Effect of helixor A on natural killer cell activity in endometriosis.

BACKGROUND AND AIM: NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosis MATERIALS AND METHODS: We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker. RESULTS: NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p=0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p=0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p=0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p=0.014) in stage III/IV. CONCLUSIONS: Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results open new role of helixor A as an imune modulation therapy, or in combination with hormonal agents, for the treatment of endometriosis.

Comparison of the inhibitory effect of gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM), antiprogesterone on myoma cell proliferation in vitro.

Uterine myomas are the most common gynecologic tumor in women of reproductive age. Treatment options of uterine myomas consist of surgical, medical and interventional therapy such as uterine artery embolization or myolysis. Given that it is the most common type of tumor in women of reproductive age, the treatment of uterine myomas must prioritize uterine conservation. There are several drugs for medical treatment of uterine myoma such as gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM) and antiprogesterone. The objective of this study was to compare the effect of GnRH agonist, SERM, and antiprogesterone in the treatment of uterine myomas in vitro. The effect of drugs was evaluated through the cell viability assay in cultured leiomyoma cells, western blot analysis of proliferating cell nuclear antigen (PCNA), and BCL-2 protein expression. As a result, mifepristone single-treated group represents the most significant reduction in myoma cell viability and proliferation. When pretreated with leuprolide acetate, raloxifene shows more significant reduction in myoma cell viability and proliferation than mifepristone. This study suggests one of the possible mechanisms how medications act on uterine myoma, especially at the molecular level.

Comparison of selective uterine artery double ligation at the isthmic level of uterus and bipolar uterine artery coagulation in total laparoscopic hysterectomy.

In this article, we would like to compare the clinical characteristics and effectiveness of selective uterine artery double ligation and bipolar uterine artery coagulation in total laparoscopic hysterectomy (TLH) retrospectively. TLH was performed on 72 patients with selective uterine artery double ligation and on 312 patients with uterine artery bipolar coagulation in tertiary university hospital from January 2004 through January 2006. Both groups were similar with respect to age, body mass index, parities, rate of menopause and uterine weight. The mean transfusion, postoperative hospital stay and drain insertion in the selective uterine artery double ligation group were significantly lower than those in the bipolar uterine artery coagulation group in TLH, respectively (p < .05). There were no differences in the hemoglobin, hematocrite change, additional operations, operation time, rate of complication between the two kinds of operation (p > .05). In conclusion, selective uterine artery double ligation in TLH showed lower transfusion rate, less hospitalization and less discomfort due to drain than bipolar uterine artery coagulation. Also, it did not take a longer time for operation and thus provides a feasible and secure method to manage uterine vessels at the level of uterine isthmus inside of the broad ligament.

Antioxidant effect of estrogen on bovine aortic endothelial cells.

OBJECTIVE: This study discussed the role of estrogen as an antioxidant in the damage of vascular endothelial cells. DESIGN: We treated bovine aortic endothelial cells (bAEC) either with 1mM of H(2)O(2) alone or with 1 microM of 17beta-estradiol (E(2)) for 24h followed by 1mM of H(2)O(2) for 3h. The cell survival was evaluated by MTT assay, cellular apoptosis by fluorescence activated cell sorter (FACS) and Hoechst 33342 staining, oxidative stress by intracellular reactive oxygen species (ROS) and apoptosis after oxidative stress by western blotting for phospho-p38, p38, and Bcl-2. RESULTS: MTT assay showed that bAEC viability was reduced to 55.7+/-3.0% and 39.1+/-3.7% after 30 and 60 min of H(2)O(2) treatment, respectively. E(2) and H(2)O(2) treated cells did not show significant decrease in the cell survival. Similarly the FACS analysis and Hoechst 33342 stain showed that the latter decreased cellular apoptosis induced by H(2)O(2). Intracellular ROS increased by 181.6+/-68.9% in the former and by 37.0+/-3.9% in the latter (P<0.05). The expression of phospho-p38 mitogen-activated protein kinase (MAPK) was higher in the latter. CONCLUSIONS: E(2) mediates antioxidant effects on the oxidative stress induced by H(2)O(2). This antioxidant effect on bAEC may elucidate the scientific basis of hormone therapy for maintaining cardiovascular integrity in postmenopausal women.

Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer.

OBJECTIVES: The toxicity and effectivity of intravenous paclitaxel and cisplatin as neoadjuvant chemotherapy were assessed in cervical cancer patients. Patients and methods. Forty-three consecutive patients affected by International Federation of Gynecology and Obstetrics (FIGO) stage IB2 to IIB were treated with paclitaxel 60 mg/m(2) that was administered intravenously over a 3-h period, followed by cisplatin 60 mg/m(2), also administered intravenously. The chemotherapy was administered every 10 days and for three courses. The toxicity of the regimen in each cycle was determined according to the WHO toxicity criteria and in cases with grade 3 or 4 toxicity, chemotherapy was postponed until the toxicity was disappeared. Before the neoadjuvant chemotherapy, the lesion was pathologically confirmed by punch biopsy, and the size of the tumor mass was measured by pelvic examination and pelvic magnetic resonance imaging (MRI). The response to the treatment was determined 10 days after three cycles of chemotherapy by pelvic examination and pelvic MRI. Two weeks after the neoadjuvant chemotherapy was completed, the patients were either given an operation or radiation therapy, depending on their overall condition, the operational risks, and personal willingness for an operation. RESULTS: A total of 43 patients were enrolled in this study and all of them were given an operation. Hematologic toxicity was seen in 17 patients. But most of them were anemia and there was no grade 3 or 4. Grade 1 neurotoxicities developed in 29 patients and all of them were peripheral neurotoxicity. Clinical responses occurred in 90.7% (39/43) of patients, including 39.5% (17/43) with a complete response (CR), 11.6% (5/43) with a pathologically determined complete response, 51.2% (22/43) with a partial response (PR), and 9.3% (4/43) showed stable disease (ST). A down-staging response was seen in 72.1% (31/43) of those patients showing a response. CONCLUSION: The combination of paclitaxel with cisplatin for use in neoadjuvnant chemotherapy seems to be tolerated and very active in cervical cancer. Especially, every 10 days treatment did not delay the optimal time of main treatment. A larger number of cases need to be studied to confirm the efficacy of the treatment.