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Sclerosing stromal tumor (SST) is histologically benign and accounts for 6% of the tumors derived from the stroma of the ovaries [1]. The patients who are diagnosed with an SST are predominantly in their 20s and 30s, unlike other stromal tumors [2,3]. Clinical imaging by magnetic resonance imaging (MRI) shows high vascularity and a solid part in SSTs. Many cases are suspected as a malignant tumor before surgery, during which, a unilateral ovary is removed without partial preservation. Case 1: A 25-year-old woman, gravida 0, para 0 who reported that she had never had sexual intercourse was admitted with the complaint of irregular and frequent menstruation every 15e30 days. A 10-cm-diameter pelvic mass at the front of the uterus was revealed by transrectal ultrasonography. MRI showed findings suggesting a possible malignant tumor in the right ovary (Figure 1). Gastroscopy and colon fiberoscopy were normal. Enhanced computed tomography showed no enlarged pelvic or para-aortic lymph nodes and no metastasis. The findings related to tumor markers [carbohydrate antigen (CA)-125, CA19-9, CA72-4, and human chorionic gonadotropin) and a hormonal analysis was within normal limits. A right salpingo-oophorectomywasperformedbecause the lesion wasmostly a solid tumor, but edematouswithyellowisheclear liquid (Figure 1). A fresh specimen from the solid part was used to obtain a frozen section, and massive ovarian edema was diagnosed.

Objective To measure the levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) induced by thrombin in endometrial stromal cells (ESC). Design Evaluation of the effects of thrombin, thrombin receptor activator peptide 6 (TRAP-6), and d-phenylalanyl-1-propyl-l arginine chloromethyl ketone (PPACK) on the production of VEGF and MMPs by ESC. Setting Research laboratory at the Oita University Medical School. Patient(s) Eight endometrial specimens in the secretory phase. Intervention(s) ESC were incubated for 24 hours with thrombin, TRAP-6, and PPACK. Main Outcome Measure(s) The levels of VEGF, MMP-1, and active MMP-2 were measured by enzyme-linked immunosorbent assay (ELISA). The presence of protease-activated receptor-1 (PAR-1) and activation of mitogen-activated protein (MAP) kinase were detected by Western blot analysis. Result(s) Following stimulation by thrombin and TRP-6, the production of VEGF, MMP-1, and active MMP-2 statistically significantly increased; U0126 and PPACK statistically significantly suppressed the increases in the production of VEGF, MMP-1, and active MMP-2 induced by thrombin and TRAP-6. Activity by MAP kinase was induced by treatment with thrombin and TRAP-6 and was suppressed by PPACK. Conclusion(s) The results suggest that thrombin stimulates the production of VEGF and MMPs by a mechanism involving the MAP kinase system. The increases in VEGF and MMPs may contribute to neovascularization, which promotes the proliferation of endometrium and placentation.

Objective To evaluate the involvement of transforming growth factor (TGF)-β isoforms (TGF-β1, TGF-β2, and TGF-β3) on endometrial tissue remodeling during the perimenstrual period. Design The effects of TGF-β isoforms on the cell proliferation, motility, and contractivity of cultured human endometrial stromal cells (ESCs) were investigated. Setting Research laboratory at a medical school. Patient(s) Nine endometrial specimens in the late secretory phase were used. Intervention(s) Endometrial stromal cells were incubated with recombinant human recombinant TGF-β1, TGF-β2, and TGF-β3. Main Outcome Measure(s) The cell proliferation, motility, and contractivity of ESCs were accessed by a modified methylthiazoletetrazolium assay, in vitro wound repair assay, transwell invasion assay, and collagen gel contraction assay. Result(s) All three isoforms of TGF-β significantly inhibited the cell proliferation of ESCs in a dose-dependent manner. In vitro wound repair assay and transwell invasion assay demonstrated that the TGF-β isoforms significantly inhibited the motility of ESCs. However, the TGF-β isoforms were shown to have a clear effect on the collagen gel contractivity of ESCs. Conclusion(s) These results suggest that TGF-β isoforms may promote endometrial tissue repair through the inhibition of the proliferation, expansion, and migration of ESCs, and through the stimulation of the contraction of the collagen gel matrix by these cells. Transforming growth factor-β may be involved in the protection of the endometrium from extensive fibrosis and scarring by regulating ESC function during the perimenstrual period.

Objective To measure the level of interleukin 6 (IL-6), IL-8, and macrophage colony-stimulating factor (M-CSF) induced by IL-1α in endometrial stromal cells (ESC) following treatment with ceramide analogues. Design The effects of IL-1α, IL-1 receptor antagonist (IL-1RA), C2-ceramide, and C6-ceramide on the production of IL-6, IL-8, and M-CSF by ESC. Setting Research laboratory at Oita University Medical School. Patient(s) Eleven premenopausal women who had undergone hysterectomies for subserous myoma provided endometrial specimens in the secretory phase. Intervention(s) The ESC were incubated for 24 hours with IL-1α, IL-1RA, C2-ceramide, and C6-ceramide. Main outcome measure(s) The levels of IL-6, IL-8, and M-CSF in the culture media were measured via enzyme-linked immunoabsorbent assay. Result(s): Following stimulation by IL-1α, the production of IL-6, IL-8, and M-CSF showed a statistically significant increase, and they were suppressed by IL-1RA in a dose-dependent manner. Production of IL-6, IL-8, and M-CSF was not statistically significantly increased by IL-1α plus C2-ceramide as compared with IL-1α alone. Production of both IL-8 and M-CSF was statistically significantly increased by IL-1α plus C6-ceramide as compared with IL-1α alone; however, IL-6 production was not increased. Conclusion(s) The results suggest that IL-1α stimulates the production of IL-8 and M-CSF by a mechanism that involves the sphingomyelin-ceramide system. Ceramide may be important in increasing the production of IL-8 and M-CSF in the human endometrium.

Objective To evaluate the effects of leptin on the production of interleukin (IL)-6 family cytokines and chemokines by human endometrial stromal cells (ESC) and epithelial cells. Design The effects of leptin on the production of IL-6, IL-11, leukemia inhibitory factor (LIF), IL-8, growth-regulated oncogene (GRO)-α, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-3α by ESC and the endometrial epithelial cell line HHUA were investigated. Setting Research laboratory at a medical university. Patient(s) Eight endometrial specimens in the late proliferative phase were used for the isolation of ESC. Intervention(s) ESC and HHUA were incubated for 24 hours with recombinant human leptin. Main outcome measure(s) The concentration of IL-6, IL-11, LIF, IL-8, GRO-α, MCP-1, and MIP-3α were measured using ELISAs. Result(s) Unstimulated ESC and HHUA constitutively secreted IL-6, IL-11, LIF, IL-8, GRO-α, MCP-1, and MIP-3α. The increase in levels of IL-6, IL-8, GRO-α, MCP-1, and MIP-3α in the culture media of ESC and HHUA paralleled the addition of increasing amounts of leptin. In contrast, the levels of IL-11 and LIF were not affected by leptin administration. Conclusion(s) The present findings suggest that leptin may be an additional modulator of IL-6 and chemokine expression in the endometrium. Leptin may contribute to the normal and pathological processes of human reproduction by the regulation of these cytokines in the local environment.

Objective: The aim is to clarify the role of platelet-activating factor and colony-stimulating factors in term and preterm parturition. Study Design: Decidual macrophage populations were obtained by an enzymic digestion, Ficoll-Paque centrifugation, or flow cytometric sorting. The effects of colony-stimulating factors on the platelet-activating factor acetylhydrolase secretion by these cells were examined. Results: Granulocyte-macrophage colony-stimulating factor inhibited the platelet-activating factor acetylhydrolase secretion by decidual macrophages. Granulocyte colony-stimulating factor also decreased the enzyme secretion but at higher concentrations than those required for granulocyte colony-stimulating factor. In contrast, macrophage colony-stimulating factor increased the enzyme secretion. These colony-stimulating factor-induced effects were specifically neutralized by the corresponding antibodies. Conclusion: Colony-stimulating factors may modulate the local concentration of platelet-activating factor in the decidua via their inhibitory or stimulatory effect on the secretion of platelet-activating factor acetylhydrolase, contributing to the regulation of term and preterm parturition at the maternal-fetal interface. (Am J Obstet Gynecol 2003;188:157-61.)

Objectives : It has been reported that prostaglandin E 2 (PGE 2 ) is synthesized in the amnion and that this synthesis increases during labor. The purpose of this study was to clarify the mechanism for the expression of cyclooxygenase-2 (COX-2) mRNA and the PGE 2 synthesis of amnion-derived (WISH) cells. Study design : Cells were cultured and treated by 12- O -tetradecanoylphorbol-13-acetate (TPA) and dexamethasone (DEX). PGE 2 in the culture medium was measured by ELISA. Total RNA was extracted from the cells, and COX-2 mRNA expression was analyzed by Northern blot analysis. Results : During the time course of PGE 2 production in response to TPA stimulation, the PGE 2 production could not be detected until incubation had continued for 2h, but this production appeared to continue after 4h of incubation. PGE 2 production was significantly increased by TPA and suppressed by treatment with TPA and DEX. During the time course of COX-2 mRNA expression in response to treatment with TPA, the COX-2 mRNA band was detected after 1.5h. The strongest expression of COX-2 mRNA was observed at 2h incubation. After pre-treatment with TPA for 1h, the TPA-induced COX-2 mRNA was suppressed by treatment with DEX for 1 or 2h incubation in a dose-dependent manner. Conclusions : These results suggest that COX-2 mRNA is induced by TPA which activate protein kinase C, and suppressed by DEX in WISH cells.

Summary PAF, a potent lipid mediator, has been implicated in a number of reproductive processes, including parturition. PAF has been shown to stimulate prostaglandin E 2 production in fetal membranes and to cause myometrial contraction. PAF metabolism in the decidua and its modulation by endotoxin or cytokines has been investigated. Decidual macrophages secrete PAF-AH activity of the plasma type that inactivates PAF. LPS, TNF-α, and IL-1β inhibited the PAF-AH secretion by decidual macrophages. The LPS-inhibition was partially reversed by IL-1ra or by neutralizing antibodies against TNF-α and IL-1β. The effect of IL-1β on the secretion was abolished by IL-1ra. IFN-γ, IL-6, and IL-8 also inhibited the PAF-AH secretion, while M-CSF increased the enzyme secretion. These observations lend additional support to the concept that PAF is pathophysiologically involved in parturition or preterm labor caused by chorioamnionitis, forming a PAF-mediated cytokine network at the fetal-maternal decidual interface.

Tumor necrosis factor-alpha stimulates the secretion of vascular endothelial growth factor by cultured human oviductal epithelial cells and stromal fibroblasts. Tumor necrosis factor-alpha-stimulated vascular endothelial growth factor secretion by these cells may control oviductal fluid secretion by regulating vascular permeability.

The purpose of this investigation was to evaluate the serum level of soluble intercellular adhesion molecule-1 (sICAM-1) in patients with squamous cell carcinoma of the cervix. Serum levels of sICAM-1 were measured by enzyme-linked immunosorbent assay in patients with cervical cancer (stage 0 through IV). Expression of mRNA in tumor tissues was evaluated by reverse transcriptase-polymerase chain reaction. Serum level of sICAM-1 in patients with advanced-stage (II-IV) or recurrent cervical cancer was found to be increased significantly. Expression of ICAM-1 mRNA was observed in most tumor tissues. Results suggest that sICAM-1 is shed from the cancerous tissue in patients with squamous cell carcinoma of the cervix.

Background:Wepreviously demonstrated a remarkably higher association of pelvic endometriosis in women with ovarian endometrioma. However, information regarding occurrence of pelvic endometriosis in women with demoid cyst is unknown even thesewomenexperience similar retrogrademenstruation like womenwithovarianendometriosis.During theprocessof endometrial cell attachment, an event of immunedefect or tolerance occurs that finally decide the survival or clearance of autologous cells in pelvic environment. Here, we retrospectively evaluated recorded files of laparoscopy from 1982 to 2008 at our university and examined the incidence of pelvic endometriosis in women with benign ovarian cysts. Material and methods: We performed a retrospective study conducted in 2988 cases that had undergone laparoscopic surgery between September 1982 and April 2008 for the indication of ectopic pregnancy, tubal infertility and other benign gynecologic diseases. We analyzed occurrence of pelvic endometriosis in women with ovarian endometrioma and dermoid cyst during 25 years observation period.With informed consent, cystwall from20 womenwithdermoidcysts and20womenwithovarianendometrioma and corresponding eutopic endometria and peritoneal tissues were prospectively collected during laparoscopy. Tissue expression of FOXP3+ Treg cells was examined by immunohistochemistry and peritoneal fluid (PF) levels of TGF and IL-6 were measured by ELISA. Results: Among 2988 laparoscopy cases, 350 cases (11.7%)were found to have ovarian endometrioma, 414 (13.8%) cases had dermoid cyst and 398 (13.3%) cases were treated for fertility screening or uterine myoma with bilateral pathology free ovary. A predominance of both ovarian endometrioma and dermoid cysts was found inwomen in their 20th and30thyears of age.Womenwithdermoid cysts had a significantly decreased occurrence of pelvic endometriosis (74 cases, 18.6%) when compared with that of women with ovarian endometrioma (267 cases, 76.3%) and with women with bilateral normal ovary (188 cases, 47.2%). A significantly higher expressionof FOXP3, a transcriptional factorofTregcells,was found in cyst wall and peritoneum of women with dermoid cysts having peritoneal lesions comparing to similar tissues derived from dermoid cysts without any peritoneal lesions. A relationship between FOXP3 expression and TGF /interleukin-6 levels in peritoneal fluid (PF) will be discussed. Conclusions: Higher FOXP3+ Treg cells in the peritoneum may be associated with decreased occurrence of peritoneal lesions in women with benign ovarian cyst. A possible immunosurveillance secondary to different pelvic environmentmight be involved in this protective effect against endometriosis.