reserved only for appropriate indications. Myomectomy would be preferred over hysterectomy in those wishing subsequent childbearing. Preoperative GnRH-analogue treatment reduces the myoma size and vascularity but may render the capsule more difficult to resect. Poor surgical risk women with large symptomatic myomas or those wishing to avoid major surgical procedures may be offered uterine artery embolization. Serial follow-up for growth and symptoms may be appropriate for asymptomatic perimenopausal women. The present article reviews the available therapeutic modalities for uterine myomas.

Topics: Antifibrinolytic Agents; Disease Management; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Myoma; Norpregnadienes; Progestins; Uterine Artery Embolization; Uterine Myomectomy; Uterine Neoplasms

Although the traditional concept supports a crucial role of estrogen in promoting leiomyoma growth, unequivocal evidence has emerged indicating that progesterone also plays a vital role in the regulation of leiomyoma growth. Recent clinical trials have demonstrated the efficacy of asoprisnil, a selective progesterone receptor modulator, and CDB-2914, a novel progesterone receptor modulator, for the treatment of women with symptomatic leiomyomata. These compounds significantly reduced leiomyoma and uterine volume and improved leiomyoma-related symptoms without serious complications. However, the precise mechanism whereby these compounds cause leiomyoma regression remains poorly understood. Our extensive in vitro studies have provided novel evidence for the growth inhibitory effects of asoprisnil and CDB-2914 on cultured leiomyoma cells. Both compounds exhibited antiproliferative, proapoptotic, and antifibrotic actions on cultured leiomyoma cells in the absence of comparable effects on cultured normal myometrial cells. Asoprisnil and/or CDB-2914 modulated the ratio of progesterone receptor isoforms (PR-A and PR-B) in cultured leiomyoma cells; decreased the cell viability; suppressed the expression of growth factors, angiogenic factors, and their receptors in those cells; and induced apoptosis through activating the mitochondrial and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathways and eliciting endoplasmic reticulum stress. Furthermore, these compounds suppressed types I and III collagen synthesis by modulating extracellular matrix-remodeling enzymes in cultured leiomyoma cells without affecting those syntheses in cultured normal myometrial cells. These findings indicate that both compounds exert antiproliferative, proapoptotic, and antifibrotic actions on leiomyoma cells in a cell-type specific manner. This supports the notion that asoprisnil and CDB-2914 hold promise for the nonsurgical treatment of uterine leiomyomata.

Topics: Angiogenesis Inhibitors; Apoptosis; Cell Proliferation; Endoplasmic Reticulum; Estrenes; Extracellular Matrix; Female; Humans; Leiomyoma; Myometrium; Norpregnadienes; Oximes; Randomized Controlled Trials as Topic; Receptors, Progesterone; Stress, Physiological; Uterine Neoplasms

In view of the spate of recent publications related to mifepristone and some second generation progesterone receptor modulators (PRMs), this appears to be an opportune time to view the clinical status of these compounds.. Randomized double-blind placebo-controlled trials have been conducted with mifepristone, CDB-4124 (Proellex), CDB-2914 (VA 2914, Ulipristal) and asoprisnil (J867). All these PRMs are effective in the treatment of uterine fibroids where they are associated with a reduction in pain, bleeding and improvement in quality of life and decrease in fibroid size. CDB-4124 is also efficacious in endometriosis. Long-term treatment with PRMs may be associated with endometrial thickening on ultrasound and there have been reports of endometrial hyperplasia. Several reassuring recent publications have done much to explain the mechanism underlying these endometrial changes. The most common histological finding is cystic glandular dilatation often associated with both admixed estrogen (mitotic) and progestin (secretory) epithelial effects. This histology has not been previously encountered in clinical practice and should not be confused with endometrial hyperplasia. The endometrial thickness is related to this cystic glandular dilatation.. At this stage of development, PRMs cannot be administered for longer than 3 or 4 months. Even over this time, there is improvement of symptoms associated with fibroids and endometriosis. Clinicians and pathologists need to be aware that the endometrial thickening and histological appearance do not represent endometrial hyperplasia.

Topics: Drug Administration Schedule; Endometriosis; Endometrium; Estrenes; Female; Hormone Antagonists; Humans; Leiomyoma; Mifepristone; Norpregnadienes; Oximes; Randomized Controlled Trials as Topic; Receptors, Progesterone; Time Factors; Uterine Neoplasms

We have found that the use of levonorgestrel-releasing IUS results in a remarkable decrease in endometrial proliferation and a remarkable increase in apoptosis in the endometrium; therefore, it is effective for long-term management of menorrhagic women with uterine myomas because of the striking reduction in menorrhagia. This prompted us to characterize the effects of progesterone (P(4)) and progesterone receptor modulator (PRM) CDB2914 on uterine myoma growth. In vitro studies with cultured uterine leiomyoma cells and normal myometrial cells revealed that P(4) stimulated the proliferative activity in leiomyoma cells, but not in normal myometrial cells. P(4) increased EGF expression, whereas E(2) augmented EGF-R expression in leiomyoma cells, indicating that P(4) and E(2) act in combination to stimulate leiomyoma cell growth. P(4) also increased Bcl-2 expression and decreased TNF-alpha expression in those cells. Unlike the EGF expression, IGF-I expression in leiomyoma cells was inhibited by P(4). These results suggest that P(4) has dual actions on leiomyoma growth: one is to stimulate the growth through up-regulating EGF and Bcl-2 expression, and the other is to inhibit the growth through down-regulating IGF-I expression in the cells. By contrast, CDB2914 inhibited proliferation and stimulated apoptosis of leiomyoma cells without affecting normal myometrial cells. Furthermore, CDB2914 inhibited vascular endothelial growth factor and adrenomedullin expression in leiomyoma cells, but not in normal myometrial cells. The cell type-specific action of CDB2914 on leiomyoma cells, without affecting the surrounding normal myometrial cells, is meaningful for understanding the usefulness of CDB2914 in the medical treatment of uterine myomas.

Topics: Contraceptive Agents, Female; Endometrium; Female; Humans; Intrauterine Devices, Medicated; Leiomyoma; Levonorgestrel; Norpregnadienes; Progesterone; Receptors, Progesterone; Uterine Neoplasms

Fibroids are the most common benign tumours found in the uterus and can cause various symptoms. In 20-50 % of the women, an intervention is required. When conservative options fail, invasive options such as hysterectomy, uterine artery embolization or myomectomy are eligible options. Ulipristal acetate (UPA) was launched as the sole available long term pharmaceutical treatment, with the potential to avoid surgery. It is suggested that UPA improves quality of life, reduces symptoms and fibroid volumes. However, UPA is an expensive medicine, is possibly associated with liver injury and has never been directly compared to surgical treatment. The aim of this trial is to compare UPA to surgical treatment on both effectiveness and cost-effectiveness. Primary outcome is the reduction in symptom severity scores (part of the Uterine Fibroid Symptom and Quality of Life questionnaire) at 24 months of follow-up compared to baseline. Secondary outcomes include quality of life, societal costs, societal participation, liver function variation, patient satisfaction and preference. Outcomes will be analysed according to intention-to-treat principle.. The MYOMEX-2 trial is an open-label, multicentre, non-inferiority randomized controlled trial. Patients are pre-menopausal women with symptomatic fibroids eligible for surgical treatment (hysterectomy, myomectomy or UAE). Fibroid symptoms may comprise (but are not limited to) heavy menstrual bleeding, bulk symptoms or pain. Patients are randomised 2:1 in a parallel group design between two treatment arms: 119 patients in the UPA group and 60 patients in the surgery group. Follow up comprises of online questionnaires, outpatient visits and phone appointments on several follow up moments, up to 24 months after surgery or start UPA.. MYOMEX-2 trial; protocol version 4, date 22-02-2019; NTR6860; NL62638.029.18. All items from the World Health Organization Trial Registration Data Set are provided in the online supplementary file (Appendix-B).

Topics: Female; Humans; Leiomyoma; Multicenter Studies as Topic; Norpregnadienes; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Uterine Myomectomy; Uterine Neoplasms

To investigate effects of ulipristal acetate on health-related quality of life (QOL) and symptom severity in women with symptomatic uterine leiomyomas and abnormal uterine bleeding.. Women were randomized to ulipristal (5 mg, 10 mg) or placebo in two phase 3, multicenter, double-blind, placebo-controlled trials (VENUS I and II). Health-related QOL and symptom severity were assessed at baseline, and over one (VENUS I and II) and two (VENUS II) 12-week treatment courses using the Uterine Fibroid Symptom Health-Related Quality of Life questionnaire. In pooled VENUS I and II data, change from baseline to the end of the first course for each Uterine Fibroid Symptom Health-Related Quality of Life scale was analyzed, including a Revised Activities subscale that measured physical and social activities. The proportion of women achieving meaningful change in the Symptom Severity (20 or more points), Health-Related QOL Total (20 or more points), and Revised Activities (30 or more points) scales was calculated. In VENUS II data, change from baseline to the end of each course in each scale was analyzed for each treatment arm.. In pooled analyses, the intent-to-treat population included 589 patients (placebo, n=169; ulipristal 5 mg, n=215; ulipristal 10 mg, n=205). Significantly greater improvements from baseline in all Uterine Fibroid Symptom Health-Related Quality of Life scales were observed with both ulipristal doses compared with placebo (P<.001). A meaningful change in Revised Activities was achieved by 51 patients receiving placebo (34.9%), compared with 144 (73.5%; OR 5.0 [97.5% CI 2.9-8.6]) and 141 (80.6%; OR 7.9 [97.5% CI 4.3-14.6]) patients receiving ulipristal 5 mg, and 10 mg, respectively. In VENUS II, at end of courses 1 and 2, both ulipristal doses demonstrated significant improvements from baseline compared with placebo for all Uterine Fibroid Symptom Health-Related Quality of Life scales (P<.01). Mean Revised Activities scores showed that beneficial ulipristal effects were maintained in course 2, and improvements occurred on switching to ulipristal; results for other scales were similar.. Ulipristal was associated with significant improvements in health-related QOL and symptom severity compared with placebo for women with symptomatic uterine leiomyomas.. ClinicalTrials.gov, NCT02147197 and NCT02147158.. Allergan plc, Dublin, Ireland.

Topics: Administration, Oral; Adult; Antineoplastic Agents, Hormonal; Double-Blind Method; Female; Humans; Leiomyoma; Norpregnadienes; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Uterine Neoplasms

To evaluate the efficacy and tolerability of the P receptor modulator CDB-2914 (Ulipristal, CDB).. Randomized, placebo-controlled double-blind clinical trial.. Clinical research center.. Premenopausal women with symptomatic uterine fibroids.. Once-daily oral CDB (10 or 20 mg) or placebo (PLC) for 12 weeks (treatment 1). A second 3-month treatment with CDB (treatment 2) was offered. A computer-generated blocked randomization was used.. Magnetic resonance imaging (MRI)-determined total fibroid volume (TFV) change was the primary outcome; amenorrhea and quality of life (QOL) were secondary end points.. Treatment 1 TFV increased 7% in the PLC group, but decreased 17% and 24% in the CDB10 and CDB20 groups. The TFV decreased further in treatment 2 (-11%). Amenorrhea occurred in 20/26 women taking CDB and none on PLC. Ovulation resumed after CDB. Hemoglobin improved only with CDB (11.9 ± 1.5 to 12.9 ± 1.0 g/dL) as did the Fibroid QOL Questionnaire symptom severity, energy/mood, and concern subscores, and overall QOL scores. The CDB was well tolerated, with no serious adverse events. Adverse events were unchanged during treatments.. Administration of CDB-2914 for 3-6 months controls bleeding, reduces fibroid size, and improves QOL.

Topics: Adult; Algorithms; Antineoplastic Agents, Hormonal; Double-Blind Method; Female; Hormone Antagonists; Humans; Leiomyoma; Middle Aged; Norpregnadienes; Placebos; Progesterone; Treatment Outcome; Uterine Neoplasms

To evaluate whether 3-month administration of CDB-2914, a selective progesterone receptor modulator, reduces leiomyoma size and symptoms.. Premenopausal women with symptomatic uterine leiomyomata were randomly assigned to CDB-2914 at 10 mg (T1) or 20 mg (T2) daily or to placebo (PLC) for 3 cycles or 90-102 days if no menses occurred. The primary outcome was leiomyoma volume change determined by magnetic resonance imaging at study entry and within 2 weeks of hysterectomy. Secondary outcomes included the proportion of amenorrhea, change in hemoglobin and hematocrit, ovulation inhibition, and quality-of-life assessment.. Twenty-two patients were allocated, and 18 completed the trial. Age and body mass index were similar among groups. Leiomyoma volume was significantly reduced with CDB-2914 administration (PLC 6%; CDB-2914 -29%; P=.01), decreasing 36% and 21% in the T1 and T2 groups, respectively. During treatment, hemoglobin was unchanged, and the median estradiol was greater than 50 pg/mL in all groups. CDB-2914 eliminated menstrual bleeding and inhibited ovulation (% ovulatory cycles: CDB-2914, 20%; PLC, 83%; P=.001). CDB-2914 improved the concern scores of the uterine leiomyoma symptom quality-of-life subscale (P=.04). One CDB-2914 woman developed endometrial cystic hyperplasia without evidence of atypia. No serious adverse events were reported.. Compared with PLC, CDB-2914 significantly reduced leiomyoma volume after three cycles, or 90-102 days. CDB-2914 treatment resulted in improvements in the concern subscale of the Uterine Fibroid Symptom Quality of Life assessment. In this small study, CDB-2914 was well-tolerated without serious adverse events. Thus, there may be a role for CDB-2914 in the treatment of leiomyomata.. ClinicalTrials.gov,www.clinicaltrials.gov, NCT00290251. I.

Topics: Adult; Female; Health Status Indicators; Hematocrit; Humans; Leiomyoma; Magnetic Resonance Imaging; Middle Aged; Norpregnadienes; Quality of Life; Treatment Outcome; Uterine Neoplasms

We report for the first time on a case of infertile advance-age patient with large intramural fibroid, who conceived following a course of Ulipristal. The patient underwent two fresh fertility preserving IVF cycles, with cryopreservation of 9 day-3 embryos, followed by a 12 weeks course of Ulipristal (5 mg per day) and a subsequent frozen-thawed embryo transfer with her own previously cryopreserved embryos. We, therefore, believe that Ulipristal is a valuable addition to treatment armamentarium of advance-age infertile patient with prominent intramural fibroid.

Topics: Adult; Blastocyst; Cryopreservation; Embryo Transfer; Female; Fertility Preservation; Fertilization in Vitro; Humans; Infertility, Female; Leiomyoma; Maternal Age; Norpregnadienes; Ovulation Induction; Pregnancy; Pregnancy Complications, Neoplastic; Reproductive Techniques, Assisted; Tumor Burden; Uterine Neoplasms

Topics: Chemical and Drug Induced Liver Injury; Drug Approval; Female; Humans; Leiomyoma; Norpregnadienes; Periodicals as Topic; Pharmacovigilance; Progestins; Randomized Controlled Trials as Topic; Uterine Neoplasms

Uterine leiomyoma is a benign tumor that grows within the muscle tissue of the uterus. Ulipristal acetate (UPA) is a pre‑operative drug used to reduce the size of leiomyoma. The aim of the present study was to examine the in vitro mechanistic details of action of UPA on uterine leiomyomas. Primary cultures of leiomyoma cells were isolated from patient myomectomy specimens and incubated in the presence or absence of UPA at various concentrations. The proliferation, cell viability and doubling time properties of the treated cells were analyzed. In addition, the mRNA and protein expression levels of p21, p27, cyclin E, cyclin‑dependent kinase 2 (CDK2), matrix metalloproteinase (MMP)‑2 and MMP‑9 were examined, as well as the structure of F‑actin in the primary‑cultured leiomyoma cells. The results demonstrated that UPA exerted inhibitory effects on proliferation of primary‑cultured leiomyoma cells. Expression of p21 and p27 was upregulated, while cyclin E and CDK2 were downregulated in UPA‑treated primary‑cultured leiomyoma cells. An increased expression of MMP‑2 was observed in primary‑cultured leiomyoma cells and a leiomyoma tissue sample of a patient with previous history of UPA treatment. Furthermore, a pronounced formation of F‑actin stress fibers was observed in leiomyoma cells of the UPA‑treated patient. These data suggest that UPA treatment attenuated the proliferation of uterine fibroid cells via upregulation of p21 and p27, resulting in cell cycle delay. The findings in the current study also suggest that UPA may cause extracellular matrix constriction, leading to the shrinkage in size of the leiomyoma possibly via stimulation of MMP‑2 expression and induction of actin stress fibers.

Topics: Adult; Cell Cycle; Extracellular Matrix; Female; Gene Expression Regulation, Neoplastic; Humans; Leiomyoma; Middle Aged; Neoplasm Proteins; Norpregnadienes; Tumor Cells, Cultured; Uterine Neoplasms

Topics: Female; Humans; Hysterectomy; Leiomyoma; Mediator Complex; Molecular Targeted Therapy; Norpregnadienes; Radiology, Interventional; Receptors, Progesterone; Uterine Myomectomy; Uterine Neoplasms

Topics: Administration, Oral; Contraceptive Agents, Female; Drug Evaluation, Preclinical; Endometrium; Female; Humans; Leiomyoma; Norpregnadienes; Uterine Neoplasms

Topics: Apoptosis; Clinical Trials as Topic; Female; Humans; Intrauterine Devices; Leiomyoma; Levonorgestrel; Menorrhagia; Norpregnadienes; Proliferating Cell Nuclear Antigen; Receptors, Progesterone; Translational Research, Biomedical; Uterine Neoplasms; Women's Health

Topics: Female; Hormone Antagonists; Humans; Leiomyoma; Mifepristone; Norpregnadienes; Quality of Life; Randomized Controlled Trials as Topic; Uterine Neoplasms

Effects of progesterone receptor modulator CDB-2914 on the expression of the extracellular matrix (ECM) components were examined in cultured human uterine leiomyoma and myometrial cells. ECM metalloproteinase inducer (EMMPRIN), matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs) and collagen levels were assessed by Western blot analysis, MMP activity assay and real-time RT-PCR. RNA interference (RNAi) of EMMPRIN was performed using small interfering mRNA. In cultured leiomyoma cells, CDB-2914 treatment at concentrations greater than or equal to 10(-8) M significantly increased EMMPRIN, MMP-1 and MMP-8 protein contents and MMP-1, MMP-2, MMP-3 and MMP-9 mRNA levels, and activity of MMP-1, MMP-2, MMP-3 and MMP-9 in the medium. TIMP-1 and TIMP-2 were significantly decreased at mRNA and protein levels by CDB-2914 treatment at concentrations > or =10(-7) M in these cells. CDB-2914 treatment decreased types I and III collagen protein contents. However, CDB-2914 treatment did not affect the ECM component expression in cultured myometrial cells. RNAi of EMMPRIN abrogated CDB-2914-mediated both induction of MMPs and reduction of TIMPs and collagens in cultured leiomyoma cells. These results suggest that CDB-2914 modulates the expression of EMMPRIN, MMPs, TIMPs and collagens in cultured leiomyoma cells without comparable effects on myometrial cells.

Topics: Adult; Basigin; Blotting, Western; Cells, Cultured; Female; Humans; Leiomyoma; Matrix Metalloproteinases; Middle Aged; Myometrium; Norpregnadienes; Receptors, Progesterone; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tumor Cells, Cultured; Uterine Neoplasms

This study was conducted to evaluate the effects of graded concentrations (10(-8), 10(-7) and 10(-6) M) of progesterone receptor (PR) modulator CDB-2914 on the protein contents of PR, of vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and their receptors in cultured human uterine leiomyoma and matching myometrial cells.. PR-A, PR-B, VEGF-A, VEGF-B, VEGF receptor (VEGFR)-1, VEGFR-2, ADM and ADM receptor (ADMR) contents were assessed by Western blot analysis.. Treatment with 100 ng/ml progesterone increased VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells and normal myometrial cells. The concomitant treatment with 10(-6) M CDB-2914 significantly decreased the progesterone-induced VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment alone decreased VEGFR-1, VEGFR-2 and ADMR contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment increased PR-A and decreased PR-B contents in cultured leiomyoma cells in a dose-dependent manner compared with untreated cultures, whereas no significant changes in PR isoform contents were observed in normal myometrial cells.. These results suggest that CDB-2914 down-regulates VEGF, ADM and their receptor contents and modulates PR isoform contents in cultured leiomyoma cells in a cell-type-specific manner.

Topics: Adrenomedullin; Animals; Cell Line, Tumor; Down-Regulation; Female; Humans; Leiomyoma; Myometrium; Norpregnadienes; Receptors, Progesterone; Uterine Neoplasms; Vascular Endothelial Growth Factor A

The present study was conducted to evaluate the effects of the progesterone receptor modulator CDB-2914 on proliferative activity and apoptosis in cultured human uterine leiomyoma cells. Isolated leiomyoma cells were subcultured in phenol red-free DMEM supplemented with 10% fetal bovine serum for 120 h and then stepped down to serum-free conditions for 12, 24, 48, and 96 h in the absence or presence of graded concentrations of CDB-2914 (10(-9), 10(-8), 10(-7), and 10(-6) M). The number of viable cultured leiomyoma cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazodium bromide assay. Proliferating cell nuclear antigen (PCNA) expression was evaluated by immunocytochemistry and Western blot analysis. Apoptosis was examined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay. Caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), and Bcl-2 expression were assessed by Western blot analysis. Compared with untreated control cultures, treatment with CDB-2914 decreased the number of viable cultured leiomyoma cells and the PCNA-positive rate in those cells and increased the TUNEL-positive rate in cultured leiomyoma cells in a dose-dependent manner. Western blot analysis revealed that treatment with CDB-2914 significantly decreased the expression of PCNA and Bcl-2 protein and increased the expression of cleaved caspase-3 and cleaved PARP in a dose-dependent manner compared with untreated control cultures. These results suggest that CDB-2914 inhibits the proliferation of cultured leiomyoma cells by down-regulating PCNA expression and induces apoptosis by up-regulating cleaved caspase-3 and PARP expression and down-regulating Bcl-2 protein expression in those cells.

Topics: Apoptosis; Blotting, Western; Caspase 3; Caspases; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Leiomyoma; Norpregnadienes; Poly(ADP-ribose) Polymerases; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Receptors, Progesterone; Tumor Cells, Cultured; Uterine Neoplasms